Lung Cancer

Hospitalized cancer patients have a high risk of nosocomial COVID-19 that is associated with increased mortality, so these patients should be treated in COVID-free zones, according to researchers.

In an observational study of patients with COVID-19 and cancer, 19% of patients had COVID-19 acquired during a non-COVID-related hospital stay, and 81% had community-acquired COVID-19.

At a median follow-up of 23 days, the overall mortality rate was 28%. However, the all-cause mortality rate in patients with nosocomial COVID-19 was more than double that of patients with community-acquired COVID-19, at 47% and 23%, respectively.

Arielle Elkrief, MD, of the University of Montreal, reported these results during the AACR virtual meeting: COVID-19 and Cancer.

“This is the first report that describes a high rate of hospital-acquired COVID-19 in patients with cancer, at a rate of 19%,” Dr. Elkrief said. “This was associated with high mortality in both univariate and multivariate analyses.”

The study included 250 adults and 3 children with COVID-19 and cancer who were identified between March 3 and May 23, 2020. They ranged in age from 4 to 95 years, but the median age was 73 years.

All patients had either laboratory-confirmed (95%) or presumed COVID-19 (5%) and invasive cancer. The most common cancer types were similar to those seen in the general population. Lung and breast cancer were the most common, followed by lymphoma, prostate cancer, and colorectal cancer. Most patients were on active anticancer therapy, most often chemotherapy.

Most patients (n = 236) were residents of Quebec, but 17 patients were residents of British Columbia.

“It is important to note that Quebec was one of the most heavily affected areas in North America at the time of the study,” Dr. Elkrief said.
 

Outcomes by group

There were 206 patients (81%) who had community-acquired COVID-19 and 47 (19%) who had nosocomial COVID-19. The two groups were similar with respect to sex, performance status, and cancer stage. A small trend toward more patients on active therapy was seen in the nosocomial group, but the difference did not reach statistical significance.

The median overall survival was 27 days in the nosocomial group and 71 days in the community-acquired group (hazard ratio, 2.2; P = .002).

A multivariate analysis showed that nosocomial infection was “strongly and independently associated with death,” Dr. Elkrief said. “Other risk factors for poor prognosis included age, poor [performance] status, and advanced stage of cancer.”

There were no significant differences between the hospital-acquired and community-acquired groups for other outcomes, including oxygen requirements (43% and 47%, respectively), ICU admission (13% and 11%), need for mechanical ventilation (6% and 5%), or length of stay (median, 9.5 days and 8.5 days).

The low rate of ICU admission, considering the mortality rate of 28%, “could reflect that patients with cancer are less likely to be admitted to the ICU,” Dr. Elkrief noted.
 

Applying the findings to practice

The findings reinforce the importance of adherence to stringent infection control guidelines to protect vulnerable patients, such as those with cancer, Dr. Elkrief said.

In ambulatory settings, this means decreasing in-person visits through increased use of teleconsultations, and for those who need to be seen in person, screening for symptoms or use of polymerase chain reaction testing should be used when resources are available, she said.

“Similar principles apply to chemotherapy treatment units,” Dr. Elkrief said. She added that staff must avoid cross-contamination between COVID and COVID-free zones, and that “dedicated personnel and equipment should be maintained and separate between these two zones.

“Adequate protective personal equipment and strict hand hygiene protocols are also of utmost importance,” Dr. Elkrief said. “The threat of COVID-19 is not behind us, and so we continue to enforce these strategies to protect our patients.”

Session moderator Gypsyamber D’Souza, PhD, an infectious disease epidemiologist at Johns Hopkins University in Baltimore, raised the question of whether the high nosocomial infection and death rate in this study was related to patients having more severe disease because of underlying comorbidities.

Dr. Elkrief explained that the overall mortality rate was indeed higher than the 13% reported in other studies, and it may reflect an overrepresentation of hospitalized or more severely ill patients in the cohort.

However, the investigators made every effort to include all patients with both cancer and COVID-19 by using systematic screening of inpatient and outpatients lists and registries.

Further, the multivariate analysis included both inpatients and outpatients and adjusted for known negative prognostic factors for COVID-19 outcomes. These included increasing age, poor performance status, and different comorbidities.

The finding that nosocomial infection was an independent predictor of death “pushed us to look at nosocomial infection as a new independent risk factor,” Dr. Elkrief said.

Dr. Elkrief reported grant support from AstraZeneca. Dr. D’Souza did not report any disclosures.

sworcester@mdedge.com

SOURCE: Elkrief A et al. AACR: COVID and Cancer, Abstract S12-01.

Hospitalized cancer patients have a high risk of nosocomial COVID-19 that is associated with increased mortality, so these patients should be treated in COVID-free zones, according to researchers.

In an observational study of patients with COVID-19 and cancer, 19% of patients had COVID-19 acquired during a non-COVID-related hospital stay, and 81% had community-acquired COVID-19.

At a median follow-up of 23 days, the overall mortality rate was 28%. However, the all-cause mortality rate in patients with nosocomial COVID-19 was more than double that of patients with community-acquired COVID-19, at 47% and 23%, respectively.

Arielle Elkrief, MD, of the University of Montreal, reported these results during the AACR virtual meeting: COVID-19 and Cancer.

“This is the first report that describes a high rate of hospital-acquired COVID-19 in patients with cancer, at a rate of 19%,” Dr. Elkrief said. “This was associated with high mortality in both univariate and multivariate analyses.”

The study included 250 adults and 3 children with COVID-19 and cancer who were identified between March 3 and May 23, 2020. They ranged in age from 4 to 95 years, but the median age was 73 years.

All patients had either laboratory-confirmed (95%) or presumed COVID-19 (5%) and invasive cancer. The most common cancer types were similar to those seen in the general population. Lung and breast cancer were the most common, followed by lymphoma, prostate cancer, and colorectal cancer. Most patients were on active anticancer therapy, most often chemotherapy.

Most patients (n = 236) were residents of Quebec, but 17 patients were residents of British Columbia.

“It is important to note that Quebec was one of the most heavily affected areas in North America at the time of the study,” Dr. Elkrief said.
 

Outcomes by group

There were 206 patients (81%) who had community-acquired COVID-19 and 47 (19%) who had nosocomial COVID-19. The two groups were similar with respect to sex, performance status, and cancer stage. A small trend toward more patients on active therapy was seen in the nosocomial group, but the difference did not reach statistical significance.

The median overall survival was 27 days in the nosocomial group and 71 days in the community-acquired group (hazard ratio, 2.2; P = .002).

A multivariate analysis showed that nosocomial infection was “strongly and independently associated with death,” Dr. Elkrief said. “Other risk factors for poor prognosis included age, poor [performance] status, and advanced stage of cancer.”

There were no significant differences between the hospital-acquired and community-acquired groups for other outcomes, including oxygen requirements (43% and 47%, respectively), ICU admission (13% and 11%), need for mechanical ventilation (6% and 5%), or length of stay (median, 9.5 days and 8.5 days).

The low rate of ICU admission, considering the mortality rate of 28%, “could reflect that patients with cancer are less likely to be admitted to the ICU,” Dr. Elkrief noted.
 

Applying the findings to practice

The findings reinforce the importance of adherence to stringent infection control guidelines to protect vulnerable patients, such as those with cancer, Dr. Elkrief said.

In ambulatory settings, this means decreasing in-person visits through increased use of teleconsultations, and for those who need to be seen in person, screening for symptoms or use of polymerase chain reaction testing should be used when resources are available, she said.

“Similar principles apply to chemotherapy treatment units,” Dr. Elkrief said. She added that staff must avoid cross-contamination between COVID and COVID-free zones, and that “dedicated personnel and equipment should be maintained and separate between these two zones.

“Adequate protective personal equipment and strict hand hygiene protocols are also of utmost importance,” Dr. Elkrief said. “The threat of COVID-19 is not behind us, and so we continue to enforce these strategies to protect our patients.”

Session moderator Gypsyamber D’Souza, PhD, an infectious disease epidemiologist at Johns Hopkins University in Baltimore, raised the question of whether the high nosocomial infection and death rate in this study was related to patients having more severe disease because of underlying comorbidities.

Dr. Elkrief explained that the overall mortality rate was indeed higher than the 13% reported in other studies, and it may reflect an overrepresentation of hospitalized or more severely ill patients in the cohort.

However, the investigators made every effort to include all patients with both cancer and COVID-19 by using systematic screening of inpatient and outpatients lists and registries.

Further, the multivariate analysis included both inpatients and outpatients and adjusted for known negative prognostic factors for COVID-19 outcomes. These included increasing age, poor performance status, and different comorbidities.

The finding that nosocomial infection was an independent predictor of death “pushed us to look at nosocomial infection as a new independent risk factor,” Dr. Elkrief said.

Dr. Elkrief reported grant support from AstraZeneca. Dr. D’Souza did not report any disclosures.

sworcester@mdedge.com

SOURCE: Elkrief A et al. AACR: COVID and Cancer, Abstract S12-01.

Hospitalized cancer patients have a high risk of nosocomial COVID-19 that is associated with increased mortality, so these patients should be treated in COVID-free zones, according to researchers.

In an observational study of patients with COVID-19 and cancer, 19% of patients had COVID-19 acquired during a non-COVID-related hospital stay, and 81% had community-acquired COVID-19.

At a median follow-up of 23 days, the overall mortality rate was 28%. However, the all-cause mortality rate in patients with nosocomial COVID-19 was more than double that of patients with community-acquired COVID-19, at 47% and 23%, respectively.

Arielle Elkrief, MD, of the University of Montreal, reported these results during the AACR virtual meeting: COVID-19 and Cancer.

“This is the first report that describes a high rate of hospital-acquired COVID-19 in patients with cancer, at a rate of 19%,” Dr. Elkrief said. “This was associated with high mortality in both univariate and multivariate analyses.”

The study included 250 adults and 3 children with COVID-19 and cancer who were identified between March 3 and May 23, 2020. They ranged in age from 4 to 95 years, but the median age was 73 years.

All patients had either laboratory-confirmed (95%) or presumed COVID-19 (5%) and invasive cancer. The most common cancer types were similar to those seen in the general population. Lung and breast cancer were the most common, followed by lymphoma, prostate cancer, and colorectal cancer. Most patients were on active anticancer therapy, most often chemotherapy.

Most patients (n = 236) were residents of Quebec, but 17 patients were residents of British Columbia.

“It is important to note that Quebec was one of the most heavily affected areas in North America at the time of the study,” Dr. Elkrief said.
 

Outcomes by group

There were 206 patients (81%) who had community-acquired COVID-19 and 47 (19%) who had nosocomial COVID-19. The two groups were similar with respect to sex, performance status, and cancer stage. A small trend toward more patients on active therapy was seen in the nosocomial group, but the difference did not reach statistical significance.

The median overall survival was 27 days in the nosocomial group and 71 days in the community-acquired group (hazard ratio, 2.2; P = .002).

A multivariate analysis showed that nosocomial infection was “strongly and independently associated with death,” Dr. Elkrief said. “Other risk factors for poor prognosis included age, poor [performance] status, and advanced stage of cancer.”

There were no significant differences between the hospital-acquired and community-acquired groups for other outcomes, including oxygen requirements (43% and 47%, respectively), ICU admission (13% and 11%), need for mechanical ventilation (6% and 5%), or length of stay (median, 9.5 days and 8.5 days).

The low rate of ICU admission, considering the mortality rate of 28%, “could reflect that patients with cancer are less likely to be admitted to the ICU,” Dr. Elkrief noted.
 

Applying the findings to practice

The findings reinforce the importance of adherence to stringent infection control guidelines to protect vulnerable patients, such as those with cancer, Dr. Elkrief said.

In ambulatory settings, this means decreasing in-person visits through increased use of teleconsultations, and for those who need to be seen in person, screening for symptoms or use of polymerase chain reaction testing should be used when resources are available, she said.

“Similar principles apply to chemotherapy treatment units,” Dr. Elkrief said. She added that staff must avoid cross-contamination between COVID and COVID-free zones, and that “dedicated personnel and equipment should be maintained and separate between these two zones.

“Adequate protective personal equipment and strict hand hygiene protocols are also of utmost importance,” Dr. Elkrief said. “The threat of COVID-19 is not behind us, and so we continue to enforce these strategies to protect our patients.”

Session moderator Gypsyamber D’Souza, PhD, an infectious disease epidemiologist at Johns Hopkins University in Baltimore, raised the question of whether the high nosocomial infection and death rate in this study was related to patients having more severe disease because of underlying comorbidities.

Dr. Elkrief explained that the overall mortality rate was indeed higher than the 13% reported in other studies, and it may reflect an overrepresentation of hospitalized or more severely ill patients in the cohort.

However, the investigators made every effort to include all patients with both cancer and COVID-19 by using systematic screening of inpatient and outpatients lists and registries.

Further, the multivariate analysis included both inpatients and outpatients and adjusted for known negative prognostic factors for COVID-19 outcomes. These included increasing age, poor performance status, and different comorbidities.

The finding that nosocomial infection was an independent predictor of death “pushed us to look at nosocomial infection as a new independent risk factor,” Dr. Elkrief said.

Dr. Elkrief reported grant support from AstraZeneca. Dr. D’Souza did not report any disclosures.

sworcester@mdedge.com

SOURCE: Elkrief A et al. AACR: COVID and Cancer, Abstract S12-01.

A blood test that may be able to detect cancer years before any symptoms appear is under development. The PanSeer assay, which detects methylation markers in blood, was used in healthy individuals and successfully detected five cancer types in 91% of samples from individuals who were diagnosed with cancer 1 to 4 years later.

“We can’t say for sure that the patients didn’t have any symptoms, but we detected the cancer years before they ever walked into the hospital,” said study author Kun Zhang, PhD, a professor of bioengineering at the University of California, San Diego. “We were also able to follow up with patients, so we actually knew that they had cancer.”

Zhang noted that they also followed the individuals whose tests indicated they were cancer free. “They were healthy at the time the samples were obtained, and they remained healthy,” he said. “Follow-up was key to validating these data.”

The PanSeer test is being developed by Singlera Genomics. Zhang is a cofounder and a paid consultant of the company.

The study was published online July 21 in Nature Communications.
 

Unique among tests

Several blood tests for the detection of cancer have been reported in recent years. A test developed by Grail was able to detect more than 50 types of cancer and also identified the tissues where the cancer originated. The CancerSEEK test identified eight common cancers by measuring circulating tumor DNA from 16 genes, as well as eight protein biomarkers.

Findings regarding the CellMax Life FirstSight blood test were released last month. The test detected all 11 cases of colorectal cancer in a cohort of 354 patients and detected 40 of 53 advanced adenomas.

The latest study with the PanSeer assay is unique, say the investigators, because they had access to blood samples from patients who may have been completely asymptomatic and had not yet been diagnosed with cancer. Other blood tests have typically involved the use of specimens from people with a known diagnosis.

The specimens were collected as part of a 10-year longitudinal study that began in 2007 in China. Zhang and his team were able to test blood samples before individuals had experienced any signs or symptoms of cancer, and they were able to conduct long-term follow-up of the cohort.
 

Study details

The PanSeer assay uses DNA methylation analysis and screens for a DNA signature called CpG methylation. The results of an early-stage proof-of-concept study were published 3 years ago (Nat Genet. 2017;49:635–642).

For the current study, data were drawn from the Taizhou Longitudinal Study, which included 123,115 individuals aged 25 to 90 years who provided blood samples for long-term storage from 2007 to 2014. Participants were monitored indefinitely for cancer occurrence using local cancer registries and health insurance databases.

The team identified 575 individuals who were initially asymptomatic and healthy but were subsequently diagnosed with one of five common cancer types (stomach, esophagus, colorectum, lung, or liver cancer) within 4 years of their initial blood sampling. The authors selected these five cancer types to study because the incidence rates of these cancers in this population are high and, taken together, account for the highest mortality.

The study design allowed the authors to evaluate specimens both from patients with cancer and from those who were healthy within the same cohort. Using 191 prediagnosis samples, 223 postdiagnosis samples, and 414 healthy samples, they created a training set and validation model.

A machine learning method was created to classify samples as being either from healthy individuals or from those with cancer, using blood samples from the training set. The final classifier achieved 88% sensitivity for postdiagnosis samples and 91% sensitivity for prediagnosis samples at a specificity of 95%.

Zhang feels that initially it would be more appropriate to use the test for high-risk patients and to then evaluate the clinical benefit. “For any test, it is always more prudent to begin with a high-risk population,” he said. “You want to see some benefit with the high-risk population first, and then it can slowly be extended to others at lower risk.”

He emphasized that more rigorous testing is needing before the PanSeer assay is ready for clinical use. The logistics of designing and conducting a clinical trial that would include more than one cancer type would be very complicated. “The option was to break it down to five different studies,” he said. “We decided to begin with colon cancer, and we are currently in the process of talking with the FDA and designing the study.”
 

High bar to reach

Approached for comment, Benjamin Weinberg, MD, assistant professor of medicine, Division of Hematology and Oncology, the Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, noted that there is “quite a ways to go before this can be clinically actionable.

“A lot of us are looking at combining methylation with circulating tumor DNA and throw the kitchen sink at it, but as the paper nicely describes, there are pros and cons to all of these,” he said.

Many tests of this type are in development. Weinberg explained that a circulating tumor DNA test for colon cancer may hit the market soon, pending FDA approval, although that test will be used in a different setting. “This is something that’s used to assess for minimal residual disease in patients who have undergone surgery and appear to be ‘cured’ of the disease,” he said. “The test is looking to see if there is any circulating tumor DNA being shed from whatever tumor is left behind.”

The type of test that has piqued the most interest is one that is “tumor informed,” meaning that the company receives tumor tissue and develops a personalized test of that tumor on the basis of tumor genetics. “That is a very targeted way of surveillance,” said Weinberg, “But it would be very difficult to use a tumor-informed test on the population described in this study because you don’t know if there is going to be a tumor or not.”

The PanSeer test may also prove difficult to use in the clinic because it detects multiple cancers, Weinberg said. “If there is a positive finding, then which cancer do you look for?” he commented. “It has an issue in that regard, and that’s the problem with this type of test, as it is easier if there is one site of origin.”

Overall, the test was fairly sensitive and specific, with a very low false negative rate. Going forward, he noted, there is a very high bar for tests used as screening tools, although the authors do say that their focus is for use in a high-risk population.

“There would have to be a randomized trial, and the test will have to show a survival benefit,” Weinberg said. He noted that it can sometimes be challenging to do so.

“Colonoscopy has been shown to be beneficial, but early mammography has become controversial, and prostate cancer is a whole different animal,” he added. “And these are established tests, and they show how difficult this can be.”

The Taizhou Longitudinal Study study was supported by the National Key Research and Development Program of China, the National Natural Science Foundation of China, the Key Basic Research grants from the Science and Technology Commission of Shanghai Municipality, the International S&T Cooperation Program of China, the Municipal Science and Technology Major Project program, the International Science and Technology Cooperation Program of China, and the 111 Project (B13016). Funding for the DNA methylation assays was provided by Singlera Genomics. Zhang is a cofounder, equity holder, and paid consultant of Singlera Genomics, a company that is developing early cancer detection tests, including the PanSeer test. Weinberg is a speaker or a member of a speakers bureau for Taiho Pharmaceutical Co Ltd, Bayer HealthCare Pharmaceuticals, and Eli Lilly and Company; has received research grant from Novartis Pharmaceuticals Corporation; and has received travel reimbursement from Caris Life Sciences.

This article first appeared on Medscape.com.

A blood test that may be able to detect cancer years before any symptoms appear is under development. The PanSeer assay, which detects methylation markers in blood, was used in healthy individuals and successfully detected five cancer types in 91% of samples from individuals who were diagnosed with cancer 1 to 4 years later.

“We can’t say for sure that the patients didn’t have any symptoms, but we detected the cancer years before they ever walked into the hospital,” said study author Kun Zhang, PhD, a professor of bioengineering at the University of California, San Diego. “We were also able to follow up with patients, so we actually knew that they had cancer.”

Zhang noted that they also followed the individuals whose tests indicated they were cancer free. “They were healthy at the time the samples were obtained, and they remained healthy,” he said. “Follow-up was key to validating these data.”

The PanSeer test is being developed by Singlera Genomics. Zhang is a cofounder and a paid consultant of the company.

The study was published online July 21 in Nature Communications.
 

Unique among tests

Several blood tests for the detection of cancer have been reported in recent years. A test developed by Grail was able to detect more than 50 types of cancer and also identified the tissues where the cancer originated. The CancerSEEK test identified eight common cancers by measuring circulating tumor DNA from 16 genes, as well as eight protein biomarkers.

Findings regarding the CellMax Life FirstSight blood test were released last month. The test detected all 11 cases of colorectal cancer in a cohort of 354 patients and detected 40 of 53 advanced adenomas.

The latest study with the PanSeer assay is unique, say the investigators, because they had access to blood samples from patients who may have been completely asymptomatic and had not yet been diagnosed with cancer. Other blood tests have typically involved the use of specimens from people with a known diagnosis.

The specimens were collected as part of a 10-year longitudinal study that began in 2007 in China. Zhang and his team were able to test blood samples before individuals had experienced any signs or symptoms of cancer, and they were able to conduct long-term follow-up of the cohort.
 

Study details

The PanSeer assay uses DNA methylation analysis and screens for a DNA signature called CpG methylation. The results of an early-stage proof-of-concept study were published 3 years ago (Nat Genet. 2017;49:635–642).

For the current study, data were drawn from the Taizhou Longitudinal Study, which included 123,115 individuals aged 25 to 90 years who provided blood samples for long-term storage from 2007 to 2014. Participants were monitored indefinitely for cancer occurrence using local cancer registries and health insurance databases.

The team identified 575 individuals who were initially asymptomatic and healthy but were subsequently diagnosed with one of five common cancer types (stomach, esophagus, colorectum, lung, or liver cancer) within 4 years of their initial blood sampling. The authors selected these five cancer types to study because the incidence rates of these cancers in this population are high and, taken together, account for the highest mortality.

The study design allowed the authors to evaluate specimens both from patients with cancer and from those who were healthy within the same cohort. Using 191 prediagnosis samples, 223 postdiagnosis samples, and 414 healthy samples, they created a training set and validation model.

A machine learning method was created to classify samples as being either from healthy individuals or from those with cancer, using blood samples from the training set. The final classifier achieved 88% sensitivity for postdiagnosis samples and 91% sensitivity for prediagnosis samples at a specificity of 95%.

Zhang feels that initially it would be more appropriate to use the test for high-risk patients and to then evaluate the clinical benefit. “For any test, it is always more prudent to begin with a high-risk population,” he said. “You want to see some benefit with the high-risk population first, and then it can slowly be extended to others at lower risk.”

He emphasized that more rigorous testing is needing before the PanSeer assay is ready for clinical use. The logistics of designing and conducting a clinical trial that would include more than one cancer type would be very complicated. “The option was to break it down to five different studies,” he said. “We decided to begin with colon cancer, and we are currently in the process of talking with the FDA and designing the study.”
 

High bar to reach

Approached for comment, Benjamin Weinberg, MD, assistant professor of medicine, Division of Hematology and Oncology, the Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, noted that there is “quite a ways to go before this can be clinically actionable.

“A lot of us are looking at combining methylation with circulating tumor DNA and throw the kitchen sink at it, but as the paper nicely describes, there are pros and cons to all of these,” he said.

Many tests of this type are in development. Weinberg explained that a circulating tumor DNA test for colon cancer may hit the market soon, pending FDA approval, although that test will be used in a different setting. “This is something that’s used to assess for minimal residual disease in patients who have undergone surgery and appear to be ‘cured’ of the disease,” he said. “The test is looking to see if there is any circulating tumor DNA being shed from whatever tumor is left behind.”

The type of test that has piqued the most interest is one that is “tumor informed,” meaning that the company receives tumor tissue and develops a personalized test of that tumor on the basis of tumor genetics. “That is a very targeted way of surveillance,” said Weinberg, “But it would be very difficult to use a tumor-informed test on the population described in this study because you don’t know if there is going to be a tumor or not.”

The PanSeer test may also prove difficult to use in the clinic because it detects multiple cancers, Weinberg said. “If there is a positive finding, then which cancer do you look for?” he commented. “It has an issue in that regard, and that’s the problem with this type of test, as it is easier if there is one site of origin.”

Overall, the test was fairly sensitive and specific, with a very low false negative rate. Going forward, he noted, there is a very high bar for tests used as screening tools, although the authors do say that their focus is for use in a high-risk population.

“There would have to be a randomized trial, and the test will have to show a survival benefit,” Weinberg said. He noted that it can sometimes be challenging to do so.

“Colonoscopy has been shown to be beneficial, but early mammography has become controversial, and prostate cancer is a whole different animal,” he added. “And these are established tests, and they show how difficult this can be.”

The Taizhou Longitudinal Study study was supported by the National Key Research and Development Program of China, the National Natural Science Foundation of China, the Key Basic Research grants from the Science and Technology Commission of Shanghai Municipality, the International S&T Cooperation Program of China, the Municipal Science and Technology Major Project program, the International Science and Technology Cooperation Program of China, and the 111 Project (B13016). Funding for the DNA methylation assays was provided by Singlera Genomics. Zhang is a cofounder, equity holder, and paid consultant of Singlera Genomics, a company that is developing early cancer detection tests, including the PanSeer test. Weinberg is a speaker or a member of a speakers bureau for Taiho Pharmaceutical Co Ltd, Bayer HealthCare Pharmaceuticals, and Eli Lilly and Company; has received research grant from Novartis Pharmaceuticals Corporation; and has received travel reimbursement from Caris Life Sciences.

This article first appeared on Medscape.com.

A blood test that may be able to detect cancer years before any symptoms appear is under development. The PanSeer assay, which detects methylation markers in blood, was used in healthy individuals and successfully detected five cancer types in 91% of samples from individuals who were diagnosed with cancer 1 to 4 years later.

“We can’t say for sure that the patients didn’t have any symptoms, but we detected the cancer years before they ever walked into the hospital,” said study author Kun Zhang, PhD, a professor of bioengineering at the University of California, San Diego. “We were also able to follow up with patients, so we actually knew that they had cancer.”

Zhang noted that they also followed the individuals whose tests indicated they were cancer free. “They were healthy at the time the samples were obtained, and they remained healthy,” he said. “Follow-up was key to validating these data.”

The PanSeer test is being developed by Singlera Genomics. Zhang is a cofounder and a paid consultant of the company.

The study was published online July 21 in Nature Communications.
 

Unique among tests

Several blood tests for the detection of cancer have been reported in recent years. A test developed by Grail was able to detect more than 50 types of cancer and also identified the tissues where the cancer originated. The CancerSEEK test identified eight common cancers by measuring circulating tumor DNA from 16 genes, as well as eight protein biomarkers.

Findings regarding the CellMax Life FirstSight blood test were released last month. The test detected all 11 cases of colorectal cancer in a cohort of 354 patients and detected 40 of 53 advanced adenomas.

The latest study with the PanSeer assay is unique, say the investigators, because they had access to blood samples from patients who may have been completely asymptomatic and had not yet been diagnosed with cancer. Other blood tests have typically involved the use of specimens from people with a known diagnosis.

The specimens were collected as part of a 10-year longitudinal study that began in 2007 in China. Zhang and his team were able to test blood samples before individuals had experienced any signs or symptoms of cancer, and they were able to conduct long-term follow-up of the cohort.
 

Study details

The PanSeer assay uses DNA methylation analysis and screens for a DNA signature called CpG methylation. The results of an early-stage proof-of-concept study were published 3 years ago (Nat Genet. 2017;49:635–642).

For the current study, data were drawn from the Taizhou Longitudinal Study, which included 123,115 individuals aged 25 to 90 years who provided blood samples for long-term storage from 2007 to 2014. Participants were monitored indefinitely for cancer occurrence using local cancer registries and health insurance databases.

The team identified 575 individuals who were initially asymptomatic and healthy but were subsequently diagnosed with one of five common cancer types (stomach, esophagus, colorectum, lung, or liver cancer) within 4 years of their initial blood sampling. The authors selected these five cancer types to study because the incidence rates of these cancers in this population are high and, taken together, account for the highest mortality.

The study design allowed the authors to evaluate specimens both from patients with cancer and from those who were healthy within the same cohort. Using 191 prediagnosis samples, 223 postdiagnosis samples, and 414 healthy samples, they created a training set and validation model.

A machine learning method was created to classify samples as being either from healthy individuals or from those with cancer, using blood samples from the training set. The final classifier achieved 88% sensitivity for postdiagnosis samples and 91% sensitivity for prediagnosis samples at a specificity of 95%.

Zhang feels that initially it would be more appropriate to use the test for high-risk patients and to then evaluate the clinical benefit. “For any test, it is always more prudent to begin with a high-risk population,” he said. “You want to see some benefit with the high-risk population first, and then it can slowly be extended to others at lower risk.”

He emphasized that more rigorous testing is needing before the PanSeer assay is ready for clinical use. The logistics of designing and conducting a clinical trial that would include more than one cancer type would be very complicated. “The option was to break it down to five different studies,” he said. “We decided to begin with colon cancer, and we are currently in the process of talking with the FDA and designing the study.”
 

High bar to reach

Approached for comment, Benjamin Weinberg, MD, assistant professor of medicine, Division of Hematology and Oncology, the Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, noted that there is “quite a ways to go before this can be clinically actionable.

“A lot of us are looking at combining methylation with circulating tumor DNA and throw the kitchen sink at it, but as the paper nicely describes, there are pros and cons to all of these,” he said.

Many tests of this type are in development. Weinberg explained that a circulating tumor DNA test for colon cancer may hit the market soon, pending FDA approval, although that test will be used in a different setting. “This is something that’s used to assess for minimal residual disease in patients who have undergone surgery and appear to be ‘cured’ of the disease,” he said. “The test is looking to see if there is any circulating tumor DNA being shed from whatever tumor is left behind.”

The type of test that has piqued the most interest is one that is “tumor informed,” meaning that the company receives tumor tissue and develops a personalized test of that tumor on the basis of tumor genetics. “That is a very targeted way of surveillance,” said Weinberg, “But it would be very difficult to use a tumor-informed test on the population described in this study because you don’t know if there is going to be a tumor or not.”

The PanSeer test may also prove difficult to use in the clinic because it detects multiple cancers, Weinberg said. “If there is a positive finding, then which cancer do you look for?” he commented. “It has an issue in that regard, and that’s the problem with this type of test, as it is easier if there is one site of origin.”

Overall, the test was fairly sensitive and specific, with a very low false negative rate. Going forward, he noted, there is a very high bar for tests used as screening tools, although the authors do say that their focus is for use in a high-risk population.

“There would have to be a randomized trial, and the test will have to show a survival benefit,” Weinberg said. He noted that it can sometimes be challenging to do so.

“Colonoscopy has been shown to be beneficial, but early mammography has become controversial, and prostate cancer is a whole different animal,” he added. “And these are established tests, and they show how difficult this can be.”

The Taizhou Longitudinal Study study was supported by the National Key Research and Development Program of China, the National Natural Science Foundation of China, the Key Basic Research grants from the Science and Technology Commission of Shanghai Municipality, the International S&T Cooperation Program of China, the Municipal Science and Technology Major Project program, the International Science and Technology Cooperation Program of China, and the 111 Project (B13016). Funding for the DNA methylation assays was provided by Singlera Genomics. Zhang is a cofounder, equity holder, and paid consultant of Singlera Genomics, a company that is developing early cancer detection tests, including the PanSeer test. Weinberg is a speaker or a member of a speakers bureau for Taiho Pharmaceutical Co Ltd, Bayer HealthCare Pharmaceuticals, and Eli Lilly and Company; has received research grant from Novartis Pharmaceuticals Corporation; and has received travel reimbursement from Caris Life Sciences.

This article first appeared on Medscape.com.

Non-Hispanic black patients with cancer and patients with hematologic malignancies have a significantly increased risk of death if they develop COVID-19, according to the latest data from the COVID-19 and Cancer Consortium (CCC19) registry.

Initial results from the CCC19 registry were reported as part of the American Society of Clinical Oncology (ASCO) virtual scientific program and published in The Lancet (Lancet. 2020 Jun 20;395[10241]:1907-18).

The latest data were presented at the AACR virtual meeting: COVID-19 and Cancer by Brian I. Rini, MD, of Vanderbilt University, Nashville, Tenn. They were simultaneously published in Cancer Discovery (Cancer Discov. 2020 Jul 22;CD-20-0941).

The CCC19 registry was launched in March by a few institutions as part of “a grassroots idea ... to collect granular data regarding cancer patients and their outcomes with COVID,” Dr. Rini said.

Within a few months of its inception, the registry had partnered with more than 100 institutions worldwide and accrued data from more than 2,000 patients.

The reports in The Lancet and at ASCO included outcomes for the first 928 patients and showed a 13% mortality rate as well as a fivefold increase in the risk of 30-day mortality among patients with COVID-19 and progressing cancer.

The data also showed an increased mortality risk among older patients, men, former smokers, those with poor performance status, those with multiple comorbidities, and those treated with hydroxychloroquine and azithromycin.

The latest data

The CCC19 registry has grown to include 114 sites worldwide, including major comprehensive cancer centers and community sites. As of June 26, there were 2,749 patients enrolled.

Since the last data were reported, the mortality rate increased from 13% to 16% (versus 5% globally). In addition, the increased mortality risk among non-Hispanic black patients and patients with hematologic malignancies reached statistical significance, Dr. Rini said. He noted that the increase in mortality rate was largely attributable to improved follow-up.

Mechanical ventilation was required in 12% of patients, ICU admission was required in 16%, oxygen was required in 45%, and hospitalization was required in 60%. The composite outcome of death, severe illness requiring hospitalization, ICU admission, or mechanical ventilation was reached in 29% of patients, Dr. Rini said.

Mortality rates across cancer types ranged from 3% to 26%, with thyroid and breast cancer patients having the lowest rates (3% and 8%, respectively), and with lymphoma and lung cancer patients having the highest (22% and 26%, respectively), Dr. Rini said.

He noted that the TERAVOLT registry, a COVID-19 registry for patients with thoracic cancers, also showed a very high mortality rate in this subgroup of patients.

Results from TERAVOLT were reported at the AACR virtual meeting I, presented at ASCO, and published in The Lancet (Lancet Oncol. 2020 Jul;21[7]:914-22). The most recent results showed a mortality rate of nearly 36% and reinforce the high mortality rate seen in lung cancer patients in CCC19, Dr. Rini said.
 

Increased mortality risk

After adjustment for several demographic and disease characteristics, the updated CCC19 data showed a significantly increased risk of mortality among:

• Older patients (adjusted odds ratio [aOR] per decade of age, 1.52).
• Men (aOR, 1.43).
• Current or former smokers vs. never smokers (aOR, 1.28).
• Patients with Eastern Cooperative Oncology Group performance scores of 1 vs. 0 (aOR of 1.80) or 2 vs. 0 (aOR, 4.22).
• Stable cancer vs. remission (aOR, 1.47).
• Progressive cancer vs. remission (aOR, 2.96).
• Non-Hispanic Black vs. White patients (aOR, 1.56).
• Hematologic malignancies vs. solid tumors (aOR, 1.80).

“Importantly, there were some factors that did not reach statistical significance,” Dr. Rini said. These include obesity (aOR, 1.23), recent surgery (aOR, 1.05), receipt of cytotoxic chemotherapy vs. no chemotherapy (aOR, 1.14), and receipt of noncytotoxic chemotherapy vs. no chemotherapy (aOR, 0.75).

“I think this provides some reassurance that cancer care can and should continue for these patients,” Dr. Rini said.

He noted, however, that in TERAVOLT, chemotherapy with or without other treatment was a risk factor for mortality in lung cancer patients when compared with no chemotherapy (OR, 1.71) and when compared with immunotherapy or targeted therapy (OR, 1.64).
 

NCCAPS and other registries

Dr. Rini discussed a number of registries looking at outcomes in COVID-19 patients with cancer, and he said the findings to date appear to confirm a higher mortality rate among cancer patients, particularly those with lung cancer.

Several factors are emerging that appear to be related to risk, including both cancer-related and non–cancer-related factors, he added.

The ongoing prospective National Cancer Institute COVID-19 in Cancer Patients Study (NCCAPS) “will provide much needed longitudinal data and, importantly, biospecimen collection in a large cohort of patients who have active cancer and are receiving treatment, said Dr. Rini, who is the study’s protocol chair. NCCAPS is a natural history study in that population, he said.

The planned accrual is about 2,000 patients who will be followed for up to 2 years for data collection, imaging scans, and research specimens.

The use of specimens is “a unique and special part of this study,” Dr. Rini said, explaining that the specimens will be used to look for development of antibodies over time, to describe the trajectory of cytokine abnormalities – especially in patients with more acute inpatient courses – to perform DNA-based genome-wide association studies, and to assess coagulation parameters.

NCCAPS is activated at 546 sties, 10 patients were enrolled as of June 21, and rapid accrual is expected over the next several months, he said.

Gypsyamber D’Souza, PhD, session moderator and an infectious disease epidemiologist at Johns Hopkins University in Baltimore, acknowledged the challenge that registry administrators face when trying to balance the need to get data out against the desire to ask the right questions and to have the right comparison groups, stratification, and analyses, especially amid a crisis like the COVID-19 pandemic.

Dr. Rini said it has indeed been a bit of a struggle with CCC19 to determine what information should be published and when, and what constitutes an important update.

“It’s been a learning experience, and frankly, I think we’re still learning,” he said. “This has been such a unique time in terms of a rush to get data out, balanced against making sure that there’s quality data and that you’re actually answering important questions.”

In fact, a number of ongoing registries “should start to produce great data [that will be presented] at upcoming big conferences,” Dr. Rini said. He added that those data “will help piece together different important aspects of this and different hypotheses, and hopefully complement the clinical data that’s starting to come out.”

The CCC19 registry is sponsored by Vanderbilt-Ingram Cancer Center. Dr. Rini disclosed relationships with Pfizer, Merck, Genentech/Roche, Aveo, AstraZeneca, Bristol Myers Squibb, Exelixis, Synthorx, Peloton, Compugen, Corvus, Surface Oncology, 3DMedicines, Aravive, Alkermes, Arrowhead, and PTC Therapeutics. Dr. D’Souza did not disclose any conflicts.

sworcester@mdedge.com

SOURCE: Rini BI. AACR: COVID-19 and Cancer. Abstract IA26.

Non-Hispanic black patients with cancer and patients with hematologic malignancies have a significantly increased risk of death if they develop COVID-19, according to the latest data from the COVID-19 and Cancer Consortium (CCC19) registry.

Initial results from the CCC19 registry were reported as part of the American Society of Clinical Oncology (ASCO) virtual scientific program and published in The Lancet (Lancet. 2020 Jun 20;395[10241]:1907-18).

The latest data were presented at the AACR virtual meeting: COVID-19 and Cancer by Brian I. Rini, MD, of Vanderbilt University, Nashville, Tenn. They were simultaneously published in Cancer Discovery (Cancer Discov. 2020 Jul 22;CD-20-0941).

The CCC19 registry was launched in March by a few institutions as part of “a grassroots idea ... to collect granular data regarding cancer patients and their outcomes with COVID,” Dr. Rini said.

Within a few months of its inception, the registry had partnered with more than 100 institutions worldwide and accrued data from more than 2,000 patients.

The reports in The Lancet and at ASCO included outcomes for the first 928 patients and showed a 13% mortality rate as well as a fivefold increase in the risk of 30-day mortality among patients with COVID-19 and progressing cancer.

The data also showed an increased mortality risk among older patients, men, former smokers, those with poor performance status, those with multiple comorbidities, and those treated with hydroxychloroquine and azithromycin.

The latest data

The CCC19 registry has grown to include 114 sites worldwide, including major comprehensive cancer centers and community sites. As of June 26, there were 2,749 patients enrolled.

Since the last data were reported, the mortality rate increased from 13% to 16% (versus 5% globally). In addition, the increased mortality risk among non-Hispanic black patients and patients with hematologic malignancies reached statistical significance, Dr. Rini said. He noted that the increase in mortality rate was largely attributable to improved follow-up.

Mechanical ventilation was required in 12% of patients, ICU admission was required in 16%, oxygen was required in 45%, and hospitalization was required in 60%. The composite outcome of death, severe illness requiring hospitalization, ICU admission, or mechanical ventilation was reached in 29% of patients, Dr. Rini said.

Mortality rates across cancer types ranged from 3% to 26%, with thyroid and breast cancer patients having the lowest rates (3% and 8%, respectively), and with lymphoma and lung cancer patients having the highest (22% and 26%, respectively), Dr. Rini said.

He noted that the TERAVOLT registry, a COVID-19 registry for patients with thoracic cancers, also showed a very high mortality rate in this subgroup of patients.

Results from TERAVOLT were reported at the AACR virtual meeting I, presented at ASCO, and published in The Lancet (Lancet Oncol. 2020 Jul;21[7]:914-22). The most recent results showed a mortality rate of nearly 36% and reinforce the high mortality rate seen in lung cancer patients in CCC19, Dr. Rini said.
 

Increased mortality risk

After adjustment for several demographic and disease characteristics, the updated CCC19 data showed a significantly increased risk of mortality among:

• Older patients (adjusted odds ratio [aOR] per decade of age, 1.52).
• Men (aOR, 1.43).
• Current or former smokers vs. never smokers (aOR, 1.28).
• Patients with Eastern Cooperative Oncology Group performance scores of 1 vs. 0 (aOR of 1.80) or 2 vs. 0 (aOR, 4.22).
• Stable cancer vs. remission (aOR, 1.47).
• Progressive cancer vs. remission (aOR, 2.96).
• Non-Hispanic Black vs. White patients (aOR, 1.56).
• Hematologic malignancies vs. solid tumors (aOR, 1.80).

“Importantly, there were some factors that did not reach statistical significance,” Dr. Rini said. These include obesity (aOR, 1.23), recent surgery (aOR, 1.05), receipt of cytotoxic chemotherapy vs. no chemotherapy (aOR, 1.14), and receipt of noncytotoxic chemotherapy vs. no chemotherapy (aOR, 0.75).

“I think this provides some reassurance that cancer care can and should continue for these patients,” Dr. Rini said.

He noted, however, that in TERAVOLT, chemotherapy with or without other treatment was a risk factor for mortality in lung cancer patients when compared with no chemotherapy (OR, 1.71) and when compared with immunotherapy or targeted therapy (OR, 1.64).
 

NCCAPS and other registries

Dr. Rini discussed a number of registries looking at outcomes in COVID-19 patients with cancer, and he said the findings to date appear to confirm a higher mortality rate among cancer patients, particularly those with lung cancer.

Several factors are emerging that appear to be related to risk, including both cancer-related and non–cancer-related factors, he added.

The ongoing prospective National Cancer Institute COVID-19 in Cancer Patients Study (NCCAPS) “will provide much needed longitudinal data and, importantly, biospecimen collection in a large cohort of patients who have active cancer and are receiving treatment, said Dr. Rini, who is the study’s protocol chair. NCCAPS is a natural history study in that population, he said.

The planned accrual is about 2,000 patients who will be followed for up to 2 years for data collection, imaging scans, and research specimens.

The use of specimens is “a unique and special part of this study,” Dr. Rini said, explaining that the specimens will be used to look for development of antibodies over time, to describe the trajectory of cytokine abnormalities – especially in patients with more acute inpatient courses – to perform DNA-based genome-wide association studies, and to assess coagulation parameters.

NCCAPS is activated at 546 sties, 10 patients were enrolled as of June 21, and rapid accrual is expected over the next several months, he said.

Gypsyamber D’Souza, PhD, session moderator and an infectious disease epidemiologist at Johns Hopkins University in Baltimore, acknowledged the challenge that registry administrators face when trying to balance the need to get data out against the desire to ask the right questions and to have the right comparison groups, stratification, and analyses, especially amid a crisis like the COVID-19 pandemic.

Dr. Rini said it has indeed been a bit of a struggle with CCC19 to determine what information should be published and when, and what constitutes an important update.

“It’s been a learning experience, and frankly, I think we’re still learning,” he said. “This has been such a unique time in terms of a rush to get data out, balanced against making sure that there’s quality data and that you’re actually answering important questions.”

In fact, a number of ongoing registries “should start to produce great data [that will be presented] at upcoming big conferences,” Dr. Rini said. He added that those data “will help piece together different important aspects of this and different hypotheses, and hopefully complement the clinical data that’s starting to come out.”

The CCC19 registry is sponsored by Vanderbilt-Ingram Cancer Center. Dr. Rini disclosed relationships with Pfizer, Merck, Genentech/Roche, Aveo, AstraZeneca, Bristol Myers Squibb, Exelixis, Synthorx, Peloton, Compugen, Corvus, Surface Oncology, 3DMedicines, Aravive, Alkermes, Arrowhead, and PTC Therapeutics. Dr. D’Souza did not disclose any conflicts.

sworcester@mdedge.com

SOURCE: Rini BI. AACR: COVID-19 and Cancer. Abstract IA26.

Non-Hispanic black patients with cancer and patients with hematologic malignancies have a significantly increased risk of death if they develop COVID-19, according to the latest data from the COVID-19 and Cancer Consortium (CCC19) registry.

Initial results from the CCC19 registry were reported as part of the American Society of Clinical Oncology (ASCO) virtual scientific program and published in The Lancet (Lancet. 2020 Jun 20;395[10241]:1907-18).

The latest data were presented at the AACR virtual meeting: COVID-19 and Cancer by Brian I. Rini, MD, of Vanderbilt University, Nashville, Tenn. They were simultaneously published in Cancer Discovery (Cancer Discov. 2020 Jul 22;CD-20-0941).

The CCC19 registry was launched in March by a few institutions as part of “a grassroots idea ... to collect granular data regarding cancer patients and their outcomes with COVID,” Dr. Rini said.

Within a few months of its inception, the registry had partnered with more than 100 institutions worldwide and accrued data from more than 2,000 patients.

The reports in The Lancet and at ASCO included outcomes for the first 928 patients and showed a 13% mortality rate as well as a fivefold increase in the risk of 30-day mortality among patients with COVID-19 and progressing cancer.

The data also showed an increased mortality risk among older patients, men, former smokers, those with poor performance status, those with multiple comorbidities, and those treated with hydroxychloroquine and azithromycin.

The latest data

The CCC19 registry has grown to include 114 sites worldwide, including major comprehensive cancer centers and community sites. As of June 26, there were 2,749 patients enrolled.

Since the last data were reported, the mortality rate increased from 13% to 16% (versus 5% globally). In addition, the increased mortality risk among non-Hispanic black patients and patients with hematologic malignancies reached statistical significance, Dr. Rini said. He noted that the increase in mortality rate was largely attributable to improved follow-up.

Mechanical ventilation was required in 12% of patients, ICU admission was required in 16%, oxygen was required in 45%, and hospitalization was required in 60%. The composite outcome of death, severe illness requiring hospitalization, ICU admission, or mechanical ventilation was reached in 29% of patients, Dr. Rini said.

Mortality rates across cancer types ranged from 3% to 26%, with thyroid and breast cancer patients having the lowest rates (3% and 8%, respectively), and with lymphoma and lung cancer patients having the highest (22% and 26%, respectively), Dr. Rini said.

He noted that the TERAVOLT registry, a COVID-19 registry for patients with thoracic cancers, also showed a very high mortality rate in this subgroup of patients.

Results from TERAVOLT were reported at the AACR virtual meeting I, presented at ASCO, and published in The Lancet (Lancet Oncol. 2020 Jul;21[7]:914-22). The most recent results showed a mortality rate of nearly 36% and reinforce the high mortality rate seen in lung cancer patients in CCC19, Dr. Rini said.
 

Increased mortality risk

After adjustment for several demographic and disease characteristics, the updated CCC19 data showed a significantly increased risk of mortality among:

• Older patients (adjusted odds ratio [aOR] per decade of age, 1.52).
• Men (aOR, 1.43).
• Current or former smokers vs. never smokers (aOR, 1.28).
• Patients with Eastern Cooperative Oncology Group performance scores of 1 vs. 0 (aOR of 1.80) or 2 vs. 0 (aOR, 4.22).
• Stable cancer vs. remission (aOR, 1.47).
• Progressive cancer vs. remission (aOR, 2.96).
• Non-Hispanic Black vs. White patients (aOR, 1.56).
• Hematologic malignancies vs. solid tumors (aOR, 1.80).

“Importantly, there were some factors that did not reach statistical significance,” Dr. Rini said. These include obesity (aOR, 1.23), recent surgery (aOR, 1.05), receipt of cytotoxic chemotherapy vs. no chemotherapy (aOR, 1.14), and receipt of noncytotoxic chemotherapy vs. no chemotherapy (aOR, 0.75).

“I think this provides some reassurance that cancer care can and should continue for these patients,” Dr. Rini said.

He noted, however, that in TERAVOLT, chemotherapy with or without other treatment was a risk factor for mortality in lung cancer patients when compared with no chemotherapy (OR, 1.71) and when compared with immunotherapy or targeted therapy (OR, 1.64).
 

NCCAPS and other registries

Dr. Rini discussed a number of registries looking at outcomes in COVID-19 patients with cancer, and he said the findings to date appear to confirm a higher mortality rate among cancer patients, particularly those with lung cancer.

Several factors are emerging that appear to be related to risk, including both cancer-related and non–cancer-related factors, he added.

The ongoing prospective National Cancer Institute COVID-19 in Cancer Patients Study (NCCAPS) “will provide much needed longitudinal data and, importantly, biospecimen collection in a large cohort of patients who have active cancer and are receiving treatment, said Dr. Rini, who is the study’s protocol chair. NCCAPS is a natural history study in that population, he said.

The planned accrual is about 2,000 patients who will be followed for up to 2 years for data collection, imaging scans, and research specimens.

The use of specimens is “a unique and special part of this study,” Dr. Rini said, explaining that the specimens will be used to look for development of antibodies over time, to describe the trajectory of cytokine abnormalities – especially in patients with more acute inpatient courses – to perform DNA-based genome-wide association studies, and to assess coagulation parameters.

NCCAPS is activated at 546 sties, 10 patients were enrolled as of June 21, and rapid accrual is expected over the next several months, he said.

Gypsyamber D’Souza, PhD, session moderator and an infectious disease epidemiologist at Johns Hopkins University in Baltimore, acknowledged the challenge that registry administrators face when trying to balance the need to get data out against the desire to ask the right questions and to have the right comparison groups, stratification, and analyses, especially amid a crisis like the COVID-19 pandemic.

Dr. Rini said it has indeed been a bit of a struggle with CCC19 to determine what information should be published and when, and what constitutes an important update.

“It’s been a learning experience, and frankly, I think we’re still learning,” he said. “This has been such a unique time in terms of a rush to get data out, balanced against making sure that there’s quality data and that you’re actually answering important questions.”

In fact, a number of ongoing registries “should start to produce great data [that will be presented] at upcoming big conferences,” Dr. Rini said. He added that those data “will help piece together different important aspects of this and different hypotheses, and hopefully complement the clinical data that’s starting to come out.”

The CCC19 registry is sponsored by Vanderbilt-Ingram Cancer Center. Dr. Rini disclosed relationships with Pfizer, Merck, Genentech/Roche, Aveo, AstraZeneca, Bristol Myers Squibb, Exelixis, Synthorx, Peloton, Compugen, Corvus, Surface Oncology, 3DMedicines, Aravive, Alkermes, Arrowhead, and PTC Therapeutics. Dr. D’Souza did not disclose any conflicts.

sworcester@mdedge.com

SOURCE: Rini BI. AACR: COVID-19 and Cancer. Abstract IA26.

Delays in cancer referrals caused by the COVID-19 pandemic and the ensuing shutdown in cancer services will lead to thousands of additional deaths and tens of thousands of life-years lost, suggest two new modeling studies from the United Kingdom.

Clearing the backlog in cancer diagnoses will require a coordinated effort from the government and the National Health Service (NHS), say the authors, inasmuch as services were already running at “full capacity” before the pandemic.

Both studies were published in The Lancet Oncology on July 20.

When the UK-wide lockdown to combat the COVID-19 pandemic was implemented on March 23, cancer screening and routine outpatient referrals in the NHS were suspended, and treatment of cancer patients either halted or slowed down.

Moreover, because of physical distancing measures, which are expected to continue for up to a year, urgent 3-week referrals for suspected cancer cases have fallen by as much as 80%.

To estimate the potential impact on cancer deaths, Ajay Aggarwal, MD, from the London School of Hygiene and Tropical Medicine, United Kingdom, and colleagues conducted a population-based modeling study.

They collected data on 32,583 patients with breast cancer, 24,975 with colorectal cancer, 6744 with esophageal cancer, and 29,305 with lung cancer. Patients were diagnosed between 2010 and 2012 and were followed to 2015.

The investigators used that data to estimate the impact of diagnostic delays resulting from 12 months of physical distancing.

For breast cancer, this would lead to a 7.9%-9.6% increase in the number of cancer deaths within 5 years after diagnosis, or to 281-344 additional deaths.

For colorectal cancer, there would be a 15.3%-16.7% increase in mortality over 5 years, or an additional 1,445-1,563 deaths.

For lung cancer, there would a 4.8%-5.3% increase in mortality, or an additional 1235-1372 deaths.

For esophageal cancer, the mortality increase over 5 years would be 5.8%-6.0%, leading to 330-342 additional deaths.

Across the four tumor types, 59,204-63,229 life-years would be lost because of physical distancing compared to the prepandemic era.
 

Resources need to be increased

These additional deaths are not inevitable, the researchers suggest.

To prevent the increase in colorectal cancer deaths, for example, Aggarwal said, “It is vital that more resources are made urgently available for endoscopy and colonoscopy services, which are managing significant backlogs currently.

“Whilst currently attention is being focused on diagnostic pathways where cancer is suspected, the issue is that a significant number of cancers are diagnosed in patients awaiting investigation for symptoms not considered related to be cancer,” he added in a statement.

“Therefore we need a whole system approach to avoid the predicted excess deaths.”

Coauthor Bernard Rachet, PhD, also from the London School of Hygiene and Tropical Medicine, added that “to absorb the cancer patient backlog, the healthcare community also needs to establish clear criteria to prioritise patients on clinical grounds, in order to maintain equitability in care delivery.”

It will not be easy “to pin down the exact number of additional cancer deaths we expect to see over the coming years, but studies like this help us to understand the devastating long-term effect a pandemic like COVID-19 will have on the lives of thousands of cancer patients,” commented Michelle Mitchell, chief executive of Cancer Research UK.

Underlining the “enormous backlog” of cancer care that has built up during the pandemic, she said: “Diagnosing and treating people swiftly is vital to give people with cancer the greatest chances of survival.

“The government must work closely with the NHS to ensure it has sufficient staff and equipment to clear the backlog while giving patients the care that they need, quickly and safely,” Mitchell added.

Increasing resources will not be easy. In an accompanying editorial, William Hamilton, MD, PhD, University of Exeter, United Kingdom, warns that many NHS imaging departments, for example, were “working at full capacity before the COVID-19 pandemic.”

Consequently, they “might not be able to meet the increase in demand” resulting from the backlog in patients, especially as “the need to keep patients separate and to clean equipment has reduced their efficiency.

“The UK has had a long-term shortage of diagnostic capacity, although this shortage is not simply of equipment, but also of personnel, which is not so easily improved,” he cautions.
 

Another study, similar estimates

For the second study, Clare Turnbull, PhD, Institute of Cancer Research, London, and colleagues obtained age- and stage-stratified 10-year cancer survival estimates for patients in England diagnosed with 20 common tumor types between 2008 and 2017.

They also gathered data on cancer diagnoses made via urgent 2-week referrals between 2013 and 2016. They estimate that 6,281 patients were diagnosed with cancer of stages I-III per month.

Of those, 1,691 (27%) would die within 10 years of their diagnosis, they found.

They then calculated that delays in 2-week referrals during a 3-month lockdown would lead to an average delay in presentation of 2 months per patient.

A resulting 25% backlog in referrals would lead to 181 additional lives and 3,316 life-years lost. With a 75% backlog in referrals, an additional 276 lives and 5,075 life-years would be lost.

The team says that additional diagnostic delays spread over 3-8 months after the lockdown could increase the impact of a 25% backlog in referrals to 401 additional lives and 14,873 life-years lost.

For a 75% backlog in referrals, the additional lives lost would rise to 1,231, and the number of life-years lost would reach 22,635.

“Substantial additional deaths from diagnostic delays on top of those expected from delays in presentation – because many people are simply too afraid to visit their GP or hospital – are likely, especially if rapid provision of additional capacity, including technical provision and increased staffing, is not forthcoming,” Turnbull commented in a statement.

The study by Aggarwal and colleagues was funded by the U.K. Research and Innovation Economic and Social Research Council. Several of the researchers were supported by Cancer Research UK and Breast Cancer Now. Turnbull reports receiving support from the Movember Foundation.

This article first appeared on Medscape.com.

Delays in cancer referrals caused by the COVID-19 pandemic and the ensuing shutdown in cancer services will lead to thousands of additional deaths and tens of thousands of life-years lost, suggest two new modeling studies from the United Kingdom.

Clearing the backlog in cancer diagnoses will require a coordinated effort from the government and the National Health Service (NHS), say the authors, inasmuch as services were already running at “full capacity” before the pandemic.

Both studies were published in The Lancet Oncology on July 20.

When the UK-wide lockdown to combat the COVID-19 pandemic was implemented on March 23, cancer screening and routine outpatient referrals in the NHS were suspended, and treatment of cancer patients either halted or slowed down.

Moreover, because of physical distancing measures, which are expected to continue for up to a year, urgent 3-week referrals for suspected cancer cases have fallen by as much as 80%.

To estimate the potential impact on cancer deaths, Ajay Aggarwal, MD, from the London School of Hygiene and Tropical Medicine, United Kingdom, and colleagues conducted a population-based modeling study.

They collected data on 32,583 patients with breast cancer, 24,975 with colorectal cancer, 6744 with esophageal cancer, and 29,305 with lung cancer. Patients were diagnosed between 2010 and 2012 and were followed to 2015.

The investigators used that data to estimate the impact of diagnostic delays resulting from 12 months of physical distancing.

For breast cancer, this would lead to a 7.9%-9.6% increase in the number of cancer deaths within 5 years after diagnosis, or to 281-344 additional deaths.

For colorectal cancer, there would be a 15.3%-16.7% increase in mortality over 5 years, or an additional 1,445-1,563 deaths.

For lung cancer, there would a 4.8%-5.3% increase in mortality, or an additional 1235-1372 deaths.

For esophageal cancer, the mortality increase over 5 years would be 5.8%-6.0%, leading to 330-342 additional deaths.

Across the four tumor types, 59,204-63,229 life-years would be lost because of physical distancing compared to the prepandemic era.
 

Resources need to be increased

These additional deaths are not inevitable, the researchers suggest.

To prevent the increase in colorectal cancer deaths, for example, Aggarwal said, “It is vital that more resources are made urgently available for endoscopy and colonoscopy services, which are managing significant backlogs currently.

“Whilst currently attention is being focused on diagnostic pathways where cancer is suspected, the issue is that a significant number of cancers are diagnosed in patients awaiting investigation for symptoms not considered related to be cancer,” he added in a statement.

“Therefore we need a whole system approach to avoid the predicted excess deaths.”

Coauthor Bernard Rachet, PhD, also from the London School of Hygiene and Tropical Medicine, added that “to absorb the cancer patient backlog, the healthcare community also needs to establish clear criteria to prioritise patients on clinical grounds, in order to maintain equitability in care delivery.”

It will not be easy “to pin down the exact number of additional cancer deaths we expect to see over the coming years, but studies like this help us to understand the devastating long-term effect a pandemic like COVID-19 will have on the lives of thousands of cancer patients,” commented Michelle Mitchell, chief executive of Cancer Research UK.

Underlining the “enormous backlog” of cancer care that has built up during the pandemic, she said: “Diagnosing and treating people swiftly is vital to give people with cancer the greatest chances of survival.

“The government must work closely with the NHS to ensure it has sufficient staff and equipment to clear the backlog while giving patients the care that they need, quickly and safely,” Mitchell added.

Increasing resources will not be easy. In an accompanying editorial, William Hamilton, MD, PhD, University of Exeter, United Kingdom, warns that many NHS imaging departments, for example, were “working at full capacity before the COVID-19 pandemic.”

Consequently, they “might not be able to meet the increase in demand” resulting from the backlog in patients, especially as “the need to keep patients separate and to clean equipment has reduced their efficiency.

“The UK has had a long-term shortage of diagnostic capacity, although this shortage is not simply of equipment, but also of personnel, which is not so easily improved,” he cautions.
 

Another study, similar estimates

For the second study, Clare Turnbull, PhD, Institute of Cancer Research, London, and colleagues obtained age- and stage-stratified 10-year cancer survival estimates for patients in England diagnosed with 20 common tumor types between 2008 and 2017.

They also gathered data on cancer diagnoses made via urgent 2-week referrals between 2013 and 2016. They estimate that 6,281 patients were diagnosed with cancer of stages I-III per month.

Of those, 1,691 (27%) would die within 10 years of their diagnosis, they found.

They then calculated that delays in 2-week referrals during a 3-month lockdown would lead to an average delay in presentation of 2 months per patient.

A resulting 25% backlog in referrals would lead to 181 additional lives and 3,316 life-years lost. With a 75% backlog in referrals, an additional 276 lives and 5,075 life-years would be lost.

The team says that additional diagnostic delays spread over 3-8 months after the lockdown could increase the impact of a 25% backlog in referrals to 401 additional lives and 14,873 life-years lost.

For a 75% backlog in referrals, the additional lives lost would rise to 1,231, and the number of life-years lost would reach 22,635.

“Substantial additional deaths from diagnostic delays on top of those expected from delays in presentation – because many people are simply too afraid to visit their GP or hospital – are likely, especially if rapid provision of additional capacity, including technical provision and increased staffing, is not forthcoming,” Turnbull commented in a statement.

The study by Aggarwal and colleagues was funded by the U.K. Research and Innovation Economic and Social Research Council. Several of the researchers were supported by Cancer Research UK and Breast Cancer Now. Turnbull reports receiving support from the Movember Foundation.

This article first appeared on Medscape.com.

Delays in cancer referrals caused by the COVID-19 pandemic and the ensuing shutdown in cancer services will lead to thousands of additional deaths and tens of thousands of life-years lost, suggest two new modeling studies from the United Kingdom.

Clearing the backlog in cancer diagnoses will require a coordinated effort from the government and the National Health Service (NHS), say the authors, inasmuch as services were already running at “full capacity” before the pandemic.

Both studies were published in The Lancet Oncology on July 20.

When the UK-wide lockdown to combat the COVID-19 pandemic was implemented on March 23, cancer screening and routine outpatient referrals in the NHS were suspended, and treatment of cancer patients either halted or slowed down.

Moreover, because of physical distancing measures, which are expected to continue for up to a year, urgent 3-week referrals for suspected cancer cases have fallen by as much as 80%.

To estimate the potential impact on cancer deaths, Ajay Aggarwal, MD, from the London School of Hygiene and Tropical Medicine, United Kingdom, and colleagues conducted a population-based modeling study.

They collected data on 32,583 patients with breast cancer, 24,975 with colorectal cancer, 6744 with esophageal cancer, and 29,305 with lung cancer. Patients were diagnosed between 2010 and 2012 and were followed to 2015.

The investigators used that data to estimate the impact of diagnostic delays resulting from 12 months of physical distancing.

For breast cancer, this would lead to a 7.9%-9.6% increase in the number of cancer deaths within 5 years after diagnosis, or to 281-344 additional deaths.

For colorectal cancer, there would be a 15.3%-16.7% increase in mortality over 5 years, or an additional 1,445-1,563 deaths.

For lung cancer, there would a 4.8%-5.3% increase in mortality, or an additional 1235-1372 deaths.

For esophageal cancer, the mortality increase over 5 years would be 5.8%-6.0%, leading to 330-342 additional deaths.

Across the four tumor types, 59,204-63,229 life-years would be lost because of physical distancing compared to the prepandemic era.
 

Resources need to be increased

These additional deaths are not inevitable, the researchers suggest.

To prevent the increase in colorectal cancer deaths, for example, Aggarwal said, “It is vital that more resources are made urgently available for endoscopy and colonoscopy services, which are managing significant backlogs currently.

“Whilst currently attention is being focused on diagnostic pathways where cancer is suspected, the issue is that a significant number of cancers are diagnosed in patients awaiting investigation for symptoms not considered related to be cancer,” he added in a statement.

“Therefore we need a whole system approach to avoid the predicted excess deaths.”

Coauthor Bernard Rachet, PhD, also from the London School of Hygiene and Tropical Medicine, added that “to absorb the cancer patient backlog, the healthcare community also needs to establish clear criteria to prioritise patients on clinical grounds, in order to maintain equitability in care delivery.”

It will not be easy “to pin down the exact number of additional cancer deaths we expect to see over the coming years, but studies like this help us to understand the devastating long-term effect a pandemic like COVID-19 will have on the lives of thousands of cancer patients,” commented Michelle Mitchell, chief executive of Cancer Research UK.

Underlining the “enormous backlog” of cancer care that has built up during the pandemic, she said: “Diagnosing and treating people swiftly is vital to give people with cancer the greatest chances of survival.

“The government must work closely with the NHS to ensure it has sufficient staff and equipment to clear the backlog while giving patients the care that they need, quickly and safely,” Mitchell added.

Increasing resources will not be easy. In an accompanying editorial, William Hamilton, MD, PhD, University of Exeter, United Kingdom, warns that many NHS imaging departments, for example, were “working at full capacity before the COVID-19 pandemic.”

Consequently, they “might not be able to meet the increase in demand” resulting from the backlog in patients, especially as “the need to keep patients separate and to clean equipment has reduced their efficiency.

“The UK has had a long-term shortage of diagnostic capacity, although this shortage is not simply of equipment, but also of personnel, which is not so easily improved,” he cautions.
 

Another study, similar estimates

For the second study, Clare Turnbull, PhD, Institute of Cancer Research, London, and colleagues obtained age- and stage-stratified 10-year cancer survival estimates for patients in England diagnosed with 20 common tumor types between 2008 and 2017.

They also gathered data on cancer diagnoses made via urgent 2-week referrals between 2013 and 2016. They estimate that 6,281 patients were diagnosed with cancer of stages I-III per month.

Of those, 1,691 (27%) would die within 10 years of their diagnosis, they found.

They then calculated that delays in 2-week referrals during a 3-month lockdown would lead to an average delay in presentation of 2 months per patient.

A resulting 25% backlog in referrals would lead to 181 additional lives and 3,316 life-years lost. With a 75% backlog in referrals, an additional 276 lives and 5,075 life-years would be lost.

The team says that additional diagnostic delays spread over 3-8 months after the lockdown could increase the impact of a 25% backlog in referrals to 401 additional lives and 14,873 life-years lost.

For a 75% backlog in referrals, the additional lives lost would rise to 1,231, and the number of life-years lost would reach 22,635.

“Substantial additional deaths from diagnostic delays on top of those expected from delays in presentation – because many people are simply too afraid to visit their GP or hospital – are likely, especially if rapid provision of additional capacity, including technical provision and increased staffing, is not forthcoming,” Turnbull commented in a statement.

The study by Aggarwal and colleagues was funded by the U.K. Research and Innovation Economic and Social Research Council. Several of the researchers were supported by Cancer Research UK and Breast Cancer Now. Turnbull reports receiving support from the Movember Foundation.

This article first appeared on Medscape.com.

A bus converted into a mobile CT screening unit has been reaching high-risk individuals in underserved rural counties in Appalachian areas who may have otherwise not had a chance to be screened for lung cancer.

Results from a pilot study, published online July 13 in The Annals of Thoracic Surgery, show that the scheme is both practical and financially sustainable.

During a 10-month test run, the mobile unit screened 548 individuals at 104 sites. Five lung cancers (four of which were early stage) and a type B thymoma were discovered, and all of these individuals went on to have treatment.

Significant pulmonary findings were also discovered in 52 individuals, who were advised to undergo further testing, as well as significant nonpulmonary findings in 152 individuals (of whom 13 required further testing, but none went on to have treatment). These findings included severe coronary disease and thyroid abnormalities.

The bus reached the estimated financial break-even point of 428 scans, but future economic viability of such a program will likely rely on additional revenue from the treatment of patients with incidental findings from low-dose CT screens, acknowledged the authors, led by James R. Headrick Jr, MD, MBA, from the University of Tennessee College of Medicine in Chattanooga.

The real value of the Breathe Easy program, however, comes from bringing both patient education and lung cancer screening services to a high-risk population who might otherwise be overlooked, Headrick said in an interview with Medscape Medical News.

“We were all excited when lung screening was approved, and we got the recommendation from the United States Preventive Services Task Force [USPSTF], and the Centers for Medicare & Medicaid Services signed off on it, and we sat in our offices and clinics and hospitals — and nobody showed up. We were thinking, ‘Wow, we have this simple test, the easiest screening tool in the world, and nobody’s coming,’ “ he said.

“There was certainly an educational issue that needed to be solved,” he continued, “but we were also dealing with a population that had been told that if they smoked and didn’t live life well, there was a 100% chance they were going to get lung cancer and die,” he said.

The individuals screened in the program were very heavy smokers.

The mean pack-years of smoking was 41 — 11 pack-years higher than the minimum recommended under current lung cancer screening guidelines, and 21 pack-years higher than that recently recommended under proposed low-dose CT screening guidelines by the USPSTF.  

Albert Rizzo, MD, chief medical officer for the American Lung Association, who was not involved in the study, told Medscape Medical News any initiative that can expand lung cancer screening is welcome, particularly when a program may be self-sustaining.

“The interesting part of this article included the downstream revenue to help make something like this viable,” Rizzo said. “Just doing the scans is probably not going to cover the cost of the mobile unit itself, but if you take into account that other things are being found in addition to lung cancer, such as coronary abnormalities, then it becomes more cost-effective, especially if those patients are then treated at the site where the mobile unit is coming from,” he said.
 

Starting at square one

The first mobile CT scanner was launched in Nagano Prefecture, a rural area in Japan, in 1996. Since then, mobile screening units, primarily mounted on tractor trailers, have brought screening to centralized areas, such as shopping mall parking lots. The Levine Cancer Institute in Charlotte, North Carolina, also has a mobile CT-screening unit mounted in a modified box truck.

For Headrick and colleagues the goal was not to reinvent the wheel, but to see if a mobile lung cancer screening program could improve access and also pay for itself in a time of parsimonious support for preventive medicine.

Their first challenge was the mobile unit itself.

“CT scanners are sensitive, complex electrical machines that require climate control and a level environment to operate. Historically, they have been placed in tractor trailers and parked on level concrete slabs connected to external power supplies. We needed mobility, self-leveling, independent power, climate control, patient comfort, and drivability,” they wrote.

They assembled a team of engineers from CT and vehicle makers, and input was also provided by a thoracic surgeon, pulmonologist, radiologist, CT technician, and driver with a commercial driver’s license. Together, they designed and built the bus over 8 months. Funds for the total cost of the prototype vehicle ($650,000) came from two local nonprofit foundations. The estimated cost for a commercial version of the same vehicle was $850,000.

The Breathe Easy pilot began operation in early 2018, with the initial plan to drive the bus within a 2-hour radius of CHI Memorial Hospital, Chattanooga, Tennessee, to avoid overnight trips. The radius was later shortened to 1.5 hours when operators realized it was a burden for patients with significant screening findings to travel to as much as 4 hours (round trip) to Chattanooga for further testing.

Each screening visit takes about 15 minutes.
 

Cancer and other significant findings

As noted before, the bus traveled to 104 sites over 10 months, and 548 patients with a mean age of 62 were screened. Five lung cancers were identified, including two stage 1A, one stage 1A2, one stage 1B, and one stage 3A.

Two patients with early stage disease underwent stereotactic body radiation therapy, and two underwent minimally invasive surgery (a segmentectomy and a lobectomy). The patient with stage 3A disease underwent curative chemotherapy and radiation therapy. One patient with a type B1 thymoma underwent robotic-assisted thoracoscopic resection with en bloc pericardial resection and reconstruction.

A total of 51 patients had a significant pulmonary finding of Lung CT Screening Reporting and Data System (Lung-RADS) 3 or 4 and were advised to follow up with further testing, but 17 patients in this group did not pursue further testing. Of these 17 patients, 15 had been screened in a health clinic for the homeless at a rural site.

Significant nonpulmonary findings included moderate to severe coronary artery disease in 101 patients, abdominal findings in 15, thyroid abnormalities in 14, other thoracic findings in 10, and ascending aortic dilatation in 9. Of the 152 patients with nonpulmonary findings, only 13 required further testing and none required treatment.
 

Revisions, improvements, and priorities

The Breathe Easy bus has been in operation for more than 2 years, performing an average of approximately 100 screenings per month, with a goal of 200. The bus continued to operate throughout the COVID-19 pandemic because many patients viewed it as a safer alternative to a hospital visit, Headrick said.

Design changes planned to improve performance of the bus include a stronger chassis and structural components, as well as swapping out the 16-slice CT unit for a specially designed 64-slice mobile unit that can be operated with an iPad and provide gated coronary calcium scores.

When challenged about whether the cost of lung cancer screening is the best use of limited resources, Headrick said, “if it’s not, then when we need to go back to the drawing board and jump-start lung cancer screening.”

“When I spent a year in 2014-2015 trying to talk to radio stations, news stations, media, nobody really cared about lung cancer screening,” he said. “But as soon as I had this shiny object, which is the bus, which we labeled as the easiest and most valuable doctor visit, people had an interest.”

The pilot study was supported by local nonprofit foundations through the CHI Memorial Foundation.

This article first appeared on Medscape.com.

A bus converted into a mobile CT screening unit has been reaching high-risk individuals in underserved rural counties in Appalachian areas who may have otherwise not had a chance to be screened for lung cancer.

Results from a pilot study, published online July 13 in The Annals of Thoracic Surgery, show that the scheme is both practical and financially sustainable.

During a 10-month test run, the mobile unit screened 548 individuals at 104 sites. Five lung cancers (four of which were early stage) and a type B thymoma were discovered, and all of these individuals went on to have treatment.

Significant pulmonary findings were also discovered in 52 individuals, who were advised to undergo further testing, as well as significant nonpulmonary findings in 152 individuals (of whom 13 required further testing, but none went on to have treatment). These findings included severe coronary disease and thyroid abnormalities.

The bus reached the estimated financial break-even point of 428 scans, but future economic viability of such a program will likely rely on additional revenue from the treatment of patients with incidental findings from low-dose CT screens, acknowledged the authors, led by James R. Headrick Jr, MD, MBA, from the University of Tennessee College of Medicine in Chattanooga.

The real value of the Breathe Easy program, however, comes from bringing both patient education and lung cancer screening services to a high-risk population who might otherwise be overlooked, Headrick said in an interview with Medscape Medical News.

“We were all excited when lung screening was approved, and we got the recommendation from the United States Preventive Services Task Force [USPSTF], and the Centers for Medicare & Medicaid Services signed off on it, and we sat in our offices and clinics and hospitals — and nobody showed up. We were thinking, ‘Wow, we have this simple test, the easiest screening tool in the world, and nobody’s coming,’ “ he said.

“There was certainly an educational issue that needed to be solved,” he continued, “but we were also dealing with a population that had been told that if they smoked and didn’t live life well, there was a 100% chance they were going to get lung cancer and die,” he said.

The individuals screened in the program were very heavy smokers.

The mean pack-years of smoking was 41 — 11 pack-years higher than the minimum recommended under current lung cancer screening guidelines, and 21 pack-years higher than that recently recommended under proposed low-dose CT screening guidelines by the USPSTF.  

Albert Rizzo, MD, chief medical officer for the American Lung Association, who was not involved in the study, told Medscape Medical News any initiative that can expand lung cancer screening is welcome, particularly when a program may be self-sustaining.

“The interesting part of this article included the downstream revenue to help make something like this viable,” Rizzo said. “Just doing the scans is probably not going to cover the cost of the mobile unit itself, but if you take into account that other things are being found in addition to lung cancer, such as coronary abnormalities, then it becomes more cost-effective, especially if those patients are then treated at the site where the mobile unit is coming from,” he said.
 

Starting at square one

The first mobile CT scanner was launched in Nagano Prefecture, a rural area in Japan, in 1996. Since then, mobile screening units, primarily mounted on tractor trailers, have brought screening to centralized areas, such as shopping mall parking lots. The Levine Cancer Institute in Charlotte, North Carolina, also has a mobile CT-screening unit mounted in a modified box truck.

For Headrick and colleagues the goal was not to reinvent the wheel, but to see if a mobile lung cancer screening program could improve access and also pay for itself in a time of parsimonious support for preventive medicine.

Their first challenge was the mobile unit itself.

“CT scanners are sensitive, complex electrical machines that require climate control and a level environment to operate. Historically, they have been placed in tractor trailers and parked on level concrete slabs connected to external power supplies. We needed mobility, self-leveling, independent power, climate control, patient comfort, and drivability,” they wrote.

They assembled a team of engineers from CT and vehicle makers, and input was also provided by a thoracic surgeon, pulmonologist, radiologist, CT technician, and driver with a commercial driver’s license. Together, they designed and built the bus over 8 months. Funds for the total cost of the prototype vehicle ($650,000) came from two local nonprofit foundations. The estimated cost for a commercial version of the same vehicle was $850,000.

The Breathe Easy pilot began operation in early 2018, with the initial plan to drive the bus within a 2-hour radius of CHI Memorial Hospital, Chattanooga, Tennessee, to avoid overnight trips. The radius was later shortened to 1.5 hours when operators realized it was a burden for patients with significant screening findings to travel to as much as 4 hours (round trip) to Chattanooga for further testing.

Each screening visit takes about 15 minutes.
 

Cancer and other significant findings

As noted before, the bus traveled to 104 sites over 10 months, and 548 patients with a mean age of 62 were screened. Five lung cancers were identified, including two stage 1A, one stage 1A2, one stage 1B, and one stage 3A.

Two patients with early stage disease underwent stereotactic body radiation therapy, and two underwent minimally invasive surgery (a segmentectomy and a lobectomy). The patient with stage 3A disease underwent curative chemotherapy and radiation therapy. One patient with a type B1 thymoma underwent robotic-assisted thoracoscopic resection with en bloc pericardial resection and reconstruction.

A total of 51 patients had a significant pulmonary finding of Lung CT Screening Reporting and Data System (Lung-RADS) 3 or 4 and were advised to follow up with further testing, but 17 patients in this group did not pursue further testing. Of these 17 patients, 15 had been screened in a health clinic for the homeless at a rural site.

Significant nonpulmonary findings included moderate to severe coronary artery disease in 101 patients, abdominal findings in 15, thyroid abnormalities in 14, other thoracic findings in 10, and ascending aortic dilatation in 9. Of the 152 patients with nonpulmonary findings, only 13 required further testing and none required treatment.
 

Revisions, improvements, and priorities

The Breathe Easy bus has been in operation for more than 2 years, performing an average of approximately 100 screenings per month, with a goal of 200. The bus continued to operate throughout the COVID-19 pandemic because many patients viewed it as a safer alternative to a hospital visit, Headrick said.

Design changes planned to improve performance of the bus include a stronger chassis and structural components, as well as swapping out the 16-slice CT unit for a specially designed 64-slice mobile unit that can be operated with an iPad and provide gated coronary calcium scores.

When challenged about whether the cost of lung cancer screening is the best use of limited resources, Headrick said, “if it’s not, then when we need to go back to the drawing board and jump-start lung cancer screening.”

“When I spent a year in 2014-2015 trying to talk to radio stations, news stations, media, nobody really cared about lung cancer screening,” he said. “But as soon as I had this shiny object, which is the bus, which we labeled as the easiest and most valuable doctor visit, people had an interest.”

The pilot study was supported by local nonprofit foundations through the CHI Memorial Foundation.

This article first appeared on Medscape.com.

A bus converted into a mobile CT screening unit has been reaching high-risk individuals in underserved rural counties in Appalachian areas who may have otherwise not had a chance to be screened for lung cancer.

Results from a pilot study, published online July 13 in The Annals of Thoracic Surgery, show that the scheme is both practical and financially sustainable.

During a 10-month test run, the mobile unit screened 548 individuals at 104 sites. Five lung cancers (four of which were early stage) and a type B thymoma were discovered, and all of these individuals went on to have treatment.

Significant pulmonary findings were also discovered in 52 individuals, who were advised to undergo further testing, as well as significant nonpulmonary findings in 152 individuals (of whom 13 required further testing, but none went on to have treatment). These findings included severe coronary disease and thyroid abnormalities.

The bus reached the estimated financial break-even point of 428 scans, but future economic viability of such a program will likely rely on additional revenue from the treatment of patients with incidental findings from low-dose CT screens, acknowledged the authors, led by James R. Headrick Jr, MD, MBA, from the University of Tennessee College of Medicine in Chattanooga.

The real value of the Breathe Easy program, however, comes from bringing both patient education and lung cancer screening services to a high-risk population who might otherwise be overlooked, Headrick said in an interview with Medscape Medical News.

“We were all excited when lung screening was approved, and we got the recommendation from the United States Preventive Services Task Force [USPSTF], and the Centers for Medicare & Medicaid Services signed off on it, and we sat in our offices and clinics and hospitals — and nobody showed up. We were thinking, ‘Wow, we have this simple test, the easiest screening tool in the world, and nobody’s coming,’ “ he said.

“There was certainly an educational issue that needed to be solved,” he continued, “but we were also dealing with a population that had been told that if they smoked and didn’t live life well, there was a 100% chance they were going to get lung cancer and die,” he said.

The individuals screened in the program were very heavy smokers.

The mean pack-years of smoking was 41 — 11 pack-years higher than the minimum recommended under current lung cancer screening guidelines, and 21 pack-years higher than that recently recommended under proposed low-dose CT screening guidelines by the USPSTF.  

Albert Rizzo, MD, chief medical officer for the American Lung Association, who was not involved in the study, told Medscape Medical News any initiative that can expand lung cancer screening is welcome, particularly when a program may be self-sustaining.

“The interesting part of this article included the downstream revenue to help make something like this viable,” Rizzo said. “Just doing the scans is probably not going to cover the cost of the mobile unit itself, but if you take into account that other things are being found in addition to lung cancer, such as coronary abnormalities, then it becomes more cost-effective, especially if those patients are then treated at the site where the mobile unit is coming from,” he said.
 

Starting at square one

The first mobile CT scanner was launched in Nagano Prefecture, a rural area in Japan, in 1996. Since then, mobile screening units, primarily mounted on tractor trailers, have brought screening to centralized areas, such as shopping mall parking lots. The Levine Cancer Institute in Charlotte, North Carolina, also has a mobile CT-screening unit mounted in a modified box truck.

For Headrick and colleagues the goal was not to reinvent the wheel, but to see if a mobile lung cancer screening program could improve access and also pay for itself in a time of parsimonious support for preventive medicine.

Their first challenge was the mobile unit itself.

“CT scanners are sensitive, complex electrical machines that require climate control and a level environment to operate. Historically, they have been placed in tractor trailers and parked on level concrete slabs connected to external power supplies. We needed mobility, self-leveling, independent power, climate control, patient comfort, and drivability,” they wrote.

They assembled a team of engineers from CT and vehicle makers, and input was also provided by a thoracic surgeon, pulmonologist, radiologist, CT technician, and driver with a commercial driver’s license. Together, they designed and built the bus over 8 months. Funds for the total cost of the prototype vehicle ($650,000) came from two local nonprofit foundations. The estimated cost for a commercial version of the same vehicle was $850,000.

The Breathe Easy pilot began operation in early 2018, with the initial plan to drive the bus within a 2-hour radius of CHI Memorial Hospital, Chattanooga, Tennessee, to avoid overnight trips. The radius was later shortened to 1.5 hours when operators realized it was a burden for patients with significant screening findings to travel to as much as 4 hours (round trip) to Chattanooga for further testing.

Each screening visit takes about 15 minutes.
 

Cancer and other significant findings

As noted before, the bus traveled to 104 sites over 10 months, and 548 patients with a mean age of 62 were screened. Five lung cancers were identified, including two stage 1A, one stage 1A2, one stage 1B, and one stage 3A.

Two patients with early stage disease underwent stereotactic body radiation therapy, and two underwent minimally invasive surgery (a segmentectomy and a lobectomy). The patient with stage 3A disease underwent curative chemotherapy and radiation therapy. One patient with a type B1 thymoma underwent robotic-assisted thoracoscopic resection with en bloc pericardial resection and reconstruction.

A total of 51 patients had a significant pulmonary finding of Lung CT Screening Reporting and Data System (Lung-RADS) 3 or 4 and were advised to follow up with further testing, but 17 patients in this group did not pursue further testing. Of these 17 patients, 15 had been screened in a health clinic for the homeless at a rural site.

Significant nonpulmonary findings included moderate to severe coronary artery disease in 101 patients, abdominal findings in 15, thyroid abnormalities in 14, other thoracic findings in 10, and ascending aortic dilatation in 9. Of the 152 patients with nonpulmonary findings, only 13 required further testing and none required treatment.
 

Revisions, improvements, and priorities

The Breathe Easy bus has been in operation for more than 2 years, performing an average of approximately 100 screenings per month, with a goal of 200. The bus continued to operate throughout the COVID-19 pandemic because many patients viewed it as a safer alternative to a hospital visit, Headrick said.

Design changes planned to improve performance of the bus include a stronger chassis and structural components, as well as swapping out the 16-slice CT unit for a specially designed 64-slice mobile unit that can be operated with an iPad and provide gated coronary calcium scores.

When challenged about whether the cost of lung cancer screening is the best use of limited resources, Headrick said, “if it’s not, then when we need to go back to the drawing board and jump-start lung cancer screening.”

“When I spent a year in 2014-2015 trying to talk to radio stations, news stations, media, nobody really cared about lung cancer screening,” he said. “But as soon as I had this shiny object, which is the bus, which we labeled as the easiest and most valuable doctor visit, people had an interest.”

The pilot study was supported by local nonprofit foundations through the CHI Memorial Foundation.

This article first appeared on Medscape.com.

Clearance of circulating tumor DNA (ctDNA) correlates with longer progression-free survival (PFS) in patients with EGFR-mutant, MET-amplified non–small cell lung cancer (NSCLC) treated with EGFR- and MET-targeted therapies, according to an analysis of data from the phase 1b TATTON study.

The median PFS was 9.1 months for patients with ctDNA clearance and 3.9 months for those without ctDNA clearance three to four cycles after starting treatment with osimertinib, an EGFR tyrosine kinase inhibitor (TKI), and savolitinib, a MET TKI (P = 0.0146).

“[O]ur findings indicate that EGFR-mutant ctDNA clearance may be predictive of longer PFS for patients with EGFR-mutant, MET-amplified non–small cell lung cancer and detectable ctDNA at baseline,” said investigator Ryan Hartmaier, PhD, of AstraZeneca in Boston, Mass.

Dr. Hartmaier presented these findings at the AACR virtual meeting II.
 

Prior results of TATTON

Interim results of the TATTON study were published earlier this year (Lancet Oncol. 2020 Mar;21[3]:373-386). The trial enrolled patients with locally advanced or metastatic EGFR-mutant, MET-amplified NSCLC who had progressed on a prior EGFR TKI. Results included patients enrolled in parts B and D.

Part B consisted of patients who had previously received a third-generation EGFR TKI and patients who had not received a third-generation EGFR TKI and were either Thr790Met negative or Thr790Met positive. There were 144 patients in part B. All received oral osimertinib at 80 mg, 138 received savolitinib at 600 mg, and 8 received savolitinib at 300 mg daily. Part D included 42 patients who had not received a third-generation EGFR TKI and were Thr790Met negative. In this cohort, patients received osimertinib at 80 mg and savolitinib at 300 mg daily.

The objective response rate (all partial responses) was 48% in part B and 64% in part D. The median PFS was 7.6 months and 9.1 months, respectively.

Alexander E. Drilon, MD, of Memorial Sloan Kettering Cancer Center in New York said results of the TATTON study demonstrate that MET dependence is an actionable EGFR TKI resistance mechanism in EGFR-mutant lung cancers.

“We all would welcome the approval of an EGFR and MET TKI combination in the future,” Dr. Drilon said in a discussion of the study at the AACR meeting.

According to Dr. Hartmaier, MET-based resistance mechanisms are seen in up to 10% of patients with EGFR-mutated NSCLC following progression on first- and second-generation EGFR TKIs, and up to 25% of those progressing on osimertinib, a third-generation EGFR TKI.

“Nonclinical and clinical evidence suggests that combined treatment of a MET inhibitor and an EGFR TKI could overcome acquired MET-mediated resistance,” he said.
 

ctDNA analysis

Patients in the TATTON study had ctDNA samples collected at various time points from baseline through cycle five of treatment and until disease progression or treatment discontinuation.

Dr. Hartmaier’s analysis focused on ctDNA changes from baseline to day 1 of the third or fourth treatment cycle, time points at which the bulk of ctDNA could be observed, he said.

Among 34 evaluable patients in part B who received savolitinib at 600 mg, 22 had ctDNA clearance, and 12 had not. Among 16 evaluable patients in part D who received savolitinib at 300 mg, 13 had ctDNA clearance, and 3 had not.

Rates of ctDNA clearance were “remarkably similar” among the dosing groups, Dr. Hartmaier said.

In part B, the median PFS was 9.1 months for patients with ctDNA clearance and 3.9 months for patients without clearance (hazard ratio, 0.34; 95% confidence interval, 0.14-0.81; P = 0.0146).

Dr. Hartmaier did not present PFS results according to ctDNA clearance for patients in part D.

Dr. Drilon said serial ctDNA analyses can provide information on mechanisms of primary or acquired resistance, intra- and inter-tumoral heterogeneity, and the potential durability of benefit that can be achieved with combination targeted therapy. He acknowledged, however, that more work needs to be done in the field of MET-targeted therapy development.

“We need to work on standardizing diagnostic definitions of MET dependence, recognizing that loose definitions and poly-assay use make data challenging to interpret,” he said.

The TATTON study was supported by AstraZeneca. Dr. Hartmaier is an AstraZeneca employee and shareholder. Dr. Drilon disclosed relationships with AstraZeneca, Pfizer, Helsinn, Beigene, and other companies.

SOURCE: Hartmaier R, et al. AACR 2020, Abstract CT303.

Clearance of circulating tumor DNA (ctDNA) correlates with longer progression-free survival (PFS) in patients with EGFR-mutant, MET-amplified non–small cell lung cancer (NSCLC) treated with EGFR- and MET-targeted therapies, according to an analysis of data from the phase 1b TATTON study.

The median PFS was 9.1 months for patients with ctDNA clearance and 3.9 months for those without ctDNA clearance three to four cycles after starting treatment with osimertinib, an EGFR tyrosine kinase inhibitor (TKI), and savolitinib, a MET TKI (P = 0.0146).

“[O]ur findings indicate that EGFR-mutant ctDNA clearance may be predictive of longer PFS for patients with EGFR-mutant, MET-amplified non–small cell lung cancer and detectable ctDNA at baseline,” said investigator Ryan Hartmaier, PhD, of AstraZeneca in Boston, Mass.

Dr. Hartmaier presented these findings at the AACR virtual meeting II.
 

Prior results of TATTON

Interim results of the TATTON study were published earlier this year (Lancet Oncol. 2020 Mar;21[3]:373-386). The trial enrolled patients with locally advanced or metastatic EGFR-mutant, MET-amplified NSCLC who had progressed on a prior EGFR TKI. Results included patients enrolled in parts B and D.

Part B consisted of patients who had previously received a third-generation EGFR TKI and patients who had not received a third-generation EGFR TKI and were either Thr790Met negative or Thr790Met positive. There were 144 patients in part B. All received oral osimertinib at 80 mg, 138 received savolitinib at 600 mg, and 8 received savolitinib at 300 mg daily. Part D included 42 patients who had not received a third-generation EGFR TKI and were Thr790Met negative. In this cohort, patients received osimertinib at 80 mg and savolitinib at 300 mg daily.

The objective response rate (all partial responses) was 48% in part B and 64% in part D. The median PFS was 7.6 months and 9.1 months, respectively.

Alexander E. Drilon, MD, of Memorial Sloan Kettering Cancer Center in New York said results of the TATTON study demonstrate that MET dependence is an actionable EGFR TKI resistance mechanism in EGFR-mutant lung cancers.

“We all would welcome the approval of an EGFR and MET TKI combination in the future,” Dr. Drilon said in a discussion of the study at the AACR meeting.

According to Dr. Hartmaier, MET-based resistance mechanisms are seen in up to 10% of patients with EGFR-mutated NSCLC following progression on first- and second-generation EGFR TKIs, and up to 25% of those progressing on osimertinib, a third-generation EGFR TKI.

“Nonclinical and clinical evidence suggests that combined treatment of a MET inhibitor and an EGFR TKI could overcome acquired MET-mediated resistance,” he said.
 

ctDNA analysis

Patients in the TATTON study had ctDNA samples collected at various time points from baseline through cycle five of treatment and until disease progression or treatment discontinuation.

Dr. Hartmaier’s analysis focused on ctDNA changes from baseline to day 1 of the third or fourth treatment cycle, time points at which the bulk of ctDNA could be observed, he said.

Among 34 evaluable patients in part B who received savolitinib at 600 mg, 22 had ctDNA clearance, and 12 had not. Among 16 evaluable patients in part D who received savolitinib at 300 mg, 13 had ctDNA clearance, and 3 had not.

Rates of ctDNA clearance were “remarkably similar” among the dosing groups, Dr. Hartmaier said.

In part B, the median PFS was 9.1 months for patients with ctDNA clearance and 3.9 months for patients without clearance (hazard ratio, 0.34; 95% confidence interval, 0.14-0.81; P = 0.0146).

Dr. Hartmaier did not present PFS results according to ctDNA clearance for patients in part D.

Dr. Drilon said serial ctDNA analyses can provide information on mechanisms of primary or acquired resistance, intra- and inter-tumoral heterogeneity, and the potential durability of benefit that can be achieved with combination targeted therapy. He acknowledged, however, that more work needs to be done in the field of MET-targeted therapy development.

“We need to work on standardizing diagnostic definitions of MET dependence, recognizing that loose definitions and poly-assay use make data challenging to interpret,” he said.

The TATTON study was supported by AstraZeneca. Dr. Hartmaier is an AstraZeneca employee and shareholder. Dr. Drilon disclosed relationships with AstraZeneca, Pfizer, Helsinn, Beigene, and other companies.

SOURCE: Hartmaier R, et al. AACR 2020, Abstract CT303.

Clearance of circulating tumor DNA (ctDNA) correlates with longer progression-free survival (PFS) in patients with EGFR-mutant, MET-amplified non–small cell lung cancer (NSCLC) treated with EGFR- and MET-targeted therapies, according to an analysis of data from the phase 1b TATTON study.

The median PFS was 9.1 months for patients with ctDNA clearance and 3.9 months for those without ctDNA clearance three to four cycles after starting treatment with osimertinib, an EGFR tyrosine kinase inhibitor (TKI), and savolitinib, a MET TKI (P = 0.0146).

“[O]ur findings indicate that EGFR-mutant ctDNA clearance may be predictive of longer PFS for patients with EGFR-mutant, MET-amplified non–small cell lung cancer and detectable ctDNA at baseline,” said investigator Ryan Hartmaier, PhD, of AstraZeneca in Boston, Mass.

Dr. Hartmaier presented these findings at the AACR virtual meeting II.
 

Prior results of TATTON

Interim results of the TATTON study were published earlier this year (Lancet Oncol. 2020 Mar;21[3]:373-386). The trial enrolled patients with locally advanced or metastatic EGFR-mutant, MET-amplified NSCLC who had progressed on a prior EGFR TKI. Results included patients enrolled in parts B and D.

Part B consisted of patients who had previously received a third-generation EGFR TKI and patients who had not received a third-generation EGFR TKI and were either Thr790Met negative or Thr790Met positive. There were 144 patients in part B. All received oral osimertinib at 80 mg, 138 received savolitinib at 600 mg, and 8 received savolitinib at 300 mg daily. Part D included 42 patients who had not received a third-generation EGFR TKI and were Thr790Met negative. In this cohort, patients received osimertinib at 80 mg and savolitinib at 300 mg daily.

The objective response rate (all partial responses) was 48% in part B and 64% in part D. The median PFS was 7.6 months and 9.1 months, respectively.

Alexander E. Drilon, MD, of Memorial Sloan Kettering Cancer Center in New York said results of the TATTON study demonstrate that MET dependence is an actionable EGFR TKI resistance mechanism in EGFR-mutant lung cancers.

“We all would welcome the approval of an EGFR and MET TKI combination in the future,” Dr. Drilon said in a discussion of the study at the AACR meeting.

According to Dr. Hartmaier, MET-based resistance mechanisms are seen in up to 10% of patients with EGFR-mutated NSCLC following progression on first- and second-generation EGFR TKIs, and up to 25% of those progressing on osimertinib, a third-generation EGFR TKI.

“Nonclinical and clinical evidence suggests that combined treatment of a MET inhibitor and an EGFR TKI could overcome acquired MET-mediated resistance,” he said.
 

ctDNA analysis

Patients in the TATTON study had ctDNA samples collected at various time points from baseline through cycle five of treatment and until disease progression or treatment discontinuation.

Dr. Hartmaier’s analysis focused on ctDNA changes from baseline to day 1 of the third or fourth treatment cycle, time points at which the bulk of ctDNA could be observed, he said.

Among 34 evaluable patients in part B who received savolitinib at 600 mg, 22 had ctDNA clearance, and 12 had not. Among 16 evaluable patients in part D who received savolitinib at 300 mg, 13 had ctDNA clearance, and 3 had not.

Rates of ctDNA clearance were “remarkably similar” among the dosing groups, Dr. Hartmaier said.

In part B, the median PFS was 9.1 months for patients with ctDNA clearance and 3.9 months for patients without clearance (hazard ratio, 0.34; 95% confidence interval, 0.14-0.81; P = 0.0146).

Dr. Hartmaier did not present PFS results according to ctDNA clearance for patients in part D.

Dr. Drilon said serial ctDNA analyses can provide information on mechanisms of primary or acquired resistance, intra- and inter-tumoral heterogeneity, and the potential durability of benefit that can be achieved with combination targeted therapy. He acknowledged, however, that more work needs to be done in the field of MET-targeted therapy development.

“We need to work on standardizing diagnostic definitions of MET dependence, recognizing that loose definitions and poly-assay use make data challenging to interpret,” he said.

The TATTON study was supported by AstraZeneca. Dr. Hartmaier is an AstraZeneca employee and shareholder. Dr. Drilon disclosed relationships with AstraZeneca, Pfizer, Helsinn, Beigene, and other companies.

SOURCE: Hartmaier R, et al. AACR 2020, Abstract CT303.

Proposed changes in the eligibility criteria for lung cancer screening with low-dose CT could result in a near doubling of eligibility, and could especially benefit Black persons and women, say lung cancer experts.

The new proposals include lowering the age at which screening starts from 55 to 50 years, and to reduce the smoking history from 30 to 20 pack-years.

The draft recommendation from the United States Preventive Service Task Force (USPSTF) is available for public comment until August 3.

The task force recommends that adults age 50 to 80 who have a 20 pack-year or greater smoking history and currently smoke or have quit within the last 15 years undergo annual screening for lung cancer with low-dose CT,

“In my opinion, the proposed criteria by USPSTF represent a huge step in the right direction,” Lecia Sequist, MD, director of innovation at the Mass General Cancer Center in Boston, told Medscape Medical News.

“If these are adopted and implemented, we could see the benefit of screening (measured as reduction in lung cancer mortality) go from 9.8% with current parameters up to 13% with the broader parameters,” she said. “In addition, the new criteria should reduce racial disparities in screening eligibility.”

The recommendation also earned high marks from the American Lung Association.

The USPSTF has continued its ‘B’ recommendation – allowing for coverage of the screening with no cost for many under the Affordable Care Act – and is now proposing to expand the eligibility criteria “so that even more Americans at higher risk for lung cancer can be screened,” the ALA commented.

Start screening at 50  

Lowering the minimum age of screening to 50 would likely mean that more Black individuals and women would be eligible for screening, the recommendation authors contend. The current screening age of 55 is currently recommended under guidelines issued by the American Association for Thoracic Surgery, American Cancer Society, American College of Chest Physicians, and National Comprehensive Cancer Network.

“African Americans have a higher risk of lung cancer, compared with whites, and this risk difference is more apparent at lower levels of smoking intensity,” they write.

As previously reported by Medscape Medical News, lung cancer screening in an urban, largely black cohort yielded roughly double the rates of positive screens and detected lung cancers compared with results from the National Lung Screening Trial, which enrolled mostly White individuals.

In addition, although lung cancer risk is greater for men than women who smoke, and women generally accumulate fewer pack-years than men, there is evidence to suggest that women who smoke may develop lung cancer earlier and with lower levels of exposure.

Therefore, “a strategy of screening persons ages 50 to 80 years who have at least a 20 pack-year smoking history and currently smoke or have quit within the past 15 years (A-50-80-20-15) would lead to a relative increase in the percentage of persons eligible for screening by 81% in men and by 96% in women,” the proposed recommendation states.

What’s the harm?

One of the major concerns about low-dose CT screening for lung cancer is the relatively high rate of false-positive results reported in two large scale clinical trials, the recommendation authors acknowledged.

For example, in the NLST, which was the basis for an earlier USPSTF recommendation (for annual screening of adults 55 to 80 years of age who have a 30 pack-year smoking history and currently smoke or have quit in the previous 15 years), the false-positive rates were 26.3% at baseline, 27.2% at year 1, and 15.9% at year 2.

Similarly, in the NELSON trial, results of which were published earlier this year, false-positive rates for men were 19.8% at baseline, 7.1% at year 1, 9% at year 3, and 3.9% at year 5.5 of screening, they noted.

“Yes, false-positive results are one of the things we need to think carefully about when embarking on lung screening,” Dr. Sequist told Medscape Medical News. “The potential harm of a false-positive (unnecessary scans, biopsies or even surgery) can be minimized by having a multidisciplinary team with experience working up lung nodules see patients who have a positive screening test. In fact, the American College of Radiology recommends that all lung screening programs be paired with such a team.”

Mass General has a pulmonary nodule clinic to evaluate screen-detected lung nodules, with the goal of minimizing unnecessary procedures, she noted.

Asked about the potential harm from radiation exposure, Sequist said that exposure from low-dose CT screening is fairly minimal, comparable to that from solar radiation at sea level over a 6-month period, or about the level from three cross-country airplane trips.

“While it is not zero radiation, there is very little concern that this low level of radiation would cause a cancer or damage one’s lungs,” she said.

Albert Rizzo, MD, chief medical officer of the ALA, said that the potential harms of unnecessary interventions are outweighed by the benefits of detecting lung cancer at an early stage.

“I think what has been learned over the last 5 years is that the original recommendations that were put out really allowed the overall rate of positivity well within what’s seen with mammography, for example, and the number of patients who have needlessly gone on to procedures remains very low, and the morbidity of those procedures remains low as well,” Dr. Rizzo told Medscape Medical News.

Not enough takers

Despite the clear benefits of low-dose CT screening, however, US screening rates for high-risk individuals are still very low, ranging from 12.3% in Massachusetts to a low of 0.5% in Nevada, according to a 2019 research report on the state of lung cancer from the ALA.

“For screening to be most effective, more of the high-risk population should be screened. Currently, screening rates are very low among those at high risk. This may be because of a lack of access or low awareness and knowledge among patients and providers. As rates vary tremendously between states, it is clear that more can be done to increase screening rates,” the report stated.

“I think that there are some mixed messages sent out into the population as to whether or not an individual patient should be screened,” Dr. Rizzo said.

He noted that some physicians may be reluctant to take on the nuanced risk–benefit discussion required, or may not have the time during a brief patient visit.

“It really boils down to that discussion between the physician and the patient who falls under these risk categories, to say, ‘Look, this is what these studies have found, and you fall under a category where if we find a cancer early, it’s very likely you’re going to be saved,’ as compared for waiting for it to present by itself,” he said.

Dr. Sequist and Dr. Rizzo have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Proposed changes in the eligibility criteria for lung cancer screening with low-dose CT could result in a near doubling of eligibility, and could especially benefit Black persons and women, say lung cancer experts.

The new proposals include lowering the age at which screening starts from 55 to 50 years, and to reduce the smoking history from 30 to 20 pack-years.

The draft recommendation from the United States Preventive Service Task Force (USPSTF) is available for public comment until August 3.

The task force recommends that adults age 50 to 80 who have a 20 pack-year or greater smoking history and currently smoke or have quit within the last 15 years undergo annual screening for lung cancer with low-dose CT,

“In my opinion, the proposed criteria by USPSTF represent a huge step in the right direction,” Lecia Sequist, MD, director of innovation at the Mass General Cancer Center in Boston, told Medscape Medical News.

“If these are adopted and implemented, we could see the benefit of screening (measured as reduction in lung cancer mortality) go from 9.8% with current parameters up to 13% with the broader parameters,” she said. “In addition, the new criteria should reduce racial disparities in screening eligibility.”

The recommendation also earned high marks from the American Lung Association.

The USPSTF has continued its ‘B’ recommendation – allowing for coverage of the screening with no cost for many under the Affordable Care Act – and is now proposing to expand the eligibility criteria “so that even more Americans at higher risk for lung cancer can be screened,” the ALA commented.

Start screening at 50  

Lowering the minimum age of screening to 50 would likely mean that more Black individuals and women would be eligible for screening, the recommendation authors contend. The current screening age of 55 is currently recommended under guidelines issued by the American Association for Thoracic Surgery, American Cancer Society, American College of Chest Physicians, and National Comprehensive Cancer Network.

“African Americans have a higher risk of lung cancer, compared with whites, and this risk difference is more apparent at lower levels of smoking intensity,” they write.

As previously reported by Medscape Medical News, lung cancer screening in an urban, largely black cohort yielded roughly double the rates of positive screens and detected lung cancers compared with results from the National Lung Screening Trial, which enrolled mostly White individuals.

In addition, although lung cancer risk is greater for men than women who smoke, and women generally accumulate fewer pack-years than men, there is evidence to suggest that women who smoke may develop lung cancer earlier and with lower levels of exposure.

Therefore, “a strategy of screening persons ages 50 to 80 years who have at least a 20 pack-year smoking history and currently smoke or have quit within the past 15 years (A-50-80-20-15) would lead to a relative increase in the percentage of persons eligible for screening by 81% in men and by 96% in women,” the proposed recommendation states.

What’s the harm?

One of the major concerns about low-dose CT screening for lung cancer is the relatively high rate of false-positive results reported in two large scale clinical trials, the recommendation authors acknowledged.

For example, in the NLST, which was the basis for an earlier USPSTF recommendation (for annual screening of adults 55 to 80 years of age who have a 30 pack-year smoking history and currently smoke or have quit in the previous 15 years), the false-positive rates were 26.3% at baseline, 27.2% at year 1, and 15.9% at year 2.

Similarly, in the NELSON trial, results of which were published earlier this year, false-positive rates for men were 19.8% at baseline, 7.1% at year 1, 9% at year 3, and 3.9% at year 5.5 of screening, they noted.

“Yes, false-positive results are one of the things we need to think carefully about when embarking on lung screening,” Dr. Sequist told Medscape Medical News. “The potential harm of a false-positive (unnecessary scans, biopsies or even surgery) can be minimized by having a multidisciplinary team with experience working up lung nodules see patients who have a positive screening test. In fact, the American College of Radiology recommends that all lung screening programs be paired with such a team.”

Mass General has a pulmonary nodule clinic to evaluate screen-detected lung nodules, with the goal of minimizing unnecessary procedures, she noted.

Asked about the potential harm from radiation exposure, Sequist said that exposure from low-dose CT screening is fairly minimal, comparable to that from solar radiation at sea level over a 6-month period, or about the level from three cross-country airplane trips.

“While it is not zero radiation, there is very little concern that this low level of radiation would cause a cancer or damage one’s lungs,” she said.

Albert Rizzo, MD, chief medical officer of the ALA, said that the potential harms of unnecessary interventions are outweighed by the benefits of detecting lung cancer at an early stage.

“I think what has been learned over the last 5 years is that the original recommendations that were put out really allowed the overall rate of positivity well within what’s seen with mammography, for example, and the number of patients who have needlessly gone on to procedures remains very low, and the morbidity of those procedures remains low as well,” Dr. Rizzo told Medscape Medical News.

Not enough takers

Despite the clear benefits of low-dose CT screening, however, US screening rates for high-risk individuals are still very low, ranging from 12.3% in Massachusetts to a low of 0.5% in Nevada, according to a 2019 research report on the state of lung cancer from the ALA.

“For screening to be most effective, more of the high-risk population should be screened. Currently, screening rates are very low among those at high risk. This may be because of a lack of access or low awareness and knowledge among patients and providers. As rates vary tremendously between states, it is clear that more can be done to increase screening rates,” the report stated.

“I think that there are some mixed messages sent out into the population as to whether or not an individual patient should be screened,” Dr. Rizzo said.

He noted that some physicians may be reluctant to take on the nuanced risk–benefit discussion required, or may not have the time during a brief patient visit.

“It really boils down to that discussion between the physician and the patient who falls under these risk categories, to say, ‘Look, this is what these studies have found, and you fall under a category where if we find a cancer early, it’s very likely you’re going to be saved,’ as compared for waiting for it to present by itself,” he said.

Dr. Sequist and Dr. Rizzo have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Proposed changes in the eligibility criteria for lung cancer screening with low-dose CT could result in a near doubling of eligibility, and could especially benefit Black persons and women, say lung cancer experts.

The new proposals include lowering the age at which screening starts from 55 to 50 years, and to reduce the smoking history from 30 to 20 pack-years.

The draft recommendation from the United States Preventive Service Task Force (USPSTF) is available for public comment until August 3.

The task force recommends that adults age 50 to 80 who have a 20 pack-year or greater smoking history and currently smoke or have quit within the last 15 years undergo annual screening for lung cancer with low-dose CT,

“In my opinion, the proposed criteria by USPSTF represent a huge step in the right direction,” Lecia Sequist, MD, director of innovation at the Mass General Cancer Center in Boston, told Medscape Medical News.

“If these are adopted and implemented, we could see the benefit of screening (measured as reduction in lung cancer mortality) go from 9.8% with current parameters up to 13% with the broader parameters,” she said. “In addition, the new criteria should reduce racial disparities in screening eligibility.”

The recommendation also earned high marks from the American Lung Association.

The USPSTF has continued its ‘B’ recommendation – allowing for coverage of the screening with no cost for many under the Affordable Care Act – and is now proposing to expand the eligibility criteria “so that even more Americans at higher risk for lung cancer can be screened,” the ALA commented.

Start screening at 50  

Lowering the minimum age of screening to 50 would likely mean that more Black individuals and women would be eligible for screening, the recommendation authors contend. The current screening age of 55 is currently recommended under guidelines issued by the American Association for Thoracic Surgery, American Cancer Society, American College of Chest Physicians, and National Comprehensive Cancer Network.

“African Americans have a higher risk of lung cancer, compared with whites, and this risk difference is more apparent at lower levels of smoking intensity,” they write.

As previously reported by Medscape Medical News, lung cancer screening in an urban, largely black cohort yielded roughly double the rates of positive screens and detected lung cancers compared with results from the National Lung Screening Trial, which enrolled mostly White individuals.

In addition, although lung cancer risk is greater for men than women who smoke, and women generally accumulate fewer pack-years than men, there is evidence to suggest that women who smoke may develop lung cancer earlier and with lower levels of exposure.

Therefore, “a strategy of screening persons ages 50 to 80 years who have at least a 20 pack-year smoking history and currently smoke or have quit within the past 15 years (A-50-80-20-15) would lead to a relative increase in the percentage of persons eligible for screening by 81% in men and by 96% in women,” the proposed recommendation states.

What’s the harm?

One of the major concerns about low-dose CT screening for lung cancer is the relatively high rate of false-positive results reported in two large scale clinical trials, the recommendation authors acknowledged.

For example, in the NLST, which was the basis for an earlier USPSTF recommendation (for annual screening of adults 55 to 80 years of age who have a 30 pack-year smoking history and currently smoke or have quit in the previous 15 years), the false-positive rates were 26.3% at baseline, 27.2% at year 1, and 15.9% at year 2.

Similarly, in the NELSON trial, results of which were published earlier this year, false-positive rates for men were 19.8% at baseline, 7.1% at year 1, 9% at year 3, and 3.9% at year 5.5 of screening, they noted.

“Yes, false-positive results are one of the things we need to think carefully about when embarking on lung screening,” Dr. Sequist told Medscape Medical News. “The potential harm of a false-positive (unnecessary scans, biopsies or even surgery) can be minimized by having a multidisciplinary team with experience working up lung nodules see patients who have a positive screening test. In fact, the American College of Radiology recommends that all lung screening programs be paired with such a team.”

Mass General has a pulmonary nodule clinic to evaluate screen-detected lung nodules, with the goal of minimizing unnecessary procedures, she noted.

Asked about the potential harm from radiation exposure, Sequist said that exposure from low-dose CT screening is fairly minimal, comparable to that from solar radiation at sea level over a 6-month period, or about the level from three cross-country airplane trips.

“While it is not zero radiation, there is very little concern that this low level of radiation would cause a cancer or damage one’s lungs,” she said.

Albert Rizzo, MD, chief medical officer of the ALA, said that the potential harms of unnecessary interventions are outweighed by the benefits of detecting lung cancer at an early stage.

“I think what has been learned over the last 5 years is that the original recommendations that were put out really allowed the overall rate of positivity well within what’s seen with mammography, for example, and the number of patients who have needlessly gone on to procedures remains very low, and the morbidity of those procedures remains low as well,” Dr. Rizzo told Medscape Medical News.

Not enough takers

Despite the clear benefits of low-dose CT screening, however, US screening rates for high-risk individuals are still very low, ranging from 12.3% in Massachusetts to a low of 0.5% in Nevada, according to a 2019 research report on the state of lung cancer from the ALA.

“For screening to be most effective, more of the high-risk population should be screened. Currently, screening rates are very low among those at high risk. This may be because of a lack of access or low awareness and knowledge among patients and providers. As rates vary tremendously between states, it is clear that more can be done to increase screening rates,” the report stated.

“I think that there are some mixed messages sent out into the population as to whether or not an individual patient should be screened,” Dr. Rizzo said.

He noted that some physicians may be reluctant to take on the nuanced risk–benefit discussion required, or may not have the time during a brief patient visit.

“It really boils down to that discussion between the physician and the patient who falls under these risk categories, to say, ‘Look, this is what these studies have found, and you fall under a category where if we find a cancer early, it’s very likely you’re going to be saved,’ as compared for waiting for it to present by itself,” he said.

Dr. Sequist and Dr. Rizzo have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Among adults who drink alcohol at relatively high amounts, regular weekly physical activity may reduce the mortality risk posed by alcohol-related cancers, concludes a new observational study involving 50,000-plus British adults.

Being physically active – for example, by walking, house cleaning, or playing a sport – could be promoted as a risk-minimization measure for alcohol-related cancers, say the authors, led by Emmanuel Stamatakis, PhD, professor of Physical Activity, Lifestyle, and Population Health, University of Sydney, Australia.

The researchers found a “strong direct association between alcohol consumption and mortality risk of [10] alcohol-related cancers.”

Specifically, when compared with never drinkers, there was a significantly higher risk of dying from such cancers among drinkers who consumed “hazardous” and “harmful” amounts of alcohol, and also for ex-drinkers.

Notably, occasional drinkers and drinkers within guidelines did not have statistically significantly higher risks for alcohol-related cancer mortality.

But the analysis also found that among the bigger drinkers, the risks were “substantially attenuated” in physically active participants who met at least the lower recommended limit of activity (>7.5 metabolic equivalent task [MET]–hours/week).

That’s not a taxing amount of activity because, for example, general household cleaning results in 3 METs/hour and walking slowly translates into 2 METs/hour. However, nearly a quarter of survey participants reported no physical activity.

The study was published online May 14 in the International Journal of Cancer.

The new results require confirmation because the findings “are limited in their statistical power,” with small numbers of cases in several categories, said Alpa Patel, PhD, an epidemiologist at the American Cancer Society, who was not involved in the study. For example, there were only 55 alcohol-related cancer deaths among the 1540 harmful drinkers.

Patel stressed that, “based on the collective evidence to date, it is best to both avoid alcohol consumption and engage in sufficient amounts of physical activity.” That amount is 150-300 minutes of moderate or 75-150 minutes of vigorous activity per week for cancer prevention.

Her message about abstinence is in-line with new ACS guidelines issued last month, as reported by Medscape Medical News. The ACS’s guidance was criticized by many readers in the comments section, who repeatedly encouraged “moderation.”

However, the ACS also recommended moderation, saying, for those adults who do drink, intake should be no more than 1 drink/day for women or 2 drinks/day for men. 

Study author Dr. Stamatakis commented on the alcohol debate.

“Any advice for complete abstinence is bound to alienate many people,” he told Medscape Medical News in an email. “Alcohol drinking has been an integral part of many societies for thousands of years.”

Dr. Stamatakis, who is an occasional beer drinker, also said, “there is no healthy level of alcohol drinking.”

This was also the conclusion of a 2018 study published in the Lancet, which stated that there is “no safe limit,” as even one drink a day increases the risk of cancer. A few years earlier, the 2014 World Cancer Report found a dose-response relationship between alcohol consumption and certain cancers.

However, epidemiological findings are not necessarily “clinically relevant,” commented Jennifer Ligibel, MD, a medical oncologist at the Dana-Farber Cancer Institute, Boston, Massachusetts, in a 2018 interview with Medscape Medical News.

Dr. Ligibel explained that there are 50 years of studies linking alcohol and cancers. “With the huge amount of data we have, even small differences [in consumption] are statistically significant.”

Dr. Ligibel cited an often-repeated statistic: for the average woman, there is a 12% lifetime risk of breast cancer. “If a woman consumes a drink a day, which is considered a low-level intake, that risk may become about 13% – which is statistically significant,” Dr. Ligibel explained.

But that risk increase is not clinically relevant, she added.

Mean 10 years of follow-up

The new study is the first to examine physical activity, drinking, and the 10 cancers that have been linked to alcohol consumption (oral cavity, throat, larynx, esophagus, liver, colorectal, stomach, breast, pancreas, and lung).

The authors used data from 10 British population-based health surveys from 1994-2008 and looked at adults aged 30 years and older. The mean follow-up period was 9.9 years.

Among 54,686 participants, there were 2039 alcohol-related site-specific cancer deaths.

Alcohol consumption categories were based on U.K. guidelines, with 1 unit equal to 8 grams (about 2 ounces) of pure alcohol. The categories were as follows: drinking within guidelines (<14 units/week for women, <21 units/week for men), hazardous level (14-35 units/week for women, 21-49 units/week for men), and harmful level (> 35 units/week for women, >49 units/week for men). The survey also queried participants about being ex-drinkers, occasional drinkers, and never drinkers.

Physical activity was assessed using self-reported accounts of the 4 weeks preceding the health survey and intensity of activity (light, moderate, or vigorous) was queried. Physical activity was categorized using the upper (15 MET-hours/week) and lower (the aforementioned <7 MET-hours/week) recommended limits.

The median age of participants was 51 years; 7.9% were never drinkers and 14.7% exceeded guideline amounts. For physical activity, 23% reported none. The median level of activity was 9 MET-hours/week.

The authors say that the “increased risks [among the harmful, hazardous, and ex-drinker categories] were eliminated” among the individuals who reported physical activity >7.5 MET-hours/week. That meant the hazard ratios for cancer mortality for each category were reduced to the point that they were no longer statistically significant.

For example, for all drinkers in the “hazardous” category, the risk of cancer-related mortality was significantly higher than for nondrinkers (with a hazard ratio of 1.39), but in the subgroup of these participants who were physically active at the lower recommended limit, the hazard ratio dropped to 1.21.

These “broad patterns of effect modification by physical activity persisted when the upper physical activity limit [15 MET-hours/week] was used,” write the authors.

The new study adds to the literature on cancer mortality and alcohol consumption. In another recent study, researchers looked at eight British cohorts and reported overall cancer mortality associated with alcohol consumption was eliminated among those meeting physical activity recommendations (Br J Sports Med. 2017;51:651-7). The new study added two more cohorts to this base of eight and only focused on cancers that have been linked to alcohol consumption. The earlier study included deaths from all types of cancer.

The refinement of focus in the current study is important, say Dr. Stamatakis and colleagues.

“This specificity adds biological plausibility and permits a more immediate translation of our findings into policy and practice,” they write. 

Dr. Stamatakis practices what he advocates, but is not a teetotaler.

“I exercise (e.g., dynamic yoga, HIIT cardio workouts, run, cycle, lift weights) for 45-60 minutes a day and I walk 8,000-14,000 steps daily. That would categorize me perhaps in the top 3%-5% for my age/sex group. And I enjoy 1-2 cans of craft beer a couple of times a week,” he said in an email.

Dr. Stamatakis and Dr. Patel have reported no relevant financial relationships.

This article first appeared on Medscape.com.

Among adults who drink alcohol at relatively high amounts, regular weekly physical activity may reduce the mortality risk posed by alcohol-related cancers, concludes a new observational study involving 50,000-plus British adults.

Being physically active – for example, by walking, house cleaning, or playing a sport – could be promoted as a risk-minimization measure for alcohol-related cancers, say the authors, led by Emmanuel Stamatakis, PhD, professor of Physical Activity, Lifestyle, and Population Health, University of Sydney, Australia.

The researchers found a “strong direct association between alcohol consumption and mortality risk of [10] alcohol-related cancers.”

Specifically, when compared with never drinkers, there was a significantly higher risk of dying from such cancers among drinkers who consumed “hazardous” and “harmful” amounts of alcohol, and also for ex-drinkers.

Notably, occasional drinkers and drinkers within guidelines did not have statistically significantly higher risks for alcohol-related cancer mortality.

But the analysis also found that among the bigger drinkers, the risks were “substantially attenuated” in physically active participants who met at least the lower recommended limit of activity (>7.5 metabolic equivalent task [MET]–hours/week).

That’s not a taxing amount of activity because, for example, general household cleaning results in 3 METs/hour and walking slowly translates into 2 METs/hour. However, nearly a quarter of survey participants reported no physical activity.

The study was published online May 14 in the International Journal of Cancer.

The new results require confirmation because the findings “are limited in their statistical power,” with small numbers of cases in several categories, said Alpa Patel, PhD, an epidemiologist at the American Cancer Society, who was not involved in the study. For example, there were only 55 alcohol-related cancer deaths among the 1540 harmful drinkers.

Patel stressed that, “based on the collective evidence to date, it is best to both avoid alcohol consumption and engage in sufficient amounts of physical activity.” That amount is 150-300 minutes of moderate or 75-150 minutes of vigorous activity per week for cancer prevention.

Her message about abstinence is in-line with new ACS guidelines issued last month, as reported by Medscape Medical News. The ACS’s guidance was criticized by many readers in the comments section, who repeatedly encouraged “moderation.”

However, the ACS also recommended moderation, saying, for those adults who do drink, intake should be no more than 1 drink/day for women or 2 drinks/day for men. 

Study author Dr. Stamatakis commented on the alcohol debate.

“Any advice for complete abstinence is bound to alienate many people,” he told Medscape Medical News in an email. “Alcohol drinking has been an integral part of many societies for thousands of years.”

Dr. Stamatakis, who is an occasional beer drinker, also said, “there is no healthy level of alcohol drinking.”

This was also the conclusion of a 2018 study published in the Lancet, which stated that there is “no safe limit,” as even one drink a day increases the risk of cancer. A few years earlier, the 2014 World Cancer Report found a dose-response relationship between alcohol consumption and certain cancers.

However, epidemiological findings are not necessarily “clinically relevant,” commented Jennifer Ligibel, MD, a medical oncologist at the Dana-Farber Cancer Institute, Boston, Massachusetts, in a 2018 interview with Medscape Medical News.

Dr. Ligibel explained that there are 50 years of studies linking alcohol and cancers. “With the huge amount of data we have, even small differences [in consumption] are statistically significant.”

Dr. Ligibel cited an often-repeated statistic: for the average woman, there is a 12% lifetime risk of breast cancer. “If a woman consumes a drink a day, which is considered a low-level intake, that risk may become about 13% – which is statistically significant,” Dr. Ligibel explained.

But that risk increase is not clinically relevant, she added.

Mean 10 years of follow-up

The new study is the first to examine physical activity, drinking, and the 10 cancers that have been linked to alcohol consumption (oral cavity, throat, larynx, esophagus, liver, colorectal, stomach, breast, pancreas, and lung).

The authors used data from 10 British population-based health surveys from 1994-2008 and looked at adults aged 30 years and older. The mean follow-up period was 9.9 years.

Among 54,686 participants, there were 2039 alcohol-related site-specific cancer deaths.

Alcohol consumption categories were based on U.K. guidelines, with 1 unit equal to 8 grams (about 2 ounces) of pure alcohol. The categories were as follows: drinking within guidelines (<14 units/week for women, <21 units/week for men), hazardous level (14-35 units/week for women, 21-49 units/week for men), and harmful level (> 35 units/week for women, >49 units/week for men). The survey also queried participants about being ex-drinkers, occasional drinkers, and never drinkers.

Physical activity was assessed using self-reported accounts of the 4 weeks preceding the health survey and intensity of activity (light, moderate, or vigorous) was queried. Physical activity was categorized using the upper (15 MET-hours/week) and lower (the aforementioned <7 MET-hours/week) recommended limits.

The median age of participants was 51 years; 7.9% were never drinkers and 14.7% exceeded guideline amounts. For physical activity, 23% reported none. The median level of activity was 9 MET-hours/week.

The authors say that the “increased risks [among the harmful, hazardous, and ex-drinker categories] were eliminated” among the individuals who reported physical activity >7.5 MET-hours/week. That meant the hazard ratios for cancer mortality for each category were reduced to the point that they were no longer statistically significant.

For example, for all drinkers in the “hazardous” category, the risk of cancer-related mortality was significantly higher than for nondrinkers (with a hazard ratio of 1.39), but in the subgroup of these participants who were physically active at the lower recommended limit, the hazard ratio dropped to 1.21.

These “broad patterns of effect modification by physical activity persisted when the upper physical activity limit [15 MET-hours/week] was used,” write the authors.

The new study adds to the literature on cancer mortality and alcohol consumption. In another recent study, researchers looked at eight British cohorts and reported overall cancer mortality associated with alcohol consumption was eliminated among those meeting physical activity recommendations (Br J Sports Med. 2017;51:651-7). The new study added two more cohorts to this base of eight and only focused on cancers that have been linked to alcohol consumption. The earlier study included deaths from all types of cancer.

The refinement of focus in the current study is important, say Dr. Stamatakis and colleagues.

“This specificity adds biological plausibility and permits a more immediate translation of our findings into policy and practice,” they write. 

Dr. Stamatakis practices what he advocates, but is not a teetotaler.

“I exercise (e.g., dynamic yoga, HIIT cardio workouts, run, cycle, lift weights) for 45-60 minutes a day and I walk 8,000-14,000 steps daily. That would categorize me perhaps in the top 3%-5% for my age/sex group. And I enjoy 1-2 cans of craft beer a couple of times a week,” he said in an email.

Dr. Stamatakis and Dr. Patel have reported no relevant financial relationships.

This article first appeared on Medscape.com.

Among adults who drink alcohol at relatively high amounts, regular weekly physical activity may reduce the mortality risk posed by alcohol-related cancers, concludes a new observational study involving 50,000-plus British adults.

Being physically active – for example, by walking, house cleaning, or playing a sport – could be promoted as a risk-minimization measure for alcohol-related cancers, say the authors, led by Emmanuel Stamatakis, PhD, professor of Physical Activity, Lifestyle, and Population Health, University of Sydney, Australia.

The researchers found a “strong direct association between alcohol consumption and mortality risk of [10] alcohol-related cancers.”

Specifically, when compared with never drinkers, there was a significantly higher risk of dying from such cancers among drinkers who consumed “hazardous” and “harmful” amounts of alcohol, and also for ex-drinkers.

Notably, occasional drinkers and drinkers within guidelines did not have statistically significantly higher risks for alcohol-related cancer mortality.

But the analysis also found that among the bigger drinkers, the risks were “substantially attenuated” in physically active participants who met at least the lower recommended limit of activity (>7.5 metabolic equivalent task [MET]–hours/week).

That’s not a taxing amount of activity because, for example, general household cleaning results in 3 METs/hour and walking slowly translates into 2 METs/hour. However, nearly a quarter of survey participants reported no physical activity.

The study was published online May 14 in the International Journal of Cancer.

The new results require confirmation because the findings “are limited in their statistical power,” with small numbers of cases in several categories, said Alpa Patel, PhD, an epidemiologist at the American Cancer Society, who was not involved in the study. For example, there were only 55 alcohol-related cancer deaths among the 1540 harmful drinkers.

Patel stressed that, “based on the collective evidence to date, it is best to both avoid alcohol consumption and engage in sufficient amounts of physical activity.” That amount is 150-300 minutes of moderate or 75-150 minutes of vigorous activity per week for cancer prevention.

Her message about abstinence is in-line with new ACS guidelines issued last month, as reported by Medscape Medical News. The ACS’s guidance was criticized by many readers in the comments section, who repeatedly encouraged “moderation.”

However, the ACS also recommended moderation, saying, for those adults who do drink, intake should be no more than 1 drink/day for women or 2 drinks/day for men. 

Study author Dr. Stamatakis commented on the alcohol debate.

“Any advice for complete abstinence is bound to alienate many people,” he told Medscape Medical News in an email. “Alcohol drinking has been an integral part of many societies for thousands of years.”

Dr. Stamatakis, who is an occasional beer drinker, also said, “there is no healthy level of alcohol drinking.”

This was also the conclusion of a 2018 study published in the Lancet, which stated that there is “no safe limit,” as even one drink a day increases the risk of cancer. A few years earlier, the 2014 World Cancer Report found a dose-response relationship between alcohol consumption and certain cancers.

However, epidemiological findings are not necessarily “clinically relevant,” commented Jennifer Ligibel, MD, a medical oncologist at the Dana-Farber Cancer Institute, Boston, Massachusetts, in a 2018 interview with Medscape Medical News.

Dr. Ligibel explained that there are 50 years of studies linking alcohol and cancers. “With the huge amount of data we have, even small differences [in consumption] are statistically significant.”

Dr. Ligibel cited an often-repeated statistic: for the average woman, there is a 12% lifetime risk of breast cancer. “If a woman consumes a drink a day, which is considered a low-level intake, that risk may become about 13% – which is statistically significant,” Dr. Ligibel explained.

But that risk increase is not clinically relevant, she added.

Mean 10 years of follow-up

The new study is the first to examine physical activity, drinking, and the 10 cancers that have been linked to alcohol consumption (oral cavity, throat, larynx, esophagus, liver, colorectal, stomach, breast, pancreas, and lung).

The authors used data from 10 British population-based health surveys from 1994-2008 and looked at adults aged 30 years and older. The mean follow-up period was 9.9 years.

Among 54,686 participants, there were 2039 alcohol-related site-specific cancer deaths.

Alcohol consumption categories were based on U.K. guidelines, with 1 unit equal to 8 grams (about 2 ounces) of pure alcohol. The categories were as follows: drinking within guidelines (<14 units/week for women, <21 units/week for men), hazardous level (14-35 units/week for women, 21-49 units/week for men), and harmful level (> 35 units/week for women, >49 units/week for men). The survey also queried participants about being ex-drinkers, occasional drinkers, and never drinkers.

Physical activity was assessed using self-reported accounts of the 4 weeks preceding the health survey and intensity of activity (light, moderate, or vigorous) was queried. Physical activity was categorized using the upper (15 MET-hours/week) and lower (the aforementioned <7 MET-hours/week) recommended limits.

The median age of participants was 51 years; 7.9% were never drinkers and 14.7% exceeded guideline amounts. For physical activity, 23% reported none. The median level of activity was 9 MET-hours/week.

The authors say that the “increased risks [among the harmful, hazardous, and ex-drinker categories] were eliminated” among the individuals who reported physical activity >7.5 MET-hours/week. That meant the hazard ratios for cancer mortality for each category were reduced to the point that they were no longer statistically significant.

For example, for all drinkers in the “hazardous” category, the risk of cancer-related mortality was significantly higher than for nondrinkers (with a hazard ratio of 1.39), but in the subgroup of these participants who were physically active at the lower recommended limit, the hazard ratio dropped to 1.21.

These “broad patterns of effect modification by physical activity persisted when the upper physical activity limit [15 MET-hours/week] was used,” write the authors.

The new study adds to the literature on cancer mortality and alcohol consumption. In another recent study, researchers looked at eight British cohorts and reported overall cancer mortality associated with alcohol consumption was eliminated among those meeting physical activity recommendations (Br J Sports Med. 2017;51:651-7). The new study added two more cohorts to this base of eight and only focused on cancers that have been linked to alcohol consumption. The earlier study included deaths from all types of cancer.

The refinement of focus in the current study is important, say Dr. Stamatakis and colleagues.

“This specificity adds biological plausibility and permits a more immediate translation of our findings into policy and practice,” they write. 

Dr. Stamatakis practices what he advocates, but is not a teetotaler.

“I exercise (e.g., dynamic yoga, HIIT cardio workouts, run, cycle, lift weights) for 45-60 minutes a day and I walk 8,000-14,000 steps daily. That would categorize me perhaps in the top 3%-5% for my age/sex group. And I enjoy 1-2 cans of craft beer a couple of times a week,” he said in an email.

Dr. Stamatakis and Dr. Patel have reported no relevant financial relationships.

This article first appeared on Medscape.com.

Radiomics, a growing area of cancer research that extracts noninvasive biomarkers from medical imaging, may be able to improve lung cancer screening by identifying patients with early stage disease at high risk for poorer outcomes.

This is the conclusion from a group of researchers who used data from the National Lung Screening Trial (NLST) to develop and validate a model based on radiomics that could identify a vulnerable high-risk group of early stage patients associated with poor outcomes. These patients would generally require aggressive follow-up and/or adjuvant therapy.

The study was published June 29 in Nature Scientific Reports.

Radiomics, also known as quantitative image features, are noninvasive biomarkers that are generated from medical imaging. An emerging translational field of research, radiomics extracts large amounts of features from radiographic medical images using data-characterization algorithms, which reflect the underlying tumor pathophysiology and heterogeneity.

The authors note that radiomics has many advantages over circulating and tissue-based biomarkers, as these quantitative image features are rapidly calculated from standard-of-care imaging and reflect the entire tumor burden – and not just a sample as is the case with tissue-based biomarkers.

“We view radiomics as a decision support tool across the cancer control continuum, whether it be screening and early detection, diagnosis, prognostication, or treatment response,” said lead author Matthew B. Schabath, PhD, associate member in cancer epidemiology at the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Florida.

“Radiomic features are generated from standard-of-care imaging and validated radiomic models can provide real-time decision support information to clinicians,” he explained.

Last year, another study showed that combining radiomics and imaging may be able to determine which patients with lung cancer were most likely to respond to chemotherapy. The researchers used CT imaging of radiomic features from within and outside the lung nodule and found it could predict time to progression and overall survival, as well as response to chemotherapy, in patients with non–small cell lung cancer (NSCLC).

Anant Madabhushi, PhD, a professor of biomedical engineering and director of the Center for Computational Imaging and Personalized Diagnostics at Case Western Reserve University, Cleveland, commented that the new study is “complementary and supports the premise that radiomics both from inside and outside the tumor can tell us about outcome and treatment response.”

Dr. Madabhushi also noted his group has released several other studies along similar lines, including a study showing how radiomics can predict the benefit of adjuvant therapy in lung cancer, a study showing how radiomics can predict recurrence in early stage NSCLC, and a study showing that radiomics can predict survival and response to immunotherapy in NSCLC.

Improving current lung cancer screening

The landmark NLST showed that, as compared with chest x-rays, low-dose helical computed tomography (LDCT) was associated with a 20% relative reduction in lung cancer mortality in high-risk individuals. However, LDCT screening can lead to overdiagnosis and subsequent overtreatment of slow-growing, indolent cancers.

“Current lung cancer screening inclusion criteria in the US are largely based on the criteria used in the NLST,” Dr. Schabath told Medscape Medical News. “Though the NLST clearly demonstrated that screening LDCT is a lifesaving tool, the NLST was not designed to create public policy.”

He pointed out that fewer than 30% of Americans diagnosed with lung cancer meet the current screening entry criteria and that subsequent trials (e.g., NELSON, LUSI, or MILD) used broader and more inclusive criteria and also showed the efficacy of LDCT for early detection of lung cancer. “Thus, there should be consideration in making the lung cancer screening guidelines more inclusive,” said Dr. Schabath.

“Additionally, adjunct risk-stratification tools, such as blood-based biomarkers, could be an important complement to determine who should be part of a lung cancer screening program,” he said. “This could be particularly salient for people who have no or very few risk factors, such as never smokers.”

Pinpointing poor outcomes

In the current study, Dr. Schabath and colleagues used publicly available data and LDCT images from the NLST to generate radiomic features from screen detected, incidentally-diagnosed lung cancers. Radiomic features describing size, shape, volume, and textural characteristics were then calculated from both the intratumoral and peritumoral regions.

Patients were divided into training and test cohorts, and an external cohort of non-screen-detected lung cancer patients was used for further validation. There were no statistically significant differences between training and test cohorts for most demographics, including age, sex, smoking status, number of pack-years smoked, treatment, stage, and baseline screening result. However, self-reported chronic obstructive pulmonary disease (COPD) was significantly higher in the test cohort compared with the training group (16% vs. 7%; P = .02).

A total of 91 stable and reproducible radiomics features (peritumoral and intratumoral) were identified and 40 (26 peritumoral and 14 intratumoral) were significantly associated with overall survival in the training cohort. The features were subsequently narrowed to four, and backward elimination analyses identified a single model. Patients were then stratified into three risk-groups: low risk, intermediate risk, and high risk.

According to their model, the high-risk group had worse overall survival (hazard ratio, 9.91; 25% 2.5-year and 0% 5-year OS) as compared with the low-risk group (HR, 1.00; 93% 2.5-year and 78% 5-year OS).

The final model was validated in the test group and then replicated in the non–screen-detected patients with adenocarcinoma patients. Since the disease stage differed significantly across the risk groups, the model was stratified by stage and the authors found “compelling” results among early-stage patients, who generally have good outcomes. In this subset, the high-risk group was associated with a worse overall survival (HR, 2.63; 56% 2.5-year and 42% 5-year OS) vs. the low-risk group (HR, 1.00; 75% 2.5-year and 75% 5-year OS).

“We have ongoing studies to determine if these results are consistent in the real-world setting of lung cancer screening across multiple centers,” said Dr. Schabath. “If the NELSON, LUSI, or MILD trial data become publicly available, we will certainly pursue validating our results in those clinical trials.”

The study was funded by the National Cancer Institute. Dr. Schabath and Dr. Madabhushi have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Radiomics, a growing area of cancer research that extracts noninvasive biomarkers from medical imaging, may be able to improve lung cancer screening by identifying patients with early stage disease at high risk for poorer outcomes.

This is the conclusion from a group of researchers who used data from the National Lung Screening Trial (NLST) to develop and validate a model based on radiomics that could identify a vulnerable high-risk group of early stage patients associated with poor outcomes. These patients would generally require aggressive follow-up and/or adjuvant therapy.

The study was published June 29 in Nature Scientific Reports.

Radiomics, also known as quantitative image features, are noninvasive biomarkers that are generated from medical imaging. An emerging translational field of research, radiomics extracts large amounts of features from radiographic medical images using data-characterization algorithms, which reflect the underlying tumor pathophysiology and heterogeneity.

The authors note that radiomics has many advantages over circulating and tissue-based biomarkers, as these quantitative image features are rapidly calculated from standard-of-care imaging and reflect the entire tumor burden – and not just a sample as is the case with tissue-based biomarkers.

“We view radiomics as a decision support tool across the cancer control continuum, whether it be screening and early detection, diagnosis, prognostication, or treatment response,” said lead author Matthew B. Schabath, PhD, associate member in cancer epidemiology at the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Florida.

“Radiomic features are generated from standard-of-care imaging and validated radiomic models can provide real-time decision support information to clinicians,” he explained.

Last year, another study showed that combining radiomics and imaging may be able to determine which patients with lung cancer were most likely to respond to chemotherapy. The researchers used CT imaging of radiomic features from within and outside the lung nodule and found it could predict time to progression and overall survival, as well as response to chemotherapy, in patients with non–small cell lung cancer (NSCLC).

Anant Madabhushi, PhD, a professor of biomedical engineering and director of the Center for Computational Imaging and Personalized Diagnostics at Case Western Reserve University, Cleveland, commented that the new study is “complementary and supports the premise that radiomics both from inside and outside the tumor can tell us about outcome and treatment response.”

Dr. Madabhushi also noted his group has released several other studies along similar lines, including a study showing how radiomics can predict the benefit of adjuvant therapy in lung cancer, a study showing how radiomics can predict recurrence in early stage NSCLC, and a study showing that radiomics can predict survival and response to immunotherapy in NSCLC.

Improving current lung cancer screening

The landmark NLST showed that, as compared with chest x-rays, low-dose helical computed tomography (LDCT) was associated with a 20% relative reduction in lung cancer mortality in high-risk individuals. However, LDCT screening can lead to overdiagnosis and subsequent overtreatment of slow-growing, indolent cancers.

“Current lung cancer screening inclusion criteria in the US are largely based on the criteria used in the NLST,” Dr. Schabath told Medscape Medical News. “Though the NLST clearly demonstrated that screening LDCT is a lifesaving tool, the NLST was not designed to create public policy.”

He pointed out that fewer than 30% of Americans diagnosed with lung cancer meet the current screening entry criteria and that subsequent trials (e.g., NELSON, LUSI, or MILD) used broader and more inclusive criteria and also showed the efficacy of LDCT for early detection of lung cancer. “Thus, there should be consideration in making the lung cancer screening guidelines more inclusive,” said Dr. Schabath.

“Additionally, adjunct risk-stratification tools, such as blood-based biomarkers, could be an important complement to determine who should be part of a lung cancer screening program,” he said. “This could be particularly salient for people who have no or very few risk factors, such as never smokers.”

Pinpointing poor outcomes

In the current study, Dr. Schabath and colleagues used publicly available data and LDCT images from the NLST to generate radiomic features from screen detected, incidentally-diagnosed lung cancers. Radiomic features describing size, shape, volume, and textural characteristics were then calculated from both the intratumoral and peritumoral regions.

Patients were divided into training and test cohorts, and an external cohort of non-screen-detected lung cancer patients was used for further validation. There were no statistically significant differences between training and test cohorts for most demographics, including age, sex, smoking status, number of pack-years smoked, treatment, stage, and baseline screening result. However, self-reported chronic obstructive pulmonary disease (COPD) was significantly higher in the test cohort compared with the training group (16% vs. 7%; P = .02).

A total of 91 stable and reproducible radiomics features (peritumoral and intratumoral) were identified and 40 (26 peritumoral and 14 intratumoral) were significantly associated with overall survival in the training cohort. The features were subsequently narrowed to four, and backward elimination analyses identified a single model. Patients were then stratified into three risk-groups: low risk, intermediate risk, and high risk.

According to their model, the high-risk group had worse overall survival (hazard ratio, 9.91; 25% 2.5-year and 0% 5-year OS) as compared with the low-risk group (HR, 1.00; 93% 2.5-year and 78% 5-year OS).

The final model was validated in the test group and then replicated in the non–screen-detected patients with adenocarcinoma patients. Since the disease stage differed significantly across the risk groups, the model was stratified by stage and the authors found “compelling” results among early-stage patients, who generally have good outcomes. In this subset, the high-risk group was associated with a worse overall survival (HR, 2.63; 56% 2.5-year and 42% 5-year OS) vs. the low-risk group (HR, 1.00; 75% 2.5-year and 75% 5-year OS).

“We have ongoing studies to determine if these results are consistent in the real-world setting of lung cancer screening across multiple centers,” said Dr. Schabath. “If the NELSON, LUSI, or MILD trial data become publicly available, we will certainly pursue validating our results in those clinical trials.”

The study was funded by the National Cancer Institute. Dr. Schabath and Dr. Madabhushi have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Radiomics, a growing area of cancer research that extracts noninvasive biomarkers from medical imaging, may be able to improve lung cancer screening by identifying patients with early stage disease at high risk for poorer outcomes.

This is the conclusion from a group of researchers who used data from the National Lung Screening Trial (NLST) to develop and validate a model based on radiomics that could identify a vulnerable high-risk group of early stage patients associated with poor outcomes. These patients would generally require aggressive follow-up and/or adjuvant therapy.

The study was published June 29 in Nature Scientific Reports.

Radiomics, also known as quantitative image features, are noninvasive biomarkers that are generated from medical imaging. An emerging translational field of research, radiomics extracts large amounts of features from radiographic medical images using data-characterization algorithms, which reflect the underlying tumor pathophysiology and heterogeneity.

The authors note that radiomics has many advantages over circulating and tissue-based biomarkers, as these quantitative image features are rapidly calculated from standard-of-care imaging and reflect the entire tumor burden – and not just a sample as is the case with tissue-based biomarkers.

“We view radiomics as a decision support tool across the cancer control continuum, whether it be screening and early detection, diagnosis, prognostication, or treatment response,” said lead author Matthew B. Schabath, PhD, associate member in cancer epidemiology at the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Florida.

“Radiomic features are generated from standard-of-care imaging and validated radiomic models can provide real-time decision support information to clinicians,” he explained.

Last year, another study showed that combining radiomics and imaging may be able to determine which patients with lung cancer were most likely to respond to chemotherapy. The researchers used CT imaging of radiomic features from within and outside the lung nodule and found it could predict time to progression and overall survival, as well as response to chemotherapy, in patients with non–small cell lung cancer (NSCLC).

Anant Madabhushi, PhD, a professor of biomedical engineering and director of the Center for Computational Imaging and Personalized Diagnostics at Case Western Reserve University, Cleveland, commented that the new study is “complementary and supports the premise that radiomics both from inside and outside the tumor can tell us about outcome and treatment response.”

Dr. Madabhushi also noted his group has released several other studies along similar lines, including a study showing how radiomics can predict the benefit of adjuvant therapy in lung cancer, a study showing how radiomics can predict recurrence in early stage NSCLC, and a study showing that radiomics can predict survival and response to immunotherapy in NSCLC.

Improving current lung cancer screening

The landmark NLST showed that, as compared with chest x-rays, low-dose helical computed tomography (LDCT) was associated with a 20% relative reduction in lung cancer mortality in high-risk individuals. However, LDCT screening can lead to overdiagnosis and subsequent overtreatment of slow-growing, indolent cancers.

“Current lung cancer screening inclusion criteria in the US are largely based on the criteria used in the NLST,” Dr. Schabath told Medscape Medical News. “Though the NLST clearly demonstrated that screening LDCT is a lifesaving tool, the NLST was not designed to create public policy.”

He pointed out that fewer than 30% of Americans diagnosed with lung cancer meet the current screening entry criteria and that subsequent trials (e.g., NELSON, LUSI, or MILD) used broader and more inclusive criteria and also showed the efficacy of LDCT for early detection of lung cancer. “Thus, there should be consideration in making the lung cancer screening guidelines more inclusive,” said Dr. Schabath.

“Additionally, adjunct risk-stratification tools, such as blood-based biomarkers, could be an important complement to determine who should be part of a lung cancer screening program,” he said. “This could be particularly salient for people who have no or very few risk factors, such as never smokers.”

Pinpointing poor outcomes

In the current study, Dr. Schabath and colleagues used publicly available data and LDCT images from the NLST to generate radiomic features from screen detected, incidentally-diagnosed lung cancers. Radiomic features describing size, shape, volume, and textural characteristics were then calculated from both the intratumoral and peritumoral regions.

Patients were divided into training and test cohorts, and an external cohort of non-screen-detected lung cancer patients was used for further validation. There were no statistically significant differences between training and test cohorts for most demographics, including age, sex, smoking status, number of pack-years smoked, treatment, stage, and baseline screening result. However, self-reported chronic obstructive pulmonary disease (COPD) was significantly higher in the test cohort compared with the training group (16% vs. 7%; P = .02).

A total of 91 stable and reproducible radiomics features (peritumoral and intratumoral) were identified and 40 (26 peritumoral and 14 intratumoral) were significantly associated with overall survival in the training cohort. The features were subsequently narrowed to four, and backward elimination analyses identified a single model. Patients were then stratified into three risk-groups: low risk, intermediate risk, and high risk.

According to their model, the high-risk group had worse overall survival (hazard ratio, 9.91; 25% 2.5-year and 0% 5-year OS) as compared with the low-risk group (HR, 1.00; 93% 2.5-year and 78% 5-year OS).

The final model was validated in the test group and then replicated in the non–screen-detected patients with adenocarcinoma patients. Since the disease stage differed significantly across the risk groups, the model was stratified by stage and the authors found “compelling” results among early-stage patients, who generally have good outcomes. In this subset, the high-risk group was associated with a worse overall survival (HR, 2.63; 56% 2.5-year and 42% 5-year OS) vs. the low-risk group (HR, 1.00; 75% 2.5-year and 75% 5-year OS).

“We have ongoing studies to determine if these results are consistent in the real-world setting of lung cancer screening across multiple centers,” said Dr. Schabath. “If the NELSON, LUSI, or MILD trial data become publicly available, we will certainly pursue validating our results in those clinical trials.”

The study was funded by the National Cancer Institute. Dr. Schabath and Dr. Madabhushi have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The Food and Drug Administration recently announced two new types of cancer that can be treated by the anti–PD-1 antibody pembrolizumab.

The new indications expand the use of pembrolizumab (Keytruda) to include treatment of patients with unresectable or metastatic tumor mutational burden–high (TMB-H) solid tumors as well as patients with cutaneous squamous cell carcinoma (cSCC). The FDA announced the new indications just 8 days apart, on June 16 and June 24.

In addition, on June 29, the FDA approved a third new indication for pembrolizumab, this time as first-line treatment for patients with unresectable or metastatic microsatellite instability–high or mismatch repair–deficient colorectal cancer.



The new approvals add to a wide range of oncology indications for which pembrolizumab can be used.

Accelerated approval to treat solid tumors

The FDA granted accelerated approval for pembrolizumab to treat children and adults with unresectable or metastatic TMB-H solid tumors that progressed after previous treatment or in instances where there are no satisfactory alternative treatment options.

The tumor mutational burden must be confirmed by an FDA-approved test. To that end, the FDA approved the FoundationOneCDx assay, which is designed to help physicians determine which patients meet the threshold for TMB-H malignancies (10 or more mutations per megabase).

The efficacy of pembrolizumab in TMB-H solid tumors was investigated in 10 cohorts from the multicenter, open-label KEYNOTE-158 trial. Participants received 200 mg of pembrolizumab intravenously every 3 weeks until their disease progressed or they experienced unacceptable toxicity.

Within this population, 102 patients had tumors that met the TMB-H definition. In this group, the overall response rate was 29%, including a 25% partial response rate and a 4% complete response rate.

The median duration of response was not reached, but 57% of participants experienced a response lasting 12 months or longer, and 50% had a response lasting 24 months or longer.

The most common adverse events associated with pembrolizumab in this trial were fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain. Pembrolizumab is associated with immune-mediated side effects, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin adverse reactions, the FDA noted.

Safety and efficacy of pembrolizumab in pediatric patients with TMB-H central nervous system cancers have not been established.
 

New option for recurrent or metastatic cSCC

Physicians treating patients with cSCC that is not curable by surgery or radiation now have pembrolizumab to consider as another treatment option.

The cSCC approval is based on results of the multicenter, open-label KEYNOTE-629 trial. The dosage regimen was 200 mg of pembrolizumab intravenously every 3 weeks until cancer progressed, unacceptable toxicity arose, or 24 months of treatment were completed.

The objective response rate was 34%, and the median duration of response was not reached.

Adverse events were similar to those occurring in patients who received pembrolizumab as a single agent in other clinical trials, the FDA noted.

The Food and Drug Administration recently announced two new types of cancer that can be treated by the anti–PD-1 antibody pembrolizumab.

The new indications expand the use of pembrolizumab (Keytruda) to include treatment of patients with unresectable or metastatic tumor mutational burden–high (TMB-H) solid tumors as well as patients with cutaneous squamous cell carcinoma (cSCC). The FDA announced the new indications just 8 days apart, on June 16 and June 24.

In addition, on June 29, the FDA approved a third new indication for pembrolizumab, this time as first-line treatment for patients with unresectable or metastatic microsatellite instability–high or mismatch repair–deficient colorectal cancer.



The new approvals add to a wide range of oncology indications for which pembrolizumab can be used.

Accelerated approval to treat solid tumors

The FDA granted accelerated approval for pembrolizumab to treat children and adults with unresectable or metastatic TMB-H solid tumors that progressed after previous treatment or in instances where there are no satisfactory alternative treatment options.

The tumor mutational burden must be confirmed by an FDA-approved test. To that end, the FDA approved the FoundationOneCDx assay, which is designed to help physicians determine which patients meet the threshold for TMB-H malignancies (10 or more mutations per megabase).

The efficacy of pembrolizumab in TMB-H solid tumors was investigated in 10 cohorts from the multicenter, open-label KEYNOTE-158 trial. Participants received 200 mg of pembrolizumab intravenously every 3 weeks until their disease progressed or they experienced unacceptable toxicity.

Within this population, 102 patients had tumors that met the TMB-H definition. In this group, the overall response rate was 29%, including a 25% partial response rate and a 4% complete response rate.

The median duration of response was not reached, but 57% of participants experienced a response lasting 12 months or longer, and 50% had a response lasting 24 months or longer.

The most common adverse events associated with pembrolizumab in this trial were fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain. Pembrolizumab is associated with immune-mediated side effects, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin adverse reactions, the FDA noted.

Safety and efficacy of pembrolizumab in pediatric patients with TMB-H central nervous system cancers have not been established.
 

New option for recurrent or metastatic cSCC

Physicians treating patients with cSCC that is not curable by surgery or radiation now have pembrolizumab to consider as another treatment option.

The cSCC approval is based on results of the multicenter, open-label KEYNOTE-629 trial. The dosage regimen was 200 mg of pembrolizumab intravenously every 3 weeks until cancer progressed, unacceptable toxicity arose, or 24 months of treatment were completed.

The objective response rate was 34%, and the median duration of response was not reached.

Adverse events were similar to those occurring in patients who received pembrolizumab as a single agent in other clinical trials, the FDA noted.

The Food and Drug Administration recently announced two new types of cancer that can be treated by the anti–PD-1 antibody pembrolizumab.

The new indications expand the use of pembrolizumab (Keytruda) to include treatment of patients with unresectable or metastatic tumor mutational burden–high (TMB-H) solid tumors as well as patients with cutaneous squamous cell carcinoma (cSCC). The FDA announced the new indications just 8 days apart, on June 16 and June 24.

In addition, on June 29, the FDA approved a third new indication for pembrolizumab, this time as first-line treatment for patients with unresectable or metastatic microsatellite instability–high or mismatch repair–deficient colorectal cancer.



The new approvals add to a wide range of oncology indications for which pembrolizumab can be used.

Accelerated approval to treat solid tumors

The FDA granted accelerated approval for pembrolizumab to treat children and adults with unresectable or metastatic TMB-H solid tumors that progressed after previous treatment or in instances where there are no satisfactory alternative treatment options.

The tumor mutational burden must be confirmed by an FDA-approved test. To that end, the FDA approved the FoundationOneCDx assay, which is designed to help physicians determine which patients meet the threshold for TMB-H malignancies (10 or more mutations per megabase).

The efficacy of pembrolizumab in TMB-H solid tumors was investigated in 10 cohorts from the multicenter, open-label KEYNOTE-158 trial. Participants received 200 mg of pembrolizumab intravenously every 3 weeks until their disease progressed or they experienced unacceptable toxicity.

Within this population, 102 patients had tumors that met the TMB-H definition. In this group, the overall response rate was 29%, including a 25% partial response rate and a 4% complete response rate.

The median duration of response was not reached, but 57% of participants experienced a response lasting 12 months or longer, and 50% had a response lasting 24 months or longer.

The most common adverse events associated with pembrolizumab in this trial were fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain. Pembrolizumab is associated with immune-mediated side effects, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin adverse reactions, the FDA noted.

Safety and efficacy of pembrolizumab in pediatric patients with TMB-H central nervous system cancers have not been established.
 

New option for recurrent or metastatic cSCC

Physicians treating patients with cSCC that is not curable by surgery or radiation now have pembrolizumab to consider as another treatment option.

The cSCC approval is based on results of the multicenter, open-label KEYNOTE-629 trial. The dosage regimen was 200 mg of pembrolizumab intravenously every 3 weeks until cancer progressed, unacceptable toxicity arose, or 24 months of treatment were completed.

The objective response rate was 34%, and the median duration of response was not reached.

Adverse events were similar to those occurring in patients who received pembrolizumab as a single agent in other clinical trials, the FDA noted.