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Melanoma experts say ‘no’ to routine gene profile testing
“The currently published evidence is insufficient to establish that routine use of GEP testing provides additional clinical value for melanoma staging and prognostication beyond available clinicopathologic variables,” they argued.
Patients must be protected “from potentially inaccurate testing that may provide a false sense of security or perceived increased risk” that could lead to the wrong decisions, they said in a consensus statement from the United States’ national Melanoma Prevention Working Group. The statement was published on July 29 in JAMA Dermatology.
The GEP test for melanoma that is available in the United States – DecisionDx-Melanoma from Castle Biosciences – checks the expression levels of 31 genes reported to be associated with melanoma metastasis and recurrence. It uses quantitative reverse transcriptase and polymerase chain reaction on RNA from formalin-fixed, paraffin-embedded biopsy specimens.
The test stratifies patients as being at low, intermediate, or high risk. It is marketed as a guide to whether to perform sentinel lymph node biopsies (SLNB) on patients age 55 years or older with tumors less than 2 mm deep and to decide what levels of follow-up, imaging, and adjuvant treatment are appropriate for tumors at least 0.3 mm deep.
Medicare reimburses at $7,193 per test for SLNB-eligible patients.
However, this test is not endorsed by the American Academy of Dermatology or National Comprehensive Cancer Network outside of studies because the evidence of benefit is not strong enough, the consensus authors noted.
Even so, use of the test is growing, with up to 10% of cutaneous melanomas now being tested in the United States.
Company welcomes “further discussions”
“To date, thousands of clinicians – over 4,200 US clinicians in the last 12 months – have utilized our GEP test for cutaneous melanoma in their patients after reviewing our clinical data and determining that our test provides clinically actionable information that complements current melanoma staging,” said Castle Biosciences Vice President of Research and Development Bob Cook, PhD, when asked for comment.
Citing company-funded studies, he said that “the strength of the existing evidence in support of these claims has undergone rigorous evaluation to obtain Medicare reimbursement.”
“We believe that the application of the test to help guide [the] decision to pursue SLNB has the potential to realize significant cost savings by reducing unnecessary SLNB procedures, particularly in the T1 population.”
Asked for a reaction to the consensus statement, Dr. Cook said in an interview: “We recently launched two prospective studies with multiple centers nationwide that will involve thousands of patients and provide additional data relating our tests to patient outcomes. ... We welcome further discussions to promote collaborative efforts with centers that are part of the [Melanoma Prevention Working Group] to improve patient outcomes.”
Cart before the horse
Medicare, although it reimburses the test, has its doubts. Due to the “low strength of evidence,” the Centers for Medicare & Medicaid Services said in their local coverage determination that continued reimbursement depends on demonstration of 95% or greater distant-metastasis–free survival and melanoma-specific survival at 3 years “in patients directed to no SLNB by the test compared to standard of care, and ... evidence of higher SLNB positivity in patients selected for this procedure by the test compared to standard of care.”
The statement hints at the Achilles’ heel of GEP in melanoma – that is, the lack of evidence that test results improve outcomes. This was the main concern of the consensus statement; the cart is before the horse.
One of the consensus authors, David Polsky, MD, PhD, professor of dermatologic oncology at New York University, New York City, said that “most of the data for this test come from retrospectively collected patient groups.” The prospective studies have been generally small, with no comparator group. “While they have shown some promise in intermediate thickness melanoma, they have not yet demonstrated utility for thin, stage I melanomas.”
First, do no harm
A new meta-analysis of over 800 patients with cutaneous melanoma tested by DecisionDx-Melanoma, published in JAMA Dermatology alongside the consensus statement, shows how the tests perform.
Among patients with a recurrence, DecisionDx-Melanoma correctly classified 82% with stage II disease but only 29% with stage I disease as high risk. Among those without recurrence, the test correctly classified 90% of stage I patients but only 44% with stage II disease as low risk.
Similar results were seen with the melanoma GEP test available in Europe, MelaGenix (NeraCare GmbH). This test was developed from a panel that was narrowed to seven protective genes and one high-risk gene using a training cohort of 125 cutaneous melanomas.
“The prognostic ability of GEP tests ... appeared to be poor at correctly identifying recurrence in patients with stage I disease, suggesting limited potential for clinical utility in these patients,” commented the meta-analysis authors, led by Michael Marchetti, MD, an assistant professor of dermatology at Weill Cornell Medical College in New York City.
“Unknown are the harms associated with a false-positive result, which were 10-fold more frequent than true-positive results in patients with stage I disease,” they pointed out.
“Further research is needed to define the incremental improvement in risk predictions provided by the test beyond ... all other known clinicopathologic factors,” which include patient sex, age, tumor location and thickness, ulceration, mitotic rate, lymphovascular invasion, microsatellites, and other factors proven to be linked to outcomes, they said.
Studies so far suggesting benefit have incorporated a few of those factors, but not all of them. For now, “it is not clear which patients should be tested or how to act on the results,” Dr. Marchetti and colleagues concluded.
Breast cancer standard of proof
Larger, prospective studies are needed to address whether GEP testing can replace SLNB to predict relapse “and [can identify] patients who could be spared surveillance imaging and/or benefit from adjuvant therapy,” wrote the consensus authors. Follow-up also needs to be long enough to detect delayed recurrence of thin melanomas, they added.
With more research, there is reason to hope that gene expression profiling will help in melanoma; it’s already standard of care in breast cancer, they pointed out.
On the hope front, one cohort study evaluated whether DecisionDx-Melanoma could identify patients at low risk for positive lymph nodes in T1/T2 disease who were eligible for biopsy. Only 1.6% of subjects who were aged 65 years or older and identified by the test as low risk had a positive node.
“This is a promising direction of investigation ... in a narrow, defined population,” noted authors led by Carrie Kovarik, MD, associate professor of dermatology at the University of Pennsylvania, Philadelphia, in an opinion piece last spring.
But still, until there’s “clear evidence that [DecisionDx-Melanoma] results affect patient outcomes, we should not use it to influence care decisions in patients with thin” melanomas. Dermatology “should expect the same standards” of proof as breast cancer, they wrote.
What to do right now?
Despite the marketing, “think twice before ordering GEP tests for” T1a melanomas is the message in an editorial that accompanies the consensus statement. The 5- and 10-year melanoma-specific survival rates are 99% and 98%, respectively. GEP tests are unlikely to change these estimates significantly. In fact, the new meta-analysis indicates “that there may be an approximately 12% misassignment rate in this population,” wrote editorialists Warren Chan, of Baylor College of Medicine, Houston and Hensin Tsao, MD, PhD, director of the melanoma genetics program at Massachusetts General Hospital, Boston.
“Even if you use GEP testing and discover a low-risk class assignment for a 2 mm thick melanoma, avoid the urge to bypass the sentinel lymph node discussion. ... Nodal sampling, for good reasons, remains part of all major guidelines and determines eligibility for adjuvant treatments. ... Many of us engaged in genomics research believe that accurate [melanoma] GEP will be developed in time, but better tools and greater tenacity are needed,” they wrote.
There was no industry funding for the consensus statement and meta-analysis. Authors on the consensus statement reported numerous ties to pharmaceutical and other companies, as listed in the paper.
A version of this article originally appeared on Medscape.com.
“The currently published evidence is insufficient to establish that routine use of GEP testing provides additional clinical value for melanoma staging and prognostication beyond available clinicopathologic variables,” they argued.
Patients must be protected “from potentially inaccurate testing that may provide a false sense of security or perceived increased risk” that could lead to the wrong decisions, they said in a consensus statement from the United States’ national Melanoma Prevention Working Group. The statement was published on July 29 in JAMA Dermatology.
The GEP test for melanoma that is available in the United States – DecisionDx-Melanoma from Castle Biosciences – checks the expression levels of 31 genes reported to be associated with melanoma metastasis and recurrence. It uses quantitative reverse transcriptase and polymerase chain reaction on RNA from formalin-fixed, paraffin-embedded biopsy specimens.
The test stratifies patients as being at low, intermediate, or high risk. It is marketed as a guide to whether to perform sentinel lymph node biopsies (SLNB) on patients age 55 years or older with tumors less than 2 mm deep and to decide what levels of follow-up, imaging, and adjuvant treatment are appropriate for tumors at least 0.3 mm deep.
Medicare reimburses at $7,193 per test for SLNB-eligible patients.
However, this test is not endorsed by the American Academy of Dermatology or National Comprehensive Cancer Network outside of studies because the evidence of benefit is not strong enough, the consensus authors noted.
Even so, use of the test is growing, with up to 10% of cutaneous melanomas now being tested in the United States.
Company welcomes “further discussions”
“To date, thousands of clinicians – over 4,200 US clinicians in the last 12 months – have utilized our GEP test for cutaneous melanoma in their patients after reviewing our clinical data and determining that our test provides clinically actionable information that complements current melanoma staging,” said Castle Biosciences Vice President of Research and Development Bob Cook, PhD, when asked for comment.
Citing company-funded studies, he said that “the strength of the existing evidence in support of these claims has undergone rigorous evaluation to obtain Medicare reimbursement.”
“We believe that the application of the test to help guide [the] decision to pursue SLNB has the potential to realize significant cost savings by reducing unnecessary SLNB procedures, particularly in the T1 population.”
Asked for a reaction to the consensus statement, Dr. Cook said in an interview: “We recently launched two prospective studies with multiple centers nationwide that will involve thousands of patients and provide additional data relating our tests to patient outcomes. ... We welcome further discussions to promote collaborative efforts with centers that are part of the [Melanoma Prevention Working Group] to improve patient outcomes.”
Cart before the horse
Medicare, although it reimburses the test, has its doubts. Due to the “low strength of evidence,” the Centers for Medicare & Medicaid Services said in their local coverage determination that continued reimbursement depends on demonstration of 95% or greater distant-metastasis–free survival and melanoma-specific survival at 3 years “in patients directed to no SLNB by the test compared to standard of care, and ... evidence of higher SLNB positivity in patients selected for this procedure by the test compared to standard of care.”
The statement hints at the Achilles’ heel of GEP in melanoma – that is, the lack of evidence that test results improve outcomes. This was the main concern of the consensus statement; the cart is before the horse.
One of the consensus authors, David Polsky, MD, PhD, professor of dermatologic oncology at New York University, New York City, said that “most of the data for this test come from retrospectively collected patient groups.” The prospective studies have been generally small, with no comparator group. “While they have shown some promise in intermediate thickness melanoma, they have not yet demonstrated utility for thin, stage I melanomas.”
First, do no harm
A new meta-analysis of over 800 patients with cutaneous melanoma tested by DecisionDx-Melanoma, published in JAMA Dermatology alongside the consensus statement, shows how the tests perform.
Among patients with a recurrence, DecisionDx-Melanoma correctly classified 82% with stage II disease but only 29% with stage I disease as high risk. Among those without recurrence, the test correctly classified 90% of stage I patients but only 44% with stage II disease as low risk.
Similar results were seen with the melanoma GEP test available in Europe, MelaGenix (NeraCare GmbH). This test was developed from a panel that was narrowed to seven protective genes and one high-risk gene using a training cohort of 125 cutaneous melanomas.
“The prognostic ability of GEP tests ... appeared to be poor at correctly identifying recurrence in patients with stage I disease, suggesting limited potential for clinical utility in these patients,” commented the meta-analysis authors, led by Michael Marchetti, MD, an assistant professor of dermatology at Weill Cornell Medical College in New York City.
“Unknown are the harms associated with a false-positive result, which were 10-fold more frequent than true-positive results in patients with stage I disease,” they pointed out.
“Further research is needed to define the incremental improvement in risk predictions provided by the test beyond ... all other known clinicopathologic factors,” which include patient sex, age, tumor location and thickness, ulceration, mitotic rate, lymphovascular invasion, microsatellites, and other factors proven to be linked to outcomes, they said.
Studies so far suggesting benefit have incorporated a few of those factors, but not all of them. For now, “it is not clear which patients should be tested or how to act on the results,” Dr. Marchetti and colleagues concluded.
Breast cancer standard of proof
Larger, prospective studies are needed to address whether GEP testing can replace SLNB to predict relapse “and [can identify] patients who could be spared surveillance imaging and/or benefit from adjuvant therapy,” wrote the consensus authors. Follow-up also needs to be long enough to detect delayed recurrence of thin melanomas, they added.
With more research, there is reason to hope that gene expression profiling will help in melanoma; it’s already standard of care in breast cancer, they pointed out.
On the hope front, one cohort study evaluated whether DecisionDx-Melanoma could identify patients at low risk for positive lymph nodes in T1/T2 disease who were eligible for biopsy. Only 1.6% of subjects who were aged 65 years or older and identified by the test as low risk had a positive node.
“This is a promising direction of investigation ... in a narrow, defined population,” noted authors led by Carrie Kovarik, MD, associate professor of dermatology at the University of Pennsylvania, Philadelphia, in an opinion piece last spring.
But still, until there’s “clear evidence that [DecisionDx-Melanoma] results affect patient outcomes, we should not use it to influence care decisions in patients with thin” melanomas. Dermatology “should expect the same standards” of proof as breast cancer, they wrote.
What to do right now?
Despite the marketing, “think twice before ordering GEP tests for” T1a melanomas is the message in an editorial that accompanies the consensus statement. The 5- and 10-year melanoma-specific survival rates are 99% and 98%, respectively. GEP tests are unlikely to change these estimates significantly. In fact, the new meta-analysis indicates “that there may be an approximately 12% misassignment rate in this population,” wrote editorialists Warren Chan, of Baylor College of Medicine, Houston and Hensin Tsao, MD, PhD, director of the melanoma genetics program at Massachusetts General Hospital, Boston.
“Even if you use GEP testing and discover a low-risk class assignment for a 2 mm thick melanoma, avoid the urge to bypass the sentinel lymph node discussion. ... Nodal sampling, for good reasons, remains part of all major guidelines and determines eligibility for adjuvant treatments. ... Many of us engaged in genomics research believe that accurate [melanoma] GEP will be developed in time, but better tools and greater tenacity are needed,” they wrote.
There was no industry funding for the consensus statement and meta-analysis. Authors on the consensus statement reported numerous ties to pharmaceutical and other companies, as listed in the paper.
A version of this article originally appeared on Medscape.com.
“The currently published evidence is insufficient to establish that routine use of GEP testing provides additional clinical value for melanoma staging and prognostication beyond available clinicopathologic variables,” they argued.
Patients must be protected “from potentially inaccurate testing that may provide a false sense of security or perceived increased risk” that could lead to the wrong decisions, they said in a consensus statement from the United States’ national Melanoma Prevention Working Group. The statement was published on July 29 in JAMA Dermatology.
The GEP test for melanoma that is available in the United States – DecisionDx-Melanoma from Castle Biosciences – checks the expression levels of 31 genes reported to be associated with melanoma metastasis and recurrence. It uses quantitative reverse transcriptase and polymerase chain reaction on RNA from formalin-fixed, paraffin-embedded biopsy specimens.
The test stratifies patients as being at low, intermediate, or high risk. It is marketed as a guide to whether to perform sentinel lymph node biopsies (SLNB) on patients age 55 years or older with tumors less than 2 mm deep and to decide what levels of follow-up, imaging, and adjuvant treatment are appropriate for tumors at least 0.3 mm deep.
Medicare reimburses at $7,193 per test for SLNB-eligible patients.
However, this test is not endorsed by the American Academy of Dermatology or National Comprehensive Cancer Network outside of studies because the evidence of benefit is not strong enough, the consensus authors noted.
Even so, use of the test is growing, with up to 10% of cutaneous melanomas now being tested in the United States.
Company welcomes “further discussions”
“To date, thousands of clinicians – over 4,200 US clinicians in the last 12 months – have utilized our GEP test for cutaneous melanoma in their patients after reviewing our clinical data and determining that our test provides clinically actionable information that complements current melanoma staging,” said Castle Biosciences Vice President of Research and Development Bob Cook, PhD, when asked for comment.
Citing company-funded studies, he said that “the strength of the existing evidence in support of these claims has undergone rigorous evaluation to obtain Medicare reimbursement.”
“We believe that the application of the test to help guide [the] decision to pursue SLNB has the potential to realize significant cost savings by reducing unnecessary SLNB procedures, particularly in the T1 population.”
Asked for a reaction to the consensus statement, Dr. Cook said in an interview: “We recently launched two prospective studies with multiple centers nationwide that will involve thousands of patients and provide additional data relating our tests to patient outcomes. ... We welcome further discussions to promote collaborative efforts with centers that are part of the [Melanoma Prevention Working Group] to improve patient outcomes.”
Cart before the horse
Medicare, although it reimburses the test, has its doubts. Due to the “low strength of evidence,” the Centers for Medicare & Medicaid Services said in their local coverage determination that continued reimbursement depends on demonstration of 95% or greater distant-metastasis–free survival and melanoma-specific survival at 3 years “in patients directed to no SLNB by the test compared to standard of care, and ... evidence of higher SLNB positivity in patients selected for this procedure by the test compared to standard of care.”
The statement hints at the Achilles’ heel of GEP in melanoma – that is, the lack of evidence that test results improve outcomes. This was the main concern of the consensus statement; the cart is before the horse.
One of the consensus authors, David Polsky, MD, PhD, professor of dermatologic oncology at New York University, New York City, said that “most of the data for this test come from retrospectively collected patient groups.” The prospective studies have been generally small, with no comparator group. “While they have shown some promise in intermediate thickness melanoma, they have not yet demonstrated utility for thin, stage I melanomas.”
First, do no harm
A new meta-analysis of over 800 patients with cutaneous melanoma tested by DecisionDx-Melanoma, published in JAMA Dermatology alongside the consensus statement, shows how the tests perform.
Among patients with a recurrence, DecisionDx-Melanoma correctly classified 82% with stage II disease but only 29% with stage I disease as high risk. Among those without recurrence, the test correctly classified 90% of stage I patients but only 44% with stage II disease as low risk.
Similar results were seen with the melanoma GEP test available in Europe, MelaGenix (NeraCare GmbH). This test was developed from a panel that was narrowed to seven protective genes and one high-risk gene using a training cohort of 125 cutaneous melanomas.
“The prognostic ability of GEP tests ... appeared to be poor at correctly identifying recurrence in patients with stage I disease, suggesting limited potential for clinical utility in these patients,” commented the meta-analysis authors, led by Michael Marchetti, MD, an assistant professor of dermatology at Weill Cornell Medical College in New York City.
“Unknown are the harms associated with a false-positive result, which were 10-fold more frequent than true-positive results in patients with stage I disease,” they pointed out.
“Further research is needed to define the incremental improvement in risk predictions provided by the test beyond ... all other known clinicopathologic factors,” which include patient sex, age, tumor location and thickness, ulceration, mitotic rate, lymphovascular invasion, microsatellites, and other factors proven to be linked to outcomes, they said.
Studies so far suggesting benefit have incorporated a few of those factors, but not all of them. For now, “it is not clear which patients should be tested or how to act on the results,” Dr. Marchetti and colleagues concluded.
Breast cancer standard of proof
Larger, prospective studies are needed to address whether GEP testing can replace SLNB to predict relapse “and [can identify] patients who could be spared surveillance imaging and/or benefit from adjuvant therapy,” wrote the consensus authors. Follow-up also needs to be long enough to detect delayed recurrence of thin melanomas, they added.
With more research, there is reason to hope that gene expression profiling will help in melanoma; it’s already standard of care in breast cancer, they pointed out.
On the hope front, one cohort study evaluated whether DecisionDx-Melanoma could identify patients at low risk for positive lymph nodes in T1/T2 disease who were eligible for biopsy. Only 1.6% of subjects who were aged 65 years or older and identified by the test as low risk had a positive node.
“This is a promising direction of investigation ... in a narrow, defined population,” noted authors led by Carrie Kovarik, MD, associate professor of dermatology at the University of Pennsylvania, Philadelphia, in an opinion piece last spring.
But still, until there’s “clear evidence that [DecisionDx-Melanoma] results affect patient outcomes, we should not use it to influence care decisions in patients with thin” melanomas. Dermatology “should expect the same standards” of proof as breast cancer, they wrote.
What to do right now?
Despite the marketing, “think twice before ordering GEP tests for” T1a melanomas is the message in an editorial that accompanies the consensus statement. The 5- and 10-year melanoma-specific survival rates are 99% and 98%, respectively. GEP tests are unlikely to change these estimates significantly. In fact, the new meta-analysis indicates “that there may be an approximately 12% misassignment rate in this population,” wrote editorialists Warren Chan, of Baylor College of Medicine, Houston and Hensin Tsao, MD, PhD, director of the melanoma genetics program at Massachusetts General Hospital, Boston.
“Even if you use GEP testing and discover a low-risk class assignment for a 2 mm thick melanoma, avoid the urge to bypass the sentinel lymph node discussion. ... Nodal sampling, for good reasons, remains part of all major guidelines and determines eligibility for adjuvant treatments. ... Many of us engaged in genomics research believe that accurate [melanoma] GEP will be developed in time, but better tools and greater tenacity are needed,” they wrote.
There was no industry funding for the consensus statement and meta-analysis. Authors on the consensus statement reported numerous ties to pharmaceutical and other companies, as listed in the paper.
A version of this article originally appeared on Medscape.com.
VTE, sepsis risk increased among COVID-19 patients with cancer
, according to data from a registry study.
Researchers analyzed data on 5,556 patients with COVID-19 who had an inpatient or emergency encounter at Mount Sinai Health System (MSHS) in New York between March 1 and May 27, 2020. Patients were included in an anonymous MSHS COVID-19 registry.
There were 421 patients who had cancer: 96 with a hematologic malignancy and 325 with solid tumors.
After adjustment for age, gender, and number of comorbidities, the odds ratios for acute VTE and sepsis for patients with cancer (versus those without cancer) were 1.77 and 1.34, respectively. The adjusted odds ratio for mortality in cancer patients was 1.02.
The results remained “relatively consistent” after stratification by solid and nonsolid cancer types, with no significant difference in outcomes between those two groups, and results remained consistent in a propensity-matched model, according to Naomi Alpert, a biostatistician at Icahn School of Medicine at Mount Sinai, New York.
Ms. Alpert reported these findings at the AACR virtual meeting: COVID-19 and Cancer.
She noted that the cancer patients were older than the noncancer patients (mean age, 69.2 years vs. 63.8 years), and cancer patients were more likely to have two or more comorbid conditions (48.2% vs. 30.4%). Cancer patients also had significantly lower hemoglobin levels and red blood cell, platelet, and white blood cell counts (P < .01 for all).
“Low white blood cell count may be one of the reasons for higher risk of sepsis in cancer patients, as it may lead to a higher risk of infection,” Ms. Alpert said. “However, it’s not clear what role cancer therapies play in the risks of COVID-19 morbidity and mortality, so there is still quite a bit to learn.”
In fact, the findings are limited by a lack of information about cancer treatment, as the registry was not designed for that purpose, she noted.
Another study limitation is the short follow-up of a month or less in most patients, due, in part, to the novelty of COVID-19, but also to the lack of information on patients after they left the hospital.
“However, we had a very large sample size, with more than 400 cancer patients included, and, to our knowledge, this is the largest analysis of its kind to be done so far,” Ms. Alpert said. “In the future, it’s going to be very important to assess the effect of cancer therapies on COVID-19 complications and to see if prior therapies had any effect on outcomes.”
Longer follow-up would also be helpful for assessing the chronic effects of COVID-19 on cancer patients over time, she said. “It would be important to see whether some of these elevated risks of venous thromboembolism and sepsis are associated with longer-term mortality risks than what we were able to measure here,” she added.
Asked about the discrepancy between mortality in this study and those of larger registries, such as the COVID-19 and Cancer Consortium (CCC19) and TERAVOLT, Ms. Alpert noted that the current study included only patients who required hospitalization or emergency care.
“Our mortality rate was actually a bit higher than what was reported in some of the other studies,” she said. “We had about a 30% mortality rate in the cancer patients and about 25% for the noncancer patients, so ... we’re sort of looking at a subset of patients who we know are the sickest of the sick, which may explain some of the higher mortality that we’re seeing.”
Ms. Alpert reported having no disclosures.
SOURCE: Alpert N et al. AACR COVID-19 and Cancer, Abstract S12-02.
, according to data from a registry study.
Researchers analyzed data on 5,556 patients with COVID-19 who had an inpatient or emergency encounter at Mount Sinai Health System (MSHS) in New York between March 1 and May 27, 2020. Patients were included in an anonymous MSHS COVID-19 registry.
There were 421 patients who had cancer: 96 with a hematologic malignancy and 325 with solid tumors.
After adjustment for age, gender, and number of comorbidities, the odds ratios for acute VTE and sepsis for patients with cancer (versus those without cancer) were 1.77 and 1.34, respectively. The adjusted odds ratio for mortality in cancer patients was 1.02.
The results remained “relatively consistent” after stratification by solid and nonsolid cancer types, with no significant difference in outcomes between those two groups, and results remained consistent in a propensity-matched model, according to Naomi Alpert, a biostatistician at Icahn School of Medicine at Mount Sinai, New York.
Ms. Alpert reported these findings at the AACR virtual meeting: COVID-19 and Cancer.
She noted that the cancer patients were older than the noncancer patients (mean age, 69.2 years vs. 63.8 years), and cancer patients were more likely to have two or more comorbid conditions (48.2% vs. 30.4%). Cancer patients also had significantly lower hemoglobin levels and red blood cell, platelet, and white blood cell counts (P < .01 for all).
“Low white blood cell count may be one of the reasons for higher risk of sepsis in cancer patients, as it may lead to a higher risk of infection,” Ms. Alpert said. “However, it’s not clear what role cancer therapies play in the risks of COVID-19 morbidity and mortality, so there is still quite a bit to learn.”
In fact, the findings are limited by a lack of information about cancer treatment, as the registry was not designed for that purpose, she noted.
Another study limitation is the short follow-up of a month or less in most patients, due, in part, to the novelty of COVID-19, but also to the lack of information on patients after they left the hospital.
“However, we had a very large sample size, with more than 400 cancer patients included, and, to our knowledge, this is the largest analysis of its kind to be done so far,” Ms. Alpert said. “In the future, it’s going to be very important to assess the effect of cancer therapies on COVID-19 complications and to see if prior therapies had any effect on outcomes.”
Longer follow-up would also be helpful for assessing the chronic effects of COVID-19 on cancer patients over time, she said. “It would be important to see whether some of these elevated risks of venous thromboembolism and sepsis are associated with longer-term mortality risks than what we were able to measure here,” she added.
Asked about the discrepancy between mortality in this study and those of larger registries, such as the COVID-19 and Cancer Consortium (CCC19) and TERAVOLT, Ms. Alpert noted that the current study included only patients who required hospitalization or emergency care.
“Our mortality rate was actually a bit higher than what was reported in some of the other studies,” she said. “We had about a 30% mortality rate in the cancer patients and about 25% for the noncancer patients, so ... we’re sort of looking at a subset of patients who we know are the sickest of the sick, which may explain some of the higher mortality that we’re seeing.”
Ms. Alpert reported having no disclosures.
SOURCE: Alpert N et al. AACR COVID-19 and Cancer, Abstract S12-02.
, according to data from a registry study.
Researchers analyzed data on 5,556 patients with COVID-19 who had an inpatient or emergency encounter at Mount Sinai Health System (MSHS) in New York between March 1 and May 27, 2020. Patients were included in an anonymous MSHS COVID-19 registry.
There were 421 patients who had cancer: 96 with a hematologic malignancy and 325 with solid tumors.
After adjustment for age, gender, and number of comorbidities, the odds ratios for acute VTE and sepsis for patients with cancer (versus those without cancer) were 1.77 and 1.34, respectively. The adjusted odds ratio for mortality in cancer patients was 1.02.
The results remained “relatively consistent” after stratification by solid and nonsolid cancer types, with no significant difference in outcomes between those two groups, and results remained consistent in a propensity-matched model, according to Naomi Alpert, a biostatistician at Icahn School of Medicine at Mount Sinai, New York.
Ms. Alpert reported these findings at the AACR virtual meeting: COVID-19 and Cancer.
She noted that the cancer patients were older than the noncancer patients (mean age, 69.2 years vs. 63.8 years), and cancer patients were more likely to have two or more comorbid conditions (48.2% vs. 30.4%). Cancer patients also had significantly lower hemoglobin levels and red blood cell, platelet, and white blood cell counts (P < .01 for all).
“Low white blood cell count may be one of the reasons for higher risk of sepsis in cancer patients, as it may lead to a higher risk of infection,” Ms. Alpert said. “However, it’s not clear what role cancer therapies play in the risks of COVID-19 morbidity and mortality, so there is still quite a bit to learn.”
In fact, the findings are limited by a lack of information about cancer treatment, as the registry was not designed for that purpose, she noted.
Another study limitation is the short follow-up of a month or less in most patients, due, in part, to the novelty of COVID-19, but also to the lack of information on patients after they left the hospital.
“However, we had a very large sample size, with more than 400 cancer patients included, and, to our knowledge, this is the largest analysis of its kind to be done so far,” Ms. Alpert said. “In the future, it’s going to be very important to assess the effect of cancer therapies on COVID-19 complications and to see if prior therapies had any effect on outcomes.”
Longer follow-up would also be helpful for assessing the chronic effects of COVID-19 on cancer patients over time, she said. “It would be important to see whether some of these elevated risks of venous thromboembolism and sepsis are associated with longer-term mortality risks than what we were able to measure here,” she added.
Asked about the discrepancy between mortality in this study and those of larger registries, such as the COVID-19 and Cancer Consortium (CCC19) and TERAVOLT, Ms. Alpert noted that the current study included only patients who required hospitalization or emergency care.
“Our mortality rate was actually a bit higher than what was reported in some of the other studies,” she said. “We had about a 30% mortality rate in the cancer patients and about 25% for the noncancer patients, so ... we’re sort of looking at a subset of patients who we know are the sickest of the sick, which may explain some of the higher mortality that we’re seeing.”
Ms. Alpert reported having no disclosures.
SOURCE: Alpert N et al. AACR COVID-19 and Cancer, Abstract S12-02.
FROM AACR: COVID-19 AND CANCER
Immunotherapy should not be withheld because of sex, age, or PS
The improvement in survival in many cancer types that is seen with immune checkpoint inhibitors (ICIs), when compared to control therapies, is not affected by the patient’s sex, age, or Eastern Cooperative Oncology Group (ECOG) performance status (PS), according to a new meta-analysis.
Therefore, treatment with these immunotherapies should not be withheld on the basis of these factors, the authors concluded.
Asked whether there have been such instances of withholding ICIs, lead author Yucai Wang, MD, PhD, Mayo Clinic, Rochester, Minnesota, told Medscape Medical News: “We did this study solely based on scientific questions we had and not because we were seeing any bias at the moment in the use of ICIs.
“And we saw that the survival benefits were very similar across all of the categories [we analyzed], with a survival benefit of about 20% from immunotherapy across the board, which is clinically meaningful,” he added.
The study was published online August 7 in JAMA Network Open.
“The comparable survival advantage between patients of different sex, age, and ECOG PS may encourage more patients to receive ICI treatment regardless of cancer types, lines of therapy, agents of immunotherapy, and intervention therapies,” the authors commented.
Wang noted that there have been conflicting reports in the literature suggesting that male patients may benefit more from immunotherapy than female patients and that older patients may benefit more from the same treatment than younger patients.
However, there are also suggestions in the literature that women experience a stronger immune response than men and that, with aging, the immune system generally undergoes immunosenescence.
In addition, the PS of oncology patients has been implicated in how well patients respond to immunotherapy.
Wang noted that the findings of past studies have contradicted each other.
Findings of the Meta-Analysis
The meta-analysis included 37 randomized clinical trials that involved a total of 23,760 patients with a variety of advanced cancers. “Most of the trials were phase 3 (n = 34) and conduced for subsequent lines of therapy (n = 22),” the authors explained.
The most common cancers treated with an ICI were non–small cell lung cancer and melanoma.
Pooled overall survival (OS) hazard ratios (HRs) were calculated on the basis of sex, age (younger than 65 years and 65 years and older), and an ECOG PS of 0 and 1 or higher.
Responses were stratified on the basis of cancer type, line of therapy, the ICI used, and the immunotherapy strategy used in the ICI arm.
Most of the drugs evaluated were PD-1 and PD-L1 inhibitors. The specific drugs assessed included ipilimumab, tremelimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab.
A total of 32 trials that involved more than 20,000 patients reported HRs for death according to the patients’ sex. Thirty-four trials that involved more than 21,000 patients reported HRs for death according to patients’ age, and 30 trials that involved more than 19,000 patients reported HRs for death according to patients’ ECOG PS.
No significant differences in OS benefit were seen by cancer type, line of therapy, agent of immunotherapy, or intervention strategy, the investigators pointed out.
There were also no differences in survival benefit associated with immunotherapy vs control therapies for patients with an ECOG PS of 0 and an ECOG PS of 1 or greater. The OS benefit was 0.81 for those with an ECOG PS of 0 and 0.79 for those with an ECOG PS of 1 or greater.
Wang has disclosed no relevant financial relationships.
This article first appeared on Medscape.com .
The improvement in survival in many cancer types that is seen with immune checkpoint inhibitors (ICIs), when compared to control therapies, is not affected by the patient’s sex, age, or Eastern Cooperative Oncology Group (ECOG) performance status (PS), according to a new meta-analysis.
Therefore, treatment with these immunotherapies should not be withheld on the basis of these factors, the authors concluded.
Asked whether there have been such instances of withholding ICIs, lead author Yucai Wang, MD, PhD, Mayo Clinic, Rochester, Minnesota, told Medscape Medical News: “We did this study solely based on scientific questions we had and not because we were seeing any bias at the moment in the use of ICIs.
“And we saw that the survival benefits were very similar across all of the categories [we analyzed], with a survival benefit of about 20% from immunotherapy across the board, which is clinically meaningful,” he added.
The study was published online August 7 in JAMA Network Open.
“The comparable survival advantage between patients of different sex, age, and ECOG PS may encourage more patients to receive ICI treatment regardless of cancer types, lines of therapy, agents of immunotherapy, and intervention therapies,” the authors commented.
Wang noted that there have been conflicting reports in the literature suggesting that male patients may benefit more from immunotherapy than female patients and that older patients may benefit more from the same treatment than younger patients.
However, there are also suggestions in the literature that women experience a stronger immune response than men and that, with aging, the immune system generally undergoes immunosenescence.
In addition, the PS of oncology patients has been implicated in how well patients respond to immunotherapy.
Wang noted that the findings of past studies have contradicted each other.
Findings of the Meta-Analysis
The meta-analysis included 37 randomized clinical trials that involved a total of 23,760 patients with a variety of advanced cancers. “Most of the trials were phase 3 (n = 34) and conduced for subsequent lines of therapy (n = 22),” the authors explained.
The most common cancers treated with an ICI were non–small cell lung cancer and melanoma.
Pooled overall survival (OS) hazard ratios (HRs) were calculated on the basis of sex, age (younger than 65 years and 65 years and older), and an ECOG PS of 0 and 1 or higher.
Responses were stratified on the basis of cancer type, line of therapy, the ICI used, and the immunotherapy strategy used in the ICI arm.
Most of the drugs evaluated were PD-1 and PD-L1 inhibitors. The specific drugs assessed included ipilimumab, tremelimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab.
A total of 32 trials that involved more than 20,000 patients reported HRs for death according to the patients’ sex. Thirty-four trials that involved more than 21,000 patients reported HRs for death according to patients’ age, and 30 trials that involved more than 19,000 patients reported HRs for death according to patients’ ECOG PS.
No significant differences in OS benefit were seen by cancer type, line of therapy, agent of immunotherapy, or intervention strategy, the investigators pointed out.
There were also no differences in survival benefit associated with immunotherapy vs control therapies for patients with an ECOG PS of 0 and an ECOG PS of 1 or greater. The OS benefit was 0.81 for those with an ECOG PS of 0 and 0.79 for those with an ECOG PS of 1 or greater.
Wang has disclosed no relevant financial relationships.
This article first appeared on Medscape.com .
The improvement in survival in many cancer types that is seen with immune checkpoint inhibitors (ICIs), when compared to control therapies, is not affected by the patient’s sex, age, or Eastern Cooperative Oncology Group (ECOG) performance status (PS), according to a new meta-analysis.
Therefore, treatment with these immunotherapies should not be withheld on the basis of these factors, the authors concluded.
Asked whether there have been such instances of withholding ICIs, lead author Yucai Wang, MD, PhD, Mayo Clinic, Rochester, Minnesota, told Medscape Medical News: “We did this study solely based on scientific questions we had and not because we were seeing any bias at the moment in the use of ICIs.
“And we saw that the survival benefits were very similar across all of the categories [we analyzed], with a survival benefit of about 20% from immunotherapy across the board, which is clinically meaningful,” he added.
The study was published online August 7 in JAMA Network Open.
“The comparable survival advantage between patients of different sex, age, and ECOG PS may encourage more patients to receive ICI treatment regardless of cancer types, lines of therapy, agents of immunotherapy, and intervention therapies,” the authors commented.
Wang noted that there have been conflicting reports in the literature suggesting that male patients may benefit more from immunotherapy than female patients and that older patients may benefit more from the same treatment than younger patients.
However, there are also suggestions in the literature that women experience a stronger immune response than men and that, with aging, the immune system generally undergoes immunosenescence.
In addition, the PS of oncology patients has been implicated in how well patients respond to immunotherapy.
Wang noted that the findings of past studies have contradicted each other.
Findings of the Meta-Analysis
The meta-analysis included 37 randomized clinical trials that involved a total of 23,760 patients with a variety of advanced cancers. “Most of the trials were phase 3 (n = 34) and conduced for subsequent lines of therapy (n = 22),” the authors explained.
The most common cancers treated with an ICI were non–small cell lung cancer and melanoma.
Pooled overall survival (OS) hazard ratios (HRs) were calculated on the basis of sex, age (younger than 65 years and 65 years and older), and an ECOG PS of 0 and 1 or higher.
Responses were stratified on the basis of cancer type, line of therapy, the ICI used, and the immunotherapy strategy used in the ICI arm.
Most of the drugs evaluated were PD-1 and PD-L1 inhibitors. The specific drugs assessed included ipilimumab, tremelimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab.
A total of 32 trials that involved more than 20,000 patients reported HRs for death according to the patients’ sex. Thirty-four trials that involved more than 21,000 patients reported HRs for death according to patients’ age, and 30 trials that involved more than 19,000 patients reported HRs for death according to patients’ ECOG PS.
No significant differences in OS benefit were seen by cancer type, line of therapy, agent of immunotherapy, or intervention strategy, the investigators pointed out.
There were also no differences in survival benefit associated with immunotherapy vs control therapies for patients with an ECOG PS of 0 and an ECOG PS of 1 or greater. The OS benefit was 0.81 for those with an ECOG PS of 0 and 0.79 for those with an ECOG PS of 1 or greater.
Wang has disclosed no relevant financial relationships.
This article first appeared on Medscape.com .
Aspirin may accelerate cancer progression in older adults
Aspirin may accelerate the progression of advanced cancers and lead to an earlier death as a result, new data from the ASPREE study suggest.
The results showed that patients 65 years and older who started taking daily low-dose aspirin had a 19% higher chance of being diagnosed with metastatic cancer, a 22% higher chance of being diagnosed with a stage 4 tumor, and a 31% increased risk of death from stage 4 cancer, when compared with patients who took a placebo.
John J. McNeil, MBBS, PhD, of Monash University in Melbourne, Australia, and colleagues detailed these findings in the Journal of the National Cancer Institute.
“If confirmed, the clinical implications of these findings could be important for the use of aspirin in an older population,” the authors wrote.
When results of the ASPREE study were first reported in 2018, they “raised important concerns,” Ernest Hawk, MD, and Karen Colbert Maresso wrote in an editorial related to the current publication.
“Unlike ARRIVE, ASCEND, and nearly all prior primary prevention CVD [cardiovascular disease] trials of aspirin, ASPREE surprisingly demonstrated increased all-cause mortality in the aspirin group, which appeared to be driven largely by an increase in cancer-related deaths,” wrote the editorialists, who are both from the University of Texas MD Anderson Cancer Center in Houston.
Even though the ASPREE investigators have now taken a deeper dive into their data, the findings “neither explain nor alleviate the concerns raised by the initial ASPREE report,” the editorialists noted.
ASPREE design and results
ASPREE is a multicenter, double-blind trial of 19,114 older adults living in Australia (n = 16,703) or the United States (n = 2,411). Most patients were 70 years or older at baseline. However, the U.S. group also included patients 65 years and older who were racial/ethnic minorities (n = 564).
Patients were randomized to receive 100 mg of enteric-coated aspirin daily (n = 9,525) or matching placebo (n = 9,589) from March 2010 through December 2014.
At inclusion, all participants were free from cardiovascular disease, dementia, or physical disability. A previous history of cancer was not used to exclude participants, and 19.1% of patients had cancer at randomization. Most patients (89%) had not used aspirin regularly before entering the trial.
At a median follow-up of 4.7 years, there were 981 incident cancer events in the aspirin-treated group and 952 in the placebo-treated group, with an overall incident cancer rate of 10.1%.
Of the 1,933 patients with newly diagnosed cancer, 65.7% had a localized cancer, 18.8% had a new metastatic cancer, 5.8% had metastatic disease from an existing cancer, and 9.7% had a new hematologic or lymphatic cancer.
A quarter of cancer patients (n = 495) died as a result of their malignancy, with 52 dying from a cancer they already had at randomization.
Aspirin was not associated with the risk of first incident cancer diagnosis or incident localized cancer diagnosis. The hazard ratios were 1.04 for all incident cancers (95% confidence interval, 0.95-1.14) and 0.99 for incident localized cancers (95% CI, 0.89-1.11).
However, aspirin was associated with an increased risk of metastatic cancer and cancer presenting at stage 4. The HR for metastatic cancer was 1.19 (95% CI, 1.00-1.43), and the HR for newly diagnosed stage 4 cancer was 1.22 (95% CI, 1.02-1.45).
Furthermore, “an increased progression to death was observed amongst those randomized to aspirin, regardless of whether the initial cancer presentation had been localized or metastatic,” the investigators wrote.
The HRs for death were 1.35 for all cancers (95% CI, 1.13-1.61), 1.47 for localized cancers (95% CI, 1.07-2.02), and 1.30 for metastatic cancers (95% CI, 1.03-1.63).
“Deaths were particularly high among those on aspirin who were diagnosed with advanced solid cancers,” study author Andrew Chan, MD, of Massachusetts General Hospital in Boston, said in a press statement.
Indeed, HRs for death in patients with solid tumors presenting at stage 3 and 4 were a respective 2.11 (95% CI, 1.03-4.33) and 1.31 (95% CI, 1.04-1.64). This suggests a possible adverse effect of aspirin on the growth of cancers once they have already developed in older adults, Dr. Chan said.
Where does that leave aspirin for cancer prevention?
“Although these results suggest that we should be cautious about starting aspirin therapy in otherwise healthy older adults, this does not mean that individuals who are already taking aspirin – particularly if they began taking it at a younger age – should stop their aspirin regimen,” Dr. Chan said.
There are decades of data supporting the use of daily aspirin to prevent multiple cancer types, particularly colorectal cancer, in individuals under the age of 70 years. In a recent meta-analysis, for example, regular aspirin use was linked to a 27% reduced risk for colorectal cancer, a 33% reduced risk for squamous cell esophageal cancer, a 39% decreased risk for adenocarcinoma of the esophagus and gastric cardia, a 36% decreased risk for stomach cancer, a 38% decreased risk for hepatobiliary tract cancer, and a 22% decreased risk for pancreatic cancer.
While these figures are mostly based on observational and case-control studies, it “reaffirms the fact that, overall, when you look at all of the ages, that there is still a benefit of aspirin for cancer,” John Cuzick, PhD, of Queen Mary University of London (England), said in an interview.
In fact, the meta-analysis goes as far as suggesting that perhaps the dose of aspirin being used is too low, with the authors noting that there was a 35% risk reduction in colorectal cancer with a dose of 325 mg daily. That’s a new finding, Dr. Cuzick said.
He noted that the ASPREE study largely consists of patients 70 years of age or older, and the authors “draw some conclusions which we can’t ignore about potential safety.”
One of the safety concerns is the increased risk for gastrointestinal bleeding, which is why Dr. Cuzick and colleagues previously recommended caution in the use of aspirin to prevent cancer in elderly patients. The group published a study in 2015 that suggested a benefit of taking aspirin daily for 5-10 years in patients aged 50-65 years, but the risk/benefit ratio was unclear for patients 70 years and older.
The ASPREE data now add to those uncertainties and suggest “there may be some side effects that we do not understand,” Dr. Cuzick said.
“I’m still optimistic that aspirin is going to be important for cancer prevention, but probably focusing on ages 50-70,” he added. “[The ASPREE data] reinforce the caution that we have to take in terms of trying to understand what the side effects are and what’s going on at these older ages.”
Dr. Cuzick is currently leading the AsCaP Project, an international effort to better understand why aspirin might work in preventing some cancer types but not others. AsCaP is supported by Cancer Research UK and also includes Dr. Chan among the researchers attempting to find out which patients may benefit the most from aspirin and which may be at greater risk of adverse effects.
The ASPREE trial was funded by grants from the National Institute on Aging, the National Cancer Institute, the National Health and Medical Research Council of Australia, Monash University, and the Victorian Cancer Agency. Several ASPREE investigators disclosed financial relationships with Bayer Pharma. The editorialists had no conflicts of interest. Dr. Cuzick has been an advisory board member for Bayer in the past.
SOURCE: McNeil J et al. J Natl Cancer Inst. 2020 Aug 11. doi: 10.1093/jnci/djaa114.
Aspirin may accelerate the progression of advanced cancers and lead to an earlier death as a result, new data from the ASPREE study suggest.
The results showed that patients 65 years and older who started taking daily low-dose aspirin had a 19% higher chance of being diagnosed with metastatic cancer, a 22% higher chance of being diagnosed with a stage 4 tumor, and a 31% increased risk of death from stage 4 cancer, when compared with patients who took a placebo.
John J. McNeil, MBBS, PhD, of Monash University in Melbourne, Australia, and colleagues detailed these findings in the Journal of the National Cancer Institute.
“If confirmed, the clinical implications of these findings could be important for the use of aspirin in an older population,” the authors wrote.
When results of the ASPREE study were first reported in 2018, they “raised important concerns,” Ernest Hawk, MD, and Karen Colbert Maresso wrote in an editorial related to the current publication.
“Unlike ARRIVE, ASCEND, and nearly all prior primary prevention CVD [cardiovascular disease] trials of aspirin, ASPREE surprisingly demonstrated increased all-cause mortality in the aspirin group, which appeared to be driven largely by an increase in cancer-related deaths,” wrote the editorialists, who are both from the University of Texas MD Anderson Cancer Center in Houston.
Even though the ASPREE investigators have now taken a deeper dive into their data, the findings “neither explain nor alleviate the concerns raised by the initial ASPREE report,” the editorialists noted.
ASPREE design and results
ASPREE is a multicenter, double-blind trial of 19,114 older adults living in Australia (n = 16,703) or the United States (n = 2,411). Most patients were 70 years or older at baseline. However, the U.S. group also included patients 65 years and older who were racial/ethnic minorities (n = 564).
Patients were randomized to receive 100 mg of enteric-coated aspirin daily (n = 9,525) or matching placebo (n = 9,589) from March 2010 through December 2014.
At inclusion, all participants were free from cardiovascular disease, dementia, or physical disability. A previous history of cancer was not used to exclude participants, and 19.1% of patients had cancer at randomization. Most patients (89%) had not used aspirin regularly before entering the trial.
At a median follow-up of 4.7 years, there were 981 incident cancer events in the aspirin-treated group and 952 in the placebo-treated group, with an overall incident cancer rate of 10.1%.
Of the 1,933 patients with newly diagnosed cancer, 65.7% had a localized cancer, 18.8% had a new metastatic cancer, 5.8% had metastatic disease from an existing cancer, and 9.7% had a new hematologic or lymphatic cancer.
A quarter of cancer patients (n = 495) died as a result of their malignancy, with 52 dying from a cancer they already had at randomization.
Aspirin was not associated with the risk of first incident cancer diagnosis or incident localized cancer diagnosis. The hazard ratios were 1.04 for all incident cancers (95% confidence interval, 0.95-1.14) and 0.99 for incident localized cancers (95% CI, 0.89-1.11).
However, aspirin was associated with an increased risk of metastatic cancer and cancer presenting at stage 4. The HR for metastatic cancer was 1.19 (95% CI, 1.00-1.43), and the HR for newly diagnosed stage 4 cancer was 1.22 (95% CI, 1.02-1.45).
Furthermore, “an increased progression to death was observed amongst those randomized to aspirin, regardless of whether the initial cancer presentation had been localized or metastatic,” the investigators wrote.
The HRs for death were 1.35 for all cancers (95% CI, 1.13-1.61), 1.47 for localized cancers (95% CI, 1.07-2.02), and 1.30 for metastatic cancers (95% CI, 1.03-1.63).
“Deaths were particularly high among those on aspirin who were diagnosed with advanced solid cancers,” study author Andrew Chan, MD, of Massachusetts General Hospital in Boston, said in a press statement.
Indeed, HRs for death in patients with solid tumors presenting at stage 3 and 4 were a respective 2.11 (95% CI, 1.03-4.33) and 1.31 (95% CI, 1.04-1.64). This suggests a possible adverse effect of aspirin on the growth of cancers once they have already developed in older adults, Dr. Chan said.
Where does that leave aspirin for cancer prevention?
“Although these results suggest that we should be cautious about starting aspirin therapy in otherwise healthy older adults, this does not mean that individuals who are already taking aspirin – particularly if they began taking it at a younger age – should stop their aspirin regimen,” Dr. Chan said.
There are decades of data supporting the use of daily aspirin to prevent multiple cancer types, particularly colorectal cancer, in individuals under the age of 70 years. In a recent meta-analysis, for example, regular aspirin use was linked to a 27% reduced risk for colorectal cancer, a 33% reduced risk for squamous cell esophageal cancer, a 39% decreased risk for adenocarcinoma of the esophagus and gastric cardia, a 36% decreased risk for stomach cancer, a 38% decreased risk for hepatobiliary tract cancer, and a 22% decreased risk for pancreatic cancer.
While these figures are mostly based on observational and case-control studies, it “reaffirms the fact that, overall, when you look at all of the ages, that there is still a benefit of aspirin for cancer,” John Cuzick, PhD, of Queen Mary University of London (England), said in an interview.
In fact, the meta-analysis goes as far as suggesting that perhaps the dose of aspirin being used is too low, with the authors noting that there was a 35% risk reduction in colorectal cancer with a dose of 325 mg daily. That’s a new finding, Dr. Cuzick said.
He noted that the ASPREE study largely consists of patients 70 years of age or older, and the authors “draw some conclusions which we can’t ignore about potential safety.”
One of the safety concerns is the increased risk for gastrointestinal bleeding, which is why Dr. Cuzick and colleagues previously recommended caution in the use of aspirin to prevent cancer in elderly patients. The group published a study in 2015 that suggested a benefit of taking aspirin daily for 5-10 years in patients aged 50-65 years, but the risk/benefit ratio was unclear for patients 70 years and older.
The ASPREE data now add to those uncertainties and suggest “there may be some side effects that we do not understand,” Dr. Cuzick said.
“I’m still optimistic that aspirin is going to be important for cancer prevention, but probably focusing on ages 50-70,” he added. “[The ASPREE data] reinforce the caution that we have to take in terms of trying to understand what the side effects are and what’s going on at these older ages.”
Dr. Cuzick is currently leading the AsCaP Project, an international effort to better understand why aspirin might work in preventing some cancer types but not others. AsCaP is supported by Cancer Research UK and also includes Dr. Chan among the researchers attempting to find out which patients may benefit the most from aspirin and which may be at greater risk of adverse effects.
The ASPREE trial was funded by grants from the National Institute on Aging, the National Cancer Institute, the National Health and Medical Research Council of Australia, Monash University, and the Victorian Cancer Agency. Several ASPREE investigators disclosed financial relationships with Bayer Pharma. The editorialists had no conflicts of interest. Dr. Cuzick has been an advisory board member for Bayer in the past.
SOURCE: McNeil J et al. J Natl Cancer Inst. 2020 Aug 11. doi: 10.1093/jnci/djaa114.
Aspirin may accelerate the progression of advanced cancers and lead to an earlier death as a result, new data from the ASPREE study suggest.
The results showed that patients 65 years and older who started taking daily low-dose aspirin had a 19% higher chance of being diagnosed with metastatic cancer, a 22% higher chance of being diagnosed with a stage 4 tumor, and a 31% increased risk of death from stage 4 cancer, when compared with patients who took a placebo.
John J. McNeil, MBBS, PhD, of Monash University in Melbourne, Australia, and colleagues detailed these findings in the Journal of the National Cancer Institute.
“If confirmed, the clinical implications of these findings could be important for the use of aspirin in an older population,” the authors wrote.
When results of the ASPREE study were first reported in 2018, they “raised important concerns,” Ernest Hawk, MD, and Karen Colbert Maresso wrote in an editorial related to the current publication.
“Unlike ARRIVE, ASCEND, and nearly all prior primary prevention CVD [cardiovascular disease] trials of aspirin, ASPREE surprisingly demonstrated increased all-cause mortality in the aspirin group, which appeared to be driven largely by an increase in cancer-related deaths,” wrote the editorialists, who are both from the University of Texas MD Anderson Cancer Center in Houston.
Even though the ASPREE investigators have now taken a deeper dive into their data, the findings “neither explain nor alleviate the concerns raised by the initial ASPREE report,” the editorialists noted.
ASPREE design and results
ASPREE is a multicenter, double-blind trial of 19,114 older adults living in Australia (n = 16,703) or the United States (n = 2,411). Most patients were 70 years or older at baseline. However, the U.S. group also included patients 65 years and older who were racial/ethnic minorities (n = 564).
Patients were randomized to receive 100 mg of enteric-coated aspirin daily (n = 9,525) or matching placebo (n = 9,589) from March 2010 through December 2014.
At inclusion, all participants were free from cardiovascular disease, dementia, or physical disability. A previous history of cancer was not used to exclude participants, and 19.1% of patients had cancer at randomization. Most patients (89%) had not used aspirin regularly before entering the trial.
At a median follow-up of 4.7 years, there were 981 incident cancer events in the aspirin-treated group and 952 in the placebo-treated group, with an overall incident cancer rate of 10.1%.
Of the 1,933 patients with newly diagnosed cancer, 65.7% had a localized cancer, 18.8% had a new metastatic cancer, 5.8% had metastatic disease from an existing cancer, and 9.7% had a new hematologic or lymphatic cancer.
A quarter of cancer patients (n = 495) died as a result of their malignancy, with 52 dying from a cancer they already had at randomization.
Aspirin was not associated with the risk of first incident cancer diagnosis or incident localized cancer diagnosis. The hazard ratios were 1.04 for all incident cancers (95% confidence interval, 0.95-1.14) and 0.99 for incident localized cancers (95% CI, 0.89-1.11).
However, aspirin was associated with an increased risk of metastatic cancer and cancer presenting at stage 4. The HR for metastatic cancer was 1.19 (95% CI, 1.00-1.43), and the HR for newly diagnosed stage 4 cancer was 1.22 (95% CI, 1.02-1.45).
Furthermore, “an increased progression to death was observed amongst those randomized to aspirin, regardless of whether the initial cancer presentation had been localized or metastatic,” the investigators wrote.
The HRs for death were 1.35 for all cancers (95% CI, 1.13-1.61), 1.47 for localized cancers (95% CI, 1.07-2.02), and 1.30 for metastatic cancers (95% CI, 1.03-1.63).
“Deaths were particularly high among those on aspirin who were diagnosed with advanced solid cancers,” study author Andrew Chan, MD, of Massachusetts General Hospital in Boston, said in a press statement.
Indeed, HRs for death in patients with solid tumors presenting at stage 3 and 4 were a respective 2.11 (95% CI, 1.03-4.33) and 1.31 (95% CI, 1.04-1.64). This suggests a possible adverse effect of aspirin on the growth of cancers once they have already developed in older adults, Dr. Chan said.
Where does that leave aspirin for cancer prevention?
“Although these results suggest that we should be cautious about starting aspirin therapy in otherwise healthy older adults, this does not mean that individuals who are already taking aspirin – particularly if they began taking it at a younger age – should stop their aspirin regimen,” Dr. Chan said.
There are decades of data supporting the use of daily aspirin to prevent multiple cancer types, particularly colorectal cancer, in individuals under the age of 70 years. In a recent meta-analysis, for example, regular aspirin use was linked to a 27% reduced risk for colorectal cancer, a 33% reduced risk for squamous cell esophageal cancer, a 39% decreased risk for adenocarcinoma of the esophagus and gastric cardia, a 36% decreased risk for stomach cancer, a 38% decreased risk for hepatobiliary tract cancer, and a 22% decreased risk for pancreatic cancer.
While these figures are mostly based on observational and case-control studies, it “reaffirms the fact that, overall, when you look at all of the ages, that there is still a benefit of aspirin for cancer,” John Cuzick, PhD, of Queen Mary University of London (England), said in an interview.
In fact, the meta-analysis goes as far as suggesting that perhaps the dose of aspirin being used is too low, with the authors noting that there was a 35% risk reduction in colorectal cancer with a dose of 325 mg daily. That’s a new finding, Dr. Cuzick said.
He noted that the ASPREE study largely consists of patients 70 years of age or older, and the authors “draw some conclusions which we can’t ignore about potential safety.”
One of the safety concerns is the increased risk for gastrointestinal bleeding, which is why Dr. Cuzick and colleagues previously recommended caution in the use of aspirin to prevent cancer in elderly patients. The group published a study in 2015 that suggested a benefit of taking aspirin daily for 5-10 years in patients aged 50-65 years, but the risk/benefit ratio was unclear for patients 70 years and older.
The ASPREE data now add to those uncertainties and suggest “there may be some side effects that we do not understand,” Dr. Cuzick said.
“I’m still optimistic that aspirin is going to be important for cancer prevention, but probably focusing on ages 50-70,” he added. “[The ASPREE data] reinforce the caution that we have to take in terms of trying to understand what the side effects are and what’s going on at these older ages.”
Dr. Cuzick is currently leading the AsCaP Project, an international effort to better understand why aspirin might work in preventing some cancer types but not others. AsCaP is supported by Cancer Research UK and also includes Dr. Chan among the researchers attempting to find out which patients may benefit the most from aspirin and which may be at greater risk of adverse effects.
The ASPREE trial was funded by grants from the National Institute on Aging, the National Cancer Institute, the National Health and Medical Research Council of Australia, Monash University, and the Victorian Cancer Agency. Several ASPREE investigators disclosed financial relationships with Bayer Pharma. The editorialists had no conflicts of interest. Dr. Cuzick has been an advisory board member for Bayer in the past.
SOURCE: McNeil J et al. J Natl Cancer Inst. 2020 Aug 11. doi: 10.1093/jnci/djaa114.
FROM JOURNAL OF THE NATIONAL CANCER INSTITUTE
Age, smoking among leading cancer risk factors for SLE patients
A new study has quantified cancer risk factors in patients with systemic lupus erythematosus, including smoking and the use of certain medications.
“As expected, older age was associated with cancer overall, as well as with the most common cancer subtypes,” wrote Sasha Bernatsky, MD, PhD, of McGill University, Montreal, and coauthors. The study was published in Arthritis Care & Research.
To determine the risk of cancer in people with clinically confirmed incident systemic lupus erythematosus (SLE), the researchers analyzed data from 1,668 newly diagnosed lupus patients with at least one follow-up visit. All patients were enrolled in the Systemic Lupus International Collaborating Clinics inception cohort from across 33 different centers in North America, Europe, and Asia. A total of 89% (n = 1,480) were women, and 49% (n = 824) were white. The average follow-up period was 9 years.
Of the 1,668 SLE patients, 65 developed some type of cancer. The cancers included 15 breast;, 10 nonmelanoma skin; 7 lung; 6 hematologic, 6 prostate; 5 melanoma; 3 cervical; 3 renal; 2 gastric; 2 head and neck; 2 thyroid; and 1 rectal, sarcoma, thymoma, or uterine. No patient had more than one type, and the mean age of the cancer patients at time of SLE diagnosis was 45.6 (standard deviation, 14.5).
Almost half of the 65 cancers occurred in past or current smokers, including all of the lung cancers, while only 33% of patients without cancers smoked prior to baseline. After univariate analysis, characteristics associated with a higher risk of all cancers included older age at SLE diagnosis (adjusted hazard ratio, 1.05; 95% confidence interval, 1.03-1.06), White race/ethnicity (aHR 1.34; 95% CI, 0.76-2.37), and smoking (aHR 1.21; 95% CI, 0.73-2.01).
After multivariate analysis, the two characteristics most associated with increased cancer risk were older age at SLE diagnosis and being male. The analyses also confirmed that older age was a risk factor for breast cancer (aHR 1.06; 95% CI, 1.02-1.10) and nonmelanoma skin cancer (aHR, 1.06; 95% CI, 1.02-1.11), while use of antimalarial drugs was associated with a lower risk of both breast (aHR, 0.28; 95% CI, 0.09-0.90) and nonmelanoma skin (aHR, 0.23; 95% CI, 0.05-0.95) cancers. For lung cancer, the highest risk factor was smoking 15 or more cigarettes a day (aHR, 6.64; 95% CI, 1.43-30.9); for hematologic cancers, it was being in the top quartile of SLE disease activity (aHR, 7.14; 95% CI, 1.13-45.3).
The authors acknowledged their study’s limitations, including the small number of cancers overall and purposefully not comparing cancer risk in SLE patients with risk in the general population. Although their methods – “physicians recording events at annual visits, confirmed by review of charts” – were recognized as very suitable for the current analysis, they noted that a broader comparison would “potentially be problematic due to differential misclassification error” in cancer registry data.
Two of the study’s authors reported potential conflicts of interest, including receiving grants and consulting and personal fees from various pharmaceutical companies. No other potential conflicts were reported.
SOURCE: Bernatsky S et al. Arthritis Care Res. 2020 Aug 19. doi: 10.1002/acr.24425.
A new study has quantified cancer risk factors in patients with systemic lupus erythematosus, including smoking and the use of certain medications.
“As expected, older age was associated with cancer overall, as well as with the most common cancer subtypes,” wrote Sasha Bernatsky, MD, PhD, of McGill University, Montreal, and coauthors. The study was published in Arthritis Care & Research.
To determine the risk of cancer in people with clinically confirmed incident systemic lupus erythematosus (SLE), the researchers analyzed data from 1,668 newly diagnosed lupus patients with at least one follow-up visit. All patients were enrolled in the Systemic Lupus International Collaborating Clinics inception cohort from across 33 different centers in North America, Europe, and Asia. A total of 89% (n = 1,480) were women, and 49% (n = 824) were white. The average follow-up period was 9 years.
Of the 1,668 SLE patients, 65 developed some type of cancer. The cancers included 15 breast;, 10 nonmelanoma skin; 7 lung; 6 hematologic, 6 prostate; 5 melanoma; 3 cervical; 3 renal; 2 gastric; 2 head and neck; 2 thyroid; and 1 rectal, sarcoma, thymoma, or uterine. No patient had more than one type, and the mean age of the cancer patients at time of SLE diagnosis was 45.6 (standard deviation, 14.5).
Almost half of the 65 cancers occurred in past or current smokers, including all of the lung cancers, while only 33% of patients without cancers smoked prior to baseline. After univariate analysis, characteristics associated with a higher risk of all cancers included older age at SLE diagnosis (adjusted hazard ratio, 1.05; 95% confidence interval, 1.03-1.06), White race/ethnicity (aHR 1.34; 95% CI, 0.76-2.37), and smoking (aHR 1.21; 95% CI, 0.73-2.01).
After multivariate analysis, the two characteristics most associated with increased cancer risk were older age at SLE diagnosis and being male. The analyses also confirmed that older age was a risk factor for breast cancer (aHR 1.06; 95% CI, 1.02-1.10) and nonmelanoma skin cancer (aHR, 1.06; 95% CI, 1.02-1.11), while use of antimalarial drugs was associated with a lower risk of both breast (aHR, 0.28; 95% CI, 0.09-0.90) and nonmelanoma skin (aHR, 0.23; 95% CI, 0.05-0.95) cancers. For lung cancer, the highest risk factor was smoking 15 or more cigarettes a day (aHR, 6.64; 95% CI, 1.43-30.9); for hematologic cancers, it was being in the top quartile of SLE disease activity (aHR, 7.14; 95% CI, 1.13-45.3).
The authors acknowledged their study’s limitations, including the small number of cancers overall and purposefully not comparing cancer risk in SLE patients with risk in the general population. Although their methods – “physicians recording events at annual visits, confirmed by review of charts” – were recognized as very suitable for the current analysis, they noted that a broader comparison would “potentially be problematic due to differential misclassification error” in cancer registry data.
Two of the study’s authors reported potential conflicts of interest, including receiving grants and consulting and personal fees from various pharmaceutical companies. No other potential conflicts were reported.
SOURCE: Bernatsky S et al. Arthritis Care Res. 2020 Aug 19. doi: 10.1002/acr.24425.
A new study has quantified cancer risk factors in patients with systemic lupus erythematosus, including smoking and the use of certain medications.
“As expected, older age was associated with cancer overall, as well as with the most common cancer subtypes,” wrote Sasha Bernatsky, MD, PhD, of McGill University, Montreal, and coauthors. The study was published in Arthritis Care & Research.
To determine the risk of cancer in people with clinically confirmed incident systemic lupus erythematosus (SLE), the researchers analyzed data from 1,668 newly diagnosed lupus patients with at least one follow-up visit. All patients were enrolled in the Systemic Lupus International Collaborating Clinics inception cohort from across 33 different centers in North America, Europe, and Asia. A total of 89% (n = 1,480) were women, and 49% (n = 824) were white. The average follow-up period was 9 years.
Of the 1,668 SLE patients, 65 developed some type of cancer. The cancers included 15 breast;, 10 nonmelanoma skin; 7 lung; 6 hematologic, 6 prostate; 5 melanoma; 3 cervical; 3 renal; 2 gastric; 2 head and neck; 2 thyroid; and 1 rectal, sarcoma, thymoma, or uterine. No patient had more than one type, and the mean age of the cancer patients at time of SLE diagnosis was 45.6 (standard deviation, 14.5).
Almost half of the 65 cancers occurred in past or current smokers, including all of the lung cancers, while only 33% of patients without cancers smoked prior to baseline. After univariate analysis, characteristics associated with a higher risk of all cancers included older age at SLE diagnosis (adjusted hazard ratio, 1.05; 95% confidence interval, 1.03-1.06), White race/ethnicity (aHR 1.34; 95% CI, 0.76-2.37), and smoking (aHR 1.21; 95% CI, 0.73-2.01).
After multivariate analysis, the two characteristics most associated with increased cancer risk were older age at SLE diagnosis and being male. The analyses also confirmed that older age was a risk factor for breast cancer (aHR 1.06; 95% CI, 1.02-1.10) and nonmelanoma skin cancer (aHR, 1.06; 95% CI, 1.02-1.11), while use of antimalarial drugs was associated with a lower risk of both breast (aHR, 0.28; 95% CI, 0.09-0.90) and nonmelanoma skin (aHR, 0.23; 95% CI, 0.05-0.95) cancers. For lung cancer, the highest risk factor was smoking 15 or more cigarettes a day (aHR, 6.64; 95% CI, 1.43-30.9); for hematologic cancers, it was being in the top quartile of SLE disease activity (aHR, 7.14; 95% CI, 1.13-45.3).
The authors acknowledged their study’s limitations, including the small number of cancers overall and purposefully not comparing cancer risk in SLE patients with risk in the general population. Although their methods – “physicians recording events at annual visits, confirmed by review of charts” – were recognized as very suitable for the current analysis, they noted that a broader comparison would “potentially be problematic due to differential misclassification error” in cancer registry data.
Two of the study’s authors reported potential conflicts of interest, including receiving grants and consulting and personal fees from various pharmaceutical companies. No other potential conflicts were reported.
SOURCE: Bernatsky S et al. Arthritis Care Res. 2020 Aug 19. doi: 10.1002/acr.24425.
FROM ARTHRITIS CARE & RESEARCH
COVID-19 impact: Less chemo, immune checkpoint inhibitors, and steroids
While neoadjuvant treatment recommendations were not strongly affected by the pandemic, about half of oncologists reported increased hesitancy over recommending frontline chemotherapy for metastatic disease, and a vast majority said they would recommend second- or third-line chemotherapy less often in the metastatic setting.
Most oncologists said they did not perform routine COVID-19 testing via reverse transcriptase–polymerase chain reaction (RT-PCR) before treating cancer patients. In fact, only 3% said they performed COVID-19 RT-PCR testing routinely.
Yüksel Ürün, MD, of Ankara (Turkey) University, and colleagues reported these findings in JCO Global Oncology.
The goal of the survey was to “understand readiness measures taken by oncologists to protect patients and health care workers from the novel coronavirus (COVID-19) and how their clinical decision-making was influenced by the pandemic,” the authors wrote.
The online survey was conducted among 343 oncologists from 28 countries. Responses were collected anonymously, a majority (71%) from university or academic centers, with 95% received between April 1 and April 29, 2020.
Use of telemedicine was common (80%) among respondents, as was use of surgical masks (90%) and personal protective equipment in general.
Only 33% of respondents described using N95 masks. However, the proportion of oncologists who had access to N95 masks while caring for patients known to have COVID-19, especially while doing invasive procedures such as intubation, bronchoscopy, and any airway-related manipulations, was not captured by the survey.
COVID testing and cancer treatment
Most respondents (58%) said they did not perform routine COVID-19 RT-PCR testing prior to administering systemic cancer treatment, with 39% stating they performed RT-PCR tests in selected patients, and 3% saying they performed such testing in all patients.
The survey indicated that hormonal treatments, tyrosine kinase inhibitors, and bone-modifying agents were considered relatively safe, but cytotoxic chemotherapy and immune therapies were not.
Nearly all oncologists said the pandemic would cause them to make no change to their recommendations regarding hormone therapy, and nearly 80% said they would make no changes regarding tyrosine kinase inhibitors or bone-modifying agents.
However, more than 90% of respondents said they would recommend cytotoxic chemotherapy less often, about 70% said they would recommend corticosteroids less often, and around 50% said they would recommend anti–programmed death-1/PD-ligand 1 or anti–cytotoxic T-lymphocyte–associated protein 4 antibodies less often.
The pandemic made most respondents more reluctant to recommend second- or third-line chemotherapy in the metastatic setting. About 80% and 70% of respondents, respectively, would recommend second- or third-line chemotherapy less often.
However, first-line chemotherapy for metastatic disease, as well as adjuvant and neoadjuvant therapy, were less affected. About 30% of respondents said they would recommend neoadjuvant therapy less often, and 50%-55% would recommend adjuvant therapy or frontline chemotherapy for metastatic disease less often.
Most respondents (78%) said they would use granulocyte colony–stimulating factor (G-CSF) more frequently during the pandemic.
The factors most likely to affect oncologists’ treatment decisions were patient age (81%) and concomitant disease (92%). Additionally, 80% of respondents’ treatment decisions were influenced by Eastern Cooperative Oncology Group performance status of 2 or higher, or the presence of chronic obstructive pulmonary disease.
Interpretation and implications
“These results highlight that, even in the early phases of COVID-19 – during which there was considerable uncertainty – basic core principles were guideposts for oncologists,” observed Aly-Khan Lalani, MD, of Juravinski Cancer Centre and McMaster University, Hamilton, Ont., who was not involved in this study.
“For example, [oncologists were] prioritizing strategies for treatments with the largest expected impact and carefully tailoring treatment according to patient comorbidities and performance status,” Dr. Lalani said.
Another oncologist who was not involved in the study expressed concern over reductions in adjuvant therapy supported by half of oncologists surveyed.
“Although benefits may be marginal in some cases, these are curative settings and especially warrant careful individual-level risk/benefit discussions,” said Kartik Sehgal, MD, of Dana-Farber Cancer Institute/Brigham and Women’s Hospital in Boston.
His concern extended as well to the small proportion (3%) of oncologists testing for COVID-19 in all patients. “Systematic testing is the need of the hour,” Dr. Sehgal said.
In their discussion of the findings, Dr. Ürün and colleagues noted a lack of consensus on monoclonal antibody and immunotherapy safety among surveyed oncologists. The steroids needed to manage severe immune-mediated toxicity with immune checkpoint inhibitors has led to some prescribing reluctance during the pandemic.
Immunosuppressive properties of immune checkpoint inhibitors also raise concern that they can increase COVID-19 severity. Studies are few, and findings to date are inconsistent with respect to the effect of immune checkpoint inhibitors on COVID-19 clinical course. However, a recently presented study suggested that immune checkpoint inhibitors do not increase the risk of death among cancer patients with COVID-19 (AACR: COVID-19 and Cancer, Abstract S02-01).
Dr. Ürün and colleagues noted that greater COVID-19 severity has been shown in patients with performance status greater than 1, hematologic malignancies, lung cancer, stage IV metastatic disease, chemotherapy within the prior 3 months, cancer treatment in the last 14 days, and the presence of chronic obstructive pulmonary disease. Nonmetastatic cancer has not been shown to affect COVID-19 severity, however.
Dr. Ürün and colleagues also underscored the need for research evidence to balance potential reductions in neutropenic complications with G-CSF (and therefore, reduced hospitalizations) with a theoretical risk of G-CSF–mediated pulmonary injury through its stimulation of an excessive immune response.
Finally, the authors urged oncologists to evaluate each proposed therapy’s risk/benefit ratio on an individual patient basis, and the team tasked the oncology community with gathering comprehensive, rigorous data.
There was no funding source declared for this study. Dr. Ürün and colleagues disclosed various relationships with many pharmaceutical companies, which included receiving research funding. Dr. Sehgal and Dr. Lalani reported no relevant conflicts.
SOURCE: Ürün Y et al. JCO Glob Oncol. 2020 Aug;6:1248-57.
While neoadjuvant treatment recommendations were not strongly affected by the pandemic, about half of oncologists reported increased hesitancy over recommending frontline chemotherapy for metastatic disease, and a vast majority said they would recommend second- or third-line chemotherapy less often in the metastatic setting.
Most oncologists said they did not perform routine COVID-19 testing via reverse transcriptase–polymerase chain reaction (RT-PCR) before treating cancer patients. In fact, only 3% said they performed COVID-19 RT-PCR testing routinely.
Yüksel Ürün, MD, of Ankara (Turkey) University, and colleagues reported these findings in JCO Global Oncology.
The goal of the survey was to “understand readiness measures taken by oncologists to protect patients and health care workers from the novel coronavirus (COVID-19) and how their clinical decision-making was influenced by the pandemic,” the authors wrote.
The online survey was conducted among 343 oncologists from 28 countries. Responses were collected anonymously, a majority (71%) from university or academic centers, with 95% received between April 1 and April 29, 2020.
Use of telemedicine was common (80%) among respondents, as was use of surgical masks (90%) and personal protective equipment in general.
Only 33% of respondents described using N95 masks. However, the proportion of oncologists who had access to N95 masks while caring for patients known to have COVID-19, especially while doing invasive procedures such as intubation, bronchoscopy, and any airway-related manipulations, was not captured by the survey.
COVID testing and cancer treatment
Most respondents (58%) said they did not perform routine COVID-19 RT-PCR testing prior to administering systemic cancer treatment, with 39% stating they performed RT-PCR tests in selected patients, and 3% saying they performed such testing in all patients.
The survey indicated that hormonal treatments, tyrosine kinase inhibitors, and bone-modifying agents were considered relatively safe, but cytotoxic chemotherapy and immune therapies were not.
Nearly all oncologists said the pandemic would cause them to make no change to their recommendations regarding hormone therapy, and nearly 80% said they would make no changes regarding tyrosine kinase inhibitors or bone-modifying agents.
However, more than 90% of respondents said they would recommend cytotoxic chemotherapy less often, about 70% said they would recommend corticosteroids less often, and around 50% said they would recommend anti–programmed death-1/PD-ligand 1 or anti–cytotoxic T-lymphocyte–associated protein 4 antibodies less often.
The pandemic made most respondents more reluctant to recommend second- or third-line chemotherapy in the metastatic setting. About 80% and 70% of respondents, respectively, would recommend second- or third-line chemotherapy less often.
However, first-line chemotherapy for metastatic disease, as well as adjuvant and neoadjuvant therapy, were less affected. About 30% of respondents said they would recommend neoadjuvant therapy less often, and 50%-55% would recommend adjuvant therapy or frontline chemotherapy for metastatic disease less often.
Most respondents (78%) said they would use granulocyte colony–stimulating factor (G-CSF) more frequently during the pandemic.
The factors most likely to affect oncologists’ treatment decisions were patient age (81%) and concomitant disease (92%). Additionally, 80% of respondents’ treatment decisions were influenced by Eastern Cooperative Oncology Group performance status of 2 or higher, or the presence of chronic obstructive pulmonary disease.
Interpretation and implications
“These results highlight that, even in the early phases of COVID-19 – during which there was considerable uncertainty – basic core principles were guideposts for oncologists,” observed Aly-Khan Lalani, MD, of Juravinski Cancer Centre and McMaster University, Hamilton, Ont., who was not involved in this study.
“For example, [oncologists were] prioritizing strategies for treatments with the largest expected impact and carefully tailoring treatment according to patient comorbidities and performance status,” Dr. Lalani said.
Another oncologist who was not involved in the study expressed concern over reductions in adjuvant therapy supported by half of oncologists surveyed.
“Although benefits may be marginal in some cases, these are curative settings and especially warrant careful individual-level risk/benefit discussions,” said Kartik Sehgal, MD, of Dana-Farber Cancer Institute/Brigham and Women’s Hospital in Boston.
His concern extended as well to the small proportion (3%) of oncologists testing for COVID-19 in all patients. “Systematic testing is the need of the hour,” Dr. Sehgal said.
In their discussion of the findings, Dr. Ürün and colleagues noted a lack of consensus on monoclonal antibody and immunotherapy safety among surveyed oncologists. The steroids needed to manage severe immune-mediated toxicity with immune checkpoint inhibitors has led to some prescribing reluctance during the pandemic.
Immunosuppressive properties of immune checkpoint inhibitors also raise concern that they can increase COVID-19 severity. Studies are few, and findings to date are inconsistent with respect to the effect of immune checkpoint inhibitors on COVID-19 clinical course. However, a recently presented study suggested that immune checkpoint inhibitors do not increase the risk of death among cancer patients with COVID-19 (AACR: COVID-19 and Cancer, Abstract S02-01).
Dr. Ürün and colleagues noted that greater COVID-19 severity has been shown in patients with performance status greater than 1, hematologic malignancies, lung cancer, stage IV metastatic disease, chemotherapy within the prior 3 months, cancer treatment in the last 14 days, and the presence of chronic obstructive pulmonary disease. Nonmetastatic cancer has not been shown to affect COVID-19 severity, however.
Dr. Ürün and colleagues also underscored the need for research evidence to balance potential reductions in neutropenic complications with G-CSF (and therefore, reduced hospitalizations) with a theoretical risk of G-CSF–mediated pulmonary injury through its stimulation of an excessive immune response.
Finally, the authors urged oncologists to evaluate each proposed therapy’s risk/benefit ratio on an individual patient basis, and the team tasked the oncology community with gathering comprehensive, rigorous data.
There was no funding source declared for this study. Dr. Ürün and colleagues disclosed various relationships with many pharmaceutical companies, which included receiving research funding. Dr. Sehgal and Dr. Lalani reported no relevant conflicts.
SOURCE: Ürün Y et al. JCO Glob Oncol. 2020 Aug;6:1248-57.
While neoadjuvant treatment recommendations were not strongly affected by the pandemic, about half of oncologists reported increased hesitancy over recommending frontline chemotherapy for metastatic disease, and a vast majority said they would recommend second- or third-line chemotherapy less often in the metastatic setting.
Most oncologists said they did not perform routine COVID-19 testing via reverse transcriptase–polymerase chain reaction (RT-PCR) before treating cancer patients. In fact, only 3% said they performed COVID-19 RT-PCR testing routinely.
Yüksel Ürün, MD, of Ankara (Turkey) University, and colleagues reported these findings in JCO Global Oncology.
The goal of the survey was to “understand readiness measures taken by oncologists to protect patients and health care workers from the novel coronavirus (COVID-19) and how their clinical decision-making was influenced by the pandemic,” the authors wrote.
The online survey was conducted among 343 oncologists from 28 countries. Responses were collected anonymously, a majority (71%) from university or academic centers, with 95% received between April 1 and April 29, 2020.
Use of telemedicine was common (80%) among respondents, as was use of surgical masks (90%) and personal protective equipment in general.
Only 33% of respondents described using N95 masks. However, the proportion of oncologists who had access to N95 masks while caring for patients known to have COVID-19, especially while doing invasive procedures such as intubation, bronchoscopy, and any airway-related manipulations, was not captured by the survey.
COVID testing and cancer treatment
Most respondents (58%) said they did not perform routine COVID-19 RT-PCR testing prior to administering systemic cancer treatment, with 39% stating they performed RT-PCR tests in selected patients, and 3% saying they performed such testing in all patients.
The survey indicated that hormonal treatments, tyrosine kinase inhibitors, and bone-modifying agents were considered relatively safe, but cytotoxic chemotherapy and immune therapies were not.
Nearly all oncologists said the pandemic would cause them to make no change to their recommendations regarding hormone therapy, and nearly 80% said they would make no changes regarding tyrosine kinase inhibitors or bone-modifying agents.
However, more than 90% of respondents said they would recommend cytotoxic chemotherapy less often, about 70% said they would recommend corticosteroids less often, and around 50% said they would recommend anti–programmed death-1/PD-ligand 1 or anti–cytotoxic T-lymphocyte–associated protein 4 antibodies less often.
The pandemic made most respondents more reluctant to recommend second- or third-line chemotherapy in the metastatic setting. About 80% and 70% of respondents, respectively, would recommend second- or third-line chemotherapy less often.
However, first-line chemotherapy for metastatic disease, as well as adjuvant and neoadjuvant therapy, were less affected. About 30% of respondents said they would recommend neoadjuvant therapy less often, and 50%-55% would recommend adjuvant therapy or frontline chemotherapy for metastatic disease less often.
Most respondents (78%) said they would use granulocyte colony–stimulating factor (G-CSF) more frequently during the pandemic.
The factors most likely to affect oncologists’ treatment decisions were patient age (81%) and concomitant disease (92%). Additionally, 80% of respondents’ treatment decisions were influenced by Eastern Cooperative Oncology Group performance status of 2 or higher, or the presence of chronic obstructive pulmonary disease.
Interpretation and implications
“These results highlight that, even in the early phases of COVID-19 – during which there was considerable uncertainty – basic core principles were guideposts for oncologists,” observed Aly-Khan Lalani, MD, of Juravinski Cancer Centre and McMaster University, Hamilton, Ont., who was not involved in this study.
“For example, [oncologists were] prioritizing strategies for treatments with the largest expected impact and carefully tailoring treatment according to patient comorbidities and performance status,” Dr. Lalani said.
Another oncologist who was not involved in the study expressed concern over reductions in adjuvant therapy supported by half of oncologists surveyed.
“Although benefits may be marginal in some cases, these are curative settings and especially warrant careful individual-level risk/benefit discussions,” said Kartik Sehgal, MD, of Dana-Farber Cancer Institute/Brigham and Women’s Hospital in Boston.
His concern extended as well to the small proportion (3%) of oncologists testing for COVID-19 in all patients. “Systematic testing is the need of the hour,” Dr. Sehgal said.
In their discussion of the findings, Dr. Ürün and colleagues noted a lack of consensus on monoclonal antibody and immunotherapy safety among surveyed oncologists. The steroids needed to manage severe immune-mediated toxicity with immune checkpoint inhibitors has led to some prescribing reluctance during the pandemic.
Immunosuppressive properties of immune checkpoint inhibitors also raise concern that they can increase COVID-19 severity. Studies are few, and findings to date are inconsistent with respect to the effect of immune checkpoint inhibitors on COVID-19 clinical course. However, a recently presented study suggested that immune checkpoint inhibitors do not increase the risk of death among cancer patients with COVID-19 (AACR: COVID-19 and Cancer, Abstract S02-01).
Dr. Ürün and colleagues noted that greater COVID-19 severity has been shown in patients with performance status greater than 1, hematologic malignancies, lung cancer, stage IV metastatic disease, chemotherapy within the prior 3 months, cancer treatment in the last 14 days, and the presence of chronic obstructive pulmonary disease. Nonmetastatic cancer has not been shown to affect COVID-19 severity, however.
Dr. Ürün and colleagues also underscored the need for research evidence to balance potential reductions in neutropenic complications with G-CSF (and therefore, reduced hospitalizations) with a theoretical risk of G-CSF–mediated pulmonary injury through its stimulation of an excessive immune response.
Finally, the authors urged oncologists to evaluate each proposed therapy’s risk/benefit ratio on an individual patient basis, and the team tasked the oncology community with gathering comprehensive, rigorous data.
There was no funding source declared for this study. Dr. Ürün and colleagues disclosed various relationships with many pharmaceutical companies, which included receiving research funding. Dr. Sehgal and Dr. Lalani reported no relevant conflicts.
SOURCE: Ürün Y et al. JCO Glob Oncol. 2020 Aug;6:1248-57.
FROM JCO GLOBAL ONCOLOGY
Scalp Wound Closures in Mohs Micrographic Surgery: A Survey of Staples vs Sutures
Limited data exist comparing staples and sutures for scalp closures during Mohs micrographic surgery (MMS). As a result, the closure method for these scalp wounds is based on surgeon preference without established consensus. The purpose of this study was to survey practicing Mohs surgeons on their scalp wound closure preferences as well as the clinical and economic variables that impact their decisions. Understanding practice habits can guide future trial design, with a goal of creating established criterion for MMS scalp wound closures.
Methods
An anonymous survey was distributed from April 2019 to June 2019 to fellowship-trained Mohs surgeons using an electronic mailing list from the American College of Mohs Surgery (ACMS). The 10-question survey was approved by the University of Kansas institutional review board and the executive committee of the ACMS. Surgeons were asked about their preferred method for scalp wound closure as well as clinical and economic variables that impacted those preferences. Respondents indicated their frequency of using deep sutures, epidermal sutures, and wound undermining on a sliding scale of 0% to 100%. Comparisons were made between practice habits, preferences, and surgeon demographics using t tests. Statistical significance was determined as P<.05.
Results
Sixty-eight ACMS fellowship-trained Mohs surgeons completed the survey. The average age of respondents was 45 years; 69.1% (n=47) of respondents were male, and 76.5% (n=52) practiced in a private setting (Table 1). Regardless of epidermal closure type, deep suture placement was used in an average (standard deviation [SD]) of 88.8% (19.5%) of cases overall, which did not statistically differ between years of Mohs experience or practice setting (Table 2). Wound undermining was performed in an average (SD) of 83.0% (24.3%) of cases overall and was more prevalent in private vs academic settings (87.6% [17.8%] vs 65.7% [35.0%]; P<.01). Epidermal sutures were used in an average (SD) of 27.1% (33.5%) of scalp wound cases overall. Surgeons with less experience (≤5 years) used them more frequently (average [SD], 42.7% [36.2%] of cases) than surgeons with more experience (≥16 years; average [SD], 18.8% [32.6%] of cases; P=.037). There was no significant difference between epidermal suture placement rates and practice setting (average [SD], 18.1% [28.1%] of cases for academic providers vs 30.0% [34.8%] of cases with private providers; P=.210).
Clinical and economic factors that were most important during wound closure were ranked (beginning with most important) as the following: risk of complications, cosmetic outcome, hair preservation, patient comfort during closure, healing time, and closure cost. In all demographic cases, risk of complications was ranked 1 or 2 (1=most important; 6=least important) overall; cost was the least important factor overall (Table 2).
Surgeons perceived staples to be superior for speed of closure and for closing wounds in high-tension areas, whereas sutures were perceived as superior when considering cost of closure and ease of removal (Table 3). Successful healing rate, healing time, hair preservation, overall cosmetic outcome, and lower risk of complications were viewed as equivalent when comparing staples and sutures.
In cases in which surgeons did not use staples for closure, the most important factors for opting to not use them were patient discomfort (52.9% [n=36]), cost (25.0% [n=17]), and worse overall cosmetic outcome (23.5% [n=16])(Table 4). The most frequent locations outside of scalp wounds that physicians considered the use of staples for closure were the back (19.1% [n=13]), thigh (10.3% [n=7]), and shoulder (8.8% [n=6]).
Comment
Epidermal closure with sutures was reportedly used in an average of only 27.1% of scalp wound cases, with clinical factors such as cosmetic outcome, risk of complications, and closure time seen as either equivalent or inferior to staples. Our data suggest that surgeon closure perceptions generally are in agreement with established head and neck literature within different medical specialties that favor staple closures, particularly in high-tension areas.1 Interestingly, the most common reasons given for not using staples included patient discomfort, cost, and worse cosmetic outcomes, which are unsubstantiated with head and neck comparative studies.2-4
Although cost was the least important variable for determining closure type in our surveyed cohort, it is likely that the overall cost of closure is frequently underestimated. A higher material cost is noted with staples; however, the largest determinant of overall cost remains the surgeon’s time, which is reduced by factors of 10 or more when closing with staples.2,3 This difference—coupled with the unchanged cosmetic outcome and complication rates—makes staples more advantageous for high-tension scalp wounds.4 Moreover, the stapling technique is more reproducible than suturing, which requires more surgical skill and experience.
Limitations of this study include a lack of directly comparable data for staple and suture scalp wound closures. In addition, the small cohort of respondents in this preliminary study can serve to guide future studies.
Conclusion
Scalp wounds during MMS were most frequently closed using staples vs sutures, with the perception that these methods are equivalent in complication risk, cosmetic outcome, and overall patient satisfaction. These results agree with comparative literature for head and neck surgery and assist with establishing an epidemiologic baseline for future studies comparing their use during MMS.
- Ritchie AJ, Rocke LG. Staples versus sutures in the closure of scalp wounds: a prospective, double-blind, randomized trial. Injury. 1989;20:217-218.
- Batra J, Bekal RK, Byadgi S, et al. Comparison of skin staples and standard sutures for closing incisions after head and neck cancer surgery: a double-blind, randomized and prospective study. J Maxillofac Oral Surg. 2016;15:243-250.
- Kanegaye JT, Vance CW, Chan L, et al. Comparison of skin stapling devices and standard sutures for pediatric scalp lacerations: a randomized study of cost and time benefits. J Pediatr. 1997;130:808-813.
- Khan ANGA, Dayan PS, Miller S, et al. Cosmetic outcome of scalp wound closure with staples in the pediatric emergency department: a prospective, randomized trial. Pediatr Emerg Care. 2002;18:171-173.
Limited data exist comparing staples and sutures for scalp closures during Mohs micrographic surgery (MMS). As a result, the closure method for these scalp wounds is based on surgeon preference without established consensus. The purpose of this study was to survey practicing Mohs surgeons on their scalp wound closure preferences as well as the clinical and economic variables that impact their decisions. Understanding practice habits can guide future trial design, with a goal of creating established criterion for MMS scalp wound closures.
Methods
An anonymous survey was distributed from April 2019 to June 2019 to fellowship-trained Mohs surgeons using an electronic mailing list from the American College of Mohs Surgery (ACMS). The 10-question survey was approved by the University of Kansas institutional review board and the executive committee of the ACMS. Surgeons were asked about their preferred method for scalp wound closure as well as clinical and economic variables that impacted those preferences. Respondents indicated their frequency of using deep sutures, epidermal sutures, and wound undermining on a sliding scale of 0% to 100%. Comparisons were made between practice habits, preferences, and surgeon demographics using t tests. Statistical significance was determined as P<.05.
Results
Sixty-eight ACMS fellowship-trained Mohs surgeons completed the survey. The average age of respondents was 45 years; 69.1% (n=47) of respondents were male, and 76.5% (n=52) practiced in a private setting (Table 1). Regardless of epidermal closure type, deep suture placement was used in an average (standard deviation [SD]) of 88.8% (19.5%) of cases overall, which did not statistically differ between years of Mohs experience or practice setting (Table 2). Wound undermining was performed in an average (SD) of 83.0% (24.3%) of cases overall and was more prevalent in private vs academic settings (87.6% [17.8%] vs 65.7% [35.0%]; P<.01). Epidermal sutures were used in an average (SD) of 27.1% (33.5%) of scalp wound cases overall. Surgeons with less experience (≤5 years) used them more frequently (average [SD], 42.7% [36.2%] of cases) than surgeons with more experience (≥16 years; average [SD], 18.8% [32.6%] of cases; P=.037). There was no significant difference between epidermal suture placement rates and practice setting (average [SD], 18.1% [28.1%] of cases for academic providers vs 30.0% [34.8%] of cases with private providers; P=.210).
Clinical and economic factors that were most important during wound closure were ranked (beginning with most important) as the following: risk of complications, cosmetic outcome, hair preservation, patient comfort during closure, healing time, and closure cost. In all demographic cases, risk of complications was ranked 1 or 2 (1=most important; 6=least important) overall; cost was the least important factor overall (Table 2).
Surgeons perceived staples to be superior for speed of closure and for closing wounds in high-tension areas, whereas sutures were perceived as superior when considering cost of closure and ease of removal (Table 3). Successful healing rate, healing time, hair preservation, overall cosmetic outcome, and lower risk of complications were viewed as equivalent when comparing staples and sutures.
In cases in which surgeons did not use staples for closure, the most important factors for opting to not use them were patient discomfort (52.9% [n=36]), cost (25.0% [n=17]), and worse overall cosmetic outcome (23.5% [n=16])(Table 4). The most frequent locations outside of scalp wounds that physicians considered the use of staples for closure were the back (19.1% [n=13]), thigh (10.3% [n=7]), and shoulder (8.8% [n=6]).
Comment
Epidermal closure with sutures was reportedly used in an average of only 27.1% of scalp wound cases, with clinical factors such as cosmetic outcome, risk of complications, and closure time seen as either equivalent or inferior to staples. Our data suggest that surgeon closure perceptions generally are in agreement with established head and neck literature within different medical specialties that favor staple closures, particularly in high-tension areas.1 Interestingly, the most common reasons given for not using staples included patient discomfort, cost, and worse cosmetic outcomes, which are unsubstantiated with head and neck comparative studies.2-4
Although cost was the least important variable for determining closure type in our surveyed cohort, it is likely that the overall cost of closure is frequently underestimated. A higher material cost is noted with staples; however, the largest determinant of overall cost remains the surgeon’s time, which is reduced by factors of 10 or more when closing with staples.2,3 This difference—coupled with the unchanged cosmetic outcome and complication rates—makes staples more advantageous for high-tension scalp wounds.4 Moreover, the stapling technique is more reproducible than suturing, which requires more surgical skill and experience.
Limitations of this study include a lack of directly comparable data for staple and suture scalp wound closures. In addition, the small cohort of respondents in this preliminary study can serve to guide future studies.
Conclusion
Scalp wounds during MMS were most frequently closed using staples vs sutures, with the perception that these methods are equivalent in complication risk, cosmetic outcome, and overall patient satisfaction. These results agree with comparative literature for head and neck surgery and assist with establishing an epidemiologic baseline for future studies comparing their use during MMS.
Limited data exist comparing staples and sutures for scalp closures during Mohs micrographic surgery (MMS). As a result, the closure method for these scalp wounds is based on surgeon preference without established consensus. The purpose of this study was to survey practicing Mohs surgeons on their scalp wound closure preferences as well as the clinical and economic variables that impact their decisions. Understanding practice habits can guide future trial design, with a goal of creating established criterion for MMS scalp wound closures.
Methods
An anonymous survey was distributed from April 2019 to June 2019 to fellowship-trained Mohs surgeons using an electronic mailing list from the American College of Mohs Surgery (ACMS). The 10-question survey was approved by the University of Kansas institutional review board and the executive committee of the ACMS. Surgeons were asked about their preferred method for scalp wound closure as well as clinical and economic variables that impacted those preferences. Respondents indicated their frequency of using deep sutures, epidermal sutures, and wound undermining on a sliding scale of 0% to 100%. Comparisons were made between practice habits, preferences, and surgeon demographics using t tests. Statistical significance was determined as P<.05.
Results
Sixty-eight ACMS fellowship-trained Mohs surgeons completed the survey. The average age of respondents was 45 years; 69.1% (n=47) of respondents were male, and 76.5% (n=52) practiced in a private setting (Table 1). Regardless of epidermal closure type, deep suture placement was used in an average (standard deviation [SD]) of 88.8% (19.5%) of cases overall, which did not statistically differ between years of Mohs experience or practice setting (Table 2). Wound undermining was performed in an average (SD) of 83.0% (24.3%) of cases overall and was more prevalent in private vs academic settings (87.6% [17.8%] vs 65.7% [35.0%]; P<.01). Epidermal sutures were used in an average (SD) of 27.1% (33.5%) of scalp wound cases overall. Surgeons with less experience (≤5 years) used them more frequently (average [SD], 42.7% [36.2%] of cases) than surgeons with more experience (≥16 years; average [SD], 18.8% [32.6%] of cases; P=.037). There was no significant difference between epidermal suture placement rates and practice setting (average [SD], 18.1% [28.1%] of cases for academic providers vs 30.0% [34.8%] of cases with private providers; P=.210).
Clinical and economic factors that were most important during wound closure were ranked (beginning with most important) as the following: risk of complications, cosmetic outcome, hair preservation, patient comfort during closure, healing time, and closure cost. In all demographic cases, risk of complications was ranked 1 or 2 (1=most important; 6=least important) overall; cost was the least important factor overall (Table 2).
Surgeons perceived staples to be superior for speed of closure and for closing wounds in high-tension areas, whereas sutures were perceived as superior when considering cost of closure and ease of removal (Table 3). Successful healing rate, healing time, hair preservation, overall cosmetic outcome, and lower risk of complications were viewed as equivalent when comparing staples and sutures.
In cases in which surgeons did not use staples for closure, the most important factors for opting to not use them were patient discomfort (52.9% [n=36]), cost (25.0% [n=17]), and worse overall cosmetic outcome (23.5% [n=16])(Table 4). The most frequent locations outside of scalp wounds that physicians considered the use of staples for closure were the back (19.1% [n=13]), thigh (10.3% [n=7]), and shoulder (8.8% [n=6]).
Comment
Epidermal closure with sutures was reportedly used in an average of only 27.1% of scalp wound cases, with clinical factors such as cosmetic outcome, risk of complications, and closure time seen as either equivalent or inferior to staples. Our data suggest that surgeon closure perceptions generally are in agreement with established head and neck literature within different medical specialties that favor staple closures, particularly in high-tension areas.1 Interestingly, the most common reasons given for not using staples included patient discomfort, cost, and worse cosmetic outcomes, which are unsubstantiated with head and neck comparative studies.2-4
Although cost was the least important variable for determining closure type in our surveyed cohort, it is likely that the overall cost of closure is frequently underestimated. A higher material cost is noted with staples; however, the largest determinant of overall cost remains the surgeon’s time, which is reduced by factors of 10 or more when closing with staples.2,3 This difference—coupled with the unchanged cosmetic outcome and complication rates—makes staples more advantageous for high-tension scalp wounds.4 Moreover, the stapling technique is more reproducible than suturing, which requires more surgical skill and experience.
Limitations of this study include a lack of directly comparable data for staple and suture scalp wound closures. In addition, the small cohort of respondents in this preliminary study can serve to guide future studies.
Conclusion
Scalp wounds during MMS were most frequently closed using staples vs sutures, with the perception that these methods are equivalent in complication risk, cosmetic outcome, and overall patient satisfaction. These results agree with comparative literature for head and neck surgery and assist with establishing an epidemiologic baseline for future studies comparing their use during MMS.
- Ritchie AJ, Rocke LG. Staples versus sutures in the closure of scalp wounds: a prospective, double-blind, randomized trial. Injury. 1989;20:217-218.
- Batra J, Bekal RK, Byadgi S, et al. Comparison of skin staples and standard sutures for closing incisions after head and neck cancer surgery: a double-blind, randomized and prospective study. J Maxillofac Oral Surg. 2016;15:243-250.
- Kanegaye JT, Vance CW, Chan L, et al. Comparison of skin stapling devices and standard sutures for pediatric scalp lacerations: a randomized study of cost and time benefits. J Pediatr. 1997;130:808-813.
- Khan ANGA, Dayan PS, Miller S, et al. Cosmetic outcome of scalp wound closure with staples in the pediatric emergency department: a prospective, randomized trial. Pediatr Emerg Care. 2002;18:171-173.
- Ritchie AJ, Rocke LG. Staples versus sutures in the closure of scalp wounds: a prospective, double-blind, randomized trial. Injury. 1989;20:217-218.
- Batra J, Bekal RK, Byadgi S, et al. Comparison of skin staples and standard sutures for closing incisions after head and neck cancer surgery: a double-blind, randomized and prospective study. J Maxillofac Oral Surg. 2016;15:243-250.
- Kanegaye JT, Vance CW, Chan L, et al. Comparison of skin stapling devices and standard sutures for pediatric scalp lacerations: a randomized study of cost and time benefits. J Pediatr. 1997;130:808-813.
- Khan ANGA, Dayan PS, Miller S, et al. Cosmetic outcome of scalp wound closure with staples in the pediatric emergency department: a prospective, randomized trial. Pediatr Emerg Care. 2002;18:171-173.
Practice Points
- Scalp wounds present a unique challenge for closure during Mohs micrographic surgery due to the scalp's tendency to bleed, limited elasticity, and hair-bearing nature.
- Among fellowship-trained Mohs surgeons, scalp wounds were closed with staples more often than with epidermal sutures.
- Staples and sutures for scalp wounds were perceived to be equivalent in risk of complications, cosmetic outcome, and overall patient satisfaction.
- Compared to epidermal sutures, staples were perceived as advantageous in high-tension areas and for speed of closure.
Artificial intelligence matches cancer genotypes to patient phenotypes
Precision medicine is driven by technologies such as rapid genome sequencing and artificial intelligence (AI), according to a presentation at the AACR virtual meeting II.
AI can be applied to the sequencing information derived from advanced cancers to make highly personalized treatment recommendations for patients, said Olivier Elemento, PhD, of Weill Cornell Medicine, New York.
Dr. Elemento described such work during the opening plenary session of the meeting.
Dr. Elemento advocated for whole-genome sequencing (WGS) of metastatic sites, as it can reveal “branched evolution” as tumors progress from localized to metastatic (Nat Genet. 2016 Dec;48[12]:1490-9).
The metastases share common mutations with the primaries from which they arise but also develop their own mutational profiles, which facilitate site-of-origin-agnostic, predictive treatment choices.
As examples, Dr. Elemento mentioned HER2 amplification found in a patient with urothelial cancer (J Natl Compr Canc Netw. 2019 Mar 1;17[3]:194-200) and a patient with uterine serous carcinoma (Gynecol Oncol Rep. 2019 Feb 21;28:54-7), both of whom experienced long-lasting remissions to HER2-targeted therapy.
Dr. Elemento also noted that WGS can reveal complex structural variants in lung adenocarcinomas that lack alterations in the RTK/RAS/RAF pathway (unpublished data).
Application of machine learning
One study suggested that microRNA expression and machine learning can be used to identify malignant thyroid lesions (Clin Cancer Res. 2012 Apr 1;18[7]:2032-8). The approach diagnosed malignant lesions with 90% accuracy, 100% sensitivity, and 86% specificity.
Dr. Elemento and colleagues used a similar approach to predict response to immunotherapy in melanoma (unpublished data).
The idea was to mine the cancer genome and transcriptome, allowing for identification of signals from neoantigens, immune gene expression, immune cell composition, and T-cell receptor repertoires, Dr. Elemento said. Integrating these signals with clinical outcome data via machine learning technology enabled the researchers to predict immunotherapy response in malignant melanoma with nearly 90% accuracy.
AI and image analysis
Studies have indicated that AI can be applied to medical images to improve diagnosis and treatment. The approach has been shown to:
- Facilitate correct diagnoses of malignant skin lesions (Nature. 2017 Feb 2;542[7639]:115-8).
- Distinguish lung adenocarcinoma from squamous cell cancer with 100% accuracy (EBioMedicine. 2018 Jan;27:317-28).
- Recognize distinct breast cancer subtypes (ductal, lobular, mucinous, papillary) and biomarkers (bioRxiv 242818. doi: 10.1101/242818; EBioMedicine. 2018 Jan;27:317-28)
- Predict mesothelioma prognosis (Nat Med. 2019 Oct;25[10]:1519-25).
- Predict prostate biopsy results (unpublished data) and calculate Gleason scores that can predict survival in prostate cancer patients (AACR 2020, Abstract 867).
Drug development through applied AI
In another study, Dr. Elemento and colleagues used a Bayesian machine learning approach to predict targets of molecules without a known mechanism of action (Nat Commun. 2019 Nov 19;10[1]:5221).
The method involved using data on gene expression profiles, cell line viability, side effects in animals, and structures of the molecules. The researchers applied this method to a large library of orphan small molecules and found it could predict targets in about 40% of cases.
Of 24 AI-predicted microtubule-targeting molecules, 14 depolymerized microtubules in the lab. Five of these molecules were effective in cell lines that were resistant to other microtubule-targeted drugs.
Dr. Elemento went on to describe how Oncoceutics was developing an antineoplastic agent called ONC201, but the company lacked information about the agent’s target. Using AI, the target was identified as dopamine receptor 2 (DRD2; Clin Cancer Res. 2019 Apr 1;25[7]:2305-13).
With that information, Oncoceutics initiated trials of ONC201 in tumors expressing high levels of DRD2, including a highly resistant glioma (J Neurooncol. 2019 Oct;145[1]:97-105). Responses were seen, and ONC201 is now being tested against other DRD2-expressing cancers.
Challenges to acknowledge
Potential benefits of AI in the clinic are exciting, but there are many bench-to-bedside challenges.
A clinically obvious example of AI’s applications is radiographic image analysis. There is no biologic rationale for our RECIST “cut values” for partial response, minimal response, and stable disease.
If AI can measure subtle changes on imaging that correlate with tumor biology (i.e., radiomics), we stand a better chance of predicting treatment outcomes than we can with conventional measurements of shrinkage of arbitrarily selected “target lesions.”
A tremendous amount of work is needed to build the required large image banks. During that time, AI will only improve – and without the human risks of fatigue, inconsistency, or burnout.
Those human frailties notwithstanding, AI cannot substitute for the key discussions between patient and clinician regarding goals of care, trade-offs of risks and benefits, and shared decision-making regarding management options.
At least initially (but painfully), complex technologies like WGS and digital image analysis via AI may further disadvantage patients who are medically disadvantaged by geography or socioeconomic circumstances.
In the discussion period, AACR President Antoni Ribas, MD, of University of California, Los Angeles, asked whether AI can simulate crosstalk between gene pathways so that unique treatment combinations can be identified. Dr. Elemento said those simulations are the subject of ongoing investigation.
The theme of the opening plenary session at the AACR virtual meeting II was “Turning Science into Life-Saving Care.” Applications of AI to optimize personalized use of genomics, digital image analysis, and drug development show great promise for being among the technologies that can help to realize AACR’s thematic vision.
Dr. Elemento disclosed relationships with Volastra Therapeutics, OneThree Biotech, Owkin, Freenome, Genetic Intelligence, Acuamark Diagnostics, Eli Lilly, Janssen, and Sanofi.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
Precision medicine is driven by technologies such as rapid genome sequencing and artificial intelligence (AI), according to a presentation at the AACR virtual meeting II.
AI can be applied to the sequencing information derived from advanced cancers to make highly personalized treatment recommendations for patients, said Olivier Elemento, PhD, of Weill Cornell Medicine, New York.
Dr. Elemento described such work during the opening plenary session of the meeting.
Dr. Elemento advocated for whole-genome sequencing (WGS) of metastatic sites, as it can reveal “branched evolution” as tumors progress from localized to metastatic (Nat Genet. 2016 Dec;48[12]:1490-9).
The metastases share common mutations with the primaries from which they arise but also develop their own mutational profiles, which facilitate site-of-origin-agnostic, predictive treatment choices.
As examples, Dr. Elemento mentioned HER2 amplification found in a patient with urothelial cancer (J Natl Compr Canc Netw. 2019 Mar 1;17[3]:194-200) and a patient with uterine serous carcinoma (Gynecol Oncol Rep. 2019 Feb 21;28:54-7), both of whom experienced long-lasting remissions to HER2-targeted therapy.
Dr. Elemento also noted that WGS can reveal complex structural variants in lung adenocarcinomas that lack alterations in the RTK/RAS/RAF pathway (unpublished data).
Application of machine learning
One study suggested that microRNA expression and machine learning can be used to identify malignant thyroid lesions (Clin Cancer Res. 2012 Apr 1;18[7]:2032-8). The approach diagnosed malignant lesions with 90% accuracy, 100% sensitivity, and 86% specificity.
Dr. Elemento and colleagues used a similar approach to predict response to immunotherapy in melanoma (unpublished data).
The idea was to mine the cancer genome and transcriptome, allowing for identification of signals from neoantigens, immune gene expression, immune cell composition, and T-cell receptor repertoires, Dr. Elemento said. Integrating these signals with clinical outcome data via machine learning technology enabled the researchers to predict immunotherapy response in malignant melanoma with nearly 90% accuracy.
AI and image analysis
Studies have indicated that AI can be applied to medical images to improve diagnosis and treatment. The approach has been shown to:
- Facilitate correct diagnoses of malignant skin lesions (Nature. 2017 Feb 2;542[7639]:115-8).
- Distinguish lung adenocarcinoma from squamous cell cancer with 100% accuracy (EBioMedicine. 2018 Jan;27:317-28).
- Recognize distinct breast cancer subtypes (ductal, lobular, mucinous, papillary) and biomarkers (bioRxiv 242818. doi: 10.1101/242818; EBioMedicine. 2018 Jan;27:317-28)
- Predict mesothelioma prognosis (Nat Med. 2019 Oct;25[10]:1519-25).
- Predict prostate biopsy results (unpublished data) and calculate Gleason scores that can predict survival in prostate cancer patients (AACR 2020, Abstract 867).
Drug development through applied AI
In another study, Dr. Elemento and colleagues used a Bayesian machine learning approach to predict targets of molecules without a known mechanism of action (Nat Commun. 2019 Nov 19;10[1]:5221).
The method involved using data on gene expression profiles, cell line viability, side effects in animals, and structures of the molecules. The researchers applied this method to a large library of orphan small molecules and found it could predict targets in about 40% of cases.
Of 24 AI-predicted microtubule-targeting molecules, 14 depolymerized microtubules in the lab. Five of these molecules were effective in cell lines that were resistant to other microtubule-targeted drugs.
Dr. Elemento went on to describe how Oncoceutics was developing an antineoplastic agent called ONC201, but the company lacked information about the agent’s target. Using AI, the target was identified as dopamine receptor 2 (DRD2; Clin Cancer Res. 2019 Apr 1;25[7]:2305-13).
With that information, Oncoceutics initiated trials of ONC201 in tumors expressing high levels of DRD2, including a highly resistant glioma (J Neurooncol. 2019 Oct;145[1]:97-105). Responses were seen, and ONC201 is now being tested against other DRD2-expressing cancers.
Challenges to acknowledge
Potential benefits of AI in the clinic are exciting, but there are many bench-to-bedside challenges.
A clinically obvious example of AI’s applications is radiographic image analysis. There is no biologic rationale for our RECIST “cut values” for partial response, minimal response, and stable disease.
If AI can measure subtle changes on imaging that correlate with tumor biology (i.e., radiomics), we stand a better chance of predicting treatment outcomes than we can with conventional measurements of shrinkage of arbitrarily selected “target lesions.”
A tremendous amount of work is needed to build the required large image banks. During that time, AI will only improve – and without the human risks of fatigue, inconsistency, or burnout.
Those human frailties notwithstanding, AI cannot substitute for the key discussions between patient and clinician regarding goals of care, trade-offs of risks and benefits, and shared decision-making regarding management options.
At least initially (but painfully), complex technologies like WGS and digital image analysis via AI may further disadvantage patients who are medically disadvantaged by geography or socioeconomic circumstances.
In the discussion period, AACR President Antoni Ribas, MD, of University of California, Los Angeles, asked whether AI can simulate crosstalk between gene pathways so that unique treatment combinations can be identified. Dr. Elemento said those simulations are the subject of ongoing investigation.
The theme of the opening plenary session at the AACR virtual meeting II was “Turning Science into Life-Saving Care.” Applications of AI to optimize personalized use of genomics, digital image analysis, and drug development show great promise for being among the technologies that can help to realize AACR’s thematic vision.
Dr. Elemento disclosed relationships with Volastra Therapeutics, OneThree Biotech, Owkin, Freenome, Genetic Intelligence, Acuamark Diagnostics, Eli Lilly, Janssen, and Sanofi.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
Precision medicine is driven by technologies such as rapid genome sequencing and artificial intelligence (AI), according to a presentation at the AACR virtual meeting II.
AI can be applied to the sequencing information derived from advanced cancers to make highly personalized treatment recommendations for patients, said Olivier Elemento, PhD, of Weill Cornell Medicine, New York.
Dr. Elemento described such work during the opening plenary session of the meeting.
Dr. Elemento advocated for whole-genome sequencing (WGS) of metastatic sites, as it can reveal “branched evolution” as tumors progress from localized to metastatic (Nat Genet. 2016 Dec;48[12]:1490-9).
The metastases share common mutations with the primaries from which they arise but also develop their own mutational profiles, which facilitate site-of-origin-agnostic, predictive treatment choices.
As examples, Dr. Elemento mentioned HER2 amplification found in a patient with urothelial cancer (J Natl Compr Canc Netw. 2019 Mar 1;17[3]:194-200) and a patient with uterine serous carcinoma (Gynecol Oncol Rep. 2019 Feb 21;28:54-7), both of whom experienced long-lasting remissions to HER2-targeted therapy.
Dr. Elemento also noted that WGS can reveal complex structural variants in lung adenocarcinomas that lack alterations in the RTK/RAS/RAF pathway (unpublished data).
Application of machine learning
One study suggested that microRNA expression and machine learning can be used to identify malignant thyroid lesions (Clin Cancer Res. 2012 Apr 1;18[7]:2032-8). The approach diagnosed malignant lesions with 90% accuracy, 100% sensitivity, and 86% specificity.
Dr. Elemento and colleagues used a similar approach to predict response to immunotherapy in melanoma (unpublished data).
The idea was to mine the cancer genome and transcriptome, allowing for identification of signals from neoantigens, immune gene expression, immune cell composition, and T-cell receptor repertoires, Dr. Elemento said. Integrating these signals with clinical outcome data via machine learning technology enabled the researchers to predict immunotherapy response in malignant melanoma with nearly 90% accuracy.
AI and image analysis
Studies have indicated that AI can be applied to medical images to improve diagnosis and treatment. The approach has been shown to:
- Facilitate correct diagnoses of malignant skin lesions (Nature. 2017 Feb 2;542[7639]:115-8).
- Distinguish lung adenocarcinoma from squamous cell cancer with 100% accuracy (EBioMedicine. 2018 Jan;27:317-28).
- Recognize distinct breast cancer subtypes (ductal, lobular, mucinous, papillary) and biomarkers (bioRxiv 242818. doi: 10.1101/242818; EBioMedicine. 2018 Jan;27:317-28)
- Predict mesothelioma prognosis (Nat Med. 2019 Oct;25[10]:1519-25).
- Predict prostate biopsy results (unpublished data) and calculate Gleason scores that can predict survival in prostate cancer patients (AACR 2020, Abstract 867).
Drug development through applied AI
In another study, Dr. Elemento and colleagues used a Bayesian machine learning approach to predict targets of molecules without a known mechanism of action (Nat Commun. 2019 Nov 19;10[1]:5221).
The method involved using data on gene expression profiles, cell line viability, side effects in animals, and structures of the molecules. The researchers applied this method to a large library of orphan small molecules and found it could predict targets in about 40% of cases.
Of 24 AI-predicted microtubule-targeting molecules, 14 depolymerized microtubules in the lab. Five of these molecules were effective in cell lines that were resistant to other microtubule-targeted drugs.
Dr. Elemento went on to describe how Oncoceutics was developing an antineoplastic agent called ONC201, but the company lacked information about the agent’s target. Using AI, the target was identified as dopamine receptor 2 (DRD2; Clin Cancer Res. 2019 Apr 1;25[7]:2305-13).
With that information, Oncoceutics initiated trials of ONC201 in tumors expressing high levels of DRD2, including a highly resistant glioma (J Neurooncol. 2019 Oct;145[1]:97-105). Responses were seen, and ONC201 is now being tested against other DRD2-expressing cancers.
Challenges to acknowledge
Potential benefits of AI in the clinic are exciting, but there are many bench-to-bedside challenges.
A clinically obvious example of AI’s applications is radiographic image analysis. There is no biologic rationale for our RECIST “cut values” for partial response, minimal response, and stable disease.
If AI can measure subtle changes on imaging that correlate with tumor biology (i.e., radiomics), we stand a better chance of predicting treatment outcomes than we can with conventional measurements of shrinkage of arbitrarily selected “target lesions.”
A tremendous amount of work is needed to build the required large image banks. During that time, AI will only improve – and without the human risks of fatigue, inconsistency, or burnout.
Those human frailties notwithstanding, AI cannot substitute for the key discussions between patient and clinician regarding goals of care, trade-offs of risks and benefits, and shared decision-making regarding management options.
At least initially (but painfully), complex technologies like WGS and digital image analysis via AI may further disadvantage patients who are medically disadvantaged by geography or socioeconomic circumstances.
In the discussion period, AACR President Antoni Ribas, MD, of University of California, Los Angeles, asked whether AI can simulate crosstalk between gene pathways so that unique treatment combinations can be identified. Dr. Elemento said those simulations are the subject of ongoing investigation.
The theme of the opening plenary session at the AACR virtual meeting II was “Turning Science into Life-Saving Care.” Applications of AI to optimize personalized use of genomics, digital image analysis, and drug development show great promise for being among the technologies that can help to realize AACR’s thematic vision.
Dr. Elemento disclosed relationships with Volastra Therapeutics, OneThree Biotech, Owkin, Freenome, Genetic Intelligence, Acuamark Diagnostics, Eli Lilly, Janssen, and Sanofi.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
FROM AACR 2020
Study: Immune checkpoint inhibitors don’t increase risk of death in cancer patients with COVID-19
The study included 113 cancer patients who had laboratory-confirmed COVID-19 within 12 months of receiving immune checkpoint inhibitor therapy. The patients did not receive chemotherapy within 3 months of testing positive for COVID-19.
In all, 33 patients were admitted to the hospital, including 6 who were admitted to the ICU, and 9 patients died.
“Nine out of 113 patients is a mortality rate of 8%, which is in the middle of the earlier reported rates for cancer patients in general [7.6%-12%],” said Aljosja Rogiers, MD, PhD, of the Melanoma Institute Australia in Sydney.
COVID-19 was the primary cause of death in seven of the patients, including three of those who were admitted to the ICU, Dr. Rogiers noted.
He reported these results during the AACR virtual meeting: COVID-19 and Cancer.
Study details
Patients in this study were treated at 19 hospitals in North America, Europe, and Australia, and the data cutoff was May 15, 2020. Most patients (64%) were treated in Europe, which was the epicenter for the COVID-19 pandemic at the time of data collection, Dr. Rogiers noted. A third of patients were in North America, and 3% were in Australia.
The patients’ median age was 63 years (range, 27-86 years). Most patients were men (65%), and most had Eastern Cooperative Oncology Group performance scores of 0-1 (90%).
The most common malignancies were melanoma (57%), non–small cell lung cancer (17%), and renal cell carcinoma (9%). Treatment was for early cancer in 26% of patients and for advanced cancer in 74%. Comorbidities included cardiovascular disease in 27% of patients, diabetes in 15%, pulmonary disease in 12%, and renal disease in 5%.
Immunosuppressive therapy equivalent to a prednisone dose of 10 mg or greater daily was given in 13% of patients, and other immunosuppressive therapies, such as infliximab, were given in 3%.
Among the 60% of patients with COVID-19 symptoms, 68% had fever, 59% had cough, 34% had dyspnea, and 15% had myalgia. Most of the 40% of asymptomatic patients were tested because they had COVID-19–positive contact, Dr. Rogiers noted.
Immune checkpoint inhibitor treatment included monotherapy with a programmed death–1/PD–ligand 1 inhibitor in 82% of patients, combination anti-PD-1 and anti-CTLA4 therapy in 13%, and other therapy – usually a checkpoint inhibitor combined with a different type of targeted agent – in 5%.
At the time of COVID-19 diagnosis, 30% of patients had achieved a partial response, complete response, or had no evidence of disease, 18% had stable disease, and 15% had progression. Response data were not available in 37% of cases, usually because treatment was only recently started prior to COVID-19 diagnosis, Dr. Rogiers said.
Treatments administered for COVID-19 included antibiotic therapy in 25% of patients, oxygen therapy in 20%, glucocorticoids in 10%, antiviral drugs in 6%, and intravenous immunoglobulin or anti–interleukin-6 in 2% each.
Among patients admitted to the ICU, 3% required mechanical ventilation, 2% had vasopressin, and 1% received renal replacement therapy.
At the data cutoff, 20 of 33 hospitalized patients (61%) had been discharged, and 4 (12%) were still in the hospital.
Mortality results
Nine patients died. The rate of death was 8% overall and 27% among hospitalized patients.
“The mortality rate of COVID-19 in the general population without comorbidities is about 1.4%,” Dr. Rogiers said. “For cancer patients, this is reported to be in the range of 7.6%-12%. To what extent patients on immune checkpoint inhibition are at a higher risk of mortality is currently unknown.”
Theoretically, immune checkpoint inhibition could either mitigate or exacerbate COVID-19 infection. It has been hypothesized that immune checkpoint inhibitors could increase the risk of severe acute lung injury or other complications of COVID-19, Dr. Rogiers said, explaining the rationale for the study.
The study shows that the patients who died had a median age of 72 years (range, 49-81 years), which is slightly higher than the median overall age of 63 years. Six patients were from North America, and three were from Italy.
“Two melanoma patients and two non–small cell lung cancer patients died,” Dr. Rogiers said. He noted that two other deaths were in patients with renal cell carcinoma, and three deaths were in other cancer types. All patients had advanced or metastatic disease.
Given that 57% of patients in the study had melanoma and 17% had NSCLC, this finding may indicate that COVID-19 has a slightly higher mortality rate in NSCLC patients than in melanoma patients, but the numbers are small, Dr. Rogiers said.
Notably, six of the patients who died were not admitted to the ICU. In four cases, this was because of underlying malignancy; in the other two cases, it was because of a constrained health care system, Dr. Rogiers said.
Overall, the findings show that the mortality rate of patients with COVID-19 and cancer treated with immune checkpoint inhibitors is similar to the mortality rate reported in the general cancer population, Dr. Rogiers said.
“Treatment with immune checkpoint inhibition does not seem to pose an additional mortality risk for cancer patients with COVID-19,” he concluded.
Dr. Rogiers reported having no conflicts of interest. There was no funding disclosed for the study.
SOURCE: Rogiers A et al. AACR: COVID-19 and Cancer, Abstract S02-01.
The study included 113 cancer patients who had laboratory-confirmed COVID-19 within 12 months of receiving immune checkpoint inhibitor therapy. The patients did not receive chemotherapy within 3 months of testing positive for COVID-19.
In all, 33 patients were admitted to the hospital, including 6 who were admitted to the ICU, and 9 patients died.
“Nine out of 113 patients is a mortality rate of 8%, which is in the middle of the earlier reported rates for cancer patients in general [7.6%-12%],” said Aljosja Rogiers, MD, PhD, of the Melanoma Institute Australia in Sydney.
COVID-19 was the primary cause of death in seven of the patients, including three of those who were admitted to the ICU, Dr. Rogiers noted.
He reported these results during the AACR virtual meeting: COVID-19 and Cancer.
Study details
Patients in this study were treated at 19 hospitals in North America, Europe, and Australia, and the data cutoff was May 15, 2020. Most patients (64%) were treated in Europe, which was the epicenter for the COVID-19 pandemic at the time of data collection, Dr. Rogiers noted. A third of patients were in North America, and 3% were in Australia.
The patients’ median age was 63 years (range, 27-86 years). Most patients were men (65%), and most had Eastern Cooperative Oncology Group performance scores of 0-1 (90%).
The most common malignancies were melanoma (57%), non–small cell lung cancer (17%), and renal cell carcinoma (9%). Treatment was for early cancer in 26% of patients and for advanced cancer in 74%. Comorbidities included cardiovascular disease in 27% of patients, diabetes in 15%, pulmonary disease in 12%, and renal disease in 5%.
Immunosuppressive therapy equivalent to a prednisone dose of 10 mg or greater daily was given in 13% of patients, and other immunosuppressive therapies, such as infliximab, were given in 3%.
Among the 60% of patients with COVID-19 symptoms, 68% had fever, 59% had cough, 34% had dyspnea, and 15% had myalgia. Most of the 40% of asymptomatic patients were tested because they had COVID-19–positive contact, Dr. Rogiers noted.
Immune checkpoint inhibitor treatment included monotherapy with a programmed death–1/PD–ligand 1 inhibitor in 82% of patients, combination anti-PD-1 and anti-CTLA4 therapy in 13%, and other therapy – usually a checkpoint inhibitor combined with a different type of targeted agent – in 5%.
At the time of COVID-19 diagnosis, 30% of patients had achieved a partial response, complete response, or had no evidence of disease, 18% had stable disease, and 15% had progression. Response data were not available in 37% of cases, usually because treatment was only recently started prior to COVID-19 diagnosis, Dr. Rogiers said.
Treatments administered for COVID-19 included antibiotic therapy in 25% of patients, oxygen therapy in 20%, glucocorticoids in 10%, antiviral drugs in 6%, and intravenous immunoglobulin or anti–interleukin-6 in 2% each.
Among patients admitted to the ICU, 3% required mechanical ventilation, 2% had vasopressin, and 1% received renal replacement therapy.
At the data cutoff, 20 of 33 hospitalized patients (61%) had been discharged, and 4 (12%) were still in the hospital.
Mortality results
Nine patients died. The rate of death was 8% overall and 27% among hospitalized patients.
“The mortality rate of COVID-19 in the general population without comorbidities is about 1.4%,” Dr. Rogiers said. “For cancer patients, this is reported to be in the range of 7.6%-12%. To what extent patients on immune checkpoint inhibition are at a higher risk of mortality is currently unknown.”
Theoretically, immune checkpoint inhibition could either mitigate or exacerbate COVID-19 infection. It has been hypothesized that immune checkpoint inhibitors could increase the risk of severe acute lung injury or other complications of COVID-19, Dr. Rogiers said, explaining the rationale for the study.
The study shows that the patients who died had a median age of 72 years (range, 49-81 years), which is slightly higher than the median overall age of 63 years. Six patients were from North America, and three were from Italy.
“Two melanoma patients and two non–small cell lung cancer patients died,” Dr. Rogiers said. He noted that two other deaths were in patients with renal cell carcinoma, and three deaths were in other cancer types. All patients had advanced or metastatic disease.
Given that 57% of patients in the study had melanoma and 17% had NSCLC, this finding may indicate that COVID-19 has a slightly higher mortality rate in NSCLC patients than in melanoma patients, but the numbers are small, Dr. Rogiers said.
Notably, six of the patients who died were not admitted to the ICU. In four cases, this was because of underlying malignancy; in the other two cases, it was because of a constrained health care system, Dr. Rogiers said.
Overall, the findings show that the mortality rate of patients with COVID-19 and cancer treated with immune checkpoint inhibitors is similar to the mortality rate reported in the general cancer population, Dr. Rogiers said.
“Treatment with immune checkpoint inhibition does not seem to pose an additional mortality risk for cancer patients with COVID-19,” he concluded.
Dr. Rogiers reported having no conflicts of interest. There was no funding disclosed for the study.
SOURCE: Rogiers A et al. AACR: COVID-19 and Cancer, Abstract S02-01.
The study included 113 cancer patients who had laboratory-confirmed COVID-19 within 12 months of receiving immune checkpoint inhibitor therapy. The patients did not receive chemotherapy within 3 months of testing positive for COVID-19.
In all, 33 patients were admitted to the hospital, including 6 who were admitted to the ICU, and 9 patients died.
“Nine out of 113 patients is a mortality rate of 8%, which is in the middle of the earlier reported rates for cancer patients in general [7.6%-12%],” said Aljosja Rogiers, MD, PhD, of the Melanoma Institute Australia in Sydney.
COVID-19 was the primary cause of death in seven of the patients, including three of those who were admitted to the ICU, Dr. Rogiers noted.
He reported these results during the AACR virtual meeting: COVID-19 and Cancer.
Study details
Patients in this study were treated at 19 hospitals in North America, Europe, and Australia, and the data cutoff was May 15, 2020. Most patients (64%) were treated in Europe, which was the epicenter for the COVID-19 pandemic at the time of data collection, Dr. Rogiers noted. A third of patients were in North America, and 3% were in Australia.
The patients’ median age was 63 years (range, 27-86 years). Most patients were men (65%), and most had Eastern Cooperative Oncology Group performance scores of 0-1 (90%).
The most common malignancies were melanoma (57%), non–small cell lung cancer (17%), and renal cell carcinoma (9%). Treatment was for early cancer in 26% of patients and for advanced cancer in 74%. Comorbidities included cardiovascular disease in 27% of patients, diabetes in 15%, pulmonary disease in 12%, and renal disease in 5%.
Immunosuppressive therapy equivalent to a prednisone dose of 10 mg or greater daily was given in 13% of patients, and other immunosuppressive therapies, such as infliximab, were given in 3%.
Among the 60% of patients with COVID-19 symptoms, 68% had fever, 59% had cough, 34% had dyspnea, and 15% had myalgia. Most of the 40% of asymptomatic patients were tested because they had COVID-19–positive contact, Dr. Rogiers noted.
Immune checkpoint inhibitor treatment included monotherapy with a programmed death–1/PD–ligand 1 inhibitor in 82% of patients, combination anti-PD-1 and anti-CTLA4 therapy in 13%, and other therapy – usually a checkpoint inhibitor combined with a different type of targeted agent – in 5%.
At the time of COVID-19 diagnosis, 30% of patients had achieved a partial response, complete response, or had no evidence of disease, 18% had stable disease, and 15% had progression. Response data were not available in 37% of cases, usually because treatment was only recently started prior to COVID-19 diagnosis, Dr. Rogiers said.
Treatments administered for COVID-19 included antibiotic therapy in 25% of patients, oxygen therapy in 20%, glucocorticoids in 10%, antiviral drugs in 6%, and intravenous immunoglobulin or anti–interleukin-6 in 2% each.
Among patients admitted to the ICU, 3% required mechanical ventilation, 2% had vasopressin, and 1% received renal replacement therapy.
At the data cutoff, 20 of 33 hospitalized patients (61%) had been discharged, and 4 (12%) were still in the hospital.
Mortality results
Nine patients died. The rate of death was 8% overall and 27% among hospitalized patients.
“The mortality rate of COVID-19 in the general population without comorbidities is about 1.4%,” Dr. Rogiers said. “For cancer patients, this is reported to be in the range of 7.6%-12%. To what extent patients on immune checkpoint inhibition are at a higher risk of mortality is currently unknown.”
Theoretically, immune checkpoint inhibition could either mitigate or exacerbate COVID-19 infection. It has been hypothesized that immune checkpoint inhibitors could increase the risk of severe acute lung injury or other complications of COVID-19, Dr. Rogiers said, explaining the rationale for the study.
The study shows that the patients who died had a median age of 72 years (range, 49-81 years), which is slightly higher than the median overall age of 63 years. Six patients were from North America, and three were from Italy.
“Two melanoma patients and two non–small cell lung cancer patients died,” Dr. Rogiers said. He noted that two other deaths were in patients with renal cell carcinoma, and three deaths were in other cancer types. All patients had advanced or metastatic disease.
Given that 57% of patients in the study had melanoma and 17% had NSCLC, this finding may indicate that COVID-19 has a slightly higher mortality rate in NSCLC patients than in melanoma patients, but the numbers are small, Dr. Rogiers said.
Notably, six of the patients who died were not admitted to the ICU. In four cases, this was because of underlying malignancy; in the other two cases, it was because of a constrained health care system, Dr. Rogiers said.
Overall, the findings show that the mortality rate of patients with COVID-19 and cancer treated with immune checkpoint inhibitors is similar to the mortality rate reported in the general cancer population, Dr. Rogiers said.
“Treatment with immune checkpoint inhibition does not seem to pose an additional mortality risk for cancer patients with COVID-19,” he concluded.
Dr. Rogiers reported having no conflicts of interest. There was no funding disclosed for the study.
SOURCE: Rogiers A et al. AACR: COVID-19 and Cancer, Abstract S02-01.
FROM AACR: COVID-19 AND CANCER
Risk Factors and Management of Skin Cancer Among Active-Duty Servicemembers and Veterans
Melanoma Risk for Servicemembers
Dr. Dunn: Active-duty jobs are quite diverse. We have had almost every civilian occupation category—everything from clerical to food service to outdoor construction workers. Federal service and active-duty military service could lead to assignments that involve high sunlight exposure and subsequently higher risk for melanoma and nonmelanoma skin cancer.
Dr. Miller: I found 2 articles on the topic. The first published in June 2018 reviewed melanoma and nonmelanoma skin cancers in the military.1 Riemenschneider and colleagues1 looked at 9 studies. Statistically, there was increased risk of melanoma associated with service and/or prisoner-of-war status. In World War II, they found tropical environments had the highest risk. And the highest rates were in the US Air Force.
The other article provided US Department of Defense data on skin cancer incidence rates, incidence rates of malignant melanoma in relation to years of military service overall, and the rates for differing military occupational groups.2 The researchers demonstrated that fixed-wing pilots and crew members had the highest rates of developing melanoma. The general trend was that the incidence rate was exponentially higher with more missions flown in relation to years of active service, which I thought was rather interesting.
For other occupational categories, the rate increase was not as great as those involved in aviation. Yes, it’s probably related to exposure. Flying at 40,000 feet on a transcontinental airplane trip is equivalent to the radiation dosage of a chest X-ray. Given all the training time and operational flying for the Air Force, it is anticipated that that mutagenic radiation would increase rates. An aircraft does not offer a lot of protection, especially in the cockpit.
We just had the anniversary of the Apollo 11 mission. Those astronauts received the equivalent of about 40 chest X-rays going to the moon and back. Exposure to UV and at higher altitudes cosmic radiation explains why we would see that more in Air Force personnel.
Dr. Bandino: At high altitude there is less ozone protecting you, although the shielding in a cockpit is better in modern aircraft. As an Air Force member, that was one of the first things I thought about was that an aviator has increased skin cancer risk. But it’s apt to think of military service in general as an occupational risk because there are so many contingency operations and deployments. Regarding sun exposure, sunscreen is provided nowadays and there is more sun awareness, but there is still a stigma and reluctance to apply the sunscreen. It leaves people’s skin feeling greasy, which is not ideal when one has to handle a firearm. It can also get in someone’s eyes and affect vision and performance during combat operations. In other words, there are many reasons that would reduce the desire to wear sunscreen and therefore increase exposure to the elements.
A great current example is coronavirus disease 2019 (COVID-19) operations. Although I’m a dermatologist and typically work inside, I’ve been tasked to run a COVID-19 screening tent in the middle of a field in San Antonio, and thus I’ve got to make sure I take my sunscreen out there every day. The general population may not have that variability in their work cycle and sudden change in occupational UV exposure.
Dr. Miller: I was deployed in a combat zone for operations Desert Shield and Desert Storm. I was with the 2nd Armored Division of the US Army deployed to the desert. There really wasn’t an emphasis on photoprotection. It’s just the logistics. The commanders have a lot more important things to think about, and that’s something, usually, that doesn’t get a high priority. The US military is deploying to more places near the equator, so from an operational sense, there’s probably something to brief the commanders about in terms of the long-term consequences of radiation exposure for military servicemembers.
Dr. Dunn: If you look at deployments over the past 2 decades, we have been putting tens of thousands of individuals in high UV exposure regions. Then you have to look at the long-term consequence of the increased incidence of skin cancer in those individuals. What is the cost of that when it comes to treatment of precancerous lesions and skin cancer throughout a life expectancy of 80-plus years?
Dr. Bandino: With most skin cancers there is such long lag time between exposures and development. I wish there were some better data and research out there that really showed whether military service truly is an independent risk factor or if it’s just specific occupation types within the military. I have family members who both work in contracting services and had served in the military. Would their skin cancer risk be the same as others who are doing similar jobs without the military service?
Dr. Dunn: I have had county employees present for skin cancer surgery and with them comes a form that relates to disability. For groundskeepers or police, we assumed that skin cancer is occupation related due to the patient’s increased sun exposure. Their cancers may be unrelated to their actual years of service, but it seems that many light-skinned individuals in the military are going to develop basal cell and squamous cell skin cancer in the coming decades, which likely is going to be attributed to their years of federal service, even though they may have had other significant recreational exposure outside of work. So, my gut feeling is that we are going to see skin cancer as a disability tied to federal service, which is going to cost us.
Dr. Logemann: Yes, I think there are always going to be confounders—what if the servicemembers used tanning beds, or they were avid surfers? It’s going to be difficult to always parse that out.
Dr. Miller: In talking about melanoma, you really have to parse out the subsets. Is it melanoma in situ, is it superficial, is it acral, is it nodular? They all have different initiation events.
Nodular melanomas probably don’t need UV light to initiate a tumor. Another risk factor is having more than 100 moles or many atypical moles, which puts that person in a higher risk category. Perhaps when soldiers, airmen, and navy personnel get inducted, they should be screened for their mole population because that is a risk factor for developing melanoma, and then we can intervene a little bit and have them watch their UV exposure.
Dr. Jarell: You can’t overstate the importance of how heterogeneous melanoma is as a disease. While there are clearly some types of melanoma that are caused by UV radiation, there are also many types that aren’t. We don’t understand why someone gets melanoma on the inner thigh, bottom of the foot, top of the sole, inside the mouth, or in the genital region—these aren’t places of high sun exposure.
Lentigo maligna, as an example, is clearly caused by UV radiation in most cases. But there are so many other different types of melanoma that you can’t just attribute to UV radiation, and so you get into this whole other discussion as to why people are getting melanoma—military or not.
Dr. Bandino: When volunteering for military service, there’s the DoDMERB (Department of Defense Medical Examination Review Board) system that screens individuals for medical issues incompatible with military service such as severe psoriasis or atopic dermatitis. But to my knowledge, the DoDMERB process focuses more on current or past issues and does little to investigate for future risk of disease. A cutaneous example would be assessing quantity of dysplastic nevi, Fitzpatrick scale 1 phenotype, and family history of melanoma to determine risk of developing melanoma in someone who may have more UV exposure during their military service than a civilian. This dermatological future risk assessment was certainly not something I was trained to do as a flight surgeon when performing basic trainee flight physicals prior to becoming a dermatologist.
Dr. Jarell: I am a little bit hard-pressed to generalize the military as high occupational risk for melanoma. There are clearly other professions—landscapers, fishermen—that are probably at much higher risk than, say, your general military all-comers. Us physicians in the military were probably not at increased risk compared to other physicians in the United States. We have to be careful not to go down a slippery slope and designate all MOSs (military occupational specialties) as at increased risk for skin cancer, in particular melanoma. Nonmelanoma skin cancer, such as basal cell and squamous cell carcinoma, is clearly related to the proportional amount of UV exposure. But melanoma is quite a diverse cancer that has many, many disparate etiologies.
Dr. Dunn: The entry physical into the military is an opportunity to make an impact on the number of nonmelanoma skin cancers that would arise in that population. There is an educational opportunity to tell inductees that nonmelanoma skin cancer is going to occur on convex surfaces of the sun-exposed skin—nose, ears, forehead, chin, tops of the shoulders. If offered sun protection for those areas and you stretch the potential impact of that information over tens of thousands of military members over decades, you might actually come up with a big number of people that not only decreases their morbidity but also dramatically decreased the cost to the system as a whole.
Dr. Jarell: You also have to factor in ethnicity and the role it plays in someone’s likelihood to get skin cancer—melanoma or nonmelanoma skin cancer. Darker-skinned people are at certainly decreased risk for different types of skin cancers.
Dr. Dunn: Yes, that would have to be part of the education and should be. If you have light skin and freckles, then you’re at much higher risk for nonmelanoma skin cancer and need to know the high-risk areas that can be protected by sunblock and clothing.
Dr. Logemann: One thing that might be a little bit unique in the military is that you’re living in San Antonio one minute, and then the next minute you’re over in Afghanistan with a different climate and different environment. When you’re deployed overseas, you might have a little bit less control over your situation; you might not have a lot of sunscreen in a field hospital in Afghanistan. Whereas if you were just living in San Antonio, you could go down to the store and buy it.
Dr. Miller: Is sunblock now encouraged or available to individuals in deployment situations or training situations where they’re going to have prolonged sun exposure every day? Is it part of the regimen, just like carrying extra water because of the risk for dehydration?
Dr. Logemann: To the best of my knowledge, it is not always included in your normal rations or uniform and it may be up to the servicemember to procure sunscreen.
Dr. Bandino: There have been improvements, and usually you at least have access to sunscreen. In many deployed locations, for example, you have the equivalent of a small PX (post exchange) or BX (base exchange), where they have a variety of products for sale from toothbrushes to flip-flops, and now also sunscreen. Of course, the type and quality of the sunscreen may not be that great. It’s likely going to be basic SPF (sun protection factor) 15 or 30 in small tubes. As a recent example, I participated in a humanitarian medical exercise in South America last summer and was actually issued sunscreen combined with DEET, which is great but it was only SPF 30. The combination product is a good idea for tropical locations, but in addition to people just not wanting to wear it, the DEET combination tends to burn and sting a little bit more; you can get a heat sensation from the DEET; and the DEET can damage plastic surfaces, which may not be ideal for deployed equipment.
The other problem is quantity. We all learned in residency the appropriate sunscreen quantity of at least 1 fl oz for the average adult body, and that’s what we counsel our patients on, but what they issued me was 1 small 2- to 3-fl oz tube. It fit in the palm of my hand, and that was my sunscreen for the trip.
So, I do think, even though there have been some improvements, much of sun protection will still fall on the individual servicemember. And, as mentioned, depending on your ethnicity, some people may need it more than others. But it is an area where there probably could be continued improvements.
Dr. Logemann: In addition to sunscreen, I think that maybe we should be taking into consideration some simple measures. For example, is it necessary for people to stand out in formation at 2
Dr. Dunn: I think we all kind of agree that the military service is diverse and that many of the subcategories of occupations within the military lead to increased sun exposure by mandate. We advise sun protection by physical barriers and sunblock.
Diagnosis of Skin Cancer Via Telemedicine
Dr. Dunn: I have friends who remain in the VA (US Department of Veterans Affairs) system, and they are involved with telemedicine in dermatology, which can reduce waiting time and increase the number of patients seen by the dermatologist. In-person and teledermatology visits now are available to servicemembers on active duty and retirees.
Dr. Bandino: At our residency program (San Antonio Uniformed Services Health Education Consortium), we’ve had asynchronous teledermatology for over a decade, even before I was a resident. We provide it primarily as a service for patients at small bases without access to dermatology. Some bases also use it as part of their prescreening process prior to authorizing an in-person dermatology consultation.
Certainly, with the coronavirus pandemic, civilian dermatology is seeing a boom in the teledermatology world that had been slowly increasing in popularity for the last few years. In our residency program, teledermatology has traditionally been just for active-duty servicemembers or their dependents, but now due to the coronavirus pandemic, our teledermatology services have significantly expanded to include adding synchronous capability. We have patients take pictures before their virtual appointment and/or FaceTime during the appointment. Even after the pandemic, there will likely be more integration of synchronous teledermatology going forward as we’re seeing some of the value. Of course, I’m sure we would all agree that accurate diagnosis of pigmented lesions can be very challenging with teledermatology, not to mention other diagnostic limitations. But I think there is still utility and it should only get better with time as technology improves. So, I’m hopeful that we can incorporate more of it in the military.
Dr. Logemann: I’m definitely aware that we have different telehealth opportunities available, even using some newer modalities that are command approved in recent weeks. My experience has been for more complicated dermatology, so people are in remote locations, and they’re being seen by a nondermatologist, and they have questions about how to approach management. But I’m not aware of telemedicine as a screening tool for skin cancer in the military or among my civilian colleagues. I would hope that it could be someday because we’re developing these total-body photography machines as well. It could be a way for a nondermatologist who identifies a lesion to have it triaged by a dermatologist. To say, “Oh yeah, that looks like a melanoma. They need to get in sooner vs later,” but not on a large-scale sort of screening modality.
Dr. Bandino: In my recent experience, it has definitely been a helpful triage tool. In the military, this form of triage can be particularly helpful if someone is overseas to determine whether he/she needs to evacuated and evaluated in-person right away.
Dr. Jarell: It’s been useful in looking at benign things. People have shown me in the past few weeks a lot of seborrheic keratoses and a lot of benign dermal nevus-type things, and I say, “Don’t worry about that.” And you can tell if the resolution is good enough. But a lot of people have shown me things in the past few weeks that have clearly been basal cell carcinoma, which we can probably let that ride out for a few more weeks, but I’m not sure if maybe somebody has an amelanotic melanoma. Maybe you need to come in and get that biopsied ASAP. Or something that looks like a melanoma. The patient should probably come in and get that biopsied.
Dr. Miller: I think we can rely on teledermatology. It’s all predicated on the resolution because we’re all trained in pattern recognition. I think it’s very useful to screen for things that look clinically benign. We have to understand that most dermatology is practiced by nondermatologists in the United States, and many studies show that their diagnostic accuracy is 20%, at best maybe 50%. So, they do need to reach out to a dermatologist and perhaps get some guidance on what to do. I think it could be a very useful tool if used appropriately.
Dr. Dunn: If used appropriately, teledermatology could function in a couple of ways. One, it could allow us to declare lesions to be wholly benign, and only should a lesion change would it need attention. The second is that it would allow us to accelerate the process of getting a patient to us—physically in front of us—for a biopsy if a suspicious lesion is seen. A by-product of that process would be that if patients who have wholly benign, nonworrisome lesions could be screened by telemedicine, then physical appointments where a patient is in front of the doctor would be more open. In other words, let’s say if 25% of all lesional visits could be declared benign via telemedicine that would allow dermatology to preserve its face-to-face appointments for patients who are more likely to have cancer and require procedures like skin biopsy.
Love it or hate it, I think we’re getting it no matter what now. Telemedicine creeped along forever and within 6 weeks it’s become ubiquitous. It’s phenomenal how fast we had to adapt to a system or perish in private practice. Sometimes these episodes that we go through have good consequences as well as bad consequences. Telemedicine probably has been needed for a long time and the insurers were not covering it very well, but suddenly a stay-at-home mandate has unveiled valuable technology—something that we probably should have been able to use more and be adequately reimbursed.
Surgical Treatment of Skin Cancer
Dr. Dunn: Treatment historically has been surgical for nonmelanoma and melanoma skin cancers. Some radiation devices have gained popularity again in the past decade or so, but excisional surgery remains the standard treatment for skin cancer. Nonmelanoma skin cancers almost all are probably treated surgically still, with a small percentage treated with superficial radiation.
Access to care is important to discuss. Are Mohs surgeons readily available, or are plastic surgeons, general surgeons, or vascular surgeons in the federal system contributing to the care of skin cancer? Are they doing excisional surgery after biopsies are done? Are they doing excisional biopsies with the intent of cure?
Dr. Logemann: For active duty, I don’t see any issues getting access to the medical center for Mohs micrographic surgery. Sometimes, if we have a lot of volume, some patients may get deferred to the network, but in my experience, it would not typically be an active-duty servicemember. An active-duty servicemember would get care rendered at one of the medical centers for Mohs surgery. Typically the active-duty–aged population isn’t getting much skin cancer. It certainly does happen, but most of the skin cancers frequently that are treated at medical centers are not infrequently retirees.
Dr. Bandino: Because of our residency program, we are required to have Mohs surgery capability to be ACGME (Accreditation Council for Graduate Medical Education) accredited. We typically have 3 Mohs surgeons, so we never have a problem with access.
In the military, I just refer cases to our Mohs surgeons and everything is taken care of in-house. In fact, this is an area where we may even have better access than the civilian world because there are no insurance hurdles or significant delay in care since our Mohs surgeons aren’t typically booked up for 3 to 4 months like many civilian Mohs surgeons. This is especially true for complex cases since we provide hospital-based care with all specialty services under the same umbrella. So, for example, if the Mohs surgeons have an extensive and complex case requiring multidisciplinary care such as ENT (ear, nose, and throat), facial plastics, or radiation-oncology, they’re all in-house with no insurance issues to navigate. This of course is not usual for most military bases and is only capable at bases attached to a large medical center. There are some similar scenarios in the civilian world with university medical centers and managed care organizations, but we may still have a slight advantage in accessibility and cost.
Dr. Dunn: There are guidelines from the National Comprehensive Cancer Network as to how to treat nonmelanoma and melanoma skin cancer. Almost all of them are surgical and almost all of them are safe, outpatient, local anesthetic procedures with a high cure rate. The vast majority of melanoma and nonmelanoma skin cancers can be handled safely and effectively with minimal morbidity and almost no known mortalities from the treatments themselves. Some of the cancers have been identified as high risk for metastasis and mortality, but they’re relatively uncommon still. The good news about skin cancer is that the risk of death remains very small.
- Riemenschneider K, Liu J, Powers JG. Skin cancer in the military: a systematic review of melanoma and nonmelanoma skin cancer incidence, prevention, and screening among active duty and veteran personnel.J Am Acad Dermatol. 2018;78:1185-1192.
- Brundage JF, Williams VF, Stahlman S, et al. Incidence rates of malignant melanoma in relation to years of military service, overall and in selected military occupational groups, active component, U.S. Armed Forces, 2001-2015. MSMR. 2017;24:8-14.
Melanoma Risk for Servicemembers
Dr. Dunn: Active-duty jobs are quite diverse. We have had almost every civilian occupation category—everything from clerical to food service to outdoor construction workers. Federal service and active-duty military service could lead to assignments that involve high sunlight exposure and subsequently higher risk for melanoma and nonmelanoma skin cancer.
Dr. Miller: I found 2 articles on the topic. The first published in June 2018 reviewed melanoma and nonmelanoma skin cancers in the military.1 Riemenschneider and colleagues1 looked at 9 studies. Statistically, there was increased risk of melanoma associated with service and/or prisoner-of-war status. In World War II, they found tropical environments had the highest risk. And the highest rates were in the US Air Force.
The other article provided US Department of Defense data on skin cancer incidence rates, incidence rates of malignant melanoma in relation to years of military service overall, and the rates for differing military occupational groups.2 The researchers demonstrated that fixed-wing pilots and crew members had the highest rates of developing melanoma. The general trend was that the incidence rate was exponentially higher with more missions flown in relation to years of active service, which I thought was rather interesting.
For other occupational categories, the rate increase was not as great as those involved in aviation. Yes, it’s probably related to exposure. Flying at 40,000 feet on a transcontinental airplane trip is equivalent to the radiation dosage of a chest X-ray. Given all the training time and operational flying for the Air Force, it is anticipated that that mutagenic radiation would increase rates. An aircraft does not offer a lot of protection, especially in the cockpit.
We just had the anniversary of the Apollo 11 mission. Those astronauts received the equivalent of about 40 chest X-rays going to the moon and back. Exposure to UV and at higher altitudes cosmic radiation explains why we would see that more in Air Force personnel.
Dr. Bandino: At high altitude there is less ozone protecting you, although the shielding in a cockpit is better in modern aircraft. As an Air Force member, that was one of the first things I thought about was that an aviator has increased skin cancer risk. But it’s apt to think of military service in general as an occupational risk because there are so many contingency operations and deployments. Regarding sun exposure, sunscreen is provided nowadays and there is more sun awareness, but there is still a stigma and reluctance to apply the sunscreen. It leaves people’s skin feeling greasy, which is not ideal when one has to handle a firearm. It can also get in someone’s eyes and affect vision and performance during combat operations. In other words, there are many reasons that would reduce the desire to wear sunscreen and therefore increase exposure to the elements.
A great current example is coronavirus disease 2019 (COVID-19) operations. Although I’m a dermatologist and typically work inside, I’ve been tasked to run a COVID-19 screening tent in the middle of a field in San Antonio, and thus I’ve got to make sure I take my sunscreen out there every day. The general population may not have that variability in their work cycle and sudden change in occupational UV exposure.
Dr. Miller: I was deployed in a combat zone for operations Desert Shield and Desert Storm. I was with the 2nd Armored Division of the US Army deployed to the desert. There really wasn’t an emphasis on photoprotection. It’s just the logistics. The commanders have a lot more important things to think about, and that’s something, usually, that doesn’t get a high priority. The US military is deploying to more places near the equator, so from an operational sense, there’s probably something to brief the commanders about in terms of the long-term consequences of radiation exposure for military servicemembers.
Dr. Dunn: If you look at deployments over the past 2 decades, we have been putting tens of thousands of individuals in high UV exposure regions. Then you have to look at the long-term consequence of the increased incidence of skin cancer in those individuals. What is the cost of that when it comes to treatment of precancerous lesions and skin cancer throughout a life expectancy of 80-plus years?
Dr. Bandino: With most skin cancers there is such long lag time between exposures and development. I wish there were some better data and research out there that really showed whether military service truly is an independent risk factor or if it’s just specific occupation types within the military. I have family members who both work in contracting services and had served in the military. Would their skin cancer risk be the same as others who are doing similar jobs without the military service?
Dr. Dunn: I have had county employees present for skin cancer surgery and with them comes a form that relates to disability. For groundskeepers or police, we assumed that skin cancer is occupation related due to the patient’s increased sun exposure. Their cancers may be unrelated to their actual years of service, but it seems that many light-skinned individuals in the military are going to develop basal cell and squamous cell skin cancer in the coming decades, which likely is going to be attributed to their years of federal service, even though they may have had other significant recreational exposure outside of work. So, my gut feeling is that we are going to see skin cancer as a disability tied to federal service, which is going to cost us.
Dr. Logemann: Yes, I think there are always going to be confounders—what if the servicemembers used tanning beds, or they were avid surfers? It’s going to be difficult to always parse that out.
Dr. Miller: In talking about melanoma, you really have to parse out the subsets. Is it melanoma in situ, is it superficial, is it acral, is it nodular? They all have different initiation events.
Nodular melanomas probably don’t need UV light to initiate a tumor. Another risk factor is having more than 100 moles or many atypical moles, which puts that person in a higher risk category. Perhaps when soldiers, airmen, and navy personnel get inducted, they should be screened for their mole population because that is a risk factor for developing melanoma, and then we can intervene a little bit and have them watch their UV exposure.
Dr. Jarell: You can’t overstate the importance of how heterogeneous melanoma is as a disease. While there are clearly some types of melanoma that are caused by UV radiation, there are also many types that aren’t. We don’t understand why someone gets melanoma on the inner thigh, bottom of the foot, top of the sole, inside the mouth, or in the genital region—these aren’t places of high sun exposure.
Lentigo maligna, as an example, is clearly caused by UV radiation in most cases. But there are so many other different types of melanoma that you can’t just attribute to UV radiation, and so you get into this whole other discussion as to why people are getting melanoma—military or not.
Dr. Bandino: When volunteering for military service, there’s the DoDMERB (Department of Defense Medical Examination Review Board) system that screens individuals for medical issues incompatible with military service such as severe psoriasis or atopic dermatitis. But to my knowledge, the DoDMERB process focuses more on current or past issues and does little to investigate for future risk of disease. A cutaneous example would be assessing quantity of dysplastic nevi, Fitzpatrick scale 1 phenotype, and family history of melanoma to determine risk of developing melanoma in someone who may have more UV exposure during their military service than a civilian. This dermatological future risk assessment was certainly not something I was trained to do as a flight surgeon when performing basic trainee flight physicals prior to becoming a dermatologist.
Dr. Jarell: I am a little bit hard-pressed to generalize the military as high occupational risk for melanoma. There are clearly other professions—landscapers, fishermen—that are probably at much higher risk than, say, your general military all-comers. Us physicians in the military were probably not at increased risk compared to other physicians in the United States. We have to be careful not to go down a slippery slope and designate all MOSs (military occupational specialties) as at increased risk for skin cancer, in particular melanoma. Nonmelanoma skin cancer, such as basal cell and squamous cell carcinoma, is clearly related to the proportional amount of UV exposure. But melanoma is quite a diverse cancer that has many, many disparate etiologies.
Dr. Dunn: The entry physical into the military is an opportunity to make an impact on the number of nonmelanoma skin cancers that would arise in that population. There is an educational opportunity to tell inductees that nonmelanoma skin cancer is going to occur on convex surfaces of the sun-exposed skin—nose, ears, forehead, chin, tops of the shoulders. If offered sun protection for those areas and you stretch the potential impact of that information over tens of thousands of military members over decades, you might actually come up with a big number of people that not only decreases their morbidity but also dramatically decreased the cost to the system as a whole.
Dr. Jarell: You also have to factor in ethnicity and the role it plays in someone’s likelihood to get skin cancer—melanoma or nonmelanoma skin cancer. Darker-skinned people are at certainly decreased risk for different types of skin cancers.
Dr. Dunn: Yes, that would have to be part of the education and should be. If you have light skin and freckles, then you’re at much higher risk for nonmelanoma skin cancer and need to know the high-risk areas that can be protected by sunblock and clothing.
Dr. Logemann: One thing that might be a little bit unique in the military is that you’re living in San Antonio one minute, and then the next minute you’re over in Afghanistan with a different climate and different environment. When you’re deployed overseas, you might have a little bit less control over your situation; you might not have a lot of sunscreen in a field hospital in Afghanistan. Whereas if you were just living in San Antonio, you could go down to the store and buy it.
Dr. Miller: Is sunblock now encouraged or available to individuals in deployment situations or training situations where they’re going to have prolonged sun exposure every day? Is it part of the regimen, just like carrying extra water because of the risk for dehydration?
Dr. Logemann: To the best of my knowledge, it is not always included in your normal rations or uniform and it may be up to the servicemember to procure sunscreen.
Dr. Bandino: There have been improvements, and usually you at least have access to sunscreen. In many deployed locations, for example, you have the equivalent of a small PX (post exchange) or BX (base exchange), where they have a variety of products for sale from toothbrushes to flip-flops, and now also sunscreen. Of course, the type and quality of the sunscreen may not be that great. It’s likely going to be basic SPF (sun protection factor) 15 or 30 in small tubes. As a recent example, I participated in a humanitarian medical exercise in South America last summer and was actually issued sunscreen combined with DEET, which is great but it was only SPF 30. The combination product is a good idea for tropical locations, but in addition to people just not wanting to wear it, the DEET combination tends to burn and sting a little bit more; you can get a heat sensation from the DEET; and the DEET can damage plastic surfaces, which may not be ideal for deployed equipment.
The other problem is quantity. We all learned in residency the appropriate sunscreen quantity of at least 1 fl oz for the average adult body, and that’s what we counsel our patients on, but what they issued me was 1 small 2- to 3-fl oz tube. It fit in the palm of my hand, and that was my sunscreen for the trip.
So, I do think, even though there have been some improvements, much of sun protection will still fall on the individual servicemember. And, as mentioned, depending on your ethnicity, some people may need it more than others. But it is an area where there probably could be continued improvements.
Dr. Logemann: In addition to sunscreen, I think that maybe we should be taking into consideration some simple measures. For example, is it necessary for people to stand out in formation at 2
Dr. Dunn: I think we all kind of agree that the military service is diverse and that many of the subcategories of occupations within the military lead to increased sun exposure by mandate. We advise sun protection by physical barriers and sunblock.
Diagnosis of Skin Cancer Via Telemedicine
Dr. Dunn: I have friends who remain in the VA (US Department of Veterans Affairs) system, and they are involved with telemedicine in dermatology, which can reduce waiting time and increase the number of patients seen by the dermatologist. In-person and teledermatology visits now are available to servicemembers on active duty and retirees.
Dr. Bandino: At our residency program (San Antonio Uniformed Services Health Education Consortium), we’ve had asynchronous teledermatology for over a decade, even before I was a resident. We provide it primarily as a service for patients at small bases without access to dermatology. Some bases also use it as part of their prescreening process prior to authorizing an in-person dermatology consultation.
Certainly, with the coronavirus pandemic, civilian dermatology is seeing a boom in the teledermatology world that had been slowly increasing in popularity for the last few years. In our residency program, teledermatology has traditionally been just for active-duty servicemembers or their dependents, but now due to the coronavirus pandemic, our teledermatology services have significantly expanded to include adding synchronous capability. We have patients take pictures before their virtual appointment and/or FaceTime during the appointment. Even after the pandemic, there will likely be more integration of synchronous teledermatology going forward as we’re seeing some of the value. Of course, I’m sure we would all agree that accurate diagnosis of pigmented lesions can be very challenging with teledermatology, not to mention other diagnostic limitations. But I think there is still utility and it should only get better with time as technology improves. So, I’m hopeful that we can incorporate more of it in the military.
Dr. Logemann: I’m definitely aware that we have different telehealth opportunities available, even using some newer modalities that are command approved in recent weeks. My experience has been for more complicated dermatology, so people are in remote locations, and they’re being seen by a nondermatologist, and they have questions about how to approach management. But I’m not aware of telemedicine as a screening tool for skin cancer in the military or among my civilian colleagues. I would hope that it could be someday because we’re developing these total-body photography machines as well. It could be a way for a nondermatologist who identifies a lesion to have it triaged by a dermatologist. To say, “Oh yeah, that looks like a melanoma. They need to get in sooner vs later,” but not on a large-scale sort of screening modality.
Dr. Bandino: In my recent experience, it has definitely been a helpful triage tool. In the military, this form of triage can be particularly helpful if someone is overseas to determine whether he/she needs to evacuated and evaluated in-person right away.
Dr. Jarell: It’s been useful in looking at benign things. People have shown me in the past few weeks a lot of seborrheic keratoses and a lot of benign dermal nevus-type things, and I say, “Don’t worry about that.” And you can tell if the resolution is good enough. But a lot of people have shown me things in the past few weeks that have clearly been basal cell carcinoma, which we can probably let that ride out for a few more weeks, but I’m not sure if maybe somebody has an amelanotic melanoma. Maybe you need to come in and get that biopsied ASAP. Or something that looks like a melanoma. The patient should probably come in and get that biopsied.
Dr. Miller: I think we can rely on teledermatology. It’s all predicated on the resolution because we’re all trained in pattern recognition. I think it’s very useful to screen for things that look clinically benign. We have to understand that most dermatology is practiced by nondermatologists in the United States, and many studies show that their diagnostic accuracy is 20%, at best maybe 50%. So, they do need to reach out to a dermatologist and perhaps get some guidance on what to do. I think it could be a very useful tool if used appropriately.
Dr. Dunn: If used appropriately, teledermatology could function in a couple of ways. One, it could allow us to declare lesions to be wholly benign, and only should a lesion change would it need attention. The second is that it would allow us to accelerate the process of getting a patient to us—physically in front of us—for a biopsy if a suspicious lesion is seen. A by-product of that process would be that if patients who have wholly benign, nonworrisome lesions could be screened by telemedicine, then physical appointments where a patient is in front of the doctor would be more open. In other words, let’s say if 25% of all lesional visits could be declared benign via telemedicine that would allow dermatology to preserve its face-to-face appointments for patients who are more likely to have cancer and require procedures like skin biopsy.
Love it or hate it, I think we’re getting it no matter what now. Telemedicine creeped along forever and within 6 weeks it’s become ubiquitous. It’s phenomenal how fast we had to adapt to a system or perish in private practice. Sometimes these episodes that we go through have good consequences as well as bad consequences. Telemedicine probably has been needed for a long time and the insurers were not covering it very well, but suddenly a stay-at-home mandate has unveiled valuable technology—something that we probably should have been able to use more and be adequately reimbursed.
Surgical Treatment of Skin Cancer
Dr. Dunn: Treatment historically has been surgical for nonmelanoma and melanoma skin cancers. Some radiation devices have gained popularity again in the past decade or so, but excisional surgery remains the standard treatment for skin cancer. Nonmelanoma skin cancers almost all are probably treated surgically still, with a small percentage treated with superficial radiation.
Access to care is important to discuss. Are Mohs surgeons readily available, or are plastic surgeons, general surgeons, or vascular surgeons in the federal system contributing to the care of skin cancer? Are they doing excisional surgery after biopsies are done? Are they doing excisional biopsies with the intent of cure?
Dr. Logemann: For active duty, I don’t see any issues getting access to the medical center for Mohs micrographic surgery. Sometimes, if we have a lot of volume, some patients may get deferred to the network, but in my experience, it would not typically be an active-duty servicemember. An active-duty servicemember would get care rendered at one of the medical centers for Mohs surgery. Typically the active-duty–aged population isn’t getting much skin cancer. It certainly does happen, but most of the skin cancers frequently that are treated at medical centers are not infrequently retirees.
Dr. Bandino: Because of our residency program, we are required to have Mohs surgery capability to be ACGME (Accreditation Council for Graduate Medical Education) accredited. We typically have 3 Mohs surgeons, so we never have a problem with access.
In the military, I just refer cases to our Mohs surgeons and everything is taken care of in-house. In fact, this is an area where we may even have better access than the civilian world because there are no insurance hurdles or significant delay in care since our Mohs surgeons aren’t typically booked up for 3 to 4 months like many civilian Mohs surgeons. This is especially true for complex cases since we provide hospital-based care with all specialty services under the same umbrella. So, for example, if the Mohs surgeons have an extensive and complex case requiring multidisciplinary care such as ENT (ear, nose, and throat), facial plastics, or radiation-oncology, they’re all in-house with no insurance issues to navigate. This of course is not usual for most military bases and is only capable at bases attached to a large medical center. There are some similar scenarios in the civilian world with university medical centers and managed care organizations, but we may still have a slight advantage in accessibility and cost.
Dr. Dunn: There are guidelines from the National Comprehensive Cancer Network as to how to treat nonmelanoma and melanoma skin cancer. Almost all of them are surgical and almost all of them are safe, outpatient, local anesthetic procedures with a high cure rate. The vast majority of melanoma and nonmelanoma skin cancers can be handled safely and effectively with minimal morbidity and almost no known mortalities from the treatments themselves. Some of the cancers have been identified as high risk for metastasis and mortality, but they’re relatively uncommon still. The good news about skin cancer is that the risk of death remains very small.
Melanoma Risk for Servicemembers
Dr. Dunn: Active-duty jobs are quite diverse. We have had almost every civilian occupation category—everything from clerical to food service to outdoor construction workers. Federal service and active-duty military service could lead to assignments that involve high sunlight exposure and subsequently higher risk for melanoma and nonmelanoma skin cancer.
Dr. Miller: I found 2 articles on the topic. The first published in June 2018 reviewed melanoma and nonmelanoma skin cancers in the military.1 Riemenschneider and colleagues1 looked at 9 studies. Statistically, there was increased risk of melanoma associated with service and/or prisoner-of-war status. In World War II, they found tropical environments had the highest risk. And the highest rates were in the US Air Force.
The other article provided US Department of Defense data on skin cancer incidence rates, incidence rates of malignant melanoma in relation to years of military service overall, and the rates for differing military occupational groups.2 The researchers demonstrated that fixed-wing pilots and crew members had the highest rates of developing melanoma. The general trend was that the incidence rate was exponentially higher with more missions flown in relation to years of active service, which I thought was rather interesting.
For other occupational categories, the rate increase was not as great as those involved in aviation. Yes, it’s probably related to exposure. Flying at 40,000 feet on a transcontinental airplane trip is equivalent to the radiation dosage of a chest X-ray. Given all the training time and operational flying for the Air Force, it is anticipated that that mutagenic radiation would increase rates. An aircraft does not offer a lot of protection, especially in the cockpit.
We just had the anniversary of the Apollo 11 mission. Those astronauts received the equivalent of about 40 chest X-rays going to the moon and back. Exposure to UV and at higher altitudes cosmic radiation explains why we would see that more in Air Force personnel.
Dr. Bandino: At high altitude there is less ozone protecting you, although the shielding in a cockpit is better in modern aircraft. As an Air Force member, that was one of the first things I thought about was that an aviator has increased skin cancer risk. But it’s apt to think of military service in general as an occupational risk because there are so many contingency operations and deployments. Regarding sun exposure, sunscreen is provided nowadays and there is more sun awareness, but there is still a stigma and reluctance to apply the sunscreen. It leaves people’s skin feeling greasy, which is not ideal when one has to handle a firearm. It can also get in someone’s eyes and affect vision and performance during combat operations. In other words, there are many reasons that would reduce the desire to wear sunscreen and therefore increase exposure to the elements.
A great current example is coronavirus disease 2019 (COVID-19) operations. Although I’m a dermatologist and typically work inside, I’ve been tasked to run a COVID-19 screening tent in the middle of a field in San Antonio, and thus I’ve got to make sure I take my sunscreen out there every day. The general population may not have that variability in their work cycle and sudden change in occupational UV exposure.
Dr. Miller: I was deployed in a combat zone for operations Desert Shield and Desert Storm. I was with the 2nd Armored Division of the US Army deployed to the desert. There really wasn’t an emphasis on photoprotection. It’s just the logistics. The commanders have a lot more important things to think about, and that’s something, usually, that doesn’t get a high priority. The US military is deploying to more places near the equator, so from an operational sense, there’s probably something to brief the commanders about in terms of the long-term consequences of radiation exposure for military servicemembers.
Dr. Dunn: If you look at deployments over the past 2 decades, we have been putting tens of thousands of individuals in high UV exposure regions. Then you have to look at the long-term consequence of the increased incidence of skin cancer in those individuals. What is the cost of that when it comes to treatment of precancerous lesions and skin cancer throughout a life expectancy of 80-plus years?
Dr. Bandino: With most skin cancers there is such long lag time between exposures and development. I wish there were some better data and research out there that really showed whether military service truly is an independent risk factor or if it’s just specific occupation types within the military. I have family members who both work in contracting services and had served in the military. Would their skin cancer risk be the same as others who are doing similar jobs without the military service?
Dr. Dunn: I have had county employees present for skin cancer surgery and with them comes a form that relates to disability. For groundskeepers or police, we assumed that skin cancer is occupation related due to the patient’s increased sun exposure. Their cancers may be unrelated to their actual years of service, but it seems that many light-skinned individuals in the military are going to develop basal cell and squamous cell skin cancer in the coming decades, which likely is going to be attributed to their years of federal service, even though they may have had other significant recreational exposure outside of work. So, my gut feeling is that we are going to see skin cancer as a disability tied to federal service, which is going to cost us.
Dr. Logemann: Yes, I think there are always going to be confounders—what if the servicemembers used tanning beds, or they were avid surfers? It’s going to be difficult to always parse that out.
Dr. Miller: In talking about melanoma, you really have to parse out the subsets. Is it melanoma in situ, is it superficial, is it acral, is it nodular? They all have different initiation events.
Nodular melanomas probably don’t need UV light to initiate a tumor. Another risk factor is having more than 100 moles or many atypical moles, which puts that person in a higher risk category. Perhaps when soldiers, airmen, and navy personnel get inducted, they should be screened for their mole population because that is a risk factor for developing melanoma, and then we can intervene a little bit and have them watch their UV exposure.
Dr. Jarell: You can’t overstate the importance of how heterogeneous melanoma is as a disease. While there are clearly some types of melanoma that are caused by UV radiation, there are also many types that aren’t. We don’t understand why someone gets melanoma on the inner thigh, bottom of the foot, top of the sole, inside the mouth, or in the genital region—these aren’t places of high sun exposure.
Lentigo maligna, as an example, is clearly caused by UV radiation in most cases. But there are so many other different types of melanoma that you can’t just attribute to UV radiation, and so you get into this whole other discussion as to why people are getting melanoma—military or not.
Dr. Bandino: When volunteering for military service, there’s the DoDMERB (Department of Defense Medical Examination Review Board) system that screens individuals for medical issues incompatible with military service such as severe psoriasis or atopic dermatitis. But to my knowledge, the DoDMERB process focuses more on current or past issues and does little to investigate for future risk of disease. A cutaneous example would be assessing quantity of dysplastic nevi, Fitzpatrick scale 1 phenotype, and family history of melanoma to determine risk of developing melanoma in someone who may have more UV exposure during their military service than a civilian. This dermatological future risk assessment was certainly not something I was trained to do as a flight surgeon when performing basic trainee flight physicals prior to becoming a dermatologist.
Dr. Jarell: I am a little bit hard-pressed to generalize the military as high occupational risk for melanoma. There are clearly other professions—landscapers, fishermen—that are probably at much higher risk than, say, your general military all-comers. Us physicians in the military were probably not at increased risk compared to other physicians in the United States. We have to be careful not to go down a slippery slope and designate all MOSs (military occupational specialties) as at increased risk for skin cancer, in particular melanoma. Nonmelanoma skin cancer, such as basal cell and squamous cell carcinoma, is clearly related to the proportional amount of UV exposure. But melanoma is quite a diverse cancer that has many, many disparate etiologies.
Dr. Dunn: The entry physical into the military is an opportunity to make an impact on the number of nonmelanoma skin cancers that would arise in that population. There is an educational opportunity to tell inductees that nonmelanoma skin cancer is going to occur on convex surfaces of the sun-exposed skin—nose, ears, forehead, chin, tops of the shoulders. If offered sun protection for those areas and you stretch the potential impact of that information over tens of thousands of military members over decades, you might actually come up with a big number of people that not only decreases their morbidity but also dramatically decreased the cost to the system as a whole.
Dr. Jarell: You also have to factor in ethnicity and the role it plays in someone’s likelihood to get skin cancer—melanoma or nonmelanoma skin cancer. Darker-skinned people are at certainly decreased risk for different types of skin cancers.
Dr. Dunn: Yes, that would have to be part of the education and should be. If you have light skin and freckles, then you’re at much higher risk for nonmelanoma skin cancer and need to know the high-risk areas that can be protected by sunblock and clothing.
Dr. Logemann: One thing that might be a little bit unique in the military is that you’re living in San Antonio one minute, and then the next minute you’re over in Afghanistan with a different climate and different environment. When you’re deployed overseas, you might have a little bit less control over your situation; you might not have a lot of sunscreen in a field hospital in Afghanistan. Whereas if you were just living in San Antonio, you could go down to the store and buy it.
Dr. Miller: Is sunblock now encouraged or available to individuals in deployment situations or training situations where they’re going to have prolonged sun exposure every day? Is it part of the regimen, just like carrying extra water because of the risk for dehydration?
Dr. Logemann: To the best of my knowledge, it is not always included in your normal rations or uniform and it may be up to the servicemember to procure sunscreen.
Dr. Bandino: There have been improvements, and usually you at least have access to sunscreen. In many deployed locations, for example, you have the equivalent of a small PX (post exchange) or BX (base exchange), where they have a variety of products for sale from toothbrushes to flip-flops, and now also sunscreen. Of course, the type and quality of the sunscreen may not be that great. It’s likely going to be basic SPF (sun protection factor) 15 or 30 in small tubes. As a recent example, I participated in a humanitarian medical exercise in South America last summer and was actually issued sunscreen combined with DEET, which is great but it was only SPF 30. The combination product is a good idea for tropical locations, but in addition to people just not wanting to wear it, the DEET combination tends to burn and sting a little bit more; you can get a heat sensation from the DEET; and the DEET can damage plastic surfaces, which may not be ideal for deployed equipment.
The other problem is quantity. We all learned in residency the appropriate sunscreen quantity of at least 1 fl oz for the average adult body, and that’s what we counsel our patients on, but what they issued me was 1 small 2- to 3-fl oz tube. It fit in the palm of my hand, and that was my sunscreen for the trip.
So, I do think, even though there have been some improvements, much of sun protection will still fall on the individual servicemember. And, as mentioned, depending on your ethnicity, some people may need it more than others. But it is an area where there probably could be continued improvements.
Dr. Logemann: In addition to sunscreen, I think that maybe we should be taking into consideration some simple measures. For example, is it necessary for people to stand out in formation at 2
Dr. Dunn: I think we all kind of agree that the military service is diverse and that many of the subcategories of occupations within the military lead to increased sun exposure by mandate. We advise sun protection by physical barriers and sunblock.
Diagnosis of Skin Cancer Via Telemedicine
Dr. Dunn: I have friends who remain in the VA (US Department of Veterans Affairs) system, and they are involved with telemedicine in dermatology, which can reduce waiting time and increase the number of patients seen by the dermatologist. In-person and teledermatology visits now are available to servicemembers on active duty and retirees.
Dr. Bandino: At our residency program (San Antonio Uniformed Services Health Education Consortium), we’ve had asynchronous teledermatology for over a decade, even before I was a resident. We provide it primarily as a service for patients at small bases without access to dermatology. Some bases also use it as part of their prescreening process prior to authorizing an in-person dermatology consultation.
Certainly, with the coronavirus pandemic, civilian dermatology is seeing a boom in the teledermatology world that had been slowly increasing in popularity for the last few years. In our residency program, teledermatology has traditionally been just for active-duty servicemembers or their dependents, but now due to the coronavirus pandemic, our teledermatology services have significantly expanded to include adding synchronous capability. We have patients take pictures before their virtual appointment and/or FaceTime during the appointment. Even after the pandemic, there will likely be more integration of synchronous teledermatology going forward as we’re seeing some of the value. Of course, I’m sure we would all agree that accurate diagnosis of pigmented lesions can be very challenging with teledermatology, not to mention other diagnostic limitations. But I think there is still utility and it should only get better with time as technology improves. So, I’m hopeful that we can incorporate more of it in the military.
Dr. Logemann: I’m definitely aware that we have different telehealth opportunities available, even using some newer modalities that are command approved in recent weeks. My experience has been for more complicated dermatology, so people are in remote locations, and they’re being seen by a nondermatologist, and they have questions about how to approach management. But I’m not aware of telemedicine as a screening tool for skin cancer in the military or among my civilian colleagues. I would hope that it could be someday because we’re developing these total-body photography machines as well. It could be a way for a nondermatologist who identifies a lesion to have it triaged by a dermatologist. To say, “Oh yeah, that looks like a melanoma. They need to get in sooner vs later,” but not on a large-scale sort of screening modality.
Dr. Bandino: In my recent experience, it has definitely been a helpful triage tool. In the military, this form of triage can be particularly helpful if someone is overseas to determine whether he/she needs to evacuated and evaluated in-person right away.
Dr. Jarell: It’s been useful in looking at benign things. People have shown me in the past few weeks a lot of seborrheic keratoses and a lot of benign dermal nevus-type things, and I say, “Don’t worry about that.” And you can tell if the resolution is good enough. But a lot of people have shown me things in the past few weeks that have clearly been basal cell carcinoma, which we can probably let that ride out for a few more weeks, but I’m not sure if maybe somebody has an amelanotic melanoma. Maybe you need to come in and get that biopsied ASAP. Or something that looks like a melanoma. The patient should probably come in and get that biopsied.
Dr. Miller: I think we can rely on teledermatology. It’s all predicated on the resolution because we’re all trained in pattern recognition. I think it’s very useful to screen for things that look clinically benign. We have to understand that most dermatology is practiced by nondermatologists in the United States, and many studies show that their diagnostic accuracy is 20%, at best maybe 50%. So, they do need to reach out to a dermatologist and perhaps get some guidance on what to do. I think it could be a very useful tool if used appropriately.
Dr. Dunn: If used appropriately, teledermatology could function in a couple of ways. One, it could allow us to declare lesions to be wholly benign, and only should a lesion change would it need attention. The second is that it would allow us to accelerate the process of getting a patient to us—physically in front of us—for a biopsy if a suspicious lesion is seen. A by-product of that process would be that if patients who have wholly benign, nonworrisome lesions could be screened by telemedicine, then physical appointments where a patient is in front of the doctor would be more open. In other words, let’s say if 25% of all lesional visits could be declared benign via telemedicine that would allow dermatology to preserve its face-to-face appointments for patients who are more likely to have cancer and require procedures like skin biopsy.
Love it or hate it, I think we’re getting it no matter what now. Telemedicine creeped along forever and within 6 weeks it’s become ubiquitous. It’s phenomenal how fast we had to adapt to a system or perish in private practice. Sometimes these episodes that we go through have good consequences as well as bad consequences. Telemedicine probably has been needed for a long time and the insurers were not covering it very well, but suddenly a stay-at-home mandate has unveiled valuable technology—something that we probably should have been able to use more and be adequately reimbursed.
Surgical Treatment of Skin Cancer
Dr. Dunn: Treatment historically has been surgical for nonmelanoma and melanoma skin cancers. Some radiation devices have gained popularity again in the past decade or so, but excisional surgery remains the standard treatment for skin cancer. Nonmelanoma skin cancers almost all are probably treated surgically still, with a small percentage treated with superficial radiation.
Access to care is important to discuss. Are Mohs surgeons readily available, or are plastic surgeons, general surgeons, or vascular surgeons in the federal system contributing to the care of skin cancer? Are they doing excisional surgery after biopsies are done? Are they doing excisional biopsies with the intent of cure?
Dr. Logemann: For active duty, I don’t see any issues getting access to the medical center for Mohs micrographic surgery. Sometimes, if we have a lot of volume, some patients may get deferred to the network, but in my experience, it would not typically be an active-duty servicemember. An active-duty servicemember would get care rendered at one of the medical centers for Mohs surgery. Typically the active-duty–aged population isn’t getting much skin cancer. It certainly does happen, but most of the skin cancers frequently that are treated at medical centers are not infrequently retirees.
Dr. Bandino: Because of our residency program, we are required to have Mohs surgery capability to be ACGME (Accreditation Council for Graduate Medical Education) accredited. We typically have 3 Mohs surgeons, so we never have a problem with access.
In the military, I just refer cases to our Mohs surgeons and everything is taken care of in-house. In fact, this is an area where we may even have better access than the civilian world because there are no insurance hurdles or significant delay in care since our Mohs surgeons aren’t typically booked up for 3 to 4 months like many civilian Mohs surgeons. This is especially true for complex cases since we provide hospital-based care with all specialty services under the same umbrella. So, for example, if the Mohs surgeons have an extensive and complex case requiring multidisciplinary care such as ENT (ear, nose, and throat), facial plastics, or radiation-oncology, they’re all in-house with no insurance issues to navigate. This of course is not usual for most military bases and is only capable at bases attached to a large medical center. There are some similar scenarios in the civilian world with university medical centers and managed care organizations, but we may still have a slight advantage in accessibility and cost.
Dr. Dunn: There are guidelines from the National Comprehensive Cancer Network as to how to treat nonmelanoma and melanoma skin cancer. Almost all of them are surgical and almost all of them are safe, outpatient, local anesthetic procedures with a high cure rate. The vast majority of melanoma and nonmelanoma skin cancers can be handled safely and effectively with minimal morbidity and almost no known mortalities from the treatments themselves. Some of the cancers have been identified as high risk for metastasis and mortality, but they’re relatively uncommon still. The good news about skin cancer is that the risk of death remains very small.
- Riemenschneider K, Liu J, Powers JG. Skin cancer in the military: a systematic review of melanoma and nonmelanoma skin cancer incidence, prevention, and screening among active duty and veteran personnel.J Am Acad Dermatol. 2018;78:1185-1192.
- Brundage JF, Williams VF, Stahlman S, et al. Incidence rates of malignant melanoma in relation to years of military service, overall and in selected military occupational groups, active component, U.S. Armed Forces, 2001-2015. MSMR. 2017;24:8-14.
- Riemenschneider K, Liu J, Powers JG. Skin cancer in the military: a systematic review of melanoma and nonmelanoma skin cancer incidence, prevention, and screening among active duty and veteran personnel.J Am Acad Dermatol. 2018;78:1185-1192.
- Brundage JF, Williams VF, Stahlman S, et al. Incidence rates of malignant melanoma in relation to years of military service, overall and in selected military occupational groups, active component, U.S. Armed Forces, 2001-2015. MSMR. 2017;24:8-14.