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Global melanoma incidence high and on the rise
Even by cautious calculations,
An estimated 325,000 people worldwide received a new diagnosis of cutaneous melanoma in 2020, and if present trends continue, the incidence of new cases is predicted to increase by about 50% in 2040, with melanoma deaths expected to rise by almost 70%, Melina Arnold, PhD, from the Cancer Surveillance Branch of the International Agency for Research on Cancer in Lyon, France, and colleagues reported.
“Melanoma is the most lethal form of skin cancer; this epidemiological assessment found a heavy public health and economic burden, and our projections suggest that it will remain so in the coming decades,” they wrote in a study published online in JAMA Dermatology.
In an accompanying editorial, Mavis Obeng-Kusi, MPharm and Ivo Abraham, PhD from the Center for Health Outcomes and PharmacoEconomic Research at the University of Arizona, Tucson, commented that the findings are “sobering,” but may substantially underestimate the gravity of the problem in low- and middle-income countries (LMIC).
“The study by Arnold et al. brings to the fore a public health concern that requires global attention and initiates conversations particularly related to LMIC settings, where the incidence and mortality of melanoma is thought to be minimal and for which preventive measures may be insufficient,” they wrote.
Down Under nations lead
Dr. Arnold and colleagues looked at data on age-standardized melanoma incidence and mortality rates per 100,000 person-years (PY) by country, each of 20 world regions as defined by the United Nations, and according to the UN’s four-tier Human Development Index, which stratifies countries into low-, medium-, high-, and very high–income categories.
As noted previously, the researchers estimated that there were 325,000 new melanoma cases worldwide in 2020 (174,000 cases in males and 151,000 in females). There were 57,000 estimated melanoma deaths the same year (32,000 in males and 25,000 in females.
The highest incidence rates were seen in Australia and New Zealand, at 42 per 100,000 PY among males and 31 per 100,000 PY in females, followed by Western Europe with 19 per 100,000 PY in both males and females, North America with 18 and 14 cases per 100,000 PY in males and females respectively, and Northern Europe, with 17 per 100,000 PY in males, and 18 per 100,000 PY in females.
In contrast, in most African and Asian countries melanoma was rare, with rates commonly less than 1 per 100,000 PY, the investigators noted.
The melanoma mortality rate was highest in New Zealand, at 5 per 100,000 PY. Mortality rates worldwide varied less widely than incidence rates. In most other regions of the world, mortality rates were “much lower,” ranging between 0.2-1.0 per 100,000 PY, they wrote.
The authors estimated that, if 2020 rates remain stable, the global burden from melanoma in 2040 will increase to approximately 510,000 new cases and 96,000 deaths.
Public health efforts needed
In their editorial, Ms. Obeng-Kusi and Dr. Abraham pointed out that the study was hampered by the limited availability of cancer data from LMICs, leading the authors to estimate incidence and mortality rates based on proxy data, such as statistical modeling or averaged rates from neighboring countries.
They emphasized the need for going beyond the statistics: “Specific to cutaneous melanoma data, what is most important globally, knowing the exact numbers of cases and deaths or understanding the order of magnitude of the present and future epidemiology? No doubt the latter. Melanoma can be treated more easily if caught at earlier stages.”
Projections such as those provided by Dr. Arnold and colleagues could help to raise awareness of the importance of decreasing exposure to UV radiation, which accounts for three-fourths of all incident melanomas, the editorialists said.
The study was funded in part by a grant to coauthor Anna E. Cust, PhD, MPH. Dr. Cust reported receiving a fellowship from the Australian National Health and Medical Research Council outside the submitted work. Dr. Arnold had no conflicts of interested to disclose. Dr. Abraham reported financial relationships with various entities. Ms. Obeng-Kusi had no disclosures.
Even by cautious calculations,
An estimated 325,000 people worldwide received a new diagnosis of cutaneous melanoma in 2020, and if present trends continue, the incidence of new cases is predicted to increase by about 50% in 2040, with melanoma deaths expected to rise by almost 70%, Melina Arnold, PhD, from the Cancer Surveillance Branch of the International Agency for Research on Cancer in Lyon, France, and colleagues reported.
“Melanoma is the most lethal form of skin cancer; this epidemiological assessment found a heavy public health and economic burden, and our projections suggest that it will remain so in the coming decades,” they wrote in a study published online in JAMA Dermatology.
In an accompanying editorial, Mavis Obeng-Kusi, MPharm and Ivo Abraham, PhD from the Center for Health Outcomes and PharmacoEconomic Research at the University of Arizona, Tucson, commented that the findings are “sobering,” but may substantially underestimate the gravity of the problem in low- and middle-income countries (LMIC).
“The study by Arnold et al. brings to the fore a public health concern that requires global attention and initiates conversations particularly related to LMIC settings, where the incidence and mortality of melanoma is thought to be minimal and for which preventive measures may be insufficient,” they wrote.
Down Under nations lead
Dr. Arnold and colleagues looked at data on age-standardized melanoma incidence and mortality rates per 100,000 person-years (PY) by country, each of 20 world regions as defined by the United Nations, and according to the UN’s four-tier Human Development Index, which stratifies countries into low-, medium-, high-, and very high–income categories.
As noted previously, the researchers estimated that there were 325,000 new melanoma cases worldwide in 2020 (174,000 cases in males and 151,000 in females). There were 57,000 estimated melanoma deaths the same year (32,000 in males and 25,000 in females.
The highest incidence rates were seen in Australia and New Zealand, at 42 per 100,000 PY among males and 31 per 100,000 PY in females, followed by Western Europe with 19 per 100,000 PY in both males and females, North America with 18 and 14 cases per 100,000 PY in males and females respectively, and Northern Europe, with 17 per 100,000 PY in males, and 18 per 100,000 PY in females.
In contrast, in most African and Asian countries melanoma was rare, with rates commonly less than 1 per 100,000 PY, the investigators noted.
The melanoma mortality rate was highest in New Zealand, at 5 per 100,000 PY. Mortality rates worldwide varied less widely than incidence rates. In most other regions of the world, mortality rates were “much lower,” ranging between 0.2-1.0 per 100,000 PY, they wrote.
The authors estimated that, if 2020 rates remain stable, the global burden from melanoma in 2040 will increase to approximately 510,000 new cases and 96,000 deaths.
Public health efforts needed
In their editorial, Ms. Obeng-Kusi and Dr. Abraham pointed out that the study was hampered by the limited availability of cancer data from LMICs, leading the authors to estimate incidence and mortality rates based on proxy data, such as statistical modeling or averaged rates from neighboring countries.
They emphasized the need for going beyond the statistics: “Specific to cutaneous melanoma data, what is most important globally, knowing the exact numbers of cases and deaths or understanding the order of magnitude of the present and future epidemiology? No doubt the latter. Melanoma can be treated more easily if caught at earlier stages.”
Projections such as those provided by Dr. Arnold and colleagues could help to raise awareness of the importance of decreasing exposure to UV radiation, which accounts for three-fourths of all incident melanomas, the editorialists said.
The study was funded in part by a grant to coauthor Anna E. Cust, PhD, MPH. Dr. Cust reported receiving a fellowship from the Australian National Health and Medical Research Council outside the submitted work. Dr. Arnold had no conflicts of interested to disclose. Dr. Abraham reported financial relationships with various entities. Ms. Obeng-Kusi had no disclosures.
Even by cautious calculations,
An estimated 325,000 people worldwide received a new diagnosis of cutaneous melanoma in 2020, and if present trends continue, the incidence of new cases is predicted to increase by about 50% in 2040, with melanoma deaths expected to rise by almost 70%, Melina Arnold, PhD, from the Cancer Surveillance Branch of the International Agency for Research on Cancer in Lyon, France, and colleagues reported.
“Melanoma is the most lethal form of skin cancer; this epidemiological assessment found a heavy public health and economic burden, and our projections suggest that it will remain so in the coming decades,” they wrote in a study published online in JAMA Dermatology.
In an accompanying editorial, Mavis Obeng-Kusi, MPharm and Ivo Abraham, PhD from the Center for Health Outcomes and PharmacoEconomic Research at the University of Arizona, Tucson, commented that the findings are “sobering,” but may substantially underestimate the gravity of the problem in low- and middle-income countries (LMIC).
“The study by Arnold et al. brings to the fore a public health concern that requires global attention and initiates conversations particularly related to LMIC settings, where the incidence and mortality of melanoma is thought to be minimal and for which preventive measures may be insufficient,” they wrote.
Down Under nations lead
Dr. Arnold and colleagues looked at data on age-standardized melanoma incidence and mortality rates per 100,000 person-years (PY) by country, each of 20 world regions as defined by the United Nations, and according to the UN’s four-tier Human Development Index, which stratifies countries into low-, medium-, high-, and very high–income categories.
As noted previously, the researchers estimated that there were 325,000 new melanoma cases worldwide in 2020 (174,000 cases in males and 151,000 in females). There were 57,000 estimated melanoma deaths the same year (32,000 in males and 25,000 in females.
The highest incidence rates were seen in Australia and New Zealand, at 42 per 100,000 PY among males and 31 per 100,000 PY in females, followed by Western Europe with 19 per 100,000 PY in both males and females, North America with 18 and 14 cases per 100,000 PY in males and females respectively, and Northern Europe, with 17 per 100,000 PY in males, and 18 per 100,000 PY in females.
In contrast, in most African and Asian countries melanoma was rare, with rates commonly less than 1 per 100,000 PY, the investigators noted.
The melanoma mortality rate was highest in New Zealand, at 5 per 100,000 PY. Mortality rates worldwide varied less widely than incidence rates. In most other regions of the world, mortality rates were “much lower,” ranging between 0.2-1.0 per 100,000 PY, they wrote.
The authors estimated that, if 2020 rates remain stable, the global burden from melanoma in 2040 will increase to approximately 510,000 new cases and 96,000 deaths.
Public health efforts needed
In their editorial, Ms. Obeng-Kusi and Dr. Abraham pointed out that the study was hampered by the limited availability of cancer data from LMICs, leading the authors to estimate incidence and mortality rates based on proxy data, such as statistical modeling or averaged rates from neighboring countries.
They emphasized the need for going beyond the statistics: “Specific to cutaneous melanoma data, what is most important globally, knowing the exact numbers of cases and deaths or understanding the order of magnitude of the present and future epidemiology? No doubt the latter. Melanoma can be treated more easily if caught at earlier stages.”
Projections such as those provided by Dr. Arnold and colleagues could help to raise awareness of the importance of decreasing exposure to UV radiation, which accounts for three-fourths of all incident melanomas, the editorialists said.
The study was funded in part by a grant to coauthor Anna E. Cust, PhD, MPH. Dr. Cust reported receiving a fellowship from the Australian National Health and Medical Research Council outside the submitted work. Dr. Arnold had no conflicts of interested to disclose. Dr. Abraham reported financial relationships with various entities. Ms. Obeng-Kusi had no disclosures.
FROM JAMA DERMATOLOGY
Melanoma increasing, but is this overdiagnosis?
Melanoma has been increasing in incidence in the United States over the last few decades, but is this a true increase? Or is this a case of overdiagnosis, fueled by screening?
A new study argues the case for overdiagnosis.
commented lead author lead author Adewole Adamson, MD, an assistant professor of internal medicine, division of dermatology, at the University of Texas at Austin.
He posted this conclusion on Twitter after the study was published in JAMA Dermatology.
“The discrepancies in incidence and mortality trends found in this cohort study suggest considerable overdiagnosis of melanoma occurring among White patients in the U.S.,” the authors concluded.
They estimated that an estimated 59% of White women and 60% of White men with melanoma were overdiagnosed in 2014.
These results are similar to those from a recent study from Australia, which used a different method of assessing overdiagnosis. Those findings estimated that 54%-58% of melanoma cases represented overdiagnosis in Australia, Dr. Adamson noted.
“Our estimates shed light on the HUGE scope of this problem in the United States that we need to address,” Dr. Adamson commented on Twitter. “Calls for screening for melanoma in the general public will only push these numbers higher, and make patients out of healthy people.”
“Screening the general population for melanoma has never been shown to save lives and likely is responsible for the increase in melanoma overdiagnosis,” Dr. Adamson said in an interview. “Screening average- and/or low-risk patients is of low value and the harms may outweigh the theoretical benefits.”
Screening programs should be directed to those who may derive the most benefit. “Screening should be limited to high-risk patients such as older White men, patients with a lot of atypical nevi, heavy sun exposure, fair skin, and red hair,” he said. “Just like for other cancers, such as breast, prostate, and colorectal, there should be clear guidelines as to which populations to screen, as well as when to start and when to stop screening.”
Overdiagnosis is defined as the diagnosis of cancer that would never have caused any symptoms or problems in a patient’s lifetime. But therein lies the problem, explained Dr. Adamson. “Because we do not know which early, screen-detected skin cancers would be destined to progress, we are obligated to treat all of them.” There is evidence to suggest that melanoma in situ is not an obligate precursor lesion to invasive melanoma, similar to the situation in which not all ductal carcinoma in situ leads to invasive breast cancer. “It is possible that less aggressive management strategies could be the subject of future studies,” he said.
Patients out of healthy people
For their study, Dr. Adamson and colleagues compared rates of melanoma among White and Black patients. Melanoma is much less common among Black individuals, and they are also less likely to be screened. Additionally, screening rates among Black patients have remained more or less the same over the last decades, whereas screening has increased in White patients.
The team used trends in mortality as a result of melanoma in Black patients as a marker for improvements in medical care. From this, they estimated the expected mortality trends in White patients if medical care had not improved. This served as a marker for the change in true cancer occurrence. Overdiagnosis was calculated as the difference between observed incidence and estimated true cancer occurrence.
The incidence of melanoma rose dramatically among White patients from 1975 to 2014, increasing about fourfold in White women (incidence rate ratio, 4.01) and sixfold in White men (IRR, 5.97).
At the same time, there was much smaller increase (of less than 25%) in the incidence of melanoma in both Black women and Black men.
In that time period, melanoma-related mortality decreased approximately 25% in Black women and men; it remained stable in White women, but increased almost 50% in White men.
Had medical care not improved, estimated mortality would have increased 60% in White women and more than doubled in White men, the authors assert.
Guidelines needed
“Recognizing and addressing overdiagnosis is important,” said Anthony J. Olszanski, MD, RPh, associate professor, department of hematology/oncology at Fox Chase Cancer Center, Philadelphia, who was approached for comment on the paper.
That said, Dr. Olszanski noted that this particular study has important limitations. “It is, by nature, a retrospective study using data from the [Surveillance, Epidemiology, and End Results] database registry, limited to patients only in the U.S., and uses a control group of Black patients to estimate overdiagnosis in White patients. These important factors can certainly influence their findings. However, the paper also notes that White men have realized a true increase in diagnosis, backed by a notable increase in mortality.”
The findings should and do raise a number of provocative questions, Dr. Olszanski emphasized. “Should we curtail public screening? Should we mandate revised guidelines for biopsies or pathologic diagnosis?
“As a medical oncologist,” he continued, “I treat patients who clearly do not have benign disease and so it is easy for me to be biased toward aggressive screening. However, it is my opinion that we should develop guidelines aimed at lessening this apparent overdiagnosis.”
These guidelines should be based on prospective studies and would better define which lesions are most suspect and should be biopsied, which are rational for ongoing surveillance, and what pathologic features are most consistent with melanoma, he noted. “We also need to continue to educate the public, as all too often I see the patient who ignored a lesion that was changing over time. A changing lesion requires medical attention. Importantly, we likewise need to improve our commitment in educating the public about the risks of excessive ultraviolet radiation exposure and how to avoid it, as prevention continues to be a most prudent course.”
Screening catches disease early
Another expert approached for comment emphasized that identifying melanomas early on may prevent the need for aggressive therapy. “Many primary melanomas in the U.S. are diagnosed now at an early stage and are cured with surgery, and that hardly constitutes overdiagnosis,” said Jeffrey S. Weber, MD, PhD, deputy director of the Perlmutter Cancer Center and codirector of the melanoma research program, New York University Langone Health.
“In addition, the death rate from melanoma is likely decreased due to the advent of more effective therapies for metastatic disease, and the increasing use of adjuvant immune and targeted therapies that are highly effective at preventing relapse and undoubtedly at prolonging survival, but they have been approved only since 2017-2018,” he added.
This study was supported in part by the Robert Wood Johnson Foundation. Dr. Adamson and Dr. Olszanski disclosed no relevant financial relationships. Dr. Weber disclosed relationships with numerous pharmaceutical companies and holds equity in CytoMx, Biond, Neximmune, and Immunimax.
A version of this article first appeared on Medscape.com.
Melanoma has been increasing in incidence in the United States over the last few decades, but is this a true increase? Or is this a case of overdiagnosis, fueled by screening?
A new study argues the case for overdiagnosis.
commented lead author lead author Adewole Adamson, MD, an assistant professor of internal medicine, division of dermatology, at the University of Texas at Austin.
He posted this conclusion on Twitter after the study was published in JAMA Dermatology.
“The discrepancies in incidence and mortality trends found in this cohort study suggest considerable overdiagnosis of melanoma occurring among White patients in the U.S.,” the authors concluded.
They estimated that an estimated 59% of White women and 60% of White men with melanoma were overdiagnosed in 2014.
These results are similar to those from a recent study from Australia, which used a different method of assessing overdiagnosis. Those findings estimated that 54%-58% of melanoma cases represented overdiagnosis in Australia, Dr. Adamson noted.
“Our estimates shed light on the HUGE scope of this problem in the United States that we need to address,” Dr. Adamson commented on Twitter. “Calls for screening for melanoma in the general public will only push these numbers higher, and make patients out of healthy people.”
“Screening the general population for melanoma has never been shown to save lives and likely is responsible for the increase in melanoma overdiagnosis,” Dr. Adamson said in an interview. “Screening average- and/or low-risk patients is of low value and the harms may outweigh the theoretical benefits.”
Screening programs should be directed to those who may derive the most benefit. “Screening should be limited to high-risk patients such as older White men, patients with a lot of atypical nevi, heavy sun exposure, fair skin, and red hair,” he said. “Just like for other cancers, such as breast, prostate, and colorectal, there should be clear guidelines as to which populations to screen, as well as when to start and when to stop screening.”
Overdiagnosis is defined as the diagnosis of cancer that would never have caused any symptoms or problems in a patient’s lifetime. But therein lies the problem, explained Dr. Adamson. “Because we do not know which early, screen-detected skin cancers would be destined to progress, we are obligated to treat all of them.” There is evidence to suggest that melanoma in situ is not an obligate precursor lesion to invasive melanoma, similar to the situation in which not all ductal carcinoma in situ leads to invasive breast cancer. “It is possible that less aggressive management strategies could be the subject of future studies,” he said.
Patients out of healthy people
For their study, Dr. Adamson and colleagues compared rates of melanoma among White and Black patients. Melanoma is much less common among Black individuals, and they are also less likely to be screened. Additionally, screening rates among Black patients have remained more or less the same over the last decades, whereas screening has increased in White patients.
The team used trends in mortality as a result of melanoma in Black patients as a marker for improvements in medical care. From this, they estimated the expected mortality trends in White patients if medical care had not improved. This served as a marker for the change in true cancer occurrence. Overdiagnosis was calculated as the difference between observed incidence and estimated true cancer occurrence.
The incidence of melanoma rose dramatically among White patients from 1975 to 2014, increasing about fourfold in White women (incidence rate ratio, 4.01) and sixfold in White men (IRR, 5.97).
At the same time, there was much smaller increase (of less than 25%) in the incidence of melanoma in both Black women and Black men.
In that time period, melanoma-related mortality decreased approximately 25% in Black women and men; it remained stable in White women, but increased almost 50% in White men.
Had medical care not improved, estimated mortality would have increased 60% in White women and more than doubled in White men, the authors assert.
Guidelines needed
“Recognizing and addressing overdiagnosis is important,” said Anthony J. Olszanski, MD, RPh, associate professor, department of hematology/oncology at Fox Chase Cancer Center, Philadelphia, who was approached for comment on the paper.
That said, Dr. Olszanski noted that this particular study has important limitations. “It is, by nature, a retrospective study using data from the [Surveillance, Epidemiology, and End Results] database registry, limited to patients only in the U.S., and uses a control group of Black patients to estimate overdiagnosis in White patients. These important factors can certainly influence their findings. However, the paper also notes that White men have realized a true increase in diagnosis, backed by a notable increase in mortality.”
The findings should and do raise a number of provocative questions, Dr. Olszanski emphasized. “Should we curtail public screening? Should we mandate revised guidelines for biopsies or pathologic diagnosis?
“As a medical oncologist,” he continued, “I treat patients who clearly do not have benign disease and so it is easy for me to be biased toward aggressive screening. However, it is my opinion that we should develop guidelines aimed at lessening this apparent overdiagnosis.”
These guidelines should be based on prospective studies and would better define which lesions are most suspect and should be biopsied, which are rational for ongoing surveillance, and what pathologic features are most consistent with melanoma, he noted. “We also need to continue to educate the public, as all too often I see the patient who ignored a lesion that was changing over time. A changing lesion requires medical attention. Importantly, we likewise need to improve our commitment in educating the public about the risks of excessive ultraviolet radiation exposure and how to avoid it, as prevention continues to be a most prudent course.”
Screening catches disease early
Another expert approached for comment emphasized that identifying melanomas early on may prevent the need for aggressive therapy. “Many primary melanomas in the U.S. are diagnosed now at an early stage and are cured with surgery, and that hardly constitutes overdiagnosis,” said Jeffrey S. Weber, MD, PhD, deputy director of the Perlmutter Cancer Center and codirector of the melanoma research program, New York University Langone Health.
“In addition, the death rate from melanoma is likely decreased due to the advent of more effective therapies for metastatic disease, and the increasing use of adjuvant immune and targeted therapies that are highly effective at preventing relapse and undoubtedly at prolonging survival, but they have been approved only since 2017-2018,” he added.
This study was supported in part by the Robert Wood Johnson Foundation. Dr. Adamson and Dr. Olszanski disclosed no relevant financial relationships. Dr. Weber disclosed relationships with numerous pharmaceutical companies and holds equity in CytoMx, Biond, Neximmune, and Immunimax.
A version of this article first appeared on Medscape.com.
Melanoma has been increasing in incidence in the United States over the last few decades, but is this a true increase? Or is this a case of overdiagnosis, fueled by screening?
A new study argues the case for overdiagnosis.
commented lead author lead author Adewole Adamson, MD, an assistant professor of internal medicine, division of dermatology, at the University of Texas at Austin.
He posted this conclusion on Twitter after the study was published in JAMA Dermatology.
“The discrepancies in incidence and mortality trends found in this cohort study suggest considerable overdiagnosis of melanoma occurring among White patients in the U.S.,” the authors concluded.
They estimated that an estimated 59% of White women and 60% of White men with melanoma were overdiagnosed in 2014.
These results are similar to those from a recent study from Australia, which used a different method of assessing overdiagnosis. Those findings estimated that 54%-58% of melanoma cases represented overdiagnosis in Australia, Dr. Adamson noted.
“Our estimates shed light on the HUGE scope of this problem in the United States that we need to address,” Dr. Adamson commented on Twitter. “Calls for screening for melanoma in the general public will only push these numbers higher, and make patients out of healthy people.”
“Screening the general population for melanoma has never been shown to save lives and likely is responsible for the increase in melanoma overdiagnosis,” Dr. Adamson said in an interview. “Screening average- and/or low-risk patients is of low value and the harms may outweigh the theoretical benefits.”
Screening programs should be directed to those who may derive the most benefit. “Screening should be limited to high-risk patients such as older White men, patients with a lot of atypical nevi, heavy sun exposure, fair skin, and red hair,” he said. “Just like for other cancers, such as breast, prostate, and colorectal, there should be clear guidelines as to which populations to screen, as well as when to start and when to stop screening.”
Overdiagnosis is defined as the diagnosis of cancer that would never have caused any symptoms or problems in a patient’s lifetime. But therein lies the problem, explained Dr. Adamson. “Because we do not know which early, screen-detected skin cancers would be destined to progress, we are obligated to treat all of them.” There is evidence to suggest that melanoma in situ is not an obligate precursor lesion to invasive melanoma, similar to the situation in which not all ductal carcinoma in situ leads to invasive breast cancer. “It is possible that less aggressive management strategies could be the subject of future studies,” he said.
Patients out of healthy people
For their study, Dr. Adamson and colleagues compared rates of melanoma among White and Black patients. Melanoma is much less common among Black individuals, and they are also less likely to be screened. Additionally, screening rates among Black patients have remained more or less the same over the last decades, whereas screening has increased in White patients.
The team used trends in mortality as a result of melanoma in Black patients as a marker for improvements in medical care. From this, they estimated the expected mortality trends in White patients if medical care had not improved. This served as a marker for the change in true cancer occurrence. Overdiagnosis was calculated as the difference between observed incidence and estimated true cancer occurrence.
The incidence of melanoma rose dramatically among White patients from 1975 to 2014, increasing about fourfold in White women (incidence rate ratio, 4.01) and sixfold in White men (IRR, 5.97).
At the same time, there was much smaller increase (of less than 25%) in the incidence of melanoma in both Black women and Black men.
In that time period, melanoma-related mortality decreased approximately 25% in Black women and men; it remained stable in White women, but increased almost 50% in White men.
Had medical care not improved, estimated mortality would have increased 60% in White women and more than doubled in White men, the authors assert.
Guidelines needed
“Recognizing and addressing overdiagnosis is important,” said Anthony J. Olszanski, MD, RPh, associate professor, department of hematology/oncology at Fox Chase Cancer Center, Philadelphia, who was approached for comment on the paper.
That said, Dr. Olszanski noted that this particular study has important limitations. “It is, by nature, a retrospective study using data from the [Surveillance, Epidemiology, and End Results] database registry, limited to patients only in the U.S., and uses a control group of Black patients to estimate overdiagnosis in White patients. These important factors can certainly influence their findings. However, the paper also notes that White men have realized a true increase in diagnosis, backed by a notable increase in mortality.”
The findings should and do raise a number of provocative questions, Dr. Olszanski emphasized. “Should we curtail public screening? Should we mandate revised guidelines for biopsies or pathologic diagnosis?
“As a medical oncologist,” he continued, “I treat patients who clearly do not have benign disease and so it is easy for me to be biased toward aggressive screening. However, it is my opinion that we should develop guidelines aimed at lessening this apparent overdiagnosis.”
These guidelines should be based on prospective studies and would better define which lesions are most suspect and should be biopsied, which are rational for ongoing surveillance, and what pathologic features are most consistent with melanoma, he noted. “We also need to continue to educate the public, as all too often I see the patient who ignored a lesion that was changing over time. A changing lesion requires medical attention. Importantly, we likewise need to improve our commitment in educating the public about the risks of excessive ultraviolet radiation exposure and how to avoid it, as prevention continues to be a most prudent course.”
Screening catches disease early
Another expert approached for comment emphasized that identifying melanomas early on may prevent the need for aggressive therapy. “Many primary melanomas in the U.S. are diagnosed now at an early stage and are cured with surgery, and that hardly constitutes overdiagnosis,” said Jeffrey S. Weber, MD, PhD, deputy director of the Perlmutter Cancer Center and codirector of the melanoma research program, New York University Langone Health.
“In addition, the death rate from melanoma is likely decreased due to the advent of more effective therapies for metastatic disease, and the increasing use of adjuvant immune and targeted therapies that are highly effective at preventing relapse and undoubtedly at prolonging survival, but they have been approved only since 2017-2018,” he added.
This study was supported in part by the Robert Wood Johnson Foundation. Dr. Adamson and Dr. Olszanski disclosed no relevant financial relationships. Dr. Weber disclosed relationships with numerous pharmaceutical companies and holds equity in CytoMx, Biond, Neximmune, and Immunimax.
A version of this article first appeared on Medscape.com.
FROM JAMA DERMATOLOGY
Few new cancer drugs replace current standards of care
, a new analysis shows.
Of more than 200 agents evaluated, most (42%) received approval as second-, third-, or later-line therapies.
“While there is justified enthusiasm for the high volume of new cancer drug approvals in oncology and malignant hematology, these approvals must be evaluated in the context of their use,” the authors note in a report published online March 15 in JAMA Network Open. Later-line drugs may, for instance, “benefit patients with few alternatives but also add to cost of care and further delay palliative and comfort services” compared to first-line therapies, which may alter “the treatment paradigm for a certain indication.”
The U.S. Food and Drug Administration approves several new cancer drugs each month, but it’s not clear how many transform the treatment landscape.
To investigate, David Benjamin, MD, with the Division of Hematology and Oncology, University of California, Irvine, and colleagues evaluated all 207 cancer drugs approved in the U.S. between May 1, 2016 and May 31, 2021.
The researchers found that only 28 drugs (14%) displaced the prior first-line standard of care for an indication.
Examples of these cancer drugs include alectinib for anaplastic lymphoma kinase rearrangement–positive metastatic non–small cell lung cancer (NSCLC), osimertinib for epidermal growth factor receptor exon 19 deletion or exon 21 L858R substitution NSCLC, atezolizumab plus bevacizumab for unresectable or metastatic hepatocellular carcinoma, and cabozantinib for advanced kidney cancer.
A total of 32 drugs (15%) were approved as first-line alternatives or new drugs. These drugs were approved for use in the first-line setting but did not necessarily replace the standard of care at the time of approval or were first-of-their-class therapies.
Examples of these drug approvals include apalutamide for nonmetastatic castrate-resistant prostate cancer, tepotinib for metastatic MET exon 14-skipping NSCLC, and avapritinib for unresectable or metastatic gastrointestinal stromal tumor with platelet-derived growth factor receptor alpha exon 18 variant, including D842V variant.
A total of 61 drugs (29%) were approved as add-on therapies for use in combination with a previously approved therapy or in the adjuvant or maintenance settings. These drugs “can only increase the cost of care,” the study team says.
Most new approvals (n = 86) were for use in second-, third- or later-line settings, often for patients for whom other treatment options had been exhausted.
The authors highlight disparities among approvals based on tumor type. Lung-related tumors received the most approvals (n = 37), followed by genitourinary tumors (n = 28), leukemia (n = 25), lymphoma (n = 22), breast cancer (n = 19), and gastrointestinal cancers (n = 14).
The authors note that cancer drugs considered new standards of care or approved as first-line setting alternatives could “provide market competition and work to lower cancer drug prices.”
The study was funded by a grant from Arnold Ventures.
A version of this article first appeared on Medscape.com.
, a new analysis shows.
Of more than 200 agents evaluated, most (42%) received approval as second-, third-, or later-line therapies.
“While there is justified enthusiasm for the high volume of new cancer drug approvals in oncology and malignant hematology, these approvals must be evaluated in the context of their use,” the authors note in a report published online March 15 in JAMA Network Open. Later-line drugs may, for instance, “benefit patients with few alternatives but also add to cost of care and further delay palliative and comfort services” compared to first-line therapies, which may alter “the treatment paradigm for a certain indication.”
The U.S. Food and Drug Administration approves several new cancer drugs each month, but it’s not clear how many transform the treatment landscape.
To investigate, David Benjamin, MD, with the Division of Hematology and Oncology, University of California, Irvine, and colleagues evaluated all 207 cancer drugs approved in the U.S. between May 1, 2016 and May 31, 2021.
The researchers found that only 28 drugs (14%) displaced the prior first-line standard of care for an indication.
Examples of these cancer drugs include alectinib for anaplastic lymphoma kinase rearrangement–positive metastatic non–small cell lung cancer (NSCLC), osimertinib for epidermal growth factor receptor exon 19 deletion or exon 21 L858R substitution NSCLC, atezolizumab plus bevacizumab for unresectable or metastatic hepatocellular carcinoma, and cabozantinib for advanced kidney cancer.
A total of 32 drugs (15%) were approved as first-line alternatives or new drugs. These drugs were approved for use in the first-line setting but did not necessarily replace the standard of care at the time of approval or were first-of-their-class therapies.
Examples of these drug approvals include apalutamide for nonmetastatic castrate-resistant prostate cancer, tepotinib for metastatic MET exon 14-skipping NSCLC, and avapritinib for unresectable or metastatic gastrointestinal stromal tumor with platelet-derived growth factor receptor alpha exon 18 variant, including D842V variant.
A total of 61 drugs (29%) were approved as add-on therapies for use in combination with a previously approved therapy or in the adjuvant or maintenance settings. These drugs “can only increase the cost of care,” the study team says.
Most new approvals (n = 86) were for use in second-, third- or later-line settings, often for patients for whom other treatment options had been exhausted.
The authors highlight disparities among approvals based on tumor type. Lung-related tumors received the most approvals (n = 37), followed by genitourinary tumors (n = 28), leukemia (n = 25), lymphoma (n = 22), breast cancer (n = 19), and gastrointestinal cancers (n = 14).
The authors note that cancer drugs considered new standards of care or approved as first-line setting alternatives could “provide market competition and work to lower cancer drug prices.”
The study was funded by a grant from Arnold Ventures.
A version of this article first appeared on Medscape.com.
, a new analysis shows.
Of more than 200 agents evaluated, most (42%) received approval as second-, third-, or later-line therapies.
“While there is justified enthusiasm for the high volume of new cancer drug approvals in oncology and malignant hematology, these approvals must be evaluated in the context of their use,” the authors note in a report published online March 15 in JAMA Network Open. Later-line drugs may, for instance, “benefit patients with few alternatives but also add to cost of care and further delay palliative and comfort services” compared to first-line therapies, which may alter “the treatment paradigm for a certain indication.”
The U.S. Food and Drug Administration approves several new cancer drugs each month, but it’s not clear how many transform the treatment landscape.
To investigate, David Benjamin, MD, with the Division of Hematology and Oncology, University of California, Irvine, and colleagues evaluated all 207 cancer drugs approved in the U.S. between May 1, 2016 and May 31, 2021.
The researchers found that only 28 drugs (14%) displaced the prior first-line standard of care for an indication.
Examples of these cancer drugs include alectinib for anaplastic lymphoma kinase rearrangement–positive metastatic non–small cell lung cancer (NSCLC), osimertinib for epidermal growth factor receptor exon 19 deletion or exon 21 L858R substitution NSCLC, atezolizumab plus bevacizumab for unresectable or metastatic hepatocellular carcinoma, and cabozantinib for advanced kidney cancer.
A total of 32 drugs (15%) were approved as first-line alternatives or new drugs. These drugs were approved for use in the first-line setting but did not necessarily replace the standard of care at the time of approval or were first-of-their-class therapies.
Examples of these drug approvals include apalutamide for nonmetastatic castrate-resistant prostate cancer, tepotinib for metastatic MET exon 14-skipping NSCLC, and avapritinib for unresectable or metastatic gastrointestinal stromal tumor with platelet-derived growth factor receptor alpha exon 18 variant, including D842V variant.
A total of 61 drugs (29%) were approved as add-on therapies for use in combination with a previously approved therapy or in the adjuvant or maintenance settings. These drugs “can only increase the cost of care,” the study team says.
Most new approvals (n = 86) were for use in second-, third- or later-line settings, often for patients for whom other treatment options had been exhausted.
The authors highlight disparities among approvals based on tumor type. Lung-related tumors received the most approvals (n = 37), followed by genitourinary tumors (n = 28), leukemia (n = 25), lymphoma (n = 22), breast cancer (n = 19), and gastrointestinal cancers (n = 14).
The authors note that cancer drugs considered new standards of care or approved as first-line setting alternatives could “provide market competition and work to lower cancer drug prices.”
The study was funded by a grant from Arnold Ventures.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
FDA approves new immunotherapy combo for metastatic melanoma
in adults and children 12 years or older, according to the drug’s manufacturer, Bristol-Myers Squibb.
Approval was based on the company’s RELATIVITY-047 trial, which found a median progression-free survival (PFS) of 10.1 months among 355 patients randomly assigned to the combination therapy compared with 4.6 months among 359 patients who received nivolumab alone (hazard ratio, 0.75; P = .0055).
In the combination therapy group, 18.9% of patients reported a grade 3/4 drug-related adverse event, compared with 9.7% in the nivolumab group; 14.6% of patients in the combination group had drug-related adverse events leading to discontinuation versus 6.7% of those receiving monotherapy, the company noted in a press release.
Relatlimab is the company’s third immune checkpoint inhibitor to reach the U.S. market, joining the PD-1 inhibitor nivolumab and the CTLA-4 blocker ipilimumab. Relatlimab targets LAG-3, a cell-surface receptor found on activated CD4+ T cells.
Nivolumab plus ipilimumab is currently the standard of care for previously untreated metastatic or inoperable melanoma. Both combinations produce similar PFS, but the incidence of grade 3/4 adverse events is higher with ipilimumab, according to a Jan. 6, 2022, editorial in the New England Journal of Medicine.
Musculoskeletal pain, fatigue, rash, pruritus, and diarrhea were the most common adverse reactions with combination nivolumab/relatlimab, occurring in 20% or more of RELATIVITY-047 trial participants.
Adrenal insufficiency, anemia, colitis, pneumonia, and myocardial infarction were the most frequent serious adverse reactions, but each occurred in less than 2% of patients. There were three fatal adverse events in the trial caused by hemophagocytic lymphohistiocytosis, acute lung edema, and pneumonitis.
The approved dosage is 480 mg nivolumab and 160 mg relatlimab administered intravenously every 4 weeks.
A version of this article first appeared on Medscape.com.
in adults and children 12 years or older, according to the drug’s manufacturer, Bristol-Myers Squibb.
Approval was based on the company’s RELATIVITY-047 trial, which found a median progression-free survival (PFS) of 10.1 months among 355 patients randomly assigned to the combination therapy compared with 4.6 months among 359 patients who received nivolumab alone (hazard ratio, 0.75; P = .0055).
In the combination therapy group, 18.9% of patients reported a grade 3/4 drug-related adverse event, compared with 9.7% in the nivolumab group; 14.6% of patients in the combination group had drug-related adverse events leading to discontinuation versus 6.7% of those receiving monotherapy, the company noted in a press release.
Relatlimab is the company’s third immune checkpoint inhibitor to reach the U.S. market, joining the PD-1 inhibitor nivolumab and the CTLA-4 blocker ipilimumab. Relatlimab targets LAG-3, a cell-surface receptor found on activated CD4+ T cells.
Nivolumab plus ipilimumab is currently the standard of care for previously untreated metastatic or inoperable melanoma. Both combinations produce similar PFS, but the incidence of grade 3/4 adverse events is higher with ipilimumab, according to a Jan. 6, 2022, editorial in the New England Journal of Medicine.
Musculoskeletal pain, fatigue, rash, pruritus, and diarrhea were the most common adverse reactions with combination nivolumab/relatlimab, occurring in 20% or more of RELATIVITY-047 trial participants.
Adrenal insufficiency, anemia, colitis, pneumonia, and myocardial infarction were the most frequent serious adverse reactions, but each occurred in less than 2% of patients. There were three fatal adverse events in the trial caused by hemophagocytic lymphohistiocytosis, acute lung edema, and pneumonitis.
The approved dosage is 480 mg nivolumab and 160 mg relatlimab administered intravenously every 4 weeks.
A version of this article first appeared on Medscape.com.
in adults and children 12 years or older, according to the drug’s manufacturer, Bristol-Myers Squibb.
Approval was based on the company’s RELATIVITY-047 trial, which found a median progression-free survival (PFS) of 10.1 months among 355 patients randomly assigned to the combination therapy compared with 4.6 months among 359 patients who received nivolumab alone (hazard ratio, 0.75; P = .0055).
In the combination therapy group, 18.9% of patients reported a grade 3/4 drug-related adverse event, compared with 9.7% in the nivolumab group; 14.6% of patients in the combination group had drug-related adverse events leading to discontinuation versus 6.7% of those receiving monotherapy, the company noted in a press release.
Relatlimab is the company’s third immune checkpoint inhibitor to reach the U.S. market, joining the PD-1 inhibitor nivolumab and the CTLA-4 blocker ipilimumab. Relatlimab targets LAG-3, a cell-surface receptor found on activated CD4+ T cells.
Nivolumab plus ipilimumab is currently the standard of care for previously untreated metastatic or inoperable melanoma. Both combinations produce similar PFS, but the incidence of grade 3/4 adverse events is higher with ipilimumab, according to a Jan. 6, 2022, editorial in the New England Journal of Medicine.
Musculoskeletal pain, fatigue, rash, pruritus, and diarrhea were the most common adverse reactions with combination nivolumab/relatlimab, occurring in 20% or more of RELATIVITY-047 trial participants.
Adrenal insufficiency, anemia, colitis, pneumonia, and myocardial infarction were the most frequent serious adverse reactions, but each occurred in less than 2% of patients. There were three fatal adverse events in the trial caused by hemophagocytic lymphohistiocytosis, acute lung edema, and pneumonitis.
The approved dosage is 480 mg nivolumab and 160 mg relatlimab administered intravenously every 4 weeks.
A version of this article first appeared on Medscape.com.
Adverse skin effects of cancer immunotherapy reviewed
Immune checkpoint inhibitors (ICIs) have unquestionably revolutionized the care of patients with malignant melanoma, non-small cell lung cancer, and other types of cancer.
, according to members of a European Academy of Dermatology and Venereology (EADV) task force.
“The desirable, immune-mediated oncologic response is often achieved at the cost of immune-related adverse events (irAEs) that may potentially affect any organ system,” they write in a position statement on the management of ICI-derived dermatologic adverse events.
Recommendations from the EADV “Dermatology for Cancer Patients” task force have been published in the Journal of the European Academy of Dermatology and Venereology.
Task force members developed the recommendations based on clinical experience from published data and came up with specific recommendations for treating cutaneous toxicities associated with dermatologic immune-related adverse events (dirAEs) that occur in patients receiving immunotherapy with an ICI.
ICIs include the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) inhibitor ipilimumab (Yervoy, Bristol Myers Squibb), and inhibitors of programmed death protein 1 (PD-1) and its ligand (PD-L1), including nivolumab (Opdivo, Bristol Myers Squibb), pembrolizumab (Keytruda, Merck), and other agents.
“The basic principle of management is that the interventions should be tailored to serve the equilibrium between patients’ relief from the symptoms and signs of skin toxicity and the preservation of an unimpeded oncologic treatment,” they write.
The recommendations are in line with those included in a 2021 update of the American Society of Clinical Oncology (ASCO) guidelines on the management of irAEs in patients treated with ICIs across the whole range of organ systems, said Milan J. Anadkat, MD, professor of dermatology and director of dermatology clinical trials at Washington University School of Medicine, St. Louis. Dr. Anadkat was a coauthor of the ASCO guideline update.
Although the European recommendations focus only on dermatologic side effects of ICIs in patients with cancer, “that doesn’t diminish their importance. They do a good job of summarizing how to approach and how to manage it depending on the severity of the toxicities and the various types of toxicities,” he told this news organization.
Having a paper focused exclusively on the dermatologic side effects of ICIs allows the inclusion of photographs that can help clinicians identify specific conditions that may require referral to a dermatologist, he said.
Both Dr. Anadkat and the authors of the European recommendations noted that dermatologic irAEs are more common with CTLA-4 inhibition than with PD-1/PD-L1 inhibition.
“It has to do with where the target is,” Dr. Anadkat said. “CTLA-4 inhibition works on a central aspect of the immune system, so it’s a much less specific site, whereas PD-1 affects an interaction at the site of the tumor cell itself, so it’s a little more specific.”
Pruritus
ICI-induced pruritus can occur without apparent skin changes, they write, noting that in a recent study of patients with dirAEs, about one-third had isolated pruritus.
The task force members cite a meta-analysis indicating a pruritus incidence of 13.2% for patients treated with nivolumab and 20.2% for patients treated with pembrolizumab but respective grade 3 pruritus rates of only 0.5% and 2.3%. The reported incidence of pruritus with ipilimumab was 47% in a different study.
Recommended treatments include topical moisturizers with or without medium-to-high potency corticosteroids for grade 1 reactions, non-sedating histamines and/or GABA agonists such as pregabalin, or gabapentin for grade 2 pruritus, and suspension of ICIs until pruritus improves in patients with grade 3 pruritus.
Maculopapular rash
Maculopapular or eczema-like rashes may occur in up to 68% of patients who receive a CTLA-4 inhibitor and up to 20% of those who receive a PD1/PD-L1 inhibitor, the authors note. Rashes commonly appear within 3-6 weeks of initiating therapy.
“The clinical presentation is nonspecific and consists of a rapid onset of multiple minimally scaly, erythematous macules and papules, congregating into plaques. Lesions are mostly located on trunk and extensor surfaces of the extremities and the face is generally spared,” they write.
Maculopapular rashes are typically accompanied by itching but could be asymptomatic, they noted.
Mild (grade 1) rashes may respond to moisturizers and topical potent or super-potent corticosteroids. Patients with grade 2 rash should also receive oral antihistamines. Systemic corticosteroids may be considered for patients with grade 3 rashes but only after other dirAEs that may require specific management, such as psoriasis, are ruled out.
Psoriasis-like rash
The most common form of psoriasis seen in patients treated with ICIs is psoriasis vulgaris with plaques, but other clinical variants are also seen, the authors note.
“Topical agents (corticosteroids, Vitamin D analogues) are prescribed in Grades 1/2 and supplementary” to systemic treatment for patients with grade 3 or recalcitrant lesions, they write. “If skin-directed therapies fail to provide symptomatic control,” systemic treatment and narrow band UVB phototherapy “should be considered,” they add.
Evidence regarding the use of systemic therapies to treat psoriasis-like rash associated with ICIs is sparse. Acitretin can be safely used in patients with cancer. Low-dose methotrexate is also safe to use except in patients with non-melanoma skin cancers. Cyclosporine, however, should be avoided because of the potential for tumor-promoting effects, they emphasized.
The recommendations also cover treatment of lichen planus-like and vitiligo-like rashes, as well as hair and nail changes, autoimmune bullous disorders, and oral mucosal dirAEs.
In addition, the recommendations cover severe cutaneous adverse reactions as well as serious, potentially life-threatening dirAEs, including Stevens-Johnson syndrome/TEN, acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DRESS/DIHS).
“The dose of corticosteroids may be adapted to the severity of DRESS. The therapeutic benefit of systemic corticosteroids in the management of SJS/TEN remains controversial, and some authors favor treatment with cyclosporine. However, the use of corticosteroids in this context of ICI treatment appears reasonable and should be proposed. Short courses of steroids seem also effective in AGEP,” the task force members write.
The recommendations did not have outside funding. Of the 19 authors, 6 disclosed relationships with various pharmaceutical companies, including AbbVie, Leo Pharma, Boehringer Ingelheim, Bristol Myers Squibb, and/or Janssen. Dr. Anadkat disclosed previous relationships with Merck, Bristol Myers Squibb, and current relationships with others.
A version of this article first appeared on Medscape.com.
Immune checkpoint inhibitors (ICIs) have unquestionably revolutionized the care of patients with malignant melanoma, non-small cell lung cancer, and other types of cancer.
, according to members of a European Academy of Dermatology and Venereology (EADV) task force.
“The desirable, immune-mediated oncologic response is often achieved at the cost of immune-related adverse events (irAEs) that may potentially affect any organ system,” they write in a position statement on the management of ICI-derived dermatologic adverse events.
Recommendations from the EADV “Dermatology for Cancer Patients” task force have been published in the Journal of the European Academy of Dermatology and Venereology.
Task force members developed the recommendations based on clinical experience from published data and came up with specific recommendations for treating cutaneous toxicities associated with dermatologic immune-related adverse events (dirAEs) that occur in patients receiving immunotherapy with an ICI.
ICIs include the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) inhibitor ipilimumab (Yervoy, Bristol Myers Squibb), and inhibitors of programmed death protein 1 (PD-1) and its ligand (PD-L1), including nivolumab (Opdivo, Bristol Myers Squibb), pembrolizumab (Keytruda, Merck), and other agents.
“The basic principle of management is that the interventions should be tailored to serve the equilibrium between patients’ relief from the symptoms and signs of skin toxicity and the preservation of an unimpeded oncologic treatment,” they write.
The recommendations are in line with those included in a 2021 update of the American Society of Clinical Oncology (ASCO) guidelines on the management of irAEs in patients treated with ICIs across the whole range of organ systems, said Milan J. Anadkat, MD, professor of dermatology and director of dermatology clinical trials at Washington University School of Medicine, St. Louis. Dr. Anadkat was a coauthor of the ASCO guideline update.
Although the European recommendations focus only on dermatologic side effects of ICIs in patients with cancer, “that doesn’t diminish their importance. They do a good job of summarizing how to approach and how to manage it depending on the severity of the toxicities and the various types of toxicities,” he told this news organization.
Having a paper focused exclusively on the dermatologic side effects of ICIs allows the inclusion of photographs that can help clinicians identify specific conditions that may require referral to a dermatologist, he said.
Both Dr. Anadkat and the authors of the European recommendations noted that dermatologic irAEs are more common with CTLA-4 inhibition than with PD-1/PD-L1 inhibition.
“It has to do with where the target is,” Dr. Anadkat said. “CTLA-4 inhibition works on a central aspect of the immune system, so it’s a much less specific site, whereas PD-1 affects an interaction at the site of the tumor cell itself, so it’s a little more specific.”
Pruritus
ICI-induced pruritus can occur without apparent skin changes, they write, noting that in a recent study of patients with dirAEs, about one-third had isolated pruritus.
The task force members cite a meta-analysis indicating a pruritus incidence of 13.2% for patients treated with nivolumab and 20.2% for patients treated with pembrolizumab but respective grade 3 pruritus rates of only 0.5% and 2.3%. The reported incidence of pruritus with ipilimumab was 47% in a different study.
Recommended treatments include topical moisturizers with or without medium-to-high potency corticosteroids for grade 1 reactions, non-sedating histamines and/or GABA agonists such as pregabalin, or gabapentin for grade 2 pruritus, and suspension of ICIs until pruritus improves in patients with grade 3 pruritus.
Maculopapular rash
Maculopapular or eczema-like rashes may occur in up to 68% of patients who receive a CTLA-4 inhibitor and up to 20% of those who receive a PD1/PD-L1 inhibitor, the authors note. Rashes commonly appear within 3-6 weeks of initiating therapy.
“The clinical presentation is nonspecific and consists of a rapid onset of multiple minimally scaly, erythematous macules and papules, congregating into plaques. Lesions are mostly located on trunk and extensor surfaces of the extremities and the face is generally spared,” they write.
Maculopapular rashes are typically accompanied by itching but could be asymptomatic, they noted.
Mild (grade 1) rashes may respond to moisturizers and topical potent or super-potent corticosteroids. Patients with grade 2 rash should also receive oral antihistamines. Systemic corticosteroids may be considered for patients with grade 3 rashes but only after other dirAEs that may require specific management, such as psoriasis, are ruled out.
Psoriasis-like rash
The most common form of psoriasis seen in patients treated with ICIs is psoriasis vulgaris with plaques, but other clinical variants are also seen, the authors note.
“Topical agents (corticosteroids, Vitamin D analogues) are prescribed in Grades 1/2 and supplementary” to systemic treatment for patients with grade 3 or recalcitrant lesions, they write. “If skin-directed therapies fail to provide symptomatic control,” systemic treatment and narrow band UVB phototherapy “should be considered,” they add.
Evidence regarding the use of systemic therapies to treat psoriasis-like rash associated with ICIs is sparse. Acitretin can be safely used in patients with cancer. Low-dose methotrexate is also safe to use except in patients with non-melanoma skin cancers. Cyclosporine, however, should be avoided because of the potential for tumor-promoting effects, they emphasized.
The recommendations also cover treatment of lichen planus-like and vitiligo-like rashes, as well as hair and nail changes, autoimmune bullous disorders, and oral mucosal dirAEs.
In addition, the recommendations cover severe cutaneous adverse reactions as well as serious, potentially life-threatening dirAEs, including Stevens-Johnson syndrome/TEN, acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DRESS/DIHS).
“The dose of corticosteroids may be adapted to the severity of DRESS. The therapeutic benefit of systemic corticosteroids in the management of SJS/TEN remains controversial, and some authors favor treatment with cyclosporine. However, the use of corticosteroids in this context of ICI treatment appears reasonable and should be proposed. Short courses of steroids seem also effective in AGEP,” the task force members write.
The recommendations did not have outside funding. Of the 19 authors, 6 disclosed relationships with various pharmaceutical companies, including AbbVie, Leo Pharma, Boehringer Ingelheim, Bristol Myers Squibb, and/or Janssen. Dr. Anadkat disclosed previous relationships with Merck, Bristol Myers Squibb, and current relationships with others.
A version of this article first appeared on Medscape.com.
Immune checkpoint inhibitors (ICIs) have unquestionably revolutionized the care of patients with malignant melanoma, non-small cell lung cancer, and other types of cancer.
, according to members of a European Academy of Dermatology and Venereology (EADV) task force.
“The desirable, immune-mediated oncologic response is often achieved at the cost of immune-related adverse events (irAEs) that may potentially affect any organ system,” they write in a position statement on the management of ICI-derived dermatologic adverse events.
Recommendations from the EADV “Dermatology for Cancer Patients” task force have been published in the Journal of the European Academy of Dermatology and Venereology.
Task force members developed the recommendations based on clinical experience from published data and came up with specific recommendations for treating cutaneous toxicities associated with dermatologic immune-related adverse events (dirAEs) that occur in patients receiving immunotherapy with an ICI.
ICIs include the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) inhibitor ipilimumab (Yervoy, Bristol Myers Squibb), and inhibitors of programmed death protein 1 (PD-1) and its ligand (PD-L1), including nivolumab (Opdivo, Bristol Myers Squibb), pembrolizumab (Keytruda, Merck), and other agents.
“The basic principle of management is that the interventions should be tailored to serve the equilibrium between patients’ relief from the symptoms and signs of skin toxicity and the preservation of an unimpeded oncologic treatment,” they write.
The recommendations are in line with those included in a 2021 update of the American Society of Clinical Oncology (ASCO) guidelines on the management of irAEs in patients treated with ICIs across the whole range of organ systems, said Milan J. Anadkat, MD, professor of dermatology and director of dermatology clinical trials at Washington University School of Medicine, St. Louis. Dr. Anadkat was a coauthor of the ASCO guideline update.
Although the European recommendations focus only on dermatologic side effects of ICIs in patients with cancer, “that doesn’t diminish their importance. They do a good job of summarizing how to approach and how to manage it depending on the severity of the toxicities and the various types of toxicities,” he told this news organization.
Having a paper focused exclusively on the dermatologic side effects of ICIs allows the inclusion of photographs that can help clinicians identify specific conditions that may require referral to a dermatologist, he said.
Both Dr. Anadkat and the authors of the European recommendations noted that dermatologic irAEs are more common with CTLA-4 inhibition than with PD-1/PD-L1 inhibition.
“It has to do with where the target is,” Dr. Anadkat said. “CTLA-4 inhibition works on a central aspect of the immune system, so it’s a much less specific site, whereas PD-1 affects an interaction at the site of the tumor cell itself, so it’s a little more specific.”
Pruritus
ICI-induced pruritus can occur without apparent skin changes, they write, noting that in a recent study of patients with dirAEs, about one-third had isolated pruritus.
The task force members cite a meta-analysis indicating a pruritus incidence of 13.2% for patients treated with nivolumab and 20.2% for patients treated with pembrolizumab but respective grade 3 pruritus rates of only 0.5% and 2.3%. The reported incidence of pruritus with ipilimumab was 47% in a different study.
Recommended treatments include topical moisturizers with or without medium-to-high potency corticosteroids for grade 1 reactions, non-sedating histamines and/or GABA agonists such as pregabalin, or gabapentin for grade 2 pruritus, and suspension of ICIs until pruritus improves in patients with grade 3 pruritus.
Maculopapular rash
Maculopapular or eczema-like rashes may occur in up to 68% of patients who receive a CTLA-4 inhibitor and up to 20% of those who receive a PD1/PD-L1 inhibitor, the authors note. Rashes commonly appear within 3-6 weeks of initiating therapy.
“The clinical presentation is nonspecific and consists of a rapid onset of multiple minimally scaly, erythematous macules and papules, congregating into plaques. Lesions are mostly located on trunk and extensor surfaces of the extremities and the face is generally spared,” they write.
Maculopapular rashes are typically accompanied by itching but could be asymptomatic, they noted.
Mild (grade 1) rashes may respond to moisturizers and topical potent or super-potent corticosteroids. Patients with grade 2 rash should also receive oral antihistamines. Systemic corticosteroids may be considered for patients with grade 3 rashes but only after other dirAEs that may require specific management, such as psoriasis, are ruled out.
Psoriasis-like rash
The most common form of psoriasis seen in patients treated with ICIs is psoriasis vulgaris with plaques, but other clinical variants are also seen, the authors note.
“Topical agents (corticosteroids, Vitamin D analogues) are prescribed in Grades 1/2 and supplementary” to systemic treatment for patients with grade 3 or recalcitrant lesions, they write. “If skin-directed therapies fail to provide symptomatic control,” systemic treatment and narrow band UVB phototherapy “should be considered,” they add.
Evidence regarding the use of systemic therapies to treat psoriasis-like rash associated with ICIs is sparse. Acitretin can be safely used in patients with cancer. Low-dose methotrexate is also safe to use except in patients with non-melanoma skin cancers. Cyclosporine, however, should be avoided because of the potential for tumor-promoting effects, they emphasized.
The recommendations also cover treatment of lichen planus-like and vitiligo-like rashes, as well as hair and nail changes, autoimmune bullous disorders, and oral mucosal dirAEs.
In addition, the recommendations cover severe cutaneous adverse reactions as well as serious, potentially life-threatening dirAEs, including Stevens-Johnson syndrome/TEN, acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DRESS/DIHS).
“The dose of corticosteroids may be adapted to the severity of DRESS. The therapeutic benefit of systemic corticosteroids in the management of SJS/TEN remains controversial, and some authors favor treatment with cyclosporine. However, the use of corticosteroids in this context of ICI treatment appears reasonable and should be proposed. Short courses of steroids seem also effective in AGEP,” the task force members write.
The recommendations did not have outside funding. Of the 19 authors, 6 disclosed relationships with various pharmaceutical companies, including AbbVie, Leo Pharma, Boehringer Ingelheim, Bristol Myers Squibb, and/or Janssen. Dr. Anadkat disclosed previous relationships with Merck, Bristol Myers Squibb, and current relationships with others.
A version of this article first appeared on Medscape.com.
Ways to lessen toxic effects of chemo in older adults
Age-related changes that potentiate adverse drug reactions include alterations in absorption, distribution, metabolism, and excretion. As such, older patients often require adjustments in medications to optimize safety and use. Medication adjustment is especially important for older patients on complex medication regimens for multiple conditions, such as those undergoing cancer treatment. Three recent high-quality randomized trials evaluated the use of geriatric assessment (GA) in older adults with cancer.1-3
Interdisciplinary GA can identify aging-related conditions associated with poor outcomes in older patients with cancer (e.g., toxic effects of chemotherapy) and provide recommendations aimed at improving health outcomes. The results of these trials suggest that interdisciplinary GA can improve care outcomes and oncologists’ communication for older adults with cancer, and should be considered an emerging standard of care.
Geriatric assessment and chemotherapy-related toxic effects
A cluster randomized trial1 at City of Hope National Medical Center conducted between August 2015 and February 2019 enrolled 613 participants and randomly assigned them to receive a GA-guided intervention or usual standard of care in a 2-to-1 ratio. Participants were eligible for the study if they were aged ≥65 years; had a diagnosis of solid malignant neoplasm of any stage; were starting a new chemotherapy regimen; and were fluent in English, Spanish, or Chinese.
The intervention included a GA at baseline followed by assessments focused on six common areas: sleep problems, problems with eating and feeding, incontinence, confusion, evidence of falls, and skin breakdown. An interdisciplinary team (oncologist, nurse practitioner, pharmacist, physical therapist, occupational therapist, social worker, and nutritionist) performed the assessment and developed a plan of care. Interventions were multifactorial and could include referral to specialists; recommendations for medication changes; symptom management; nutritional intervention with diet recommendations and supplementation; and interventions targeting social, spiritual, and functional well-being. Follow-up by a nurse practitioner continued until completion of chemotherapy or 6 months after starting chemotherapy, whichever was earlier.
The primary outcome was grade 3 or higher chemotherapy-related toxic effects using National Cancer Institute criteria, and secondary outcomes were advance directive completion, emergency room visits and unplanned hospitalizations, and survival up to 12 months. Results showed a 10% absolute reduction in the incidence of grade 3 or higher toxic effects (P = .02), with a number needed to treat of 10. Advance directive completion also increased by 15%, but no differences were observed for other outcomes. This study offers high-quality evidence that a GA-based intervention can reduce toxic effects of chemotherapy regimens for older adults with cancer.
Geriatric assessment in community oncology practices
A recent study by Supriya G. Mohile, MD, and colleagues2 is the first nationwide multicenter clinical trial to demonstrate the effects of GA and GA-guided management. This study was conducted in 40 oncology practices from the University of Rochester National Cancer Institute Community Oncology Research Program network. Centers were randomly assigned to intervention or usual care (362 patients treated by 68 oncologists in the intervention group and 371 patients treated by 91 oncologists in the usual-care group). Eligibility criteria were age ≥70 years; impairment in at least one GA domain other than polypharmacy; incurable advanced solid tumor or lymphoma with a plan to start new cancer treatment with a high risk for toxic effects within 4 weeks; and English language fluency. Both study groups underwent a baseline GA that assessed patients’ physical performance, functional status, comorbidity, cognition, nutrition, social support, polypharmacy, and psychological status. For the intervention group, a summary and management recommendations were provided to the treating oncologists.
The primary outcome was grade 3 or higher toxic effects within 3 months of starting a new regimen; secondary outcomes included treatment intensity and survival and GA outcomes within 3 months. A smaller proportion of patients in the intervention group experienced toxicity (51% vs. 71%), with an absolute risk reduction of 20%. Patients in the intervention group also had fewer falls and a greater reduction in medications used; there were no other differences in secondary outcomes. This study offers very strong and generalizable evidence that incorporating GA in the care of older adults with cancer at risk for toxicity can reduce toxicity as well as improve other outcomes, such as falls and polypharmacy.
Geriatric assessment and oncologist-patient communication
A secondary analysis3 of data from Dr. Mohile and colleagues2 evaluated the effect of GA-guided recommendations on oncologist-patient communication regarding comorbidities. Patients (n = 541) included in this analysis were 76.6 years of age on average and had 3.2 (standard deviation, 1.9) comorbid conditions. All patients underwent GA, but only oncologists in the intervention arm received GA-based recommendations. Clinical encounters between oncologist and patient immediately following the GA were audio recorded and analyzed to examine communication between oncologists and participants as it relates to chronic comorbid conditions.
In the intervention arm, more discussions regarding comorbidities took place, and more participants’ concerns about comorbidities were acknowledged. More importantly, participants in the intervention group were 2.4 times more likely to have their concerns about comorbidities addressed through referral or education, compared with the usual-care group (P = .004). Moreover, 41% of oncologists in the intervention arm modified dosage or cancer treatment schedule because of concern about tolerability or comorbidities. This study demonstrates beneficial effects of GA in increasing communication and perhaps consideration of comorbidities of older adults when planning cancer treatment.
Dr. Hung is professor of geriatrics and palliative care at Mount Sinai Hospital, New York. He disclosed no relevant conflicts of interest.
References
1. Li D et al. JAMA Oncol. 2021;7:e214158.
2. Mohile SG et al. Lancet. 2021;398:1894-1904.
3. Kleckner AS et al. JCO Oncol Pract. 2022;18:e9-19.
A version of this article first appeared on Medscape.com.
Age-related changes that potentiate adverse drug reactions include alterations in absorption, distribution, metabolism, and excretion. As such, older patients often require adjustments in medications to optimize safety and use. Medication adjustment is especially important for older patients on complex medication regimens for multiple conditions, such as those undergoing cancer treatment. Three recent high-quality randomized trials evaluated the use of geriatric assessment (GA) in older adults with cancer.1-3
Interdisciplinary GA can identify aging-related conditions associated with poor outcomes in older patients with cancer (e.g., toxic effects of chemotherapy) and provide recommendations aimed at improving health outcomes. The results of these trials suggest that interdisciplinary GA can improve care outcomes and oncologists’ communication for older adults with cancer, and should be considered an emerging standard of care.
Geriatric assessment and chemotherapy-related toxic effects
A cluster randomized trial1 at City of Hope National Medical Center conducted between August 2015 and February 2019 enrolled 613 participants and randomly assigned them to receive a GA-guided intervention or usual standard of care in a 2-to-1 ratio. Participants were eligible for the study if they were aged ≥65 years; had a diagnosis of solid malignant neoplasm of any stage; were starting a new chemotherapy regimen; and were fluent in English, Spanish, or Chinese.
The intervention included a GA at baseline followed by assessments focused on six common areas: sleep problems, problems with eating and feeding, incontinence, confusion, evidence of falls, and skin breakdown. An interdisciplinary team (oncologist, nurse practitioner, pharmacist, physical therapist, occupational therapist, social worker, and nutritionist) performed the assessment and developed a plan of care. Interventions were multifactorial and could include referral to specialists; recommendations for medication changes; symptom management; nutritional intervention with diet recommendations and supplementation; and interventions targeting social, spiritual, and functional well-being. Follow-up by a nurse practitioner continued until completion of chemotherapy or 6 months after starting chemotherapy, whichever was earlier.
The primary outcome was grade 3 or higher chemotherapy-related toxic effects using National Cancer Institute criteria, and secondary outcomes were advance directive completion, emergency room visits and unplanned hospitalizations, and survival up to 12 months. Results showed a 10% absolute reduction in the incidence of grade 3 or higher toxic effects (P = .02), with a number needed to treat of 10. Advance directive completion also increased by 15%, but no differences were observed for other outcomes. This study offers high-quality evidence that a GA-based intervention can reduce toxic effects of chemotherapy regimens for older adults with cancer.
Geriatric assessment in community oncology practices
A recent study by Supriya G. Mohile, MD, and colleagues2 is the first nationwide multicenter clinical trial to demonstrate the effects of GA and GA-guided management. This study was conducted in 40 oncology practices from the University of Rochester National Cancer Institute Community Oncology Research Program network. Centers were randomly assigned to intervention or usual care (362 patients treated by 68 oncologists in the intervention group and 371 patients treated by 91 oncologists in the usual-care group). Eligibility criteria were age ≥70 years; impairment in at least one GA domain other than polypharmacy; incurable advanced solid tumor or lymphoma with a plan to start new cancer treatment with a high risk for toxic effects within 4 weeks; and English language fluency. Both study groups underwent a baseline GA that assessed patients’ physical performance, functional status, comorbidity, cognition, nutrition, social support, polypharmacy, and psychological status. For the intervention group, a summary and management recommendations were provided to the treating oncologists.
The primary outcome was grade 3 or higher toxic effects within 3 months of starting a new regimen; secondary outcomes included treatment intensity and survival and GA outcomes within 3 months. A smaller proportion of patients in the intervention group experienced toxicity (51% vs. 71%), with an absolute risk reduction of 20%. Patients in the intervention group also had fewer falls and a greater reduction in medications used; there were no other differences in secondary outcomes. This study offers very strong and generalizable evidence that incorporating GA in the care of older adults with cancer at risk for toxicity can reduce toxicity as well as improve other outcomes, such as falls and polypharmacy.
Geriatric assessment and oncologist-patient communication
A secondary analysis3 of data from Dr. Mohile and colleagues2 evaluated the effect of GA-guided recommendations on oncologist-patient communication regarding comorbidities. Patients (n = 541) included in this analysis were 76.6 years of age on average and had 3.2 (standard deviation, 1.9) comorbid conditions. All patients underwent GA, but only oncologists in the intervention arm received GA-based recommendations. Clinical encounters between oncologist and patient immediately following the GA were audio recorded and analyzed to examine communication between oncologists and participants as it relates to chronic comorbid conditions.
In the intervention arm, more discussions regarding comorbidities took place, and more participants’ concerns about comorbidities were acknowledged. More importantly, participants in the intervention group were 2.4 times more likely to have their concerns about comorbidities addressed through referral or education, compared with the usual-care group (P = .004). Moreover, 41% of oncologists in the intervention arm modified dosage or cancer treatment schedule because of concern about tolerability or comorbidities. This study demonstrates beneficial effects of GA in increasing communication and perhaps consideration of comorbidities of older adults when planning cancer treatment.
Dr. Hung is professor of geriatrics and palliative care at Mount Sinai Hospital, New York. He disclosed no relevant conflicts of interest.
References
1. Li D et al. JAMA Oncol. 2021;7:e214158.
2. Mohile SG et al. Lancet. 2021;398:1894-1904.
3. Kleckner AS et al. JCO Oncol Pract. 2022;18:e9-19.
A version of this article first appeared on Medscape.com.
Age-related changes that potentiate adverse drug reactions include alterations in absorption, distribution, metabolism, and excretion. As such, older patients often require adjustments in medications to optimize safety and use. Medication adjustment is especially important for older patients on complex medication regimens for multiple conditions, such as those undergoing cancer treatment. Three recent high-quality randomized trials evaluated the use of geriatric assessment (GA) in older adults with cancer.1-3
Interdisciplinary GA can identify aging-related conditions associated with poor outcomes in older patients with cancer (e.g., toxic effects of chemotherapy) and provide recommendations aimed at improving health outcomes. The results of these trials suggest that interdisciplinary GA can improve care outcomes and oncologists’ communication for older adults with cancer, and should be considered an emerging standard of care.
Geriatric assessment and chemotherapy-related toxic effects
A cluster randomized trial1 at City of Hope National Medical Center conducted between August 2015 and February 2019 enrolled 613 participants and randomly assigned them to receive a GA-guided intervention or usual standard of care in a 2-to-1 ratio. Participants were eligible for the study if they were aged ≥65 years; had a diagnosis of solid malignant neoplasm of any stage; were starting a new chemotherapy regimen; and were fluent in English, Spanish, or Chinese.
The intervention included a GA at baseline followed by assessments focused on six common areas: sleep problems, problems with eating and feeding, incontinence, confusion, evidence of falls, and skin breakdown. An interdisciplinary team (oncologist, nurse practitioner, pharmacist, physical therapist, occupational therapist, social worker, and nutritionist) performed the assessment and developed a plan of care. Interventions were multifactorial and could include referral to specialists; recommendations for medication changes; symptom management; nutritional intervention with diet recommendations and supplementation; and interventions targeting social, spiritual, and functional well-being. Follow-up by a nurse practitioner continued until completion of chemotherapy or 6 months after starting chemotherapy, whichever was earlier.
The primary outcome was grade 3 or higher chemotherapy-related toxic effects using National Cancer Institute criteria, and secondary outcomes were advance directive completion, emergency room visits and unplanned hospitalizations, and survival up to 12 months. Results showed a 10% absolute reduction in the incidence of grade 3 or higher toxic effects (P = .02), with a number needed to treat of 10. Advance directive completion also increased by 15%, but no differences were observed for other outcomes. This study offers high-quality evidence that a GA-based intervention can reduce toxic effects of chemotherapy regimens for older adults with cancer.
Geriatric assessment in community oncology practices
A recent study by Supriya G. Mohile, MD, and colleagues2 is the first nationwide multicenter clinical trial to demonstrate the effects of GA and GA-guided management. This study was conducted in 40 oncology practices from the University of Rochester National Cancer Institute Community Oncology Research Program network. Centers were randomly assigned to intervention or usual care (362 patients treated by 68 oncologists in the intervention group and 371 patients treated by 91 oncologists in the usual-care group). Eligibility criteria were age ≥70 years; impairment in at least one GA domain other than polypharmacy; incurable advanced solid tumor or lymphoma with a plan to start new cancer treatment with a high risk for toxic effects within 4 weeks; and English language fluency. Both study groups underwent a baseline GA that assessed patients’ physical performance, functional status, comorbidity, cognition, nutrition, social support, polypharmacy, and psychological status. For the intervention group, a summary and management recommendations were provided to the treating oncologists.
The primary outcome was grade 3 or higher toxic effects within 3 months of starting a new regimen; secondary outcomes included treatment intensity and survival and GA outcomes within 3 months. A smaller proportion of patients in the intervention group experienced toxicity (51% vs. 71%), with an absolute risk reduction of 20%. Patients in the intervention group also had fewer falls and a greater reduction in medications used; there were no other differences in secondary outcomes. This study offers very strong and generalizable evidence that incorporating GA in the care of older adults with cancer at risk for toxicity can reduce toxicity as well as improve other outcomes, such as falls and polypharmacy.
Geriatric assessment and oncologist-patient communication
A secondary analysis3 of data from Dr. Mohile and colleagues2 evaluated the effect of GA-guided recommendations on oncologist-patient communication regarding comorbidities. Patients (n = 541) included in this analysis were 76.6 years of age on average and had 3.2 (standard deviation, 1.9) comorbid conditions. All patients underwent GA, but only oncologists in the intervention arm received GA-based recommendations. Clinical encounters between oncologist and patient immediately following the GA were audio recorded and analyzed to examine communication between oncologists and participants as it relates to chronic comorbid conditions.
In the intervention arm, more discussions regarding comorbidities took place, and more participants’ concerns about comorbidities were acknowledged. More importantly, participants in the intervention group were 2.4 times more likely to have their concerns about comorbidities addressed through referral or education, compared with the usual-care group (P = .004). Moreover, 41% of oncologists in the intervention arm modified dosage or cancer treatment schedule because of concern about tolerability or comorbidities. This study demonstrates beneficial effects of GA in increasing communication and perhaps consideration of comorbidities of older adults when planning cancer treatment.
Dr. Hung is professor of geriatrics and palliative care at Mount Sinai Hospital, New York. He disclosed no relevant conflicts of interest.
References
1. Li D et al. JAMA Oncol. 2021;7:e214158.
2. Mohile SG et al. Lancet. 2021;398:1894-1904.
3. Kleckner AS et al. JCO Oncol Pract. 2022;18:e9-19.
A version of this article first appeared on Medscape.com.
Complex link between gut microbiome and immunotherapy response in advanced melanoma
A large-scale than previously thought.
Overall, researchers identified a panel of species, including Roseburia spp. and Akkermansia muciniphila, associated with responses to ICI therapy. However, no single species was a “fully consistent biomarker” across the studies, the authors explain.
This “machine learning analysis confirmed the link between the microbiome and overall response rates (ORRs) and progression-free survival (PFS) with ICIs but also revealed limited reproducibility of microbiome-based signatures across cohorts,” Karla A. Lee, PhD, a clinical research fellow at King’s College London, and colleagues report. The results suggest that “the microbiome is predictive of response in some, but not all, cohorts.”
The findings were published online Feb. 28 in Nature Medicine.
Despite recent advances in targeted therapies for melanoma, less than half of the those who receive a single-agent ICI respond, and those who receive combination ICI therapy often suffer from severe drug toxicity problems. That is why finding patients more likely to respond to a single-agent ICI has become a priority.
Previous studies have identified the gut microbiome as “a potential biomarker of response, as well as a therapeutic target” in melanoma and other malignancies, but “little consensus exists on which microbiome characteristics are associated with treatment responses in the human setting,” the authors explain.
To further clarify the microbiome–immunotherapy relationship, the researchers performed metagenomic sequencing of stool samples collected from 165 ICI-naive patients with unresectable stage III or IV cutaneous melanoma from 5 observational cohorts in the Netherlands, United Kingdom, and Spain. These data were integrated with 147 samples from publicly available datasets.
First, the authors highlighted the variability in findings across these observational studies. For instance, they analyzed stool samples from one UK-based observational study of patients with melanoma (PRIMM-UK) and found a small but statistically significant difference in the microbiome composition of immunotherapy responders versus nonresponders (P = .05) but did not find such an association in a parallel study in the Netherlands (PRIMM-NL, P = .61).
The investigators also explored biomarkers of response across different cohorts and found several standouts. In trials using ORR as an endpoint, two uncultivated Roseburia species (CAG:182 and CAG:471) were associated with responses to ICIs. For patients with available PFS data, Phascolarctobacterium succinatutens and Lactobacillus vaginalis were “enriched in responders” across 7 datasets and significant in 3 of the 8 meta-analysis approaches. A muciniphila and Dorea formicigenerans were also associated with ORR and PFS at 12 months in several meta-analyses.
However, “no single bacterium was a fully consistent biomarker of response across all datasets,” the authors wrote.
Still, the findings could have important implications for the more than 50% of patients with advanced melanoma who don’t respond to single-agent ICI therapy.
“Our study shows that studying the microbiome is important to improve and personalize immunotherapy treatments for melanoma,” study coauthor Nicola Segata, PhD, principal investigator in the Laboratory of Computational Metagenomics, University of Trento, Italy, said in a press release. “However, it also suggests that because of the person-to-person variability of the gut microbiome, even larger studies must be carried out to understand the specific gut microbial features that are more likely to lead to a positive response to immunotherapy.”
Coauthor Tim Spector, PhD, head of the Department of Twin Research & Genetic Epidemiology at King’s College London, added that “the ultimate goal is to identify which specific features of the microbiome are directly influencing the clinical benefits of immunotherapy to exploit these features in new personalized approaches to support cancer immunotherapy.”
In the meantime, he said, “this study highlights the potential impact of good diet and gut health on chances of survival in patients undergoing immunotherapy.”
This study was coordinated by King’s College London, CIBIO Department of the University of Trento and European Institute of Oncology in Italy, and the University of Groningen in the Netherlands, and was funded by the Seerave Foundation. Dr. Lee, Dr. Segata, and Dr. Spector have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A large-scale than previously thought.
Overall, researchers identified a panel of species, including Roseburia spp. and Akkermansia muciniphila, associated with responses to ICI therapy. However, no single species was a “fully consistent biomarker” across the studies, the authors explain.
This “machine learning analysis confirmed the link between the microbiome and overall response rates (ORRs) and progression-free survival (PFS) with ICIs but also revealed limited reproducibility of microbiome-based signatures across cohorts,” Karla A. Lee, PhD, a clinical research fellow at King’s College London, and colleagues report. The results suggest that “the microbiome is predictive of response in some, but not all, cohorts.”
The findings were published online Feb. 28 in Nature Medicine.
Despite recent advances in targeted therapies for melanoma, less than half of the those who receive a single-agent ICI respond, and those who receive combination ICI therapy often suffer from severe drug toxicity problems. That is why finding patients more likely to respond to a single-agent ICI has become a priority.
Previous studies have identified the gut microbiome as “a potential biomarker of response, as well as a therapeutic target” in melanoma and other malignancies, but “little consensus exists on which microbiome characteristics are associated with treatment responses in the human setting,” the authors explain.
To further clarify the microbiome–immunotherapy relationship, the researchers performed metagenomic sequencing of stool samples collected from 165 ICI-naive patients with unresectable stage III or IV cutaneous melanoma from 5 observational cohorts in the Netherlands, United Kingdom, and Spain. These data were integrated with 147 samples from publicly available datasets.
First, the authors highlighted the variability in findings across these observational studies. For instance, they analyzed stool samples from one UK-based observational study of patients with melanoma (PRIMM-UK) and found a small but statistically significant difference in the microbiome composition of immunotherapy responders versus nonresponders (P = .05) but did not find such an association in a parallel study in the Netherlands (PRIMM-NL, P = .61).
The investigators also explored biomarkers of response across different cohorts and found several standouts. In trials using ORR as an endpoint, two uncultivated Roseburia species (CAG:182 and CAG:471) were associated with responses to ICIs. For patients with available PFS data, Phascolarctobacterium succinatutens and Lactobacillus vaginalis were “enriched in responders” across 7 datasets and significant in 3 of the 8 meta-analysis approaches. A muciniphila and Dorea formicigenerans were also associated with ORR and PFS at 12 months in several meta-analyses.
However, “no single bacterium was a fully consistent biomarker of response across all datasets,” the authors wrote.
Still, the findings could have important implications for the more than 50% of patients with advanced melanoma who don’t respond to single-agent ICI therapy.
“Our study shows that studying the microbiome is important to improve and personalize immunotherapy treatments for melanoma,” study coauthor Nicola Segata, PhD, principal investigator in the Laboratory of Computational Metagenomics, University of Trento, Italy, said in a press release. “However, it also suggests that because of the person-to-person variability of the gut microbiome, even larger studies must be carried out to understand the specific gut microbial features that are more likely to lead to a positive response to immunotherapy.”
Coauthor Tim Spector, PhD, head of the Department of Twin Research & Genetic Epidemiology at King’s College London, added that “the ultimate goal is to identify which specific features of the microbiome are directly influencing the clinical benefits of immunotherapy to exploit these features in new personalized approaches to support cancer immunotherapy.”
In the meantime, he said, “this study highlights the potential impact of good diet and gut health on chances of survival in patients undergoing immunotherapy.”
This study was coordinated by King’s College London, CIBIO Department of the University of Trento and European Institute of Oncology in Italy, and the University of Groningen in the Netherlands, and was funded by the Seerave Foundation. Dr. Lee, Dr. Segata, and Dr. Spector have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A large-scale than previously thought.
Overall, researchers identified a panel of species, including Roseburia spp. and Akkermansia muciniphila, associated with responses to ICI therapy. However, no single species was a “fully consistent biomarker” across the studies, the authors explain.
This “machine learning analysis confirmed the link between the microbiome and overall response rates (ORRs) and progression-free survival (PFS) with ICIs but also revealed limited reproducibility of microbiome-based signatures across cohorts,” Karla A. Lee, PhD, a clinical research fellow at King’s College London, and colleagues report. The results suggest that “the microbiome is predictive of response in some, but not all, cohorts.”
The findings were published online Feb. 28 in Nature Medicine.
Despite recent advances in targeted therapies for melanoma, less than half of the those who receive a single-agent ICI respond, and those who receive combination ICI therapy often suffer from severe drug toxicity problems. That is why finding patients more likely to respond to a single-agent ICI has become a priority.
Previous studies have identified the gut microbiome as “a potential biomarker of response, as well as a therapeutic target” in melanoma and other malignancies, but “little consensus exists on which microbiome characteristics are associated with treatment responses in the human setting,” the authors explain.
To further clarify the microbiome–immunotherapy relationship, the researchers performed metagenomic sequencing of stool samples collected from 165 ICI-naive patients with unresectable stage III or IV cutaneous melanoma from 5 observational cohorts in the Netherlands, United Kingdom, and Spain. These data were integrated with 147 samples from publicly available datasets.
First, the authors highlighted the variability in findings across these observational studies. For instance, they analyzed stool samples from one UK-based observational study of patients with melanoma (PRIMM-UK) and found a small but statistically significant difference in the microbiome composition of immunotherapy responders versus nonresponders (P = .05) but did not find such an association in a parallel study in the Netherlands (PRIMM-NL, P = .61).
The investigators also explored biomarkers of response across different cohorts and found several standouts. In trials using ORR as an endpoint, two uncultivated Roseburia species (CAG:182 and CAG:471) were associated with responses to ICIs. For patients with available PFS data, Phascolarctobacterium succinatutens and Lactobacillus vaginalis were “enriched in responders” across 7 datasets and significant in 3 of the 8 meta-analysis approaches. A muciniphila and Dorea formicigenerans were also associated with ORR and PFS at 12 months in several meta-analyses.
However, “no single bacterium was a fully consistent biomarker of response across all datasets,” the authors wrote.
Still, the findings could have important implications for the more than 50% of patients with advanced melanoma who don’t respond to single-agent ICI therapy.
“Our study shows that studying the microbiome is important to improve and personalize immunotherapy treatments for melanoma,” study coauthor Nicola Segata, PhD, principal investigator in the Laboratory of Computational Metagenomics, University of Trento, Italy, said in a press release. “However, it also suggests that because of the person-to-person variability of the gut microbiome, even larger studies must be carried out to understand the specific gut microbial features that are more likely to lead to a positive response to immunotherapy.”
Coauthor Tim Spector, PhD, head of the Department of Twin Research & Genetic Epidemiology at King’s College London, added that “the ultimate goal is to identify which specific features of the microbiome are directly influencing the clinical benefits of immunotherapy to exploit these features in new personalized approaches to support cancer immunotherapy.”
In the meantime, he said, “this study highlights the potential impact of good diet and gut health on chances of survival in patients undergoing immunotherapy.”
This study was coordinated by King’s College London, CIBIO Department of the University of Trento and European Institute of Oncology in Italy, and the University of Groningen in the Netherlands, and was funded by the Seerave Foundation. Dr. Lee, Dr. Segata, and Dr. Spector have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
At-Home Treatment of Pigmented Lesions With a Zinc Chloride Preparation
To the Editor:
Zinc chloride originally was used by Dr. Frederic Mohs as an in vivo tissue fixative during the early phases of Mohs micrographic surgery.1 Although this technique has since been replaced with fresh frozen tissue fixation, zinc chloride still is found in topical preparations that are readily available to patients. Specifically, black salve describes variably composed topical preparations that share the common ingredients zinc chloride and Sanguinaria canadensis (bloodroot).2 Patients self-treat with these unregulated compounds, but the majority do not have their lesions evaluated by a clinician prior to use and are unaware of the potential risks.3-5 Products containing zinc chloride and S canadensis that are not marketed as black salve present a new problem for the dermatology community.
A 73-year-old man presented to our dermatology clinic for the focused evaluation of scaly lesions on the face and nose. At this visit, it was recommended he undergo a total-body skin examination for skin cancer screening given his age and substantial photodamage.
Physical examination revealed more than 20 superficial, 3- to 10-mm scars predominantly over the trunk. One scar over the left mid-back had a large, 1.2-cm peripheral rim of dark brown pigment that was clinically concerning for a melanocytic neoplasm. Shave removal of this lesion was performed. Histologic examination showed melanoma in situ with a central scar. The central scar spanned the depth of the dermis, and the melanocytic component was absent in this area, raising the question if prior biopsy or treatment had been performed on this lesion. During a discussion of the results with the patient, he was questioned about prior biopsy or treatment of this lesion. He reported prior use of a topical all-natural cream containing zinc chloride and S canadensis that he purchased online, which he had used to treat this lesion as well as numerous presumed moles.
The trend of at-home mole removal products containing the traditional ingredients in black salve seems to be one of rapidly shifting product availability as well as a departure from marketing items as black salve. Many prior black salve products are no longer available.4 The product that our patient used is a topical cream marketed as a treatment for moles and skin tags.6 Despite not being marketed as black salve, it does contain zinc chloride and S canadensis. The product’s website highlights these ingredients as being a safe and effective treatment for mole removal, with claims that the product will remove the mole or skin tag without irritating the surrounding skin and can be safely used anywhere on the body without scarring.6 A Google search at the time this article was written using the term skin tag remover revealed similar products marketed as all-natural “skin tag remover and mole corrector creams.” These similar products containing zinc chloride and S canadensis were available in the United States at the time of our initial research but have since been removed and only are available outside of the United States.7
Prior reports of melanoma masked by zinc chloride and S canadensis described the use of topical agents marketed as black salve. This new wave of products marketed as all-natural creams makes continued education on the available products and their associated risks necessary for clinicians. The lack of US Food and Drug Administration oversight for these products and their frequent introduction and discontinuation in the market makes keeping updated even more challenging. Because many patients self-treat without prior evaluation by a health care provider, treatment with these products can lead to a delay in diagnosis or inaccurate staging due to scars from the chemical destruction, both of which may have occurred in our patient.5 Until these products become regulated by the US Food and Drug Administration, it is imperative that clinicians continue to educate their patients on the lack of documented benefit and clear risks of their use as well as remain up-to-date on product trends.
- Cohen DK. Mohs micrographic surgery: past, present, and future. Dermatol Surg. 2019;45:329-339. doi:10.1097/DSS.0000000000001701
- Eastman KL. A review of topical corrosive black salve. J Altern Complement Med. 2014;20:284-289. doi:10.1089/acm.2012.0377
- Sivyer GW, Rosendahl C. Application of black salve to a thin melanoma that subsequently progressed to metastatic melanoma: a case study. Dermatol Pract Concept. 2014;4:77-80. doi:10.5826/dpc.0403a16
- McDaniel S. Consequences of using escharotic agents as primary treatment for nonmelanoma skin cancer. Arch Dermatol. 2002;138:1593-1596.
- Clark JJ. Community perceptions about the use of black salve. J Am Acad Dermatol. 2016;74:1021-1023. doi:10.1016/j.jaad.2015.10.016
- Skinprov Cream. Skinprov. Accessed February 22, 2022. https://skinprov.net
- HaloDerm. HaloDerm Inc. Accessed February 22, 2022. https://haloderm.com/
To the Editor:
Zinc chloride originally was used by Dr. Frederic Mohs as an in vivo tissue fixative during the early phases of Mohs micrographic surgery.1 Although this technique has since been replaced with fresh frozen tissue fixation, zinc chloride still is found in topical preparations that are readily available to patients. Specifically, black salve describes variably composed topical preparations that share the common ingredients zinc chloride and Sanguinaria canadensis (bloodroot).2 Patients self-treat with these unregulated compounds, but the majority do not have their lesions evaluated by a clinician prior to use and are unaware of the potential risks.3-5 Products containing zinc chloride and S canadensis that are not marketed as black salve present a new problem for the dermatology community.
A 73-year-old man presented to our dermatology clinic for the focused evaluation of scaly lesions on the face and nose. At this visit, it was recommended he undergo a total-body skin examination for skin cancer screening given his age and substantial photodamage.
Physical examination revealed more than 20 superficial, 3- to 10-mm scars predominantly over the trunk. One scar over the left mid-back had a large, 1.2-cm peripheral rim of dark brown pigment that was clinically concerning for a melanocytic neoplasm. Shave removal of this lesion was performed. Histologic examination showed melanoma in situ with a central scar. The central scar spanned the depth of the dermis, and the melanocytic component was absent in this area, raising the question if prior biopsy or treatment had been performed on this lesion. During a discussion of the results with the patient, he was questioned about prior biopsy or treatment of this lesion. He reported prior use of a topical all-natural cream containing zinc chloride and S canadensis that he purchased online, which he had used to treat this lesion as well as numerous presumed moles.
The trend of at-home mole removal products containing the traditional ingredients in black salve seems to be one of rapidly shifting product availability as well as a departure from marketing items as black salve. Many prior black salve products are no longer available.4 The product that our patient used is a topical cream marketed as a treatment for moles and skin tags.6 Despite not being marketed as black salve, it does contain zinc chloride and S canadensis. The product’s website highlights these ingredients as being a safe and effective treatment for mole removal, with claims that the product will remove the mole or skin tag without irritating the surrounding skin and can be safely used anywhere on the body without scarring.6 A Google search at the time this article was written using the term skin tag remover revealed similar products marketed as all-natural “skin tag remover and mole corrector creams.” These similar products containing zinc chloride and S canadensis were available in the United States at the time of our initial research but have since been removed and only are available outside of the United States.7
Prior reports of melanoma masked by zinc chloride and S canadensis described the use of topical agents marketed as black salve. This new wave of products marketed as all-natural creams makes continued education on the available products and their associated risks necessary for clinicians. The lack of US Food and Drug Administration oversight for these products and their frequent introduction and discontinuation in the market makes keeping updated even more challenging. Because many patients self-treat without prior evaluation by a health care provider, treatment with these products can lead to a delay in diagnosis or inaccurate staging due to scars from the chemical destruction, both of which may have occurred in our patient.5 Until these products become regulated by the US Food and Drug Administration, it is imperative that clinicians continue to educate their patients on the lack of documented benefit and clear risks of their use as well as remain up-to-date on product trends.
To the Editor:
Zinc chloride originally was used by Dr. Frederic Mohs as an in vivo tissue fixative during the early phases of Mohs micrographic surgery.1 Although this technique has since been replaced with fresh frozen tissue fixation, zinc chloride still is found in topical preparations that are readily available to patients. Specifically, black salve describes variably composed topical preparations that share the common ingredients zinc chloride and Sanguinaria canadensis (bloodroot).2 Patients self-treat with these unregulated compounds, but the majority do not have their lesions evaluated by a clinician prior to use and are unaware of the potential risks.3-5 Products containing zinc chloride and S canadensis that are not marketed as black salve present a new problem for the dermatology community.
A 73-year-old man presented to our dermatology clinic for the focused evaluation of scaly lesions on the face and nose. At this visit, it was recommended he undergo a total-body skin examination for skin cancer screening given his age and substantial photodamage.
Physical examination revealed more than 20 superficial, 3- to 10-mm scars predominantly over the trunk. One scar over the left mid-back had a large, 1.2-cm peripheral rim of dark brown pigment that was clinically concerning for a melanocytic neoplasm. Shave removal of this lesion was performed. Histologic examination showed melanoma in situ with a central scar. The central scar spanned the depth of the dermis, and the melanocytic component was absent in this area, raising the question if prior biopsy or treatment had been performed on this lesion. During a discussion of the results with the patient, he was questioned about prior biopsy or treatment of this lesion. He reported prior use of a topical all-natural cream containing zinc chloride and S canadensis that he purchased online, which he had used to treat this lesion as well as numerous presumed moles.
The trend of at-home mole removal products containing the traditional ingredients in black salve seems to be one of rapidly shifting product availability as well as a departure from marketing items as black salve. Many prior black salve products are no longer available.4 The product that our patient used is a topical cream marketed as a treatment for moles and skin tags.6 Despite not being marketed as black salve, it does contain zinc chloride and S canadensis. The product’s website highlights these ingredients as being a safe and effective treatment for mole removal, with claims that the product will remove the mole or skin tag without irritating the surrounding skin and can be safely used anywhere on the body without scarring.6 A Google search at the time this article was written using the term skin tag remover revealed similar products marketed as all-natural “skin tag remover and mole corrector creams.” These similar products containing zinc chloride and S canadensis were available in the United States at the time of our initial research but have since been removed and only are available outside of the United States.7
Prior reports of melanoma masked by zinc chloride and S canadensis described the use of topical agents marketed as black salve. This new wave of products marketed as all-natural creams makes continued education on the available products and their associated risks necessary for clinicians. The lack of US Food and Drug Administration oversight for these products and their frequent introduction and discontinuation in the market makes keeping updated even more challenging. Because many patients self-treat without prior evaluation by a health care provider, treatment with these products can lead to a delay in diagnosis or inaccurate staging due to scars from the chemical destruction, both of which may have occurred in our patient.5 Until these products become regulated by the US Food and Drug Administration, it is imperative that clinicians continue to educate their patients on the lack of documented benefit and clear risks of their use as well as remain up-to-date on product trends.
- Cohen DK. Mohs micrographic surgery: past, present, and future. Dermatol Surg. 2019;45:329-339. doi:10.1097/DSS.0000000000001701
- Eastman KL. A review of topical corrosive black salve. J Altern Complement Med. 2014;20:284-289. doi:10.1089/acm.2012.0377
- Sivyer GW, Rosendahl C. Application of black salve to a thin melanoma that subsequently progressed to metastatic melanoma: a case study. Dermatol Pract Concept. 2014;4:77-80. doi:10.5826/dpc.0403a16
- McDaniel S. Consequences of using escharotic agents as primary treatment for nonmelanoma skin cancer. Arch Dermatol. 2002;138:1593-1596.
- Clark JJ. Community perceptions about the use of black salve. J Am Acad Dermatol. 2016;74:1021-1023. doi:10.1016/j.jaad.2015.10.016
- Skinprov Cream. Skinprov. Accessed February 22, 2022. https://skinprov.net
- HaloDerm. HaloDerm Inc. Accessed February 22, 2022. https://haloderm.com/
- Cohen DK. Mohs micrographic surgery: past, present, and future. Dermatol Surg. 2019;45:329-339. doi:10.1097/DSS.0000000000001701
- Eastman KL. A review of topical corrosive black salve. J Altern Complement Med. 2014;20:284-289. doi:10.1089/acm.2012.0377
- Sivyer GW, Rosendahl C. Application of black salve to a thin melanoma that subsequently progressed to metastatic melanoma: a case study. Dermatol Pract Concept. 2014;4:77-80. doi:10.5826/dpc.0403a16
- McDaniel S. Consequences of using escharotic agents as primary treatment for nonmelanoma skin cancer. Arch Dermatol. 2002;138:1593-1596.
- Clark JJ. Community perceptions about the use of black salve. J Am Acad Dermatol. 2016;74:1021-1023. doi:10.1016/j.jaad.2015.10.016
- Skinprov Cream. Skinprov. Accessed February 22, 2022. https://skinprov.net
- HaloDerm. HaloDerm Inc. Accessed February 22, 2022. https://haloderm.com/
Practice Points
- Zinc chloride preparations are readily available over the counter and unregulated.
- Patients may attempt to self-treat pigmented lesions based on claims they see online.
- When asking patients about prior treatments, it may be prudent to specifically ask about over-the-counter products and their ingredients.
High early recurrence rates with Merkel cell carcinoma
, and more than half of all patients with stage IV disease will have a recurrence within 1 year of definitive therapy, results of a new study show.
A study of 618 patients with MCC who were enrolled in a Seattle-based data repository shows that among all patients the 5-year recurrence rate was 40%. The risk of recurrence within the first year was 11% for patients with pathologic stage I disease, 33% for those with stage IIA/IIB disease, 45% for those with stage IIIB disease, and 58% for patients with pathologic stage IV MCC.
Approximately 95% of all recurrences happened within 3 years of the initial diagnosis, report Aubriana McEvoy, MD, from the University of Washington in Seattle, and colleagues.
“This cohort study indicates that the highest yield (and likely most cost-effective) time period for detecting MCC recurrence is 1-3 years after diagnosis,” they write in a study published online in JAMA Dermatology.
The estimated annual incidence of MCC in the United States in 2018 was 2,000 according to the American Cancer Society. The annual incidence rate is rising rapidly, however, and is estimated to reach 3,284 by 2025, McEvoy and colleagues write.
Although MCC is known to have high recurrence rates and is associated with a higher mortality rate than malignant melanoma, recurrence rate data are not captured by either the Surveillance, Epidemiology, and End Results (SEER) database or by the National Cancer Database. As a result, estimates of recurrence rates with MCC have been all over the map, ranging from 27% to 77%, depending on the population studied.
But as senior author Paul Nghiem, MD, PhD, professor and chair of dermatology at the University of Washington, Seattle, told this news organization, recurrence rates over time in their study were remarkably consistent.
“The biggest surprise to me was that, when we broke our nearly 20-year cohort into three 5- or 6-year chunks, every one of the groups had a 40% recurrence rate, within 1%. So we feel really confident that’s the right number,” he said.
Dr. Nghiem and colleagues report that, in contrast to patients with MCC, approximately 19% of patients with melanoma will have a recurrence, as will an estimated 5%-9% of patients with squamous cell carcinoma and 1%-10% of patients with basal cell carcinoma.
The fact that recurrence rates of MCC have remained stable over time despite presumed improvements in definitive therapy is disappointing, Dr. Nghiem acknowledged. He noted that it’s still unclear whether immunotherapy will have the same dramatic effect on survival rates for patients with MCC as it has for patients with malignant melanoma.
The high recurrence rates following definitive therapy for patients with early-stage disease was a novel finding, commented Shawn Demehri, MD, PhD, director of the high-risk skin cancer clinic at Massachusetts General Hospital in Boston.
“When you’re looking at patients with stage I or stage II, and they have definitive surgery but still have recurrences at a higher rate than melanoma, it brings home the point that these are among the most aggressive tumors of the skin,” he said in an interview.
The high recurrence rates seen with MCC are attributable to a variety of factors.
“This is a rare cancer of mostly older individuals with a lot of comorbidities, and also a cancer that, even though it is a primary cancer, might be detected a little later than even a melanoma primary tumor, just because of the nature of the neuroendocrine tumor cells,” he said.
Dr. Demehri was not involved in the study.
Prospective cohort
The study cohort consisted of 618 patients with MCC. The median age of the patients was 69, and 227 (37%) were women. The patients were enrolled within 6 months of their diagnosis in the prospective data repository from 2003 through 2019. Of this group, 223 had a recurrence of MCC.
As noted, there was a high risk of recurrence within 1 year, ranging from 11% for patients with pathologic stage I tumors to 58% for those with stage IV disease, and 95% of all recurrences occurred within 3 years of definitive therapy.
To get a better picture of the natural history of MCC recurrence, the investigators studied a cohort of patients with pathologically confirmed MCC who were prospectively enrolled from January 2003 through April 2019 in a data repository maintained at the University of Washington.
In addition to disease stage, factors associated with increased recurrence risk in univariable analyses include immunosuppression (hazard ratio, 2.4; P < .001), male sex (HR, 1.9; P < .001), known primary lesion among patients with clinically detectable nodal disease (HR, 2.3; P = .001), and older age (HR, 1.1, P = .06 for each 10-year increase).
Of the 187 patients in the cohort who died during the study, 121 died from MCC. At 4 years after diagnosis, MCC-specific survival rates were 95% for patients with pathologic stage I, 84% with stage IIA/IIB, 80% with stage IIIA, 58% with stage IIIB, and 41% with stage IV.
Evidence supports close monitoring within the first 3 years for patients with stage I-II MCC. Local recurrence within or adjacent to the primary tumor scar was associated with a 5-year MCC-specific survival rate of 85%, compared with 88% of patients with stage I or II disease who did not have recurrences.
“Because more than 90% of MCC recurrences arise within 3 years, it is appropriate to adjust surveillance intensity accordingly. Stage- and time-specific recurrence data can assist in appropriately focusing surveillance resources on patients and time intervals in which recurrence risk is highest,” the authors wrote.
“If you’re a patient who has not had your cancer come back for 3, 4, or 5 years, you can really cut down on the intensity of your follow-up and scans,” Dr. Nghiem said.
“We do now have two excellent blood tests that are working very well, and we have really good ways to detect the cancer coming back early, and that’s important, because we have potentially curative therapies that tend to work better if you catch the cancer early,” he said.
The study was supported by the National Institutes of Health. Dr. Nghiem reported personal fees and institutional support outside the study from several companies and patents for Merkel cell therapies with the University of Washington and University of Denmark. Dr. Demehri has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, and more than half of all patients with stage IV disease will have a recurrence within 1 year of definitive therapy, results of a new study show.
A study of 618 patients with MCC who were enrolled in a Seattle-based data repository shows that among all patients the 5-year recurrence rate was 40%. The risk of recurrence within the first year was 11% for patients with pathologic stage I disease, 33% for those with stage IIA/IIB disease, 45% for those with stage IIIB disease, and 58% for patients with pathologic stage IV MCC.
Approximately 95% of all recurrences happened within 3 years of the initial diagnosis, report Aubriana McEvoy, MD, from the University of Washington in Seattle, and colleagues.
“This cohort study indicates that the highest yield (and likely most cost-effective) time period for detecting MCC recurrence is 1-3 years after diagnosis,” they write in a study published online in JAMA Dermatology.
The estimated annual incidence of MCC in the United States in 2018 was 2,000 according to the American Cancer Society. The annual incidence rate is rising rapidly, however, and is estimated to reach 3,284 by 2025, McEvoy and colleagues write.
Although MCC is known to have high recurrence rates and is associated with a higher mortality rate than malignant melanoma, recurrence rate data are not captured by either the Surveillance, Epidemiology, and End Results (SEER) database or by the National Cancer Database. As a result, estimates of recurrence rates with MCC have been all over the map, ranging from 27% to 77%, depending on the population studied.
But as senior author Paul Nghiem, MD, PhD, professor and chair of dermatology at the University of Washington, Seattle, told this news organization, recurrence rates over time in their study were remarkably consistent.
“The biggest surprise to me was that, when we broke our nearly 20-year cohort into three 5- or 6-year chunks, every one of the groups had a 40% recurrence rate, within 1%. So we feel really confident that’s the right number,” he said.
Dr. Nghiem and colleagues report that, in contrast to patients with MCC, approximately 19% of patients with melanoma will have a recurrence, as will an estimated 5%-9% of patients with squamous cell carcinoma and 1%-10% of patients with basal cell carcinoma.
The fact that recurrence rates of MCC have remained stable over time despite presumed improvements in definitive therapy is disappointing, Dr. Nghiem acknowledged. He noted that it’s still unclear whether immunotherapy will have the same dramatic effect on survival rates for patients with MCC as it has for patients with malignant melanoma.
The high recurrence rates following definitive therapy for patients with early-stage disease was a novel finding, commented Shawn Demehri, MD, PhD, director of the high-risk skin cancer clinic at Massachusetts General Hospital in Boston.
“When you’re looking at patients with stage I or stage II, and they have definitive surgery but still have recurrences at a higher rate than melanoma, it brings home the point that these are among the most aggressive tumors of the skin,” he said in an interview.
The high recurrence rates seen with MCC are attributable to a variety of factors.
“This is a rare cancer of mostly older individuals with a lot of comorbidities, and also a cancer that, even though it is a primary cancer, might be detected a little later than even a melanoma primary tumor, just because of the nature of the neuroendocrine tumor cells,” he said.
Dr. Demehri was not involved in the study.
Prospective cohort
The study cohort consisted of 618 patients with MCC. The median age of the patients was 69, and 227 (37%) were women. The patients were enrolled within 6 months of their diagnosis in the prospective data repository from 2003 through 2019. Of this group, 223 had a recurrence of MCC.
As noted, there was a high risk of recurrence within 1 year, ranging from 11% for patients with pathologic stage I tumors to 58% for those with stage IV disease, and 95% of all recurrences occurred within 3 years of definitive therapy.
To get a better picture of the natural history of MCC recurrence, the investigators studied a cohort of patients with pathologically confirmed MCC who were prospectively enrolled from January 2003 through April 2019 in a data repository maintained at the University of Washington.
In addition to disease stage, factors associated with increased recurrence risk in univariable analyses include immunosuppression (hazard ratio, 2.4; P < .001), male sex (HR, 1.9; P < .001), known primary lesion among patients with clinically detectable nodal disease (HR, 2.3; P = .001), and older age (HR, 1.1, P = .06 for each 10-year increase).
Of the 187 patients in the cohort who died during the study, 121 died from MCC. At 4 years after diagnosis, MCC-specific survival rates were 95% for patients with pathologic stage I, 84% with stage IIA/IIB, 80% with stage IIIA, 58% with stage IIIB, and 41% with stage IV.
Evidence supports close monitoring within the first 3 years for patients with stage I-II MCC. Local recurrence within or adjacent to the primary tumor scar was associated with a 5-year MCC-specific survival rate of 85%, compared with 88% of patients with stage I or II disease who did not have recurrences.
“Because more than 90% of MCC recurrences arise within 3 years, it is appropriate to adjust surveillance intensity accordingly. Stage- and time-specific recurrence data can assist in appropriately focusing surveillance resources on patients and time intervals in which recurrence risk is highest,” the authors wrote.
“If you’re a patient who has not had your cancer come back for 3, 4, or 5 years, you can really cut down on the intensity of your follow-up and scans,” Dr. Nghiem said.
“We do now have two excellent blood tests that are working very well, and we have really good ways to detect the cancer coming back early, and that’s important, because we have potentially curative therapies that tend to work better if you catch the cancer early,” he said.
The study was supported by the National Institutes of Health. Dr. Nghiem reported personal fees and institutional support outside the study from several companies and patents for Merkel cell therapies with the University of Washington and University of Denmark. Dr. Demehri has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, and more than half of all patients with stage IV disease will have a recurrence within 1 year of definitive therapy, results of a new study show.
A study of 618 patients with MCC who were enrolled in a Seattle-based data repository shows that among all patients the 5-year recurrence rate was 40%. The risk of recurrence within the first year was 11% for patients with pathologic stage I disease, 33% for those with stage IIA/IIB disease, 45% for those with stage IIIB disease, and 58% for patients with pathologic stage IV MCC.
Approximately 95% of all recurrences happened within 3 years of the initial diagnosis, report Aubriana McEvoy, MD, from the University of Washington in Seattle, and colleagues.
“This cohort study indicates that the highest yield (and likely most cost-effective) time period for detecting MCC recurrence is 1-3 years after diagnosis,” they write in a study published online in JAMA Dermatology.
The estimated annual incidence of MCC in the United States in 2018 was 2,000 according to the American Cancer Society. The annual incidence rate is rising rapidly, however, and is estimated to reach 3,284 by 2025, McEvoy and colleagues write.
Although MCC is known to have high recurrence rates and is associated with a higher mortality rate than malignant melanoma, recurrence rate data are not captured by either the Surveillance, Epidemiology, and End Results (SEER) database or by the National Cancer Database. As a result, estimates of recurrence rates with MCC have been all over the map, ranging from 27% to 77%, depending on the population studied.
But as senior author Paul Nghiem, MD, PhD, professor and chair of dermatology at the University of Washington, Seattle, told this news organization, recurrence rates over time in their study were remarkably consistent.
“The biggest surprise to me was that, when we broke our nearly 20-year cohort into three 5- or 6-year chunks, every one of the groups had a 40% recurrence rate, within 1%. So we feel really confident that’s the right number,” he said.
Dr. Nghiem and colleagues report that, in contrast to patients with MCC, approximately 19% of patients with melanoma will have a recurrence, as will an estimated 5%-9% of patients with squamous cell carcinoma and 1%-10% of patients with basal cell carcinoma.
The fact that recurrence rates of MCC have remained stable over time despite presumed improvements in definitive therapy is disappointing, Dr. Nghiem acknowledged. He noted that it’s still unclear whether immunotherapy will have the same dramatic effect on survival rates for patients with MCC as it has for patients with malignant melanoma.
The high recurrence rates following definitive therapy for patients with early-stage disease was a novel finding, commented Shawn Demehri, MD, PhD, director of the high-risk skin cancer clinic at Massachusetts General Hospital in Boston.
“When you’re looking at patients with stage I or stage II, and they have definitive surgery but still have recurrences at a higher rate than melanoma, it brings home the point that these are among the most aggressive tumors of the skin,” he said in an interview.
The high recurrence rates seen with MCC are attributable to a variety of factors.
“This is a rare cancer of mostly older individuals with a lot of comorbidities, and also a cancer that, even though it is a primary cancer, might be detected a little later than even a melanoma primary tumor, just because of the nature of the neuroendocrine tumor cells,” he said.
Dr. Demehri was not involved in the study.
Prospective cohort
The study cohort consisted of 618 patients with MCC. The median age of the patients was 69, and 227 (37%) were women. The patients were enrolled within 6 months of their diagnosis in the prospective data repository from 2003 through 2019. Of this group, 223 had a recurrence of MCC.
As noted, there was a high risk of recurrence within 1 year, ranging from 11% for patients with pathologic stage I tumors to 58% for those with stage IV disease, and 95% of all recurrences occurred within 3 years of definitive therapy.
To get a better picture of the natural history of MCC recurrence, the investigators studied a cohort of patients with pathologically confirmed MCC who were prospectively enrolled from January 2003 through April 2019 in a data repository maintained at the University of Washington.
In addition to disease stage, factors associated with increased recurrence risk in univariable analyses include immunosuppression (hazard ratio, 2.4; P < .001), male sex (HR, 1.9; P < .001), known primary lesion among patients with clinically detectable nodal disease (HR, 2.3; P = .001), and older age (HR, 1.1, P = .06 for each 10-year increase).
Of the 187 patients in the cohort who died during the study, 121 died from MCC. At 4 years after diagnosis, MCC-specific survival rates were 95% for patients with pathologic stage I, 84% with stage IIA/IIB, 80% with stage IIIA, 58% with stage IIIB, and 41% with stage IV.
Evidence supports close monitoring within the first 3 years for patients with stage I-II MCC. Local recurrence within or adjacent to the primary tumor scar was associated with a 5-year MCC-specific survival rate of 85%, compared with 88% of patients with stage I or II disease who did not have recurrences.
“Because more than 90% of MCC recurrences arise within 3 years, it is appropriate to adjust surveillance intensity accordingly. Stage- and time-specific recurrence data can assist in appropriately focusing surveillance resources on patients and time intervals in which recurrence risk is highest,” the authors wrote.
“If you’re a patient who has not had your cancer come back for 3, 4, or 5 years, you can really cut down on the intensity of your follow-up and scans,” Dr. Nghiem said.
“We do now have two excellent blood tests that are working very well, and we have really good ways to detect the cancer coming back early, and that’s important, because we have potentially curative therapies that tend to work better if you catch the cancer early,” he said.
The study was supported by the National Institutes of Health. Dr. Nghiem reported personal fees and institutional support outside the study from several companies and patents for Merkel cell therapies with the University of Washington and University of Denmark. Dr. Demehri has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA DERMATOLOGY
Survey: Artificial intelligence finds support among dermatologists
according to the results of a small survey.
Just 9% of the 90 respondents acknowledged that they have used AI in their practices, while 81% said they had not, and 10% weren’t sure or didn’t know. Despite that lack of familiarity, however, “many embrace the potential positive benefits, such as reducing misdiagnoses” and a majority (94.5%) “would use it at least in certain scenarios,” Vishal A. Patel, MD, and associates said in the Journal of Drugs in Dermatology.
Dermatologists aged 40 years and under were more likely to have used AI previously: 15% reported previous experience, compared with 4% of those over age 40 – but the difference in “age did not have a significant effect on perception of AI,” the investigators noted, adding that most of the dermatologists over 40 believe “that AI would be most beneficial and used for detection of malignant skin lesions.”
The survey also asked about ways the respondents would use AI to help their patients. Almost two-thirds of respondents (66%) chose analysis and management of electronic health records “for research purposes to improve patient outcomes,” compared with 56% who chose identifying unknown/screening skin lesions “with a list of differential diagnoses,” 32% who chose telemedicine, and 26% who chose primary surveys of skin, said Dr. Patel, director of cutaneous oncology at the George Washington University Cancer Center in Washington, and coauthors.
The respondents were fairly evenly split when asked about the possible impact of nondermatologists using AI in the near future to detect skin lesions, such as melanomas, on the need for dermatologists. Just over a quarter said that the need for dermatologists will be decreased all (about 4.4%) or some (about 21.1%) of the time, and 24.4% said that the need will be increased, with the largest share (39.9%) of respondents choosing the middle ground: neither increased or decreased, the investigators reported.
The survey form was emailed to 850 members of the Orlando Dermatology, Aesthetic & Surgical Conference listserv, with responses accepted from April 13 to May 14, 2021. The investigators noted that the response rate was low enough to be a limiting factor, making selection bias “by those with a particular interest in the topic” a possibility.
No funding sources for the study were disclosed. Dr. Patel disclosed that he is chief medical officer for Lazarus AI, the other authors had no disclosures listed.
according to the results of a small survey.
Just 9% of the 90 respondents acknowledged that they have used AI in their practices, while 81% said they had not, and 10% weren’t sure or didn’t know. Despite that lack of familiarity, however, “many embrace the potential positive benefits, such as reducing misdiagnoses” and a majority (94.5%) “would use it at least in certain scenarios,” Vishal A. Patel, MD, and associates said in the Journal of Drugs in Dermatology.
Dermatologists aged 40 years and under were more likely to have used AI previously: 15% reported previous experience, compared with 4% of those over age 40 – but the difference in “age did not have a significant effect on perception of AI,” the investigators noted, adding that most of the dermatologists over 40 believe “that AI would be most beneficial and used for detection of malignant skin lesions.”
The survey also asked about ways the respondents would use AI to help their patients. Almost two-thirds of respondents (66%) chose analysis and management of electronic health records “for research purposes to improve patient outcomes,” compared with 56% who chose identifying unknown/screening skin lesions “with a list of differential diagnoses,” 32% who chose telemedicine, and 26% who chose primary surveys of skin, said Dr. Patel, director of cutaneous oncology at the George Washington University Cancer Center in Washington, and coauthors.
The respondents were fairly evenly split when asked about the possible impact of nondermatologists using AI in the near future to detect skin lesions, such as melanomas, on the need for dermatologists. Just over a quarter said that the need for dermatologists will be decreased all (about 4.4%) or some (about 21.1%) of the time, and 24.4% said that the need will be increased, with the largest share (39.9%) of respondents choosing the middle ground: neither increased or decreased, the investigators reported.
The survey form was emailed to 850 members of the Orlando Dermatology, Aesthetic & Surgical Conference listserv, with responses accepted from April 13 to May 14, 2021. The investigators noted that the response rate was low enough to be a limiting factor, making selection bias “by those with a particular interest in the topic” a possibility.
No funding sources for the study were disclosed. Dr. Patel disclosed that he is chief medical officer for Lazarus AI, the other authors had no disclosures listed.
according to the results of a small survey.
Just 9% of the 90 respondents acknowledged that they have used AI in their practices, while 81% said they had not, and 10% weren’t sure or didn’t know. Despite that lack of familiarity, however, “many embrace the potential positive benefits, such as reducing misdiagnoses” and a majority (94.5%) “would use it at least in certain scenarios,” Vishal A. Patel, MD, and associates said in the Journal of Drugs in Dermatology.
Dermatologists aged 40 years and under were more likely to have used AI previously: 15% reported previous experience, compared with 4% of those over age 40 – but the difference in “age did not have a significant effect on perception of AI,” the investigators noted, adding that most of the dermatologists over 40 believe “that AI would be most beneficial and used for detection of malignant skin lesions.”
The survey also asked about ways the respondents would use AI to help their patients. Almost two-thirds of respondents (66%) chose analysis and management of electronic health records “for research purposes to improve patient outcomes,” compared with 56% who chose identifying unknown/screening skin lesions “with a list of differential diagnoses,” 32% who chose telemedicine, and 26% who chose primary surveys of skin, said Dr. Patel, director of cutaneous oncology at the George Washington University Cancer Center in Washington, and coauthors.
The respondents were fairly evenly split when asked about the possible impact of nondermatologists using AI in the near future to detect skin lesions, such as melanomas, on the need for dermatologists. Just over a quarter said that the need for dermatologists will be decreased all (about 4.4%) or some (about 21.1%) of the time, and 24.4% said that the need will be increased, with the largest share (39.9%) of respondents choosing the middle ground: neither increased or decreased, the investigators reported.
The survey form was emailed to 850 members of the Orlando Dermatology, Aesthetic & Surgical Conference listserv, with responses accepted from April 13 to May 14, 2021. The investigators noted that the response rate was low enough to be a limiting factor, making selection bias “by those with a particular interest in the topic” a possibility.
No funding sources for the study were disclosed. Dr. Patel disclosed that he is chief medical officer for Lazarus AI, the other authors had no disclosures listed.
FROM JOURNAL OF DRUGS IN DERMATOLOGY