Melanoma

Recent advances in treatment appear to have reversed the course of melanoma mortality since 2013, according to data published in the American Journal of Public Health.

The U.S. death rate for melanoma, which had been rising at a rate of 0.22% a year for more than 2 decades, dropped by 17.9%, or 6.24% per year, during 2013-2016. That decline “coincides with the introduction of multiple new and efficacious treatments for metastatic melanoma,” such as BRAF inhibitors and immune checkpoint inhibitors, study author Juliana Berk-Krauss, MD, of the State University of New York Downstate Medical Center in Brooklyn and colleagues wrote.

The other possible explanation for the decline in deaths, “education and early detection resulting in migration toward earlier stage melanomas with a greater chance of surgical cure,” is unlikely, according to the investigators. That’s because the small decrease in median tumor thickness that occurred during 1989-2009 “is not associated with changes in prognosis.”

The investigators’ analysis encompassed data from the Surveillance, Epidemiology, and End Results registry recorded during 1986-2016. Nine registry areas were included (Atlanta, Connecticut, Detroit, Hawaii, Iowa, New Mexico, San Francisco-Oakland, Seattle-Puget Sound, and Utah), which covered about 9.4% of the U.S. population. The analysis was limited to the white population, which accounts for more than 90% of melanoma cases in the United States.

The data showed a slight decline in annual percent change in melanoma incidence, from 3.24% for 1986-2005 to 1.72% for 2006-2016. However, over the whole period studied (1986-2016), melanoma incidence increased by 108%, or about 2.7% per year.

“Given the increased incidence of melanoma throughout this period and the lack of stage migration, these data strongly suggest that the mortality decline is due to the extended survival associated with these [newer] treatments,” the investigators wrote.

This study was funded by NYU Langone. Two investigators disclosed potential conflicts of interest, including relationships with Bio-Rad Laboratories, Novartis, Merck, and several other companies.

rfranki@mdedge.com

SOURCE: Berk-Krauss J et al. Am J Public Health. 2020 Mar 19. doi: 10.2105/AJPH.2020.305567.

Recent advances in treatment appear to have reversed the course of melanoma mortality since 2013, according to data published in the American Journal of Public Health.

The U.S. death rate for melanoma, which had been rising at a rate of 0.22% a year for more than 2 decades, dropped by 17.9%, or 6.24% per year, during 2013-2016. That decline “coincides with the introduction of multiple new and efficacious treatments for metastatic melanoma,” such as BRAF inhibitors and immune checkpoint inhibitors, study author Juliana Berk-Krauss, MD, of the State University of New York Downstate Medical Center in Brooklyn and colleagues wrote.

The other possible explanation for the decline in deaths, “education and early detection resulting in migration toward earlier stage melanomas with a greater chance of surgical cure,” is unlikely, according to the investigators. That’s because the small decrease in median tumor thickness that occurred during 1989-2009 “is not associated with changes in prognosis.”

The investigators’ analysis encompassed data from the Surveillance, Epidemiology, and End Results registry recorded during 1986-2016. Nine registry areas were included (Atlanta, Connecticut, Detroit, Hawaii, Iowa, New Mexico, San Francisco-Oakland, Seattle-Puget Sound, and Utah), which covered about 9.4% of the U.S. population. The analysis was limited to the white population, which accounts for more than 90% of melanoma cases in the United States.

The data showed a slight decline in annual percent change in melanoma incidence, from 3.24% for 1986-2005 to 1.72% for 2006-2016. However, over the whole period studied (1986-2016), melanoma incidence increased by 108%, or about 2.7% per year.

“Given the increased incidence of melanoma throughout this period and the lack of stage migration, these data strongly suggest that the mortality decline is due to the extended survival associated with these [newer] treatments,” the investigators wrote.

This study was funded by NYU Langone. Two investigators disclosed potential conflicts of interest, including relationships with Bio-Rad Laboratories, Novartis, Merck, and several other companies.

rfranki@mdedge.com

SOURCE: Berk-Krauss J et al. Am J Public Health. 2020 Mar 19. doi: 10.2105/AJPH.2020.305567.

Recent advances in treatment appear to have reversed the course of melanoma mortality since 2013, according to data published in the American Journal of Public Health.

The U.S. death rate for melanoma, which had been rising at a rate of 0.22% a year for more than 2 decades, dropped by 17.9%, or 6.24% per year, during 2013-2016. That decline “coincides with the introduction of multiple new and efficacious treatments for metastatic melanoma,” such as BRAF inhibitors and immune checkpoint inhibitors, study author Juliana Berk-Krauss, MD, of the State University of New York Downstate Medical Center in Brooklyn and colleagues wrote.

The other possible explanation for the decline in deaths, “education and early detection resulting in migration toward earlier stage melanomas with a greater chance of surgical cure,” is unlikely, according to the investigators. That’s because the small decrease in median tumor thickness that occurred during 1989-2009 “is not associated with changes in prognosis.”

The investigators’ analysis encompassed data from the Surveillance, Epidemiology, and End Results registry recorded during 1986-2016. Nine registry areas were included (Atlanta, Connecticut, Detroit, Hawaii, Iowa, New Mexico, San Francisco-Oakland, Seattle-Puget Sound, and Utah), which covered about 9.4% of the U.S. population. The analysis was limited to the white population, which accounts for more than 90% of melanoma cases in the United States.

The data showed a slight decline in annual percent change in melanoma incidence, from 3.24% for 1986-2005 to 1.72% for 2006-2016. However, over the whole period studied (1986-2016), melanoma incidence increased by 108%, or about 2.7% per year.

“Given the increased incidence of melanoma throughout this period and the lack of stage migration, these data strongly suggest that the mortality decline is due to the extended survival associated with these [newer] treatments,” the investigators wrote.

This study was funded by NYU Langone. Two investigators disclosed potential conflicts of interest, including relationships with Bio-Rad Laboratories, Novartis, Merck, and several other companies.

rfranki@mdedge.com

SOURCE: Berk-Krauss J et al. Am J Public Health. 2020 Mar 19. doi: 10.2105/AJPH.2020.305567.

Skin cancer detection does not improve when patients use a dermatoscope for smartphones to capture and send photos of lesions for diagnosis, according to the Australian SKIN Project trial.

“Mobile health applications are increasingly used in cancer prevention and early detection but rarely tested stringently for their value with regard to patient care,” noted trial investigators, who were led by Monika Janda, PhD, of the University of Queensland in Brisbane, Australia. The trial was published in Lancet Digital Health.

The investigators studied 234 adults at high risk for skin cancer, asking them to perform whole-body skin self-exams in their homes at baseline, 1 month, and 2 months.

Half of patients were randomized to perform standard naked-eye exams, note suspicious lesions on a body chart, and submit the chart by email. The other half were randomized to supplement their exams with mobile dermoscopy, and they were provided with a dermatoscope (FotoFinder) that interfaces with smartphones to capture and submit photos of suspicious lesions to a dermatologist for telediagnosis.

Both groups received Web-based instructions on how to complete whole-body skin self-exams and were examined in person within 3 months of their last self-exam to provide a reference standard.

In comparing the two approaches for early detection of skin cancer, the investigators determined that teledermoscopy-enhanced exams would have to show 20% greater sensitivity to establish their superiority.

The median number of lesions submitted was six per person in both the group using adjunctive teledermoscopy and the group performing only naked-eye exams.

At the lesion level, teledermoscopy-enhanced exams had lower sensitivity than naked-eye exams in detecting suspected skin cancers or precursor lesions (75% vs. 88%; P = .04) and similar specificity (87% vs. 89%; P = .42). At the patient level, the two approaches had statistically indistinguishable sensitivity (87% vs. 97%; P = .26) and specificity (95% vs. 96%; P = .96).

At the same time, telediagnosis showed good overall diagnostic concordance with in-person clinical skin examination (88%).

“For the early detection of skin cancer, naked-eye skin self-examination should continue to be recommended by cancer agencies,” Dr. Janda and colleagues concluded. “Further improvements to the instructions for participants on the relevance of nonpigmented skin lesions, training for partners, and the integration of automatic algorithms that rule out clearly benign skin lesions at the time of photographing might increase sensitivity of teledermoscopy in the future.”

This trial was funded by the National Health and Medical Research Council. The authors disclosed relationships with e-derm-consult, SciBase, Canfield Scientific, and other companies.

SOURCE: Janda M et al. Lancet Digit Health. 2020 March; 2(3):e129-e137.

Skin cancer detection does not improve when patients use a dermatoscope for smartphones to capture and send photos of lesions for diagnosis, according to the Australian SKIN Project trial.

“Mobile health applications are increasingly used in cancer prevention and early detection but rarely tested stringently for their value with regard to patient care,” noted trial investigators, who were led by Monika Janda, PhD, of the University of Queensland in Brisbane, Australia. The trial was published in Lancet Digital Health.

The investigators studied 234 adults at high risk for skin cancer, asking them to perform whole-body skin self-exams in their homes at baseline, 1 month, and 2 months.

Half of patients were randomized to perform standard naked-eye exams, note suspicious lesions on a body chart, and submit the chart by email. The other half were randomized to supplement their exams with mobile dermoscopy, and they were provided with a dermatoscope (FotoFinder) that interfaces with smartphones to capture and submit photos of suspicious lesions to a dermatologist for telediagnosis.

Both groups received Web-based instructions on how to complete whole-body skin self-exams and were examined in person within 3 months of their last self-exam to provide a reference standard.

In comparing the two approaches for early detection of skin cancer, the investigators determined that teledermoscopy-enhanced exams would have to show 20% greater sensitivity to establish their superiority.

The median number of lesions submitted was six per person in both the group using adjunctive teledermoscopy and the group performing only naked-eye exams.

At the lesion level, teledermoscopy-enhanced exams had lower sensitivity than naked-eye exams in detecting suspected skin cancers or precursor lesions (75% vs. 88%; P = .04) and similar specificity (87% vs. 89%; P = .42). At the patient level, the two approaches had statistically indistinguishable sensitivity (87% vs. 97%; P = .26) and specificity (95% vs. 96%; P = .96).

At the same time, telediagnosis showed good overall diagnostic concordance with in-person clinical skin examination (88%).

“For the early detection of skin cancer, naked-eye skin self-examination should continue to be recommended by cancer agencies,” Dr. Janda and colleagues concluded. “Further improvements to the instructions for participants on the relevance of nonpigmented skin lesions, training for partners, and the integration of automatic algorithms that rule out clearly benign skin lesions at the time of photographing might increase sensitivity of teledermoscopy in the future.”

This trial was funded by the National Health and Medical Research Council. The authors disclosed relationships with e-derm-consult, SciBase, Canfield Scientific, and other companies.

SOURCE: Janda M et al. Lancet Digit Health. 2020 March; 2(3):e129-e137.

Skin cancer detection does not improve when patients use a dermatoscope for smartphones to capture and send photos of lesions for diagnosis, according to the Australian SKIN Project trial.

“Mobile health applications are increasingly used in cancer prevention and early detection but rarely tested stringently for their value with regard to patient care,” noted trial investigators, who were led by Monika Janda, PhD, of the University of Queensland in Brisbane, Australia. The trial was published in Lancet Digital Health.

The investigators studied 234 adults at high risk for skin cancer, asking them to perform whole-body skin self-exams in their homes at baseline, 1 month, and 2 months.

Half of patients were randomized to perform standard naked-eye exams, note suspicious lesions on a body chart, and submit the chart by email. The other half were randomized to supplement their exams with mobile dermoscopy, and they were provided with a dermatoscope (FotoFinder) that interfaces with smartphones to capture and submit photos of suspicious lesions to a dermatologist for telediagnosis.

Both groups received Web-based instructions on how to complete whole-body skin self-exams and were examined in person within 3 months of their last self-exam to provide a reference standard.

In comparing the two approaches for early detection of skin cancer, the investigators determined that teledermoscopy-enhanced exams would have to show 20% greater sensitivity to establish their superiority.

The median number of lesions submitted was six per person in both the group using adjunctive teledermoscopy and the group performing only naked-eye exams.

At the lesion level, teledermoscopy-enhanced exams had lower sensitivity than naked-eye exams in detecting suspected skin cancers or precursor lesions (75% vs. 88%; P = .04) and similar specificity (87% vs. 89%; P = .42). At the patient level, the two approaches had statistically indistinguishable sensitivity (87% vs. 97%; P = .26) and specificity (95% vs. 96%; P = .96).

At the same time, telediagnosis showed good overall diagnostic concordance with in-person clinical skin examination (88%).

“For the early detection of skin cancer, naked-eye skin self-examination should continue to be recommended by cancer agencies,” Dr. Janda and colleagues concluded. “Further improvements to the instructions for participants on the relevance of nonpigmented skin lesions, training for partners, and the integration of automatic algorithms that rule out clearly benign skin lesions at the time of photographing might increase sensitivity of teledermoscopy in the future.”

This trial was funded by the National Health and Medical Research Council. The authors disclosed relationships with e-derm-consult, SciBase, Canfield Scientific, and other companies.

SOURCE: Janda M et al. Lancet Digit Health. 2020 March; 2(3):e129-e137.

In a small survey, 75% of dermatology patients said they would recommend the use of artificial intelligence (AI) for skin cancer screening to friends and family members, but 94% emphasized the need for symbiosis between doctors, patients, and AI.

AI under investigation in dermatology includes both direct-to-patient and clinician decision-support AI tools for skin cancer screening, but patients’ perceptions of AI in health care remains unclear, Caroline A. Nelson, MD, of Yale University in New Haven, Conn., and colleagues wrote in JAMA Dermatology.

“We sought to elucidate perceived benefits and risks, strengths and weaknesses, implementation, response to conflict between human and AI clinical decision making, and recommendation for or against AI,” the researchers wrote.

They identified 48 patients seen from May 6, 2019, to July 8, 2019, at general dermatology clinics and melanoma clinics. This included 16 patients with a history of melanoma, 16 with a history of nonmelanoma skin cancer, and 16 with no history of skin cancer. The average age of the patients was 53.3 years, 54% were women, and 94% were white.

The researchers interviewed 24 patients about a direct-to-patient AI tool and 24 patients about a clinician decision-support AI tool.

Overall, 36 patients (75%) said they would recommend the AI tool to family and friends, with 17 patients (71%) saying they would recommend the direct-to-patient tool and 19 (79%) saying they would recommend the clinician decision-support tool. Another nine patients (19%) were ambivalent about the AI tools, and three patients (6%) said they would not recommend the tools.

Diagnostic speed and health care access were the most common perceived benefits of AI (by 60% of patients for each), and increased patient anxiety was the most common perceived risk (by 40% of patients). In addition, 69% of patients perceived more accurate diagnosis to be the greatest strength of an AI tool, and 85% perceived less accurate diagnosis to be the greatest weakness.

The study findings were limited by several factors, including the small sample size, qualitative design, use of a hypothetical rather than real-world situation, and a homogeneous study population, the researchers noted. However, the results merit more studies to obtain perspectives from diverse populations, they said.

“This expansion is particularly important in light of concerns raised that AI tools may exacerbate health care disparities in dermatology,” the researchers wrote.

From the patient perspective, the use of AI “may improve health care quality but should be implemented in a manner that preserves the integrity of the human physician-patient relationship,” the authors concluded.

“Although AI technology has not been widely implemented in dermatology yet, it is the pivotal time to assess patients’ views on the subject to understand their knowledge base, as well as values, preferences, and concerns regarding AI,” wrote Carrie L. Kovarik, MD, of the University of Pennsylvania in Philadelphia, in an accompanying editorial.

“Vulnerable patients, including racial and ethnic minorities, the underinsured or uninsured, economically disadvantaged, and those with chronic health conditions, may be at risk for improper consent for or use of AI,” she wrote.

Dr. Kovarik cited the position statement on augmented intelligence from the American Academy of Dermatology, which states that, for both patients and clinicians, “there should be transparency and choice on how their medical information is gathered, utilized, and stored and when, what, and how augmented intelligence technologies are utilized in their care process. There should be clarity in the symbiotic and synergistic roles of augmented intelligence and human judgment so that it is clear to the patient and provider when and how this technology is utilized to augment human judgment and interpretation.”

Clinicians will need to understand the perspectives on AI from patients of a range of backgrounds to achieve this goal, Dr. Kovarik said.

Dr. Nelson had no financial conflicts to disclose, but her colleagues disclosed relationships with pharmaceutical companies, government agencies, and nonprofit organizations. Dr. Kovarik disclosed serving on the artificial intelligence task force for the American Academy of Dermatology.

SOURCES: Nelson CA et al. JAMA Dermatol. 2020 Mar 11. doi: 10.1001/jamadermatol.2019.5014; Kovarik CL. JAMA Dermatol. 2020 Mar 11. doi: 10.1001/jamadermatol.2019.5013.

In a small survey, 75% of dermatology patients said they would recommend the use of artificial intelligence (AI) for skin cancer screening to friends and family members, but 94% emphasized the need for symbiosis between doctors, patients, and AI.

AI under investigation in dermatology includes both direct-to-patient and clinician decision-support AI tools for skin cancer screening, but patients’ perceptions of AI in health care remains unclear, Caroline A. Nelson, MD, of Yale University in New Haven, Conn., and colleagues wrote in JAMA Dermatology.

“We sought to elucidate perceived benefits and risks, strengths and weaknesses, implementation, response to conflict between human and AI clinical decision making, and recommendation for or against AI,” the researchers wrote.

They identified 48 patients seen from May 6, 2019, to July 8, 2019, at general dermatology clinics and melanoma clinics. This included 16 patients with a history of melanoma, 16 with a history of nonmelanoma skin cancer, and 16 with no history of skin cancer. The average age of the patients was 53.3 years, 54% were women, and 94% were white.

The researchers interviewed 24 patients about a direct-to-patient AI tool and 24 patients about a clinician decision-support AI tool.

Overall, 36 patients (75%) said they would recommend the AI tool to family and friends, with 17 patients (71%) saying they would recommend the direct-to-patient tool and 19 (79%) saying they would recommend the clinician decision-support tool. Another nine patients (19%) were ambivalent about the AI tools, and three patients (6%) said they would not recommend the tools.

Diagnostic speed and health care access were the most common perceived benefits of AI (by 60% of patients for each), and increased patient anxiety was the most common perceived risk (by 40% of patients). In addition, 69% of patients perceived more accurate diagnosis to be the greatest strength of an AI tool, and 85% perceived less accurate diagnosis to be the greatest weakness.

The study findings were limited by several factors, including the small sample size, qualitative design, use of a hypothetical rather than real-world situation, and a homogeneous study population, the researchers noted. However, the results merit more studies to obtain perspectives from diverse populations, they said.

“This expansion is particularly important in light of concerns raised that AI tools may exacerbate health care disparities in dermatology,” the researchers wrote.

From the patient perspective, the use of AI “may improve health care quality but should be implemented in a manner that preserves the integrity of the human physician-patient relationship,” the authors concluded.

“Although AI technology has not been widely implemented in dermatology yet, it is the pivotal time to assess patients’ views on the subject to understand their knowledge base, as well as values, preferences, and concerns regarding AI,” wrote Carrie L. Kovarik, MD, of the University of Pennsylvania in Philadelphia, in an accompanying editorial.

“Vulnerable patients, including racial and ethnic minorities, the underinsured or uninsured, economically disadvantaged, and those with chronic health conditions, may be at risk for improper consent for or use of AI,” she wrote.

Dr. Kovarik cited the position statement on augmented intelligence from the American Academy of Dermatology, which states that, for both patients and clinicians, “there should be transparency and choice on how their medical information is gathered, utilized, and stored and when, what, and how augmented intelligence technologies are utilized in their care process. There should be clarity in the symbiotic and synergistic roles of augmented intelligence and human judgment so that it is clear to the patient and provider when and how this technology is utilized to augment human judgment and interpretation.”

Clinicians will need to understand the perspectives on AI from patients of a range of backgrounds to achieve this goal, Dr. Kovarik said.

Dr. Nelson had no financial conflicts to disclose, but her colleagues disclosed relationships with pharmaceutical companies, government agencies, and nonprofit organizations. Dr. Kovarik disclosed serving on the artificial intelligence task force for the American Academy of Dermatology.

SOURCES: Nelson CA et al. JAMA Dermatol. 2020 Mar 11. doi: 10.1001/jamadermatol.2019.5014; Kovarik CL. JAMA Dermatol. 2020 Mar 11. doi: 10.1001/jamadermatol.2019.5013.

In a small survey, 75% of dermatology patients said they would recommend the use of artificial intelligence (AI) for skin cancer screening to friends and family members, but 94% emphasized the need for symbiosis between doctors, patients, and AI.

AI under investigation in dermatology includes both direct-to-patient and clinician decision-support AI tools for skin cancer screening, but patients’ perceptions of AI in health care remains unclear, Caroline A. Nelson, MD, of Yale University in New Haven, Conn., and colleagues wrote in JAMA Dermatology.

“We sought to elucidate perceived benefits and risks, strengths and weaknesses, implementation, response to conflict between human and AI clinical decision making, and recommendation for or against AI,” the researchers wrote.

They identified 48 patients seen from May 6, 2019, to July 8, 2019, at general dermatology clinics and melanoma clinics. This included 16 patients with a history of melanoma, 16 with a history of nonmelanoma skin cancer, and 16 with no history of skin cancer. The average age of the patients was 53.3 years, 54% were women, and 94% were white.

The researchers interviewed 24 patients about a direct-to-patient AI tool and 24 patients about a clinician decision-support AI tool.

Overall, 36 patients (75%) said they would recommend the AI tool to family and friends, with 17 patients (71%) saying they would recommend the direct-to-patient tool and 19 (79%) saying they would recommend the clinician decision-support tool. Another nine patients (19%) were ambivalent about the AI tools, and three patients (6%) said they would not recommend the tools.

Diagnostic speed and health care access were the most common perceived benefits of AI (by 60% of patients for each), and increased patient anxiety was the most common perceived risk (by 40% of patients). In addition, 69% of patients perceived more accurate diagnosis to be the greatest strength of an AI tool, and 85% perceived less accurate diagnosis to be the greatest weakness.

The study findings were limited by several factors, including the small sample size, qualitative design, use of a hypothetical rather than real-world situation, and a homogeneous study population, the researchers noted. However, the results merit more studies to obtain perspectives from diverse populations, they said.

“This expansion is particularly important in light of concerns raised that AI tools may exacerbate health care disparities in dermatology,” the researchers wrote.

From the patient perspective, the use of AI “may improve health care quality but should be implemented in a manner that preserves the integrity of the human physician-patient relationship,” the authors concluded.

“Although AI technology has not been widely implemented in dermatology yet, it is the pivotal time to assess patients’ views on the subject to understand their knowledge base, as well as values, preferences, and concerns regarding AI,” wrote Carrie L. Kovarik, MD, of the University of Pennsylvania in Philadelphia, in an accompanying editorial.

“Vulnerable patients, including racial and ethnic minorities, the underinsured or uninsured, economically disadvantaged, and those with chronic health conditions, may be at risk for improper consent for or use of AI,” she wrote.

Dr. Kovarik cited the position statement on augmented intelligence from the American Academy of Dermatology, which states that, for both patients and clinicians, “there should be transparency and choice on how their medical information is gathered, utilized, and stored and when, what, and how augmented intelligence technologies are utilized in their care process. There should be clarity in the symbiotic and synergistic roles of augmented intelligence and human judgment so that it is clear to the patient and provider when and how this technology is utilized to augment human judgment and interpretation.”

Clinicians will need to understand the perspectives on AI from patients of a range of backgrounds to achieve this goal, Dr. Kovarik said.

Dr. Nelson had no financial conflicts to disclose, but her colleagues disclosed relationships with pharmaceutical companies, government agencies, and nonprofit organizations. Dr. Kovarik disclosed serving on the artificial intelligence task force for the American Academy of Dermatology.

SOURCES: Nelson CA et al. JAMA Dermatol. 2020 Mar 11. doi: 10.1001/jamadermatol.2019.5014; Kovarik CL. JAMA Dermatol. 2020 Mar 11. doi: 10.1001/jamadermatol.2019.5013.

The biggest cancer research meeting of the year has been canceled as a reaction to the novel coronavirus (COVID-19) outbreak, which has also led to many other medical conferences being canceled or postponed.

The annual meeting of the American Association for Cancer Research (AACR) was due to take place April 24-29 in San Diego, California. More than 24,000 delegates from 80 countries and more than 500 exhibitors were expected to attend.

There are plans to reschedule it for later this year.

This has been a “difficult decision,” said the AACR board of directors, but “we believe that the decision to postpone the meeting is absolutely the correct one to safeguard our meeting participants from further potential exposure to the coronavirus.”

The board goes on to explain that “this evidence-based decision was made after a thorough review and discussion of all factors impacting the annual meeting, including the US government’s enforcement of restrictions on international travelers to enter the US; the imposition of travel restrictions issued by US government agencies, cancer centers, academic institutions, and pharmaceutical and biotech companies; and the counsel of infectious disease experts. It is clear that all of these elements significantly affect the ability of delegates, speakers, presenters of proffered papers, and exhibitors to participate fully in the annual meeting.”

Other cancer conferences that were planned for March and that have been canceled include the following:

• European Breast Cancer Conference (EBCC), Barcelona, Spain, which was to have taken place March 18-20. This conference has been postponed and will now take place September 30 to October 2 at the same venue. Abstracts that have been accepted for the initial conference will remain in the program, and organizers will reopen abstract submissions in May.
• National Comprehensive Cancer Network (NCCN), Orlando, Florida, was scheduled for March 19-22. This conference has been postponed. No new dates have been provided, but the society notes that “NCCN staff is working as quickly as possible to notify all conference registrants about the postponement and further information regarding the refund process.”
• European Association of Urology (EAU), Amsterdam, the Netherlands, at which there is always new research presented on prostate, kidney, and bladder cancer, was due to take place March 20-24. This conference has been postponed to July 2020.
• Society of Gynecologic Oncology (SGO), in Toronto, Canada, which was scheduled for March 28-31. SGO is “exploring alternatives for delivering the science and education.”

Overall, the move to cancel medical conferences over the next few months is a good idea, commented F. Perry Wilson, MD, MSCE, associate professor of medicine and director of Yale’s Program of Applied Translational Research, in a Medscape Medical News commentary.

“There’s a pretty straightforward case here,” he argued. “Medical professionals are at higher risk for exposure to coronavirus because we come into contact with lots and lots of patients. Gathering a large group of medical professionals in a single place increases the risk for exposure further. Factor in airplane flights to and from the conferences, and the chance that infection is spread is significant.”

This article first appeared on Medscape.com.

The biggest cancer research meeting of the year has been canceled as a reaction to the novel coronavirus (COVID-19) outbreak, which has also led to many other medical conferences being canceled or postponed.

The annual meeting of the American Association for Cancer Research (AACR) was due to take place April 24-29 in San Diego, California. More than 24,000 delegates from 80 countries and more than 500 exhibitors were expected to attend.

There are plans to reschedule it for later this year.

This has been a “difficult decision,” said the AACR board of directors, but “we believe that the decision to postpone the meeting is absolutely the correct one to safeguard our meeting participants from further potential exposure to the coronavirus.”

The board goes on to explain that “this evidence-based decision was made after a thorough review and discussion of all factors impacting the annual meeting, including the US government’s enforcement of restrictions on international travelers to enter the US; the imposition of travel restrictions issued by US government agencies, cancer centers, academic institutions, and pharmaceutical and biotech companies; and the counsel of infectious disease experts. It is clear that all of these elements significantly affect the ability of delegates, speakers, presenters of proffered papers, and exhibitors to participate fully in the annual meeting.”

Other cancer conferences that were planned for March and that have been canceled include the following:

• European Breast Cancer Conference (EBCC), Barcelona, Spain, which was to have taken place March 18-20. This conference has been postponed and will now take place September 30 to October 2 at the same venue. Abstracts that have been accepted for the initial conference will remain in the program, and organizers will reopen abstract submissions in May.
• National Comprehensive Cancer Network (NCCN), Orlando, Florida, was scheduled for March 19-22. This conference has been postponed. No new dates have been provided, but the society notes that “NCCN staff is working as quickly as possible to notify all conference registrants about the postponement and further information regarding the refund process.”
• European Association of Urology (EAU), Amsterdam, the Netherlands, at which there is always new research presented on prostate, kidney, and bladder cancer, was due to take place March 20-24. This conference has been postponed to July 2020.
• Society of Gynecologic Oncology (SGO), in Toronto, Canada, which was scheduled for March 28-31. SGO is “exploring alternatives for delivering the science and education.”

Overall, the move to cancel medical conferences over the next few months is a good idea, commented F. Perry Wilson, MD, MSCE, associate professor of medicine and director of Yale’s Program of Applied Translational Research, in a Medscape Medical News commentary.

“There’s a pretty straightforward case here,” he argued. “Medical professionals are at higher risk for exposure to coronavirus because we come into contact with lots and lots of patients. Gathering a large group of medical professionals in a single place increases the risk for exposure further. Factor in airplane flights to and from the conferences, and the chance that infection is spread is significant.”

This article first appeared on Medscape.com.

The biggest cancer research meeting of the year has been canceled as a reaction to the novel coronavirus (COVID-19) outbreak, which has also led to many other medical conferences being canceled or postponed.

The annual meeting of the American Association for Cancer Research (AACR) was due to take place April 24-29 in San Diego, California. More than 24,000 delegates from 80 countries and more than 500 exhibitors were expected to attend.

There are plans to reschedule it for later this year.

This has been a “difficult decision,” said the AACR board of directors, but “we believe that the decision to postpone the meeting is absolutely the correct one to safeguard our meeting participants from further potential exposure to the coronavirus.”

The board goes on to explain that “this evidence-based decision was made after a thorough review and discussion of all factors impacting the annual meeting, including the US government’s enforcement of restrictions on international travelers to enter the US; the imposition of travel restrictions issued by US government agencies, cancer centers, academic institutions, and pharmaceutical and biotech companies; and the counsel of infectious disease experts. It is clear that all of these elements significantly affect the ability of delegates, speakers, presenters of proffered papers, and exhibitors to participate fully in the annual meeting.”

Other cancer conferences that were planned for March and that have been canceled include the following:

• European Breast Cancer Conference (EBCC), Barcelona, Spain, which was to have taken place March 18-20. This conference has been postponed and will now take place September 30 to October 2 at the same venue. Abstracts that have been accepted for the initial conference will remain in the program, and organizers will reopen abstract submissions in May.
• National Comprehensive Cancer Network (NCCN), Orlando, Florida, was scheduled for March 19-22. This conference has been postponed. No new dates have been provided, but the society notes that “NCCN staff is working as quickly as possible to notify all conference registrants about the postponement and further information regarding the refund process.”
• European Association of Urology (EAU), Amsterdam, the Netherlands, at which there is always new research presented on prostate, kidney, and bladder cancer, was due to take place March 20-24. This conference has been postponed to July 2020.
• Society of Gynecologic Oncology (SGO), in Toronto, Canada, which was scheduled for March 28-31. SGO is “exploring alternatives for delivering the science and education.”

Overall, the move to cancel medical conferences over the next few months is a good idea, commented F. Perry Wilson, MD, MSCE, associate professor of medicine and director of Yale’s Program of Applied Translational Research, in a Medscape Medical News commentary.

“There’s a pretty straightforward case here,” he argued. “Medical professionals are at higher risk for exposure to coronavirus because we come into contact with lots and lots of patients. Gathering a large group of medical professionals in a single place increases the risk for exposure further. Factor in airplane flights to and from the conferences, and the chance that infection is spread is significant.”

This article first appeared on Medscape.com.

LAHAINA, HAWAII – Multiple studies, including meta-analyses, have shown that dermoscopy improves sensitivity for diagnosing melanoma, without lowering specificity, but there are still some “nonbelievers,” Ashfaq A. Marghoob, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

In fact, not one study has shown that dermoscopy is less sensitive than the naked eye alone, and at clinics where dermoscopy is used, “two-thirds of the melanomas being detected now lack the classic ABCD features of melanoma,” added Dr. Marghoob, director of clinical dermatology at Memorial Sloan Kettering in Hauppauge, N.Y.

Dr. Marghoob cited a meta-analysis of 9 prospective trials, which concluded that dermoscopy was more accurate in diagnosing melanoma than the naked eye alone and did not lower specificity, with a sensitivity and specificity of 90%, compared with 71% and 81%, respectively for the naked eye (Br J Dermatol. 2008 Sep;159[3]:669-76).

“And at least from an evidence-based standpoint ... the Cochrane library has basically endorsed that, yes, dermoscopy does indeed improve your diagnostic accuracy,” Dr. Marghoob said.

He referred to a 2018 Cochrane review on 104 dermoscopy studies, with and without visual inspection, for diagnosing melanoma in adults (Cochrane Database Syst Rev. 2018 Dec 4;12:CD011902). The review authors concluded that “the evidence suggests that melanomas will be missed if visual inspection is used on its own,” and despite limitations in the evidence, “dermoscopy is a valuable tool to support the visual inspection of a suspicious skin lesion for the detection of melanoma and atypical intraepidermal melanocytic variants.”

As for the question of specificity, Dr. Marghoob said studies have found that dermoscopy results in the detection of more melanomas and reduces the number of biopsies of benign lesions and “every study looking into this has shown that, yes, it does improve” specificity.

A 10-year multicenter survey of about 300,000 cases, which included 17,172 melanomas and 283,043 melanocytic nevi, found that the number-needed-to-excise (NNE) values improved over time in specialized clinics where newer diagnostic techniques like dermoscopy were used (from 12.8 to 6.8), but the NNE did not appear to change in the nonspecialized settings (J Am Acad Dermatol. 2012 Jul;67[1]:54-9).

Looking at the benign-to-malignant ratio, there was no change among those not using dermoscopy, where the ratio remained at about 30 to 1. When dermoscopy was used, this ratio started to improve over the 10-year period, to about 5 to 1. In addition, “the dermoscopy users were finding many more melanomas than the non–dermoscopy users,” Dr. Marghoob added. And over the 10 years, the number of nevi being removed did not change among those not using dermoscopy but dropped among those using dermoscopy.

Adding photography with the ability to digitally monitor patients helps bring this ratio down further, Dr. Marghoob noted. He referred to a study that instead evaluated the ratio of melanoma to nonmelanomas diagnosed among dermatologists in three groups: those with no digital dermoscopy with little dermoscopy training (group A, the reference group), no digital dermoscopy but more dermoscopy training (group B), and those using digital dermoscopy (group C). In the group that used digital dermoscopy, that ratio was about 1 to 2.4, compared with about 1 to 8 in group B, and about 1 to 10.7 in group A (Br J Dermatol. 2012;167[4]778-86).

The use of dermoscopy is also associated with thinner tumors. Among dermoscopy users, the thickness of the tumors detected drops, and the proportion of thin to thick lesions detected increases, Dr. Marghoob said.

For example, in one study, the mean thickness in melanomas detected with dermoscopy was 1.4 mm versus 2.59 mm when dermoscopy was not used (J Eur Acad Dermatol Venereol. 2015 Jan; 29[1]:102-8). About 55% of the tumors detected with dermoscopic examination were 1 mm or less in thickness versus 23.4% of those detected without dermoscopy, “so the dermoscopy users from a proportion standpoint were also finding thinner tumors,” Dr. Marghoob said. Dermoscopy was also identified as an independent predictor of finding thinner tumors.

Even without a study, it could be assumed that the use of dermoscopy would reduce costs, since dermoscopy increases sensitivity and the total number of melanomas detected, decreases the number of benign nevi removed, and helps detect disease earlier. But there are data showing that dermoscopy reduces health care costs, Dr. Marghoob said.* For example, a Belgian study that looked at dermoscopy in two cohorts of melanoma patients concluded that adequate dermoscopy training was cost effective (Eur J Cancer. 2016 Nov;67:38-45).

It has also been shown that adding dermoscopy to a primary care setting has cost benefits, Dr. Marghoob said. He cited a study of Dutch general practices that found that the probability of a correct diagnosis was 1.25 times higher when dermoscopy was used to evaluate suspicious skin lesions and concluded that the use of dermoscopy appeared to be cost effective (J Eur Acad Dermatol Venereol. 2014 Nov;28[11]:1442-9).

Dr. Marghoob had no disclosures relevant to this presentation.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

*Correction, 2/28/20: An earlier version of this article mischaracterized the cost implications of dermoscopy use.

emechcatie@mdedge.com

LAHAINA, HAWAII – Multiple studies, including meta-analyses, have shown that dermoscopy improves sensitivity for diagnosing melanoma, without lowering specificity, but there are still some “nonbelievers,” Ashfaq A. Marghoob, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

In fact, not one study has shown that dermoscopy is less sensitive than the naked eye alone, and at clinics where dermoscopy is used, “two-thirds of the melanomas being detected now lack the classic ABCD features of melanoma,” added Dr. Marghoob, director of clinical dermatology at Memorial Sloan Kettering in Hauppauge, N.Y.

Dr. Marghoob cited a meta-analysis of 9 prospective trials, which concluded that dermoscopy was more accurate in diagnosing melanoma than the naked eye alone and did not lower specificity, with a sensitivity and specificity of 90%, compared with 71% and 81%, respectively for the naked eye (Br J Dermatol. 2008 Sep;159[3]:669-76).

“And at least from an evidence-based standpoint ... the Cochrane library has basically endorsed that, yes, dermoscopy does indeed improve your diagnostic accuracy,” Dr. Marghoob said.

He referred to a 2018 Cochrane review on 104 dermoscopy studies, with and without visual inspection, for diagnosing melanoma in adults (Cochrane Database Syst Rev. 2018 Dec 4;12:CD011902). The review authors concluded that “the evidence suggests that melanomas will be missed if visual inspection is used on its own,” and despite limitations in the evidence, “dermoscopy is a valuable tool to support the visual inspection of a suspicious skin lesion for the detection of melanoma and atypical intraepidermal melanocytic variants.”

As for the question of specificity, Dr. Marghoob said studies have found that dermoscopy results in the detection of more melanomas and reduces the number of biopsies of benign lesions and “every study looking into this has shown that, yes, it does improve” specificity.

A 10-year multicenter survey of about 300,000 cases, which included 17,172 melanomas and 283,043 melanocytic nevi, found that the number-needed-to-excise (NNE) values improved over time in specialized clinics where newer diagnostic techniques like dermoscopy were used (from 12.8 to 6.8), but the NNE did not appear to change in the nonspecialized settings (J Am Acad Dermatol. 2012 Jul;67[1]:54-9).

Looking at the benign-to-malignant ratio, there was no change among those not using dermoscopy, where the ratio remained at about 30 to 1. When dermoscopy was used, this ratio started to improve over the 10-year period, to about 5 to 1. In addition, “the dermoscopy users were finding many more melanomas than the non–dermoscopy users,” Dr. Marghoob added. And over the 10 years, the number of nevi being removed did not change among those not using dermoscopy but dropped among those using dermoscopy.

Adding photography with the ability to digitally monitor patients helps bring this ratio down further, Dr. Marghoob noted. He referred to a study that instead evaluated the ratio of melanoma to nonmelanomas diagnosed among dermatologists in three groups: those with no digital dermoscopy with little dermoscopy training (group A, the reference group), no digital dermoscopy but more dermoscopy training (group B), and those using digital dermoscopy (group C). In the group that used digital dermoscopy, that ratio was about 1 to 2.4, compared with about 1 to 8 in group B, and about 1 to 10.7 in group A (Br J Dermatol. 2012;167[4]778-86).

The use of dermoscopy is also associated with thinner tumors. Among dermoscopy users, the thickness of the tumors detected drops, and the proportion of thin to thick lesions detected increases, Dr. Marghoob said.

For example, in one study, the mean thickness in melanomas detected with dermoscopy was 1.4 mm versus 2.59 mm when dermoscopy was not used (J Eur Acad Dermatol Venereol. 2015 Jan; 29[1]:102-8). About 55% of the tumors detected with dermoscopic examination were 1 mm or less in thickness versus 23.4% of those detected without dermoscopy, “so the dermoscopy users from a proportion standpoint were also finding thinner tumors,” Dr. Marghoob said. Dermoscopy was also identified as an independent predictor of finding thinner tumors.

Even without a study, it could be assumed that the use of dermoscopy would reduce costs, since dermoscopy increases sensitivity and the total number of melanomas detected, decreases the number of benign nevi removed, and helps detect disease earlier. But there are data showing that dermoscopy reduces health care costs, Dr. Marghoob said.* For example, a Belgian study that looked at dermoscopy in two cohorts of melanoma patients concluded that adequate dermoscopy training was cost effective (Eur J Cancer. 2016 Nov;67:38-45).

It has also been shown that adding dermoscopy to a primary care setting has cost benefits, Dr. Marghoob said. He cited a study of Dutch general practices that found that the probability of a correct diagnosis was 1.25 times higher when dermoscopy was used to evaluate suspicious skin lesions and concluded that the use of dermoscopy appeared to be cost effective (J Eur Acad Dermatol Venereol. 2014 Nov;28[11]:1442-9).

Dr. Marghoob had no disclosures relevant to this presentation.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

*Correction, 2/28/20: An earlier version of this article mischaracterized the cost implications of dermoscopy use.

emechcatie@mdedge.com

LAHAINA, HAWAII – Multiple studies, including meta-analyses, have shown that dermoscopy improves sensitivity for diagnosing melanoma, without lowering specificity, but there are still some “nonbelievers,” Ashfaq A. Marghoob, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

In fact, not one study has shown that dermoscopy is less sensitive than the naked eye alone, and at clinics where dermoscopy is used, “two-thirds of the melanomas being detected now lack the classic ABCD features of melanoma,” added Dr. Marghoob, director of clinical dermatology at Memorial Sloan Kettering in Hauppauge, N.Y.

Dr. Marghoob cited a meta-analysis of 9 prospective trials, which concluded that dermoscopy was more accurate in diagnosing melanoma than the naked eye alone and did not lower specificity, with a sensitivity and specificity of 90%, compared with 71% and 81%, respectively for the naked eye (Br J Dermatol. 2008 Sep;159[3]:669-76).

“And at least from an evidence-based standpoint ... the Cochrane library has basically endorsed that, yes, dermoscopy does indeed improve your diagnostic accuracy,” Dr. Marghoob said.

He referred to a 2018 Cochrane review on 104 dermoscopy studies, with and without visual inspection, for diagnosing melanoma in adults (Cochrane Database Syst Rev. 2018 Dec 4;12:CD011902). The review authors concluded that “the evidence suggests that melanomas will be missed if visual inspection is used on its own,” and despite limitations in the evidence, “dermoscopy is a valuable tool to support the visual inspection of a suspicious skin lesion for the detection of melanoma and atypical intraepidermal melanocytic variants.”

As for the question of specificity, Dr. Marghoob said studies have found that dermoscopy results in the detection of more melanomas and reduces the number of biopsies of benign lesions and “every study looking into this has shown that, yes, it does improve” specificity.

A 10-year multicenter survey of about 300,000 cases, which included 17,172 melanomas and 283,043 melanocytic nevi, found that the number-needed-to-excise (NNE) values improved over time in specialized clinics where newer diagnostic techniques like dermoscopy were used (from 12.8 to 6.8), but the NNE did not appear to change in the nonspecialized settings (J Am Acad Dermatol. 2012 Jul;67[1]:54-9).

Looking at the benign-to-malignant ratio, there was no change among those not using dermoscopy, where the ratio remained at about 30 to 1. When dermoscopy was used, this ratio started to improve over the 10-year period, to about 5 to 1. In addition, “the dermoscopy users were finding many more melanomas than the non–dermoscopy users,” Dr. Marghoob added. And over the 10 years, the number of nevi being removed did not change among those not using dermoscopy but dropped among those using dermoscopy.

Adding photography with the ability to digitally monitor patients helps bring this ratio down further, Dr. Marghoob noted. He referred to a study that instead evaluated the ratio of melanoma to nonmelanomas diagnosed among dermatologists in three groups: those with no digital dermoscopy with little dermoscopy training (group A, the reference group), no digital dermoscopy but more dermoscopy training (group B), and those using digital dermoscopy (group C). In the group that used digital dermoscopy, that ratio was about 1 to 2.4, compared with about 1 to 8 in group B, and about 1 to 10.7 in group A (Br J Dermatol. 2012;167[4]778-86).

The use of dermoscopy is also associated with thinner tumors. Among dermoscopy users, the thickness of the tumors detected drops, and the proportion of thin to thick lesions detected increases, Dr. Marghoob said.

For example, in one study, the mean thickness in melanomas detected with dermoscopy was 1.4 mm versus 2.59 mm when dermoscopy was not used (J Eur Acad Dermatol Venereol. 2015 Jan; 29[1]:102-8). About 55% of the tumors detected with dermoscopic examination were 1 mm or less in thickness versus 23.4% of those detected without dermoscopy, “so the dermoscopy users from a proportion standpoint were also finding thinner tumors,” Dr. Marghoob said. Dermoscopy was also identified as an independent predictor of finding thinner tumors.

Even without a study, it could be assumed that the use of dermoscopy would reduce costs, since dermoscopy increases sensitivity and the total number of melanomas detected, decreases the number of benign nevi removed, and helps detect disease earlier. But there are data showing that dermoscopy reduces health care costs, Dr. Marghoob said.* For example, a Belgian study that looked at dermoscopy in two cohorts of melanoma patients concluded that adequate dermoscopy training was cost effective (Eur J Cancer. 2016 Nov;67:38-45).

It has also been shown that adding dermoscopy to a primary care setting has cost benefits, Dr. Marghoob said. He cited a study of Dutch general practices that found that the probability of a correct diagnosis was 1.25 times higher when dermoscopy was used to evaluate suspicious skin lesions and concluded that the use of dermoscopy appeared to be cost effective (J Eur Acad Dermatol Venereol. 2014 Nov;28[11]:1442-9).

Dr. Marghoob had no disclosures relevant to this presentation.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

*Correction, 2/28/20: An earlier version of this article mischaracterized the cost implications of dermoscopy use.

emechcatie@mdedge.com

A new tumor neoantigenicity metric may improve prediction of response to immunotherapy in patients with melanoma, lung cancer, and kidney cancer, a retrospective analysis suggests.

The new metric, known as the Cauchy-Schwarz index of neoantigens (CSiN) score, incorporates both immunogenicity and clonality, according to lead study author Tianshi Lu, a PhD candidate at the University of Texas Southwestern Medical Center in Dallas, and colleagues.

“The major biological insight from this study is that the neoantigen clonal structure in each tumor specimen and the immunogenicity of the neoantigens (represented by the MHC-binding strength in our study) are predictive of response to checkpoint inhibitors and prognosis,” the investigators wrote in Science Immunology.

The study involved 2,479 patients with various cancers, including immunogenic types such as renal cell carcinoma (RCC), and nonimmunogenic types, such as pediatric acute lymphocytic leukemia.

The investigators first evaluated CSiN in relation to clinical outcome among patients with immunogenic cancers who received immunotherapy. Drawing data from multiple cohorts, the investigators found that patients who had better responses to therapy were significantly more likely to have above average CSiN scores than those who had worse responses.

In one cohort of patients with melanoma who received anti–CTLA-4 therapy, those with better responses were more likely to have high CSiN scores (P = .009). In another cohort of melanoma patients who received anti–CTLA-4 therapy, those with higher CSiN scores were more likely to achieve durable clinical benefit (response or stable disease for more than 6 months), compared with patients who had lower CSiN scores (P = .033).

Among patients with clear cell RCC treated with anti-PD-1/PD-L1 therapy, there was a significant positive association between higher CSiN scores and better response (P = .036). Among T effector-high patients with metastatic clear cell RCC, there was a significant association between higher CSiN scores and better response to atezolizumab (P = .028) but not sunitinib (P = .890).

SOURCE: Lu et al. Sci Immunol. 2020 Feb 21. doi: 10.1126/sciimmunol.aaz3199.

A new tumor neoantigenicity metric may improve prediction of response to immunotherapy in patients with melanoma, lung cancer, and kidney cancer, a retrospective analysis suggests.

The new metric, known as the Cauchy-Schwarz index of neoantigens (CSiN) score, incorporates both immunogenicity and clonality, according to lead study author Tianshi Lu, a PhD candidate at the University of Texas Southwestern Medical Center in Dallas, and colleagues.

“The major biological insight from this study is that the neoantigen clonal structure in each tumor specimen and the immunogenicity of the neoantigens (represented by the MHC-binding strength in our study) are predictive of response to checkpoint inhibitors and prognosis,” the investigators wrote in Science Immunology.

The study involved 2,479 patients with various cancers, including immunogenic types such as renal cell carcinoma (RCC), and nonimmunogenic types, such as pediatric acute lymphocytic leukemia.

The investigators first evaluated CSiN in relation to clinical outcome among patients with immunogenic cancers who received immunotherapy. Drawing data from multiple cohorts, the investigators found that patients who had better responses to therapy were significantly more likely to have above average CSiN scores than those who had worse responses.

In one cohort of patients with melanoma who received anti–CTLA-4 therapy, those with better responses were more likely to have high CSiN scores (P = .009). In another cohort of melanoma patients who received anti–CTLA-4 therapy, those with higher CSiN scores were more likely to achieve durable clinical benefit (response or stable disease for more than 6 months), compared with patients who had lower CSiN scores (P = .033).

Among patients with clear cell RCC treated with anti-PD-1/PD-L1 therapy, there was a significant positive association between higher CSiN scores and better response (P = .036). Among T effector-high patients with metastatic clear cell RCC, there was a significant association between higher CSiN scores and better response to atezolizumab (P = .028) but not sunitinib (P = .890).

SOURCE: Lu et al. Sci Immunol. 2020 Feb 21. doi: 10.1126/sciimmunol.aaz3199.

A new tumor neoantigenicity metric may improve prediction of response to immunotherapy in patients with melanoma, lung cancer, and kidney cancer, a retrospective analysis suggests.

The new metric, known as the Cauchy-Schwarz index of neoantigens (CSiN) score, incorporates both immunogenicity and clonality, according to lead study author Tianshi Lu, a PhD candidate at the University of Texas Southwestern Medical Center in Dallas, and colleagues.

“The major biological insight from this study is that the neoantigen clonal structure in each tumor specimen and the immunogenicity of the neoantigens (represented by the MHC-binding strength in our study) are predictive of response to checkpoint inhibitors and prognosis,” the investigators wrote in Science Immunology.

The study involved 2,479 patients with various cancers, including immunogenic types such as renal cell carcinoma (RCC), and nonimmunogenic types, such as pediatric acute lymphocytic leukemia.

The investigators first evaluated CSiN in relation to clinical outcome among patients with immunogenic cancers who received immunotherapy. Drawing data from multiple cohorts, the investigators found that patients who had better responses to therapy were significantly more likely to have above average CSiN scores than those who had worse responses.

In one cohort of patients with melanoma who received anti–CTLA-4 therapy, those with better responses were more likely to have high CSiN scores (P = .009). In another cohort of melanoma patients who received anti–CTLA-4 therapy, those with higher CSiN scores were more likely to achieve durable clinical benefit (response or stable disease for more than 6 months), compared with patients who had lower CSiN scores (P = .033).

Among patients with clear cell RCC treated with anti-PD-1/PD-L1 therapy, there was a significant positive association between higher CSiN scores and better response (P = .036). Among T effector-high patients with metastatic clear cell RCC, there was a significant association between higher CSiN scores and better response to atezolizumab (P = .028) but not sunitinib (P = .890).

SOURCE: Lu et al. Sci Immunol. 2020 Feb 21. doi: 10.1126/sciimmunol.aaz3199.

Banning indoor tanning devices outright in the United States, Canada, and Europe could prevent as many as 448,000 melanomas and 9.7 million keratinocyte carcinomas, according to a study published in JAMA Dermatology.

The study also suggests a ban would result in a collective cost savings of $5.7 billion and productivity gains of $41.3 billion.

Compared with a ban on indoor tanning for minors, the benefits of a full ban on devices were 3.7-fold higher in the United States/Canada and 2.6-fold higher in Europe, according to study author Louisa G. Gordon, PhD, of the QIMR Berghofer Medical Research Institute in Brisbane, Australia, and colleagues.

The researchers noted that indoor tanning is regulated in more than 20 countries. Australia has instituted a ban on commercial indoor tanning devices, and Brazil has banned both commercial and private tanning devices.

In the United States, 19 states have banned the use of indoor tanning beds for minors, and 44 states as well as the District of Columbia have some regulation of tanning facilities for minors, according to the National Conference of State Legislatures.

With this study, Dr. Gordon and colleagues sought to explore what effect an outright ban on indoor tanning devices, a prohibition for minors only, or continuing current levels of indoor tanning would have on the health and economy of the United States, Canada, and Europe.

The researchers created a Markov cohort model of 110,932,523 individuals in the United States/Canada and 141,970,492 individuals in Europe, all aged 12-35 years.

The team used data from epidemiologic studies, cost reports, and official cancer registries to estimate the prevalence of indoor tanning, risk of developing melanoma, and mortality rates from skin cancer and other causes. The researchers also estimated health care costs of melanoma treatment in each region as well as the societal cost of dying prematurely from melanoma, adjusted to 2018 dollars.
 

Results

The model suggested a ban on indoor tanning in the United States and Canada would result in 244,347 fewer melanomas (–8.7%), 89,193 fewer deaths from melanoma (–6.9%), and 7.3 million fewer keratinocyte carcinomas (–7.8%) than continuing at the current levels of use. The ban would also save 428,781 life-years, have a cost savings of $3.5 billion, and confer productivity gains of $27.5 billion, the researchers said.

When applying the ban in Europe, the model estimated 203,736 fewer melanomas (­–4.9%), 98,288 fewer deaths from melanoma (–4.4%), and 2.4 million fewer keratinocyte carcinomas (­–4.4%). The researchers also noted that Europe would see a gain of 459,669 life-years, a cost savings of $2.1 billion, and a productivity gain of $13.7 billion.

Dr. Gordon and colleagues acknowledged that their model had some limitations, such as in estimating the prevalence of certain skin cancers across Europe, which can range from 10% to 56% depending on the country. In addition, the model did not account for the money spent in implementing a ban, which could include costs associated with regulation, compliance, and buy-back schemes for tanning devices.
 

Implications

In an interview, Dr. Gordon said the researchers conducted this study to stress the health benefits and cost savings of regulating indoor tanning devices in North America and Europe. She noted that she had previously published a report in 2009 that helped Australia make the decision to ban such devices there, but she said the tanning industry was in its infancy during that time, which factored into the decision to ban indoor tanning (Health Policy. 2009 Mar;89[3]:303-11).

Any ban by a regulatory agency “should include everyone,” Dr. Gordon said, because “banning minors is a halfway attempt to prevent skin cancers.” The danger isn’t just present in children. “People in their 20s and 30s are still very image conscious,” she said. “The pressure is enormous.”

Anyone interested in tanning should use tanning creams or sprays instead of using indoor tanning devices, Dr. Gordon said. “Consumers can control their UV exposure,” she noted. “Prevention is incredibly important, and skin cancer is one of a few cancers we can almost entirely prevent via protecting our skin. The same can’t be said for other horrible cancers.”

Adam Friedman, MD, a professor at George Washington University, Washington, who was not involved in this study, said it should come as no surprise to dermatologists that preventing artificial UVA heavy exposure reduces the incidence of skin cancer, but the “more compelling component of this study is cost.”

“The lay public is extremely health care cost conscientious,” he said. “This is a commonly debated topic for emerging politicians at every level; not to mention, no one enjoys bleeding money. Dermatologists can use the angle of, ‘save skin now, save money later,’ to target the financial burden of accelerated skin aging and skin cancer as a mechanism for persuading patients not to ‘shake and bake.’ ”

While the Food and Drug Administration has proposed restricting the use of indoor tanning devices for minors nationwide, it has not issued a final rule on the matter, and the prospect of an outright ban in the United States for the general population is less feasible, noted Dr. Friedman.

“I think it would be difficult to expand this [proposed] ban given the financial impact on numerous businesses,” he said. “It would likely take more evidence and support beyond the medical community to make this happen, but here’s hoping,”

This study was funded by the World Health Organization UV Radiation Programme and Cancer Council Victoria. One author disclosed personal fees from Cancer Council Victoria, and one disclosed grants from TrygFonden. The other authors and Dr. Friedman reported no relevant conflicts of interest.

SOURCE: Gordon L et al. JAMA Dermatol. 2020 Feb 19. doi: 10.1001/jamadermatol.2020.0001.

Banning indoor tanning devices outright in the United States, Canada, and Europe could prevent as many as 448,000 melanomas and 9.7 million keratinocyte carcinomas, according to a study published in JAMA Dermatology.

The study also suggests a ban would result in a collective cost savings of $5.7 billion and productivity gains of $41.3 billion.

Compared with a ban on indoor tanning for minors, the benefits of a full ban on devices were 3.7-fold higher in the United States/Canada and 2.6-fold higher in Europe, according to study author Louisa G. Gordon, PhD, of the QIMR Berghofer Medical Research Institute in Brisbane, Australia, and colleagues.

The researchers noted that indoor tanning is regulated in more than 20 countries. Australia has instituted a ban on commercial indoor tanning devices, and Brazil has banned both commercial and private tanning devices.

In the United States, 19 states have banned the use of indoor tanning beds for minors, and 44 states as well as the District of Columbia have some regulation of tanning facilities for minors, according to the National Conference of State Legislatures.

With this study, Dr. Gordon and colleagues sought to explore what effect an outright ban on indoor tanning devices, a prohibition for minors only, or continuing current levels of indoor tanning would have on the health and economy of the United States, Canada, and Europe.

The researchers created a Markov cohort model of 110,932,523 individuals in the United States/Canada and 141,970,492 individuals in Europe, all aged 12-35 years.

The team used data from epidemiologic studies, cost reports, and official cancer registries to estimate the prevalence of indoor tanning, risk of developing melanoma, and mortality rates from skin cancer and other causes. The researchers also estimated health care costs of melanoma treatment in each region as well as the societal cost of dying prematurely from melanoma, adjusted to 2018 dollars.
 

Results

The model suggested a ban on indoor tanning in the United States and Canada would result in 244,347 fewer melanomas (–8.7%), 89,193 fewer deaths from melanoma (–6.9%), and 7.3 million fewer keratinocyte carcinomas (–7.8%) than continuing at the current levels of use. The ban would also save 428,781 life-years, have a cost savings of $3.5 billion, and confer productivity gains of $27.5 billion, the researchers said.

When applying the ban in Europe, the model estimated 203,736 fewer melanomas (­–4.9%), 98,288 fewer deaths from melanoma (–4.4%), and 2.4 million fewer keratinocyte carcinomas (­–4.4%). The researchers also noted that Europe would see a gain of 459,669 life-years, a cost savings of $2.1 billion, and a productivity gain of $13.7 billion.

Dr. Gordon and colleagues acknowledged that their model had some limitations, such as in estimating the prevalence of certain skin cancers across Europe, which can range from 10% to 56% depending on the country. In addition, the model did not account for the money spent in implementing a ban, which could include costs associated with regulation, compliance, and buy-back schemes for tanning devices.
 

Implications

In an interview, Dr. Gordon said the researchers conducted this study to stress the health benefits and cost savings of regulating indoor tanning devices in North America and Europe. She noted that she had previously published a report in 2009 that helped Australia make the decision to ban such devices there, but she said the tanning industry was in its infancy during that time, which factored into the decision to ban indoor tanning (Health Policy. 2009 Mar;89[3]:303-11).

Any ban by a regulatory agency “should include everyone,” Dr. Gordon said, because “banning minors is a halfway attempt to prevent skin cancers.” The danger isn’t just present in children. “People in their 20s and 30s are still very image conscious,” she said. “The pressure is enormous.”

Anyone interested in tanning should use tanning creams or sprays instead of using indoor tanning devices, Dr. Gordon said. “Consumers can control their UV exposure,” she noted. “Prevention is incredibly important, and skin cancer is one of a few cancers we can almost entirely prevent via protecting our skin. The same can’t be said for other horrible cancers.”

Adam Friedman, MD, a professor at George Washington University, Washington, who was not involved in this study, said it should come as no surprise to dermatologists that preventing artificial UVA heavy exposure reduces the incidence of skin cancer, but the “more compelling component of this study is cost.”

“The lay public is extremely health care cost conscientious,” he said. “This is a commonly debated topic for emerging politicians at every level; not to mention, no one enjoys bleeding money. Dermatologists can use the angle of, ‘save skin now, save money later,’ to target the financial burden of accelerated skin aging and skin cancer as a mechanism for persuading patients not to ‘shake and bake.’ ”

While the Food and Drug Administration has proposed restricting the use of indoor tanning devices for minors nationwide, it has not issued a final rule on the matter, and the prospect of an outright ban in the United States for the general population is less feasible, noted Dr. Friedman.

“I think it would be difficult to expand this [proposed] ban given the financial impact on numerous businesses,” he said. “It would likely take more evidence and support beyond the medical community to make this happen, but here’s hoping,”

This study was funded by the World Health Organization UV Radiation Programme and Cancer Council Victoria. One author disclosed personal fees from Cancer Council Victoria, and one disclosed grants from TrygFonden. The other authors and Dr. Friedman reported no relevant conflicts of interest.

SOURCE: Gordon L et al. JAMA Dermatol. 2020 Feb 19. doi: 10.1001/jamadermatol.2020.0001.

Banning indoor tanning devices outright in the United States, Canada, and Europe could prevent as many as 448,000 melanomas and 9.7 million keratinocyte carcinomas, according to a study published in JAMA Dermatology.

The study also suggests a ban would result in a collective cost savings of $5.7 billion and productivity gains of $41.3 billion.

Compared with a ban on indoor tanning for minors, the benefits of a full ban on devices were 3.7-fold higher in the United States/Canada and 2.6-fold higher in Europe, according to study author Louisa G. Gordon, PhD, of the QIMR Berghofer Medical Research Institute in Brisbane, Australia, and colleagues.

The researchers noted that indoor tanning is regulated in more than 20 countries. Australia has instituted a ban on commercial indoor tanning devices, and Brazil has banned both commercial and private tanning devices.

In the United States, 19 states have banned the use of indoor tanning beds for minors, and 44 states as well as the District of Columbia have some regulation of tanning facilities for minors, according to the National Conference of State Legislatures.

With this study, Dr. Gordon and colleagues sought to explore what effect an outright ban on indoor tanning devices, a prohibition for minors only, or continuing current levels of indoor tanning would have on the health and economy of the United States, Canada, and Europe.

The researchers created a Markov cohort model of 110,932,523 individuals in the United States/Canada and 141,970,492 individuals in Europe, all aged 12-35 years.

The team used data from epidemiologic studies, cost reports, and official cancer registries to estimate the prevalence of indoor tanning, risk of developing melanoma, and mortality rates from skin cancer and other causes. The researchers also estimated health care costs of melanoma treatment in each region as well as the societal cost of dying prematurely from melanoma, adjusted to 2018 dollars.
 

Results

The model suggested a ban on indoor tanning in the United States and Canada would result in 244,347 fewer melanomas (–8.7%), 89,193 fewer deaths from melanoma (–6.9%), and 7.3 million fewer keratinocyte carcinomas (–7.8%) than continuing at the current levels of use. The ban would also save 428,781 life-years, have a cost savings of $3.5 billion, and confer productivity gains of $27.5 billion, the researchers said.

When applying the ban in Europe, the model estimated 203,736 fewer melanomas (­–4.9%), 98,288 fewer deaths from melanoma (–4.4%), and 2.4 million fewer keratinocyte carcinomas (­–4.4%). The researchers also noted that Europe would see a gain of 459,669 life-years, a cost savings of $2.1 billion, and a productivity gain of $13.7 billion.

Dr. Gordon and colleagues acknowledged that their model had some limitations, such as in estimating the prevalence of certain skin cancers across Europe, which can range from 10% to 56% depending on the country. In addition, the model did not account for the money spent in implementing a ban, which could include costs associated with regulation, compliance, and buy-back schemes for tanning devices.
 

Implications

In an interview, Dr. Gordon said the researchers conducted this study to stress the health benefits and cost savings of regulating indoor tanning devices in North America and Europe. She noted that she had previously published a report in 2009 that helped Australia make the decision to ban such devices there, but she said the tanning industry was in its infancy during that time, which factored into the decision to ban indoor tanning (Health Policy. 2009 Mar;89[3]:303-11).

Any ban by a regulatory agency “should include everyone,” Dr. Gordon said, because “banning minors is a halfway attempt to prevent skin cancers.” The danger isn’t just present in children. “People in their 20s and 30s are still very image conscious,” she said. “The pressure is enormous.”

Anyone interested in tanning should use tanning creams or sprays instead of using indoor tanning devices, Dr. Gordon said. “Consumers can control their UV exposure,” she noted. “Prevention is incredibly important, and skin cancer is one of a few cancers we can almost entirely prevent via protecting our skin. The same can’t be said for other horrible cancers.”

Adam Friedman, MD, a professor at George Washington University, Washington, who was not involved in this study, said it should come as no surprise to dermatologists that preventing artificial UVA heavy exposure reduces the incidence of skin cancer, but the “more compelling component of this study is cost.”

“The lay public is extremely health care cost conscientious,” he said. “This is a commonly debated topic for emerging politicians at every level; not to mention, no one enjoys bleeding money. Dermatologists can use the angle of, ‘save skin now, save money later,’ to target the financial burden of accelerated skin aging and skin cancer as a mechanism for persuading patients not to ‘shake and bake.’ ”

While the Food and Drug Administration has proposed restricting the use of indoor tanning devices for minors nationwide, it has not issued a final rule on the matter, and the prospect of an outright ban in the United States for the general population is less feasible, noted Dr. Friedman.

“I think it would be difficult to expand this [proposed] ban given the financial impact on numerous businesses,” he said. “It would likely take more evidence and support beyond the medical community to make this happen, but here’s hoping,”

This study was funded by the World Health Organization UV Radiation Programme and Cancer Council Victoria. One author disclosed personal fees from Cancer Council Victoria, and one disclosed grants from TrygFonden. The other authors and Dr. Friedman reported no relevant conflicts of interest.

SOURCE: Gordon L et al. JAMA Dermatol. 2020 Feb 19. doi: 10.1001/jamadermatol.2020.0001.

Smartphone applications (apps) using so-called artificial intelligence (AI) aimed at the general public for use on suspicious skin lesions are unreliable, said U.K. researchers reporting a systematic review.
 

These apps are providing information that could lead to “potentially life-or-death decisions,” commented co-lead author Hywel C. Williams, MD, from the Centre of Evidence Based Dermatology, University of Nottingham (England).

“The one thing you mustn’t do in a situation where early diagnosis can make a difference between life and death is you mustn’t miss the melanoma,” he said in an interview.

“These apps were missing melanomas, and that’s very worrisome,” he commented.

The review included nine studies of skin cancer smartphone apps, including two apps, SkinScan and SkinVision, that have been given Conformit Europenne (CE) marks, allowing them to be marketed across Europe. These apps are also available in Australia and New Zealand, but not in the United States.

The review found that SkinScan was not able to identify any melanomas in the one study that assessed this app, while SkinVision had a relatively low sensitivity and specificity, with 12% of cancerous or precancerous lesions missed and 21% of benign lesions wrongly identified as cancerous.

This means that among 1,000 people with a melanoma prevalence of 3%, 4 of 30 melanomas would be missed, and 200 people would be incorrectly told that a mole was of high concern, the authors estimated.

The research was published by The BMJ on Feb. 10.

“Although I was broad minded on the potential benefit of apps for diagnosing skin cancer, I am now worried given the results of our study and the overall poor quality of studies used to test these apps,” Dr. Williams commented in a statement.

Coauthor Jac Dinnes, PhD, from the Institute of Applied Health Research at the University of Birmingham (England), added it is “really disappointing that there is not better quality evidence available to judge the efficacy of these apps.”

“It is vital that health care professionals are aware of the current limitations both in the technologies and in their evaluations,” she added.

The results also highlight the limitations of the regulatory system governing smartphone apps in that they are currently not subject to assessment by bodies such as the U.K.’s Medicines and Healthcare Products Regulatory Agency (MHRA), the authors commented.

“Regulators need to become alert to the potential harm that poorly performing algorithm-based diagnostic or risk monitoring apps create,” said co-lead author Jonathan J. Deeks, PhD, also at the Institute of Applied Health Research.

“We rely on the CE mark as a sign of quality, but the current CE mark assessment processes are not fit for protecting the public against the risks that these apps present.”

Speaking in an interview, Williams lamented the poor quality of the research that had been conducted. “These studies were not good enough,” he said, adding that “there’s no excuse for really poor study design and poor reporting.”

He would like to see the regulations tightened around AI apps purporting to inform decision making for the general public and suggests that these devices should be assessed by the MHRA. “I really do think a CE mark is not enough,” he said.

The team noted that the skin cancer apps “all include disclaimers that the results should only be used as a guide and cannot replace health care advice,” through which the manufacturers “attempt to evade any responsibility for negative outcomes experienced by users.”

Nevertheless, the “poor and variable performance” of the apps revealed by their review indicates that they “have not yet shown sufficient promise to recommend their use,” they concluded.

The “official approval” implied by a CE mark “will give consumers the impression that the apps have been assessed as effective and safe,” wrote Ben Goldacre, DataLab director, Nuffield Department of Primary Care, University of Oxford (England), and colleagues in an accompanying editorial.

“The implicit assumption is that apps are similarly low-risk technology” to devices such as sticking plasters and reading glasses, they comment.

“But shortcomings in diagnostic apps can have serious implications,” they warn. The “risks include psychological harm from health anxiety or ‘cyberchondria,’ and physical harm from misdiagnosis or overdiagnosis; for clinicians there is a risk of increased workload, and changes to ethical or legal responsibilities around triage, referral, diagnosis, and treatment.” There is also potential for “inappropriate resource use, and even loss of credibility for digital technology in general.”

Details of the review

For their review, the authors searched the Cochrane Central Register on Controlled Trials, the MEDLNE, Embase, Cumulative Index to Nursing and Allied Health Literature, Conference Proceedings Citation index, Zetoc, and Science Citation Index databases, and online trial registers for studies published between August 2016 and April 2019.

From 80 studies identified, 9 met the eligibility criteria.

Of those, six studies, evaluating a total of 725 skin lesions, determined the accuracy of smartphone apps in risk stratifying suspicious skin lesions by comparing them against a histopathological reference standard diagnosis or expert follow-up.

Five of these studies aimed to detect only melanoma, while one sought to differentiate between malignant or premalignant lesions (including melanoma, basal cell carcinoma, and squamous cell carcinoma) and benign lesions.

The three remaining studies, which evaluated 407 lesions in all, compared smartphone app recommendations against a reference standard of expert recommendations for further investigation or intervention.

The researchers found the studies had a string of potential biases and limitations.

For example, only four studies recruited a consecutive sample of study participants and lesions, and only two included lesions selected by study participants, whereas five studies used lesions that had been selected by a clinician.

Three studies reported that it took 5-10 attempts to obtain an adequate image. In seven studies, it was the researchers and not the patients who used the app to photograph the lesions, and two studies used images obtained from dermatology databases.

This “raised concerns that the results of the studies were unlikely to be representative of real life use,” the authors comment.

In addition, the exclusion of unevaluable images “might have systematically inflated the diagnostic performance of the tested apps,” they add.

The independent research was supported by the National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham and is an update of one of a collection of reviews funded by the NIHR through its Cochrane Systematic Review Programme Grant.
 

This article first appeared on Medscape.com.

Smartphone applications (apps) using so-called artificial intelligence (AI) aimed at the general public for use on suspicious skin lesions are unreliable, said U.K. researchers reporting a systematic review.
 

These apps are providing information that could lead to “potentially life-or-death decisions,” commented co-lead author Hywel C. Williams, MD, from the Centre of Evidence Based Dermatology, University of Nottingham (England).

“The one thing you mustn’t do in a situation where early diagnosis can make a difference between life and death is you mustn’t miss the melanoma,” he said in an interview.

“These apps were missing melanomas, and that’s very worrisome,” he commented.

The review included nine studies of skin cancer smartphone apps, including two apps, SkinScan and SkinVision, that have been given Conformit Europenne (CE) marks, allowing them to be marketed across Europe. These apps are also available in Australia and New Zealand, but not in the United States.

The review found that SkinScan was not able to identify any melanomas in the one study that assessed this app, while SkinVision had a relatively low sensitivity and specificity, with 12% of cancerous or precancerous lesions missed and 21% of benign lesions wrongly identified as cancerous.

This means that among 1,000 people with a melanoma prevalence of 3%, 4 of 30 melanomas would be missed, and 200 people would be incorrectly told that a mole was of high concern, the authors estimated.

The research was published by The BMJ on Feb. 10.

“Although I was broad minded on the potential benefit of apps for diagnosing skin cancer, I am now worried given the results of our study and the overall poor quality of studies used to test these apps,” Dr. Williams commented in a statement.

Coauthor Jac Dinnes, PhD, from the Institute of Applied Health Research at the University of Birmingham (England), added it is “really disappointing that there is not better quality evidence available to judge the efficacy of these apps.”

“It is vital that health care professionals are aware of the current limitations both in the technologies and in their evaluations,” she added.

The results also highlight the limitations of the regulatory system governing smartphone apps in that they are currently not subject to assessment by bodies such as the U.K.’s Medicines and Healthcare Products Regulatory Agency (MHRA), the authors commented.

“Regulators need to become alert to the potential harm that poorly performing algorithm-based diagnostic or risk monitoring apps create,” said co-lead author Jonathan J. Deeks, PhD, also at the Institute of Applied Health Research.

“We rely on the CE mark as a sign of quality, but the current CE mark assessment processes are not fit for protecting the public against the risks that these apps present.”

Speaking in an interview, Williams lamented the poor quality of the research that had been conducted. “These studies were not good enough,” he said, adding that “there’s no excuse for really poor study design and poor reporting.”

He would like to see the regulations tightened around AI apps purporting to inform decision making for the general public and suggests that these devices should be assessed by the MHRA. “I really do think a CE mark is not enough,” he said.

The team noted that the skin cancer apps “all include disclaimers that the results should only be used as a guide and cannot replace health care advice,” through which the manufacturers “attempt to evade any responsibility for negative outcomes experienced by users.”

Nevertheless, the “poor and variable performance” of the apps revealed by their review indicates that they “have not yet shown sufficient promise to recommend their use,” they concluded.

The “official approval” implied by a CE mark “will give consumers the impression that the apps have been assessed as effective and safe,” wrote Ben Goldacre, DataLab director, Nuffield Department of Primary Care, University of Oxford (England), and colleagues in an accompanying editorial.

“The implicit assumption is that apps are similarly low-risk technology” to devices such as sticking plasters and reading glasses, they comment.

“But shortcomings in diagnostic apps can have serious implications,” they warn. The “risks include psychological harm from health anxiety or ‘cyberchondria,’ and physical harm from misdiagnosis or overdiagnosis; for clinicians there is a risk of increased workload, and changes to ethical or legal responsibilities around triage, referral, diagnosis, and treatment.” There is also potential for “inappropriate resource use, and even loss of credibility for digital technology in general.”

Details of the review

For their review, the authors searched the Cochrane Central Register on Controlled Trials, the MEDLNE, Embase, Cumulative Index to Nursing and Allied Health Literature, Conference Proceedings Citation index, Zetoc, and Science Citation Index databases, and online trial registers for studies published between August 2016 and April 2019.

From 80 studies identified, 9 met the eligibility criteria.

Of those, six studies, evaluating a total of 725 skin lesions, determined the accuracy of smartphone apps in risk stratifying suspicious skin lesions by comparing them against a histopathological reference standard diagnosis or expert follow-up.

Five of these studies aimed to detect only melanoma, while one sought to differentiate between malignant or premalignant lesions (including melanoma, basal cell carcinoma, and squamous cell carcinoma) and benign lesions.

The three remaining studies, which evaluated 407 lesions in all, compared smartphone app recommendations against a reference standard of expert recommendations for further investigation or intervention.

The researchers found the studies had a string of potential biases and limitations.

For example, only four studies recruited a consecutive sample of study participants and lesions, and only two included lesions selected by study participants, whereas five studies used lesions that had been selected by a clinician.

Three studies reported that it took 5-10 attempts to obtain an adequate image. In seven studies, it was the researchers and not the patients who used the app to photograph the lesions, and two studies used images obtained from dermatology databases.

This “raised concerns that the results of the studies were unlikely to be representative of real life use,” the authors comment.

In addition, the exclusion of unevaluable images “might have systematically inflated the diagnostic performance of the tested apps,” they add.

The independent research was supported by the National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham and is an update of one of a collection of reviews funded by the NIHR through its Cochrane Systematic Review Programme Grant.
 

This article first appeared on Medscape.com.

Smartphone applications (apps) using so-called artificial intelligence (AI) aimed at the general public for use on suspicious skin lesions are unreliable, said U.K. researchers reporting a systematic review.
 

These apps are providing information that could lead to “potentially life-or-death decisions,” commented co-lead author Hywel C. Williams, MD, from the Centre of Evidence Based Dermatology, University of Nottingham (England).

“The one thing you mustn’t do in a situation where early diagnosis can make a difference between life and death is you mustn’t miss the melanoma,” he said in an interview.

“These apps were missing melanomas, and that’s very worrisome,” he commented.

The review included nine studies of skin cancer smartphone apps, including two apps, SkinScan and SkinVision, that have been given Conformit Europenne (CE) marks, allowing them to be marketed across Europe. These apps are also available in Australia and New Zealand, but not in the United States.

The review found that SkinScan was not able to identify any melanomas in the one study that assessed this app, while SkinVision had a relatively low sensitivity and specificity, with 12% of cancerous or precancerous lesions missed and 21% of benign lesions wrongly identified as cancerous.

This means that among 1,000 people with a melanoma prevalence of 3%, 4 of 30 melanomas would be missed, and 200 people would be incorrectly told that a mole was of high concern, the authors estimated.

The research was published by The BMJ on Feb. 10.

“Although I was broad minded on the potential benefit of apps for diagnosing skin cancer, I am now worried given the results of our study and the overall poor quality of studies used to test these apps,” Dr. Williams commented in a statement.

Coauthor Jac Dinnes, PhD, from the Institute of Applied Health Research at the University of Birmingham (England), added it is “really disappointing that there is not better quality evidence available to judge the efficacy of these apps.”

“It is vital that health care professionals are aware of the current limitations both in the technologies and in their evaluations,” she added.

The results also highlight the limitations of the regulatory system governing smartphone apps in that they are currently not subject to assessment by bodies such as the U.K.’s Medicines and Healthcare Products Regulatory Agency (MHRA), the authors commented.

“Regulators need to become alert to the potential harm that poorly performing algorithm-based diagnostic or risk monitoring apps create,” said co-lead author Jonathan J. Deeks, PhD, also at the Institute of Applied Health Research.

“We rely on the CE mark as a sign of quality, but the current CE mark assessment processes are not fit for protecting the public against the risks that these apps present.”

Speaking in an interview, Williams lamented the poor quality of the research that had been conducted. “These studies were not good enough,” he said, adding that “there’s no excuse for really poor study design and poor reporting.”

He would like to see the regulations tightened around AI apps purporting to inform decision making for the general public and suggests that these devices should be assessed by the MHRA. “I really do think a CE mark is not enough,” he said.

The team noted that the skin cancer apps “all include disclaimers that the results should only be used as a guide and cannot replace health care advice,” through which the manufacturers “attempt to evade any responsibility for negative outcomes experienced by users.”

Nevertheless, the “poor and variable performance” of the apps revealed by their review indicates that they “have not yet shown sufficient promise to recommend their use,” they concluded.

The “official approval” implied by a CE mark “will give consumers the impression that the apps have been assessed as effective and safe,” wrote Ben Goldacre, DataLab director, Nuffield Department of Primary Care, University of Oxford (England), and colleagues in an accompanying editorial.

“The implicit assumption is that apps are similarly low-risk technology” to devices such as sticking plasters and reading glasses, they comment.

“But shortcomings in diagnostic apps can have serious implications,” they warn. The “risks include psychological harm from health anxiety or ‘cyberchondria,’ and physical harm from misdiagnosis or overdiagnosis; for clinicians there is a risk of increased workload, and changes to ethical or legal responsibilities around triage, referral, diagnosis, and treatment.” There is also potential for “inappropriate resource use, and even loss of credibility for digital technology in general.”

Details of the review

For their review, the authors searched the Cochrane Central Register on Controlled Trials, the MEDLNE, Embase, Cumulative Index to Nursing and Allied Health Literature, Conference Proceedings Citation index, Zetoc, and Science Citation Index databases, and online trial registers for studies published between August 2016 and April 2019.

From 80 studies identified, 9 met the eligibility criteria.

Of those, six studies, evaluating a total of 725 skin lesions, determined the accuracy of smartphone apps in risk stratifying suspicious skin lesions by comparing them against a histopathological reference standard diagnosis or expert follow-up.

Five of these studies aimed to detect only melanoma, while one sought to differentiate between malignant or premalignant lesions (including melanoma, basal cell carcinoma, and squamous cell carcinoma) and benign lesions.

The three remaining studies, which evaluated 407 lesions in all, compared smartphone app recommendations against a reference standard of expert recommendations for further investigation or intervention.

The researchers found the studies had a string of potential biases and limitations.

For example, only four studies recruited a consecutive sample of study participants and lesions, and only two included lesions selected by study participants, whereas five studies used lesions that had been selected by a clinician.

Three studies reported that it took 5-10 attempts to obtain an adequate image. In seven studies, it was the researchers and not the patients who used the app to photograph the lesions, and two studies used images obtained from dermatology databases.

This “raised concerns that the results of the studies were unlikely to be representative of real life use,” the authors comment.

In addition, the exclusion of unevaluable images “might have systematically inflated the diagnostic performance of the tested apps,” they add.

The independent research was supported by the National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham and is an update of one of a collection of reviews funded by the NIHR through its Cochrane Systematic Review Programme Grant.
 

This article first appeared on Medscape.com.

There is not enough evidence to suggest that radiofrequency radiation (RFR) associated with cell phone use causes cancer, according to a review by the Food and Drug Administration.

The FDA reviewed the published literature from 2008 to 2018 and concluded that the data don’t support any quantifiable adverse health risks from RFR. However, the evidence is not without limitations.

The FDA’s evaluation included evidence from in vivo animal studies from Jan. 1, 2008, to Aug. 1, 2018, and epidemiologic studies in humans from Jan. 1, 2008, to May 8, 2018. Both kinds of evidence had limitations, but neither produced strong indications of any causal risks from cell phone use.

The FDA noted that in vivo animal studies are limited by variability of methods and RFR exposure, which make comparisons of results difficult. These studies are also impacted by the indirect effects of temperature increases (the only currently established biological effect of RFR) and stress experienced by the animals, which make teasing out the direct effects of RFR difficult.

The FDA noted that strong epidemiologic studies can provide more relevant and accurate information than in vivo studies, but epidemiologic studies are not without limitations. For example, most have participants track and self-report their cell phone use. There’s also no way to directly track certain factors of RFR exposure, such as frequency, duration, or intensity.

Even with those caveats in mind, the FDA wrote that, “based on the studies that are described in detail in this report, there is insufficient evidence to support a causal association between RFR exposure and tumorigenesis. There is a lack of clear dose-response relationship, a lack of consistent findings or specificity, and a lack of biological mechanistic plausibility.”

The full review is available on the FDA website.

cpalmer@mdedge.com

There is not enough evidence to suggest that radiofrequency radiation (RFR) associated with cell phone use causes cancer, according to a review by the Food and Drug Administration.

The FDA reviewed the published literature from 2008 to 2018 and concluded that the data don’t support any quantifiable adverse health risks from RFR. However, the evidence is not without limitations.

The FDA’s evaluation included evidence from in vivo animal studies from Jan. 1, 2008, to Aug. 1, 2018, and epidemiologic studies in humans from Jan. 1, 2008, to May 8, 2018. Both kinds of evidence had limitations, but neither produced strong indications of any causal risks from cell phone use.

The FDA noted that in vivo animal studies are limited by variability of methods and RFR exposure, which make comparisons of results difficult. These studies are also impacted by the indirect effects of temperature increases (the only currently established biological effect of RFR) and stress experienced by the animals, which make teasing out the direct effects of RFR difficult.

The FDA noted that strong epidemiologic studies can provide more relevant and accurate information than in vivo studies, but epidemiologic studies are not without limitations. For example, most have participants track and self-report their cell phone use. There’s also no way to directly track certain factors of RFR exposure, such as frequency, duration, or intensity.

Even with those caveats in mind, the FDA wrote that, “based on the studies that are described in detail in this report, there is insufficient evidence to support a causal association between RFR exposure and tumorigenesis. There is a lack of clear dose-response relationship, a lack of consistent findings or specificity, and a lack of biological mechanistic plausibility.”

The full review is available on the FDA website.

cpalmer@mdedge.com

There is not enough evidence to suggest that radiofrequency radiation (RFR) associated with cell phone use causes cancer, according to a review by the Food and Drug Administration.

The FDA reviewed the published literature from 2008 to 2018 and concluded that the data don’t support any quantifiable adverse health risks from RFR. However, the evidence is not without limitations.

The FDA’s evaluation included evidence from in vivo animal studies from Jan. 1, 2008, to Aug. 1, 2018, and epidemiologic studies in humans from Jan. 1, 2008, to May 8, 2018. Both kinds of evidence had limitations, but neither produced strong indications of any causal risks from cell phone use.

The FDA noted that in vivo animal studies are limited by variability of methods and RFR exposure, which make comparisons of results difficult. These studies are also impacted by the indirect effects of temperature increases (the only currently established biological effect of RFR) and stress experienced by the animals, which make teasing out the direct effects of RFR difficult.

The FDA noted that strong epidemiologic studies can provide more relevant and accurate information than in vivo studies, but epidemiologic studies are not without limitations. For example, most have participants track and self-report their cell phone use. There’s also no way to directly track certain factors of RFR exposure, such as frequency, duration, or intensity.

Even with those caveats in mind, the FDA wrote that, “based on the studies that are described in detail in this report, there is insufficient evidence to support a causal association between RFR exposure and tumorigenesis. There is a lack of clear dose-response relationship, a lack of consistent findings or specificity, and a lack of biological mechanistic plausibility.”

The full review is available on the FDA website.

cpalmer@mdedge.com

A massive collaborative project spanning four continents and 744 research centers has revealed driver mutations in both protein-coding and noncoding regions of 38 cancer types.

Pan-Cancer Analysis of Whole Genomes

The Pan-Cancer Analysis of Whole Genomes (PCAWG) is an integrative analysis of the whole-genome sequences from 2,658 donors across 38 common tumor types. The findings are expected to add exponentially to what’s currently known about the complex genetics of cancer, and they point to possible strategies for improving cancer prevention, diagnosis, and care.

Six articles summarizing the findings are presented in a series of papers in Nature, and 16 more appear in affiliated publications.

“It’s humbling that it was only 14 years ago that the genomics community sequenced its very first cancer exome, and it was able to identify mutations within the roughly 20,000 protein-coding genes in the human cell,” investigator Lincoln Stein, MD, PhD, of the Ontario Institute for Cancer Research in Toronto, said in a telephone briefing.

Exome sequencing, however, covers only protein-coding genomic regions, which constitute only about 1% of the entire genome, “so assembling an accurate portrait of the cancer genome using just the exome data is like trying to put together a 100,000-piece jigsaw puzzle when you’re missing 99% of the pieces and there’s no puzzle box with a completed picture to guide you,” Dr. Stein said.

Members of the PCAWG from centers in North America, Europe, Asia, and Australia screened 2,658 whole-cancer genomes and matched samples of noncancerous tissues from the same individuals, along with 1,188 transcriptomes cataloging the sequences and expression of RNA transcripts in a given tumor. The 6-year project netted more than 800 terabytes of genomic data, roughly equivalent to the digital holdings of the U.S. Library of Congress multiplied by 11.

The findings are summarized in papers focusing on cancer drivers, noncoding changes, mutational signatures, structural variants, cancer evolution over time, and RNA alterations.
 

Driver mutations

Investigators found that the average cancer genome contains four or five driver mutations located in both coding and noncoding regions. They also found, however, that in approximately 5% of cases no driver mutations could be identified.

A substantial proportion of tumors displayed “hallmarks of genomic catastrophes.” About 22% of tumors exhibited chromothripsis, a mutational process marked by hundreds or even thousands of clustered chromosomal rearrangements. About 18% showed chromoplexy, which is characterized by scattering and rearrangement of multiple strands of DNA from one or more chromosomes.

Analyzing driver point mutations and structural variants in noncoding regions, the investigators found the usual suspects – previously reported culprits – as well as novel candidates.

For example, they identified point mutations in the five prime region of the tumor suppressor gene TP53 and the three prime untranslated regions of NFKBIZ (a nuclear factor kappa B inhibitor) and TOB1 (an antiproliferative protein), focal deletion in BRD4 (a transcriptional and epigenetic regulator), and rearrangements in chromosomal loci in members of the AKR1C family of enzymes thought to play a role in disease progression.

In addition, investigators identified mutations in noncoding regions of TERT, a telomerase gene. These mutations result in ramped-up expression of telomerase, which in turn promotes uncontrollable division of tumor cells.
 

Mutational signatures

In a related line of research, PCAWG investigators identified new DNA mutational signatures ranging from single nucleotide polymorphisms to insertions and deletions, as well as to structural variants – rearrangements of large sections of the genome.

“The substantial size of our dataset, compared with previous analyses, enabled the discovery of new signatures, the separation of overlapping signatures, and the decomposition of signatures into components that may represent associated – but distinct – DNA damage, repair, and/or replication mechanisms. By estimating the contribution of each signature to the mutational catalogs of individual cancer genomes, we revealed associations of signatures to exogenous or endogenous exposures, as well as to defective DNA maintenance processes,” the investigators wrote.

They also acknowledged, however, that “many signatures are of unknown cause.”
 

Cancer evolution

One of the six main studies focused on the evolution of cancer over time. Instead of providing a “snapshot” of the genome as captured by sequencing tissue from a single biopsy, consortium investigators created full-length features of the “life history and evolution of mutational processes and driver mutation sequences.”

They found that early cancer development was marked by relatively few mutations in driver genes and by identifiable copy-number gains, including trisomy 7 in glioblastoma, and an abnormal mirroring of the arms (isochromosome) of chromosome 17 in medulloblastoma.

In 40% of the samples, however, there were significant changes in the mutational spectrum as the cancers grew, leading to a near quadrupling of driver genes and increased genomic instability in later-stage tumors.

“Copy-number alterations often occur in mitotic crises and lead to simultaneous gains of chromosomal segments,” the investigators wrote. “Timing analyses suggest that driver mutations often precede diagnosis by many years, if not decades. Together, these results determine the evolutionary trajectories of cancer and highlight opportunities for early cancer detection.”
 

Implications for cancer care

“When I used to treat patients with cancer, I was always completely amazed and puzzled by how two patients could have what looked like the same tumor. It would look the same under the microscope, have the same size, and the two patients would receive exactly the same treatment, but the two patients would have completely opposite outcomes; one would survive, and one would die. What this analysis … has done is really laid bare the reasons for that unpredictability in clinical outcomes,” Peter Campbell, MD, PhD, of the Wellcome Sanger Institute in Hinxton, England, said during the telebriefing.

“The most striking finding out of all of the suite of papers is just how different one person’s cancer genome is from another person’s. We see thousands of different combinations of mutations that can cause the cancer, and more than 80 different underlying processes generating the mutations in a cancer, and that leads to very different shapes and patterns in the genome that result,” he added.

On a positive note, the research shows that one or more driver mutations can be identified in about 95% of all cancer patients, and it elucidates the sequence of events leading to oncogenesis and tumor evolution, providing opportunities for earlier identification and potential interventions to prevent cancer, Dr. Campbell said.

The PCAWG was a collaborative multinational effort with multiple funding sources and many investigators.

SOURCE: Nature. 2020 Feb 5. https://www.nature.com/collections/pcawg/

A massive collaborative project spanning four continents and 744 research centers has revealed driver mutations in both protein-coding and noncoding regions of 38 cancer types.

Pan-Cancer Analysis of Whole Genomes

The Pan-Cancer Analysis of Whole Genomes (PCAWG) is an integrative analysis of the whole-genome sequences from 2,658 donors across 38 common tumor types. The findings are expected to add exponentially to what’s currently known about the complex genetics of cancer, and they point to possible strategies for improving cancer prevention, diagnosis, and care.

Six articles summarizing the findings are presented in a series of papers in Nature, and 16 more appear in affiliated publications.

“It’s humbling that it was only 14 years ago that the genomics community sequenced its very first cancer exome, and it was able to identify mutations within the roughly 20,000 protein-coding genes in the human cell,” investigator Lincoln Stein, MD, PhD, of the Ontario Institute for Cancer Research in Toronto, said in a telephone briefing.

Exome sequencing, however, covers only protein-coding genomic regions, which constitute only about 1% of the entire genome, “so assembling an accurate portrait of the cancer genome using just the exome data is like trying to put together a 100,000-piece jigsaw puzzle when you’re missing 99% of the pieces and there’s no puzzle box with a completed picture to guide you,” Dr. Stein said.

Members of the PCAWG from centers in North America, Europe, Asia, and Australia screened 2,658 whole-cancer genomes and matched samples of noncancerous tissues from the same individuals, along with 1,188 transcriptomes cataloging the sequences and expression of RNA transcripts in a given tumor. The 6-year project netted more than 800 terabytes of genomic data, roughly equivalent to the digital holdings of the U.S. Library of Congress multiplied by 11.

The findings are summarized in papers focusing on cancer drivers, noncoding changes, mutational signatures, structural variants, cancer evolution over time, and RNA alterations.
 

Driver mutations

Investigators found that the average cancer genome contains four or five driver mutations located in both coding and noncoding regions. They also found, however, that in approximately 5% of cases no driver mutations could be identified.

A substantial proportion of tumors displayed “hallmarks of genomic catastrophes.” About 22% of tumors exhibited chromothripsis, a mutational process marked by hundreds or even thousands of clustered chromosomal rearrangements. About 18% showed chromoplexy, which is characterized by scattering and rearrangement of multiple strands of DNA from one or more chromosomes.

Analyzing driver point mutations and structural variants in noncoding regions, the investigators found the usual suspects – previously reported culprits – as well as novel candidates.

For example, they identified point mutations in the five prime region of the tumor suppressor gene TP53 and the three prime untranslated regions of NFKBIZ (a nuclear factor kappa B inhibitor) and TOB1 (an antiproliferative protein), focal deletion in BRD4 (a transcriptional and epigenetic regulator), and rearrangements in chromosomal loci in members of the AKR1C family of enzymes thought to play a role in disease progression.

In addition, investigators identified mutations in noncoding regions of TERT, a telomerase gene. These mutations result in ramped-up expression of telomerase, which in turn promotes uncontrollable division of tumor cells.
 

Mutational signatures

In a related line of research, PCAWG investigators identified new DNA mutational signatures ranging from single nucleotide polymorphisms to insertions and deletions, as well as to structural variants – rearrangements of large sections of the genome.

“The substantial size of our dataset, compared with previous analyses, enabled the discovery of new signatures, the separation of overlapping signatures, and the decomposition of signatures into components that may represent associated – but distinct – DNA damage, repair, and/or replication mechanisms. By estimating the contribution of each signature to the mutational catalogs of individual cancer genomes, we revealed associations of signatures to exogenous or endogenous exposures, as well as to defective DNA maintenance processes,” the investigators wrote.

They also acknowledged, however, that “many signatures are of unknown cause.”
 

Cancer evolution

One of the six main studies focused on the evolution of cancer over time. Instead of providing a “snapshot” of the genome as captured by sequencing tissue from a single biopsy, consortium investigators created full-length features of the “life history and evolution of mutational processes and driver mutation sequences.”

They found that early cancer development was marked by relatively few mutations in driver genes and by identifiable copy-number gains, including trisomy 7 in glioblastoma, and an abnormal mirroring of the arms (isochromosome) of chromosome 17 in medulloblastoma.

In 40% of the samples, however, there were significant changes in the mutational spectrum as the cancers grew, leading to a near quadrupling of driver genes and increased genomic instability in later-stage tumors.

“Copy-number alterations often occur in mitotic crises and lead to simultaneous gains of chromosomal segments,” the investigators wrote. “Timing analyses suggest that driver mutations often precede diagnosis by many years, if not decades. Together, these results determine the evolutionary trajectories of cancer and highlight opportunities for early cancer detection.”
 

Implications for cancer care

“When I used to treat patients with cancer, I was always completely amazed and puzzled by how two patients could have what looked like the same tumor. It would look the same under the microscope, have the same size, and the two patients would receive exactly the same treatment, but the two patients would have completely opposite outcomes; one would survive, and one would die. What this analysis … has done is really laid bare the reasons for that unpredictability in clinical outcomes,” Peter Campbell, MD, PhD, of the Wellcome Sanger Institute in Hinxton, England, said during the telebriefing.

“The most striking finding out of all of the suite of papers is just how different one person’s cancer genome is from another person’s. We see thousands of different combinations of mutations that can cause the cancer, and more than 80 different underlying processes generating the mutations in a cancer, and that leads to very different shapes and patterns in the genome that result,” he added.

On a positive note, the research shows that one or more driver mutations can be identified in about 95% of all cancer patients, and it elucidates the sequence of events leading to oncogenesis and tumor evolution, providing opportunities for earlier identification and potential interventions to prevent cancer, Dr. Campbell said.

The PCAWG was a collaborative multinational effort with multiple funding sources and many investigators.

SOURCE: Nature. 2020 Feb 5. https://www.nature.com/collections/pcawg/

A massive collaborative project spanning four continents and 744 research centers has revealed driver mutations in both protein-coding and noncoding regions of 38 cancer types.

Pan-Cancer Analysis of Whole Genomes

The Pan-Cancer Analysis of Whole Genomes (PCAWG) is an integrative analysis of the whole-genome sequences from 2,658 donors across 38 common tumor types. The findings are expected to add exponentially to what’s currently known about the complex genetics of cancer, and they point to possible strategies for improving cancer prevention, diagnosis, and care.

Six articles summarizing the findings are presented in a series of papers in Nature, and 16 more appear in affiliated publications.

“It’s humbling that it was only 14 years ago that the genomics community sequenced its very first cancer exome, and it was able to identify mutations within the roughly 20,000 protein-coding genes in the human cell,” investigator Lincoln Stein, MD, PhD, of the Ontario Institute for Cancer Research in Toronto, said in a telephone briefing.

Exome sequencing, however, covers only protein-coding genomic regions, which constitute only about 1% of the entire genome, “so assembling an accurate portrait of the cancer genome using just the exome data is like trying to put together a 100,000-piece jigsaw puzzle when you’re missing 99% of the pieces and there’s no puzzle box with a completed picture to guide you,” Dr. Stein said.

Members of the PCAWG from centers in North America, Europe, Asia, and Australia screened 2,658 whole-cancer genomes and matched samples of noncancerous tissues from the same individuals, along with 1,188 transcriptomes cataloging the sequences and expression of RNA transcripts in a given tumor. The 6-year project netted more than 800 terabytes of genomic data, roughly equivalent to the digital holdings of the U.S. Library of Congress multiplied by 11.

The findings are summarized in papers focusing on cancer drivers, noncoding changes, mutational signatures, structural variants, cancer evolution over time, and RNA alterations.
 

Driver mutations

Investigators found that the average cancer genome contains four or five driver mutations located in both coding and noncoding regions. They also found, however, that in approximately 5% of cases no driver mutations could be identified.

A substantial proportion of tumors displayed “hallmarks of genomic catastrophes.” About 22% of tumors exhibited chromothripsis, a mutational process marked by hundreds or even thousands of clustered chromosomal rearrangements. About 18% showed chromoplexy, which is characterized by scattering and rearrangement of multiple strands of DNA from one or more chromosomes.

Analyzing driver point mutations and structural variants in noncoding regions, the investigators found the usual suspects – previously reported culprits – as well as novel candidates.

For example, they identified point mutations in the five prime region of the tumor suppressor gene TP53 and the three prime untranslated regions of NFKBIZ (a nuclear factor kappa B inhibitor) and TOB1 (an antiproliferative protein), focal deletion in BRD4 (a transcriptional and epigenetic regulator), and rearrangements in chromosomal loci in members of the AKR1C family of enzymes thought to play a role in disease progression.

In addition, investigators identified mutations in noncoding regions of TERT, a telomerase gene. These mutations result in ramped-up expression of telomerase, which in turn promotes uncontrollable division of tumor cells.
 

Mutational signatures

In a related line of research, PCAWG investigators identified new DNA mutational signatures ranging from single nucleotide polymorphisms to insertions and deletions, as well as to structural variants – rearrangements of large sections of the genome.

“The substantial size of our dataset, compared with previous analyses, enabled the discovery of new signatures, the separation of overlapping signatures, and the decomposition of signatures into components that may represent associated – but distinct – DNA damage, repair, and/or replication mechanisms. By estimating the contribution of each signature to the mutational catalogs of individual cancer genomes, we revealed associations of signatures to exogenous or endogenous exposures, as well as to defective DNA maintenance processes,” the investigators wrote.

They also acknowledged, however, that “many signatures are of unknown cause.”
 

Cancer evolution

One of the six main studies focused on the evolution of cancer over time. Instead of providing a “snapshot” of the genome as captured by sequencing tissue from a single biopsy, consortium investigators created full-length features of the “life history and evolution of mutational processes and driver mutation sequences.”

They found that early cancer development was marked by relatively few mutations in driver genes and by identifiable copy-number gains, including trisomy 7 in glioblastoma, and an abnormal mirroring of the arms (isochromosome) of chromosome 17 in medulloblastoma.

In 40% of the samples, however, there were significant changes in the mutational spectrum as the cancers grew, leading to a near quadrupling of driver genes and increased genomic instability in later-stage tumors.

“Copy-number alterations often occur in mitotic crises and lead to simultaneous gains of chromosomal segments,” the investigators wrote. “Timing analyses suggest that driver mutations often precede diagnosis by many years, if not decades. Together, these results determine the evolutionary trajectories of cancer and highlight opportunities for early cancer detection.”
 

Implications for cancer care

“When I used to treat patients with cancer, I was always completely amazed and puzzled by how two patients could have what looked like the same tumor. It would look the same under the microscope, have the same size, and the two patients would receive exactly the same treatment, but the two patients would have completely opposite outcomes; one would survive, and one would die. What this analysis … has done is really laid bare the reasons for that unpredictability in clinical outcomes,” Peter Campbell, MD, PhD, of the Wellcome Sanger Institute in Hinxton, England, said during the telebriefing.

“The most striking finding out of all of the suite of papers is just how different one person’s cancer genome is from another person’s. We see thousands of different combinations of mutations that can cause the cancer, and more than 80 different underlying processes generating the mutations in a cancer, and that leads to very different shapes and patterns in the genome that result,” he added.

On a positive note, the research shows that one or more driver mutations can be identified in about 95% of all cancer patients, and it elucidates the sequence of events leading to oncogenesis and tumor evolution, providing opportunities for earlier identification and potential interventions to prevent cancer, Dr. Campbell said.

The PCAWG was a collaborative multinational effort with multiple funding sources and many investigators.

SOURCE: Nature. 2020 Feb 5. https://www.nature.com/collections/pcawg/