AVAHO

First, the good news: Fewer Americans aged < 50 years are dying from cancer vs just a decade ago — reflecting progress in prevention, early detection, and treatment. There is, however, one big exception. Colorectal cancer mortality has been steadily inching up, and the disease now stands as the leading cause of cancer death in this age group, up from the fifth-leading in the early 1990s.

Those are the major findings of a recent study by the American Cancer Society (ACS), published as a research letter in JAMA.

Using SEER data, researchers found that the overall age-adjusted cancer death rate among Americans aged < 50 years dropped by 44% between 1990 and 2023 — from 25.5 to 14.2 per 100,000. And for 4 of the 5 leading causes of cancer death, there were mean annual declines from 2014 to 2023. The biggest change was in lung cancer deaths, which fell by an average of 5.7% per year. Meanwhile, leukemia and breast cancer deaths showed annual declines of 2.3% and 1.4%, respectively, despite rising incidences of both diseases among younger Americans.

The outlier is colorectal cancer, where mortality has been rising by about 1% per year since 2005. And it’s a pattern seen in both men and women.

Study coauthor Nikita Sandeep Wagle, PhD, MBBS, principal scientist, Cancer Surveillance Research at the ACS, and Arif Kamal, MD, ACS chief patient officer, discussed the research and its implications with Medscape Medical News.

Can you offer some possible reasons for the declining mortality in most of the cancers you studied?

Wagle: Mortality is going down for most of the cancers because we are getting better at finding cancers earlier and treating them more effectively. We have also seen improvements in screening, imaging, and therapy, and that means more people are being diagnosed at earlier stages and are surviving longer after diagnosis.

Regarding the rise in colorectal cancer mortality, do you think it's due to the rising incidence of early-onset colorectal cancer?

Kamal: Partially, but not completely, because the relationship between incidence and mortality is not always straightforward. For example, breast cancer incidence has been increasing, while mortality is going down. The rising mortality in people younger than 50 years is likely suggestive of more aggressive cancers being diagnosed — potentially secondary to environmental, dietary, or lifestyle factors. The colon is a unique organ because everything we put in our bodies passes through the colon, so food-based risk factors — for example, low fiber intake, red meat, and ultra-processed foods — are increasingly rising to the top as culprits.

Further, we know that only about 25% of people between the ages of 45 and 50 years are up to date with recommended colon cancer screenings, which can lead to later-stage diagnoses and thus higher mortality. So higher mortality speaks to the need to focus on lifestyle and diet changes and get more younger people to complete recommended cancer screenings.

Wagle: I think the “why” of your question is very important. Many researchers are trying to understand possible causes, such as diet, lifestyle, environmental factors, and genetics. But we cannot pinpoint one single cause. We need even more focus on research toward understanding the etiology of early-onset colorectal cancer.

What makes colorectal cancer different is that, unlike some other major cancers in this age group where mortality has declined despite rising incidence, roughly 3 in 4 colorectal cancers diagnosed in people younger than 50 years are [regional or distant], where the outcomes are worse.

Can you contextualize the rise in colorectal cancer mortality? What is the absolute rate among younger Americans now?

Wagle: It is around two deaths per 100,000 population in 2023 for people younger than 50 years. That number may not seem large, but the upward trend — a 1.1% annual increase from 2014 to 2023 — is concerning when you think about how overall mortality in this age group has dropped substantially over the past few decades. Colorectal cancer is moving in the opposite direction. I think the hopeful part is that it is also one of the most preventable cancers. Screening can stop cancer before it starts by removing precancerous polyps. Early-stage disease is highly treatable, and outcomes are better. That means better awareness and timely screening could make a real difference.

How can clinicians use this new information with regard to screening?

Wagle: For cancers with established screening guidelines, such as colorectal cancer, clinicians should continue to emphasize guideline-based screening and individualized risk assessment.

For colorectal cancer, screening now is recommended to start at age 45 for individuals at average risk, and earlier for [some], due to family history or other risk factors. Clinicians can use these findings to remind younger individuals that colorectal cancer is not only a disease of older adults and that screening at the recommended age can save lives.

In addition, red-flag symptoms such as persistent rectal bleeding, unexplained abdominal pain, difficulty in bowel movements, or signs of anemia should prompt appropriate evaluation in younger individuals.

Kamal: Clinicians should continue to emphasize timely completion of regular screening, starting at age 45 [for average-risk people]. Many still believe that the recommended starting age is 50 or that colonoscopy is the only way to get screened. Highlighting home-based screening options often helps patients make cancer screening logistically fit better into their busy lives.

Could you elaborate on the red-flag symptoms you mentioned, and what is an appropriate evaluation in younger individuals?

Kamal: Appropriate evaluation for any suspected bleeding — bright red or black and tarry — starts with an in-office evaluation by a primary care physician. Referral to a specialist, such as a gastroenterologist or surgeon, is done later, typically for direct visualization, such as with a colonoscopy. Rarely, imaging such as CT scans or ultrasounds is performed. Overall, because of the rising incidence of colon cancer in younger people, any concerning symptoms should be reported to a physician for an in-office evaluation as the first step.

Do these findings suggest that the starting age for average-risk people should be lowered—to age 40, for example?

Kamal: ACS screening guidelines for all cancers are part of an ongoing guideline development process by ACS scientists and volunteers. We monitor medical and scientific literature for new evidence that may support a change in current guidelines or the development of new guidelines and for information about cancer screening that should be conveyed to clinicians and target populations.

Keith Mulvihill is a freelance writer based in New York City.

A version of this article first appeared on Medscape.com.

First, the good news: Fewer Americans aged < 50 years are dying from cancer vs just a decade ago — reflecting progress in prevention, early detection, and treatment. There is, however, one big exception. Colorectal cancer mortality has been steadily inching up, and the disease now stands as the leading cause of cancer death in this age group, up from the fifth-leading in the early 1990s.

Those are the major findings of a recent study by the American Cancer Society (ACS), published as a research letter in JAMA.

Using SEER data, researchers found that the overall age-adjusted cancer death rate among Americans aged < 50 years dropped by 44% between 1990 and 2023 — from 25.5 to 14.2 per 100,000. And for 4 of the 5 leading causes of cancer death, there were mean annual declines from 2014 to 2023. The biggest change was in lung cancer deaths, which fell by an average of 5.7% per year. Meanwhile, leukemia and breast cancer deaths showed annual declines of 2.3% and 1.4%, respectively, despite rising incidences of both diseases among younger Americans.

The outlier is colorectal cancer, where mortality has been rising by about 1% per year since 2005. And it’s a pattern seen in both men and women.

Study coauthor Nikita Sandeep Wagle, PhD, MBBS, principal scientist, Cancer Surveillance Research at the ACS, and Arif Kamal, MD, ACS chief patient officer, discussed the research and its implications with Medscape Medical News.

Can you offer some possible reasons for the declining mortality in most of the cancers you studied?

Wagle: Mortality is going down for most of the cancers because we are getting better at finding cancers earlier and treating them more effectively. We have also seen improvements in screening, imaging, and therapy, and that means more people are being diagnosed at earlier stages and are surviving longer after diagnosis.

Regarding the rise in colorectal cancer mortality, do you think it's due to the rising incidence of early-onset colorectal cancer?

Kamal: Partially, but not completely, because the relationship between incidence and mortality is not always straightforward. For example, breast cancer incidence has been increasing, while mortality is going down. The rising mortality in people younger than 50 years is likely suggestive of more aggressive cancers being diagnosed — potentially secondary to environmental, dietary, or lifestyle factors. The colon is a unique organ because everything we put in our bodies passes through the colon, so food-based risk factors — for example, low fiber intake, red meat, and ultra-processed foods — are increasingly rising to the top as culprits.

Further, we know that only about 25% of people between the ages of 45 and 50 years are up to date with recommended colon cancer screenings, which can lead to later-stage diagnoses and thus higher mortality. So higher mortality speaks to the need to focus on lifestyle and diet changes and get more younger people to complete recommended cancer screenings.

Wagle: I think the “why” of your question is very important. Many researchers are trying to understand possible causes, such as diet, lifestyle, environmental factors, and genetics. But we cannot pinpoint one single cause. We need even more focus on research toward understanding the etiology of early-onset colorectal cancer.

What makes colorectal cancer different is that, unlike some other major cancers in this age group where mortality has declined despite rising incidence, roughly 3 in 4 colorectal cancers diagnosed in people younger than 50 years are [regional or distant], where the outcomes are worse.

Can you contextualize the rise in colorectal cancer mortality? What is the absolute rate among younger Americans now?

Wagle: It is around two deaths per 100,000 population in 2023 for people younger than 50 years. That number may not seem large, but the upward trend — a 1.1% annual increase from 2014 to 2023 — is concerning when you think about how overall mortality in this age group has dropped substantially over the past few decades. Colorectal cancer is moving in the opposite direction. I think the hopeful part is that it is also one of the most preventable cancers. Screening can stop cancer before it starts by removing precancerous polyps. Early-stage disease is highly treatable, and outcomes are better. That means better awareness and timely screening could make a real difference.

How can clinicians use this new information with regard to screening?

Wagle: For cancers with established screening guidelines, such as colorectal cancer, clinicians should continue to emphasize guideline-based screening and individualized risk assessment.

For colorectal cancer, screening now is recommended to start at age 45 for individuals at average risk, and earlier for [some], due to family history or other risk factors. Clinicians can use these findings to remind younger individuals that colorectal cancer is not only a disease of older adults and that screening at the recommended age can save lives.

In addition, red-flag symptoms such as persistent rectal bleeding, unexplained abdominal pain, difficulty in bowel movements, or signs of anemia should prompt appropriate evaluation in younger individuals.

Kamal: Clinicians should continue to emphasize timely completion of regular screening, starting at age 45 [for average-risk people]. Many still believe that the recommended starting age is 50 or that colonoscopy is the only way to get screened. Highlighting home-based screening options often helps patients make cancer screening logistically fit better into their busy lives.

Could you elaborate on the red-flag symptoms you mentioned, and what is an appropriate evaluation in younger individuals?

Kamal: Appropriate evaluation for any suspected bleeding — bright red or black and tarry — starts with an in-office evaluation by a primary care physician. Referral to a specialist, such as a gastroenterologist or surgeon, is done later, typically for direct visualization, such as with a colonoscopy. Rarely, imaging such as CT scans or ultrasounds is performed. Overall, because of the rising incidence of colon cancer in younger people, any concerning symptoms should be reported to a physician for an in-office evaluation as the first step.

Do these findings suggest that the starting age for average-risk people should be lowered—to age 40, for example?

Kamal: ACS screening guidelines for all cancers are part of an ongoing guideline development process by ACS scientists and volunteers. We monitor medical and scientific literature for new evidence that may support a change in current guidelines or the development of new guidelines and for information about cancer screening that should be conveyed to clinicians and target populations.

Keith Mulvihill is a freelance writer based in New York City.

A version of this article first appeared on Medscape.com.

First, the good news: Fewer Americans aged < 50 years are dying from cancer vs just a decade ago — reflecting progress in prevention, early detection, and treatment. There is, however, one big exception. Colorectal cancer mortality has been steadily inching up, and the disease now stands as the leading cause of cancer death in this age group, up from the fifth-leading in the early 1990s.

Those are the major findings of a recent study by the American Cancer Society (ACS), published as a research letter in JAMA.

Using SEER data, researchers found that the overall age-adjusted cancer death rate among Americans aged < 50 years dropped by 44% between 1990 and 2023 — from 25.5 to 14.2 per 100,000. And for 4 of the 5 leading causes of cancer death, there were mean annual declines from 2014 to 2023. The biggest change was in lung cancer deaths, which fell by an average of 5.7% per year. Meanwhile, leukemia and breast cancer deaths showed annual declines of 2.3% and 1.4%, respectively, despite rising incidences of both diseases among younger Americans.

The outlier is colorectal cancer, where mortality has been rising by about 1% per year since 2005. And it’s a pattern seen in both men and women.

Study coauthor Nikita Sandeep Wagle, PhD, MBBS, principal scientist, Cancer Surveillance Research at the ACS, and Arif Kamal, MD, ACS chief patient officer, discussed the research and its implications with Medscape Medical News.

Can you offer some possible reasons for the declining mortality in most of the cancers you studied?

Wagle: Mortality is going down for most of the cancers because we are getting better at finding cancers earlier and treating them more effectively. We have also seen improvements in screening, imaging, and therapy, and that means more people are being diagnosed at earlier stages and are surviving longer after diagnosis.

Regarding the rise in colorectal cancer mortality, do you think it's due to the rising incidence of early-onset colorectal cancer?

Kamal: Partially, but not completely, because the relationship between incidence and mortality is not always straightforward. For example, breast cancer incidence has been increasing, while mortality is going down. The rising mortality in people younger than 50 years is likely suggestive of more aggressive cancers being diagnosed — potentially secondary to environmental, dietary, or lifestyle factors. The colon is a unique organ because everything we put in our bodies passes through the colon, so food-based risk factors — for example, low fiber intake, red meat, and ultra-processed foods — are increasingly rising to the top as culprits.

Further, we know that only about 25% of people between the ages of 45 and 50 years are up to date with recommended colon cancer screenings, which can lead to later-stage diagnoses and thus higher mortality. So higher mortality speaks to the need to focus on lifestyle and diet changes and get more younger people to complete recommended cancer screenings.

Wagle: I think the “why” of your question is very important. Many researchers are trying to understand possible causes, such as diet, lifestyle, environmental factors, and genetics. But we cannot pinpoint one single cause. We need even more focus on research toward understanding the etiology of early-onset colorectal cancer.

What makes colorectal cancer different is that, unlike some other major cancers in this age group where mortality has declined despite rising incidence, roughly 3 in 4 colorectal cancers diagnosed in people younger than 50 years are [regional or distant], where the outcomes are worse.

Can you contextualize the rise in colorectal cancer mortality? What is the absolute rate among younger Americans now?

Wagle: It is around two deaths per 100,000 population in 2023 for people younger than 50 years. That number may not seem large, but the upward trend — a 1.1% annual increase from 2014 to 2023 — is concerning when you think about how overall mortality in this age group has dropped substantially over the past few decades. Colorectal cancer is moving in the opposite direction. I think the hopeful part is that it is also one of the most preventable cancers. Screening can stop cancer before it starts by removing precancerous polyps. Early-stage disease is highly treatable, and outcomes are better. That means better awareness and timely screening could make a real difference.

How can clinicians use this new information with regard to screening?

Wagle: For cancers with established screening guidelines, such as colorectal cancer, clinicians should continue to emphasize guideline-based screening and individualized risk assessment.

For colorectal cancer, screening now is recommended to start at age 45 for individuals at average risk, and earlier for [some], due to family history or other risk factors. Clinicians can use these findings to remind younger individuals that colorectal cancer is not only a disease of older adults and that screening at the recommended age can save lives.

In addition, red-flag symptoms such as persistent rectal bleeding, unexplained abdominal pain, difficulty in bowel movements, or signs of anemia should prompt appropriate evaluation in younger individuals.

Kamal: Clinicians should continue to emphasize timely completion of regular screening, starting at age 45 [for average-risk people]. Many still believe that the recommended starting age is 50 or that colonoscopy is the only way to get screened. Highlighting home-based screening options often helps patients make cancer screening logistically fit better into their busy lives.

Could you elaborate on the red-flag symptoms you mentioned, and what is an appropriate evaluation in younger individuals?

Kamal: Appropriate evaluation for any suspected bleeding — bright red or black and tarry — starts with an in-office evaluation by a primary care physician. Referral to a specialist, such as a gastroenterologist or surgeon, is done later, typically for direct visualization, such as with a colonoscopy. Rarely, imaging such as CT scans or ultrasounds is performed. Overall, because of the rising incidence of colon cancer in younger people, any concerning symptoms should be reported to a physician for an in-office evaluation as the first step.

Do these findings suggest that the starting age for average-risk people should be lowered—to age 40, for example?

Kamal: ACS screening guidelines for all cancers are part of an ongoing guideline development process by ACS scientists and volunteers. We monitor medical and scientific literature for new evidence that may support a change in current guidelines or the development of new guidelines and for information about cancer screening that should be conveyed to clinicians and target populations.

Keith Mulvihill is a freelance writer based in New York City.

A version of this article first appeared on Medscape.com.

Diets heavy in ultraprocessed foods (UPFs) are associated with earlier death in cancer survivors, a new study finds — though issues with the research design suggest that the findings should be taken with a grain of salt.

The study, published on February 4 in Cancer Epidemiology, Biomarkers & Prevention, is among the latest to point to health hazards from eating too many foods full of preservatives, dyes, and other industrially made ingredients.

These so-called UPFs have been linked to an increased risk for cancer, but whether they have any relationship to long-term survival after cancer has been unclear.

In the new study, of 802 adults with a previous cancer diagnosis, those in the top third for UPF consumption had a 48% higher rate of death from any cause over 15 years than those in the bottom third. Similarly, heavier UPF consumers had a 57% higher rate of death from cancer.

Those excess risks were seen after adjustment for numerous variables, including age, physical activity, BMI, smoking status, and socioeconomic indicators.

“Clinicians should encourage a shift toward fresh, minimally processed foods, [and] away from heavily industrially processed products,” said lead author Marialaura Bonaccio, PhD, of the Research Unit of Epidemiology and Prevention at IRCCS Neuromed in Pozzilli, Italy.

Oncologists not involved in the work said the findings support what researchers have suspected.

“UPFs have been linked to increased risk of obesity, diabetes, inflammation, cardiovascular disease, and...all-cause mortality and cardiovascular mortality,” said Urvi A. Shah, MD, a myeloma specialist who conducts nutrition research at Memorial Sloan Kettering Cancer Center in New York City. “However, there was limited data on cancer-specific mortality to date until this study.”

The findings also dovetail with recommendations on cancer prevention that emphasize diets rich in plant foods and low in processed foods, particularly those loaded with sugar, starch, and fat.

The study “may make oncologists think twice before assuring patients to ‘eat whatever you want, it doesn’t really matter’ because these investigators show that it does,” said Donald I. Abrams, MD, an integrative oncologist at the UCSF Osher Center for Integrative Health.

However, Gideon Meyerowitz-Katz, PhD, an epidemiologist at the University of Wollongong in Wollongong, Australia, was not impressed by the analysis.

He pointed to several sources of potential bias and noted that the crude results actually showed that cancer survivors with the lowest UPF consumption had a higher rate of death than the heaviest consumers.

“The story of UPFs being bad is consistent with this data, but so is the story of UPFs being fine,” said Meyerowitz-Katz, who has written about prior research on the subject.

The broad questions of whether and how UPFs might be harming human health have been gaining research interest, partly because of their ubiquity. The foods reportedly make up about 60% of the typical American diet.

There’s no universal agreement on the precise definition of “ultraprocessed,” but researchers generally use the NOVA classification system, which assigns foods into one of four groups based on the level and purpose of processing. UPFs contain ingredients not found in the standard home kitchen (such as high-fructose corn syrup) and often have artificial flavors, colors, and other additives.

Examples of UPFs include the usual “junk food,” such as candy, soda, and processed meat, but many healthy-sounding products, such as flavored yogurts and plant-based milk, also qualify.

For their study, Bonaccio and her colleagues identified 802 cancer survivors from the Moli-sani cohort study (476 women and 326 men) who completed food-frequency questionnaires an average of 8 years postdiagnosis.

Using the NOVA system, the team calculated the amount of UPF in participants’ diets as both weight and energy ratios.

Over a median follow-up of nearly 15 years, there were 281 deaths. In the lowest third of UPF consumption (4.3% mean intake by weight), there were 3.3 deaths per 100 patient-years, compared with 2.4 per 100 patient-years in the highest UPF tertile (16.7% mean intake by weight). For cancer-specific deaths, those numbers were 1.5 and 1.4, respectively.

However, after adjustment for age and total energy intake, the top UPF-intake group showed significantly higher death rates. In the final model, which adjusted for > 20 variables, the hazard ratios for the highest versus lowest UPF consumption were 1.48 (95% CI, 1.07-2.03) for all-cause mortality and 1.57 (95% CI, 1.00-2.47) for cancer mortality.

To explore potential biological mechanisms, the researchers also analyzed certain biomarkers. They found that adjustment for inflammatory markers and resting heart rate at baseline attenuated the association between UPF and all-cause deaths by nearly 40%.

The authors acknowledged some limitations of their study, including its use of self-report and potential survivor bias.

But Meyerowitz-Katz found additional weak points. For one, he said the authors “downplayed” the impact of their analysis controlling for inflammation and heart rate.

“Inflammation and heart rate are both strong markers of future cancer risk,” Meyerowitz-Katz said. “In this cohort, there would be people who were already experiencing cancer recurrence, which is important to control for at baseline.”

He also highlighted a little-known but important issue in observational research called collider bias, which can create a false association between an exposure and outcome. In this study, he said, the researchers introduced “a huge potential for collider bias” by controlling for energy intake, because both UPF consumption and cancer recurrence are causally associated with energy intake.

Bonaccio called that particular critique “a fair methodological question” but defended her work.

She pointed out that study participants were long-term survivors, which reduces the chance that their calorie intake was mainly driven by active cancer or treatment side effects.

“And,” she said, “our models include a wide set of baseline covariates that capture major determinants of both mortality and dietary intake.”

For Bonaccio, the take-home message for patients remains the same: “Emphasizing simple, home-cooked meals and traditional dietary patterns might be especially beneficial during the survivorship phase.”

The two US experts agreed that overall diet quality is key, with limits on UPFs being part of that. They also noted that the average American’s diet contains substantially more UPFs than what was seen in this Italian study.

“I spend 20 minutes of my 60-minute new patient consult in integrative oncology advising patients to eat an organic, plant-based, antioxidant-rich, anti-inflammatory, real and whole-foods diet,” Abrams said.

For her part, Shah said that cancer survivors should aim to get at least 25-30 grams of dietary fiber daily. She also suggested they avoid particular types of UPF with little to no nutritional value, such as processed meats, sugar-laden beverages, and fast food.

The study received no commercial funding. Bonaccio, Abrams, and Meyerowitz-Katz reported no financial disclosures. Shah is principle investigator on the NUTRIVENTION trial and reported receiving research funding and/or personal fees from Celgene/BMS, Janssen, and Sanofi.

A version of this article first appeared on Medscape.com.

Diets heavy in ultraprocessed foods (UPFs) are associated with earlier death in cancer survivors, a new study finds — though issues with the research design suggest that the findings should be taken with a grain of salt.

The study, published on February 4 in Cancer Epidemiology, Biomarkers & Prevention, is among the latest to point to health hazards from eating too many foods full of preservatives, dyes, and other industrially made ingredients.

These so-called UPFs have been linked to an increased risk for cancer, but whether they have any relationship to long-term survival after cancer has been unclear.

In the new study, of 802 adults with a previous cancer diagnosis, those in the top third for UPF consumption had a 48% higher rate of death from any cause over 15 years than those in the bottom third. Similarly, heavier UPF consumers had a 57% higher rate of death from cancer.

Those excess risks were seen after adjustment for numerous variables, including age, physical activity, BMI, smoking status, and socioeconomic indicators.

“Clinicians should encourage a shift toward fresh, minimally processed foods, [and] away from heavily industrially processed products,” said lead author Marialaura Bonaccio, PhD, of the Research Unit of Epidemiology and Prevention at IRCCS Neuromed in Pozzilli, Italy.

Oncologists not involved in the work said the findings support what researchers have suspected.

“UPFs have been linked to increased risk of obesity, diabetes, inflammation, cardiovascular disease, and...all-cause mortality and cardiovascular mortality,” said Urvi A. Shah, MD, a myeloma specialist who conducts nutrition research at Memorial Sloan Kettering Cancer Center in New York City. “However, there was limited data on cancer-specific mortality to date until this study.”

The findings also dovetail with recommendations on cancer prevention that emphasize diets rich in plant foods and low in processed foods, particularly those loaded with sugar, starch, and fat.

The study “may make oncologists think twice before assuring patients to ‘eat whatever you want, it doesn’t really matter’ because these investigators show that it does,” said Donald I. Abrams, MD, an integrative oncologist at the UCSF Osher Center for Integrative Health.

However, Gideon Meyerowitz-Katz, PhD, an epidemiologist at the University of Wollongong in Wollongong, Australia, was not impressed by the analysis.

He pointed to several sources of potential bias and noted that the crude results actually showed that cancer survivors with the lowest UPF consumption had a higher rate of death than the heaviest consumers.

“The story of UPFs being bad is consistent with this data, but so is the story of UPFs being fine,” said Meyerowitz-Katz, who has written about prior research on the subject.

The broad questions of whether and how UPFs might be harming human health have been gaining research interest, partly because of their ubiquity. The foods reportedly make up about 60% of the typical American diet.

There’s no universal agreement on the precise definition of “ultraprocessed,” but researchers generally use the NOVA classification system, which assigns foods into one of four groups based on the level and purpose of processing. UPFs contain ingredients not found in the standard home kitchen (such as high-fructose corn syrup) and often have artificial flavors, colors, and other additives.

Examples of UPFs include the usual “junk food,” such as candy, soda, and processed meat, but many healthy-sounding products, such as flavored yogurts and plant-based milk, also qualify.

For their study, Bonaccio and her colleagues identified 802 cancer survivors from the Moli-sani cohort study (476 women and 326 men) who completed food-frequency questionnaires an average of 8 years postdiagnosis.

Using the NOVA system, the team calculated the amount of UPF in participants’ diets as both weight and energy ratios.

Over a median follow-up of nearly 15 years, there were 281 deaths. In the lowest third of UPF consumption (4.3% mean intake by weight), there were 3.3 deaths per 100 patient-years, compared with 2.4 per 100 patient-years in the highest UPF tertile (16.7% mean intake by weight). For cancer-specific deaths, those numbers were 1.5 and 1.4, respectively.

However, after adjustment for age and total energy intake, the top UPF-intake group showed significantly higher death rates. In the final model, which adjusted for > 20 variables, the hazard ratios for the highest versus lowest UPF consumption were 1.48 (95% CI, 1.07-2.03) for all-cause mortality and 1.57 (95% CI, 1.00-2.47) for cancer mortality.

To explore potential biological mechanisms, the researchers also analyzed certain biomarkers. They found that adjustment for inflammatory markers and resting heart rate at baseline attenuated the association between UPF and all-cause deaths by nearly 40%.

The authors acknowledged some limitations of their study, including its use of self-report and potential survivor bias.

But Meyerowitz-Katz found additional weak points. For one, he said the authors “downplayed” the impact of their analysis controlling for inflammation and heart rate.

“Inflammation and heart rate are both strong markers of future cancer risk,” Meyerowitz-Katz said. “In this cohort, there would be people who were already experiencing cancer recurrence, which is important to control for at baseline.”

He also highlighted a little-known but important issue in observational research called collider bias, which can create a false association between an exposure and outcome. In this study, he said, the researchers introduced “a huge potential for collider bias” by controlling for energy intake, because both UPF consumption and cancer recurrence are causally associated with energy intake.

Bonaccio called that particular critique “a fair methodological question” but defended her work.

She pointed out that study participants were long-term survivors, which reduces the chance that their calorie intake was mainly driven by active cancer or treatment side effects.

“And,” she said, “our models include a wide set of baseline covariates that capture major determinants of both mortality and dietary intake.”

For Bonaccio, the take-home message for patients remains the same: “Emphasizing simple, home-cooked meals and traditional dietary patterns might be especially beneficial during the survivorship phase.”

The two US experts agreed that overall diet quality is key, with limits on UPFs being part of that. They also noted that the average American’s diet contains substantially more UPFs than what was seen in this Italian study.

“I spend 20 minutes of my 60-minute new patient consult in integrative oncology advising patients to eat an organic, plant-based, antioxidant-rich, anti-inflammatory, real and whole-foods diet,” Abrams said.

For her part, Shah said that cancer survivors should aim to get at least 25-30 grams of dietary fiber daily. She also suggested they avoid particular types of UPF with little to no nutritional value, such as processed meats, sugar-laden beverages, and fast food.

The study received no commercial funding. Bonaccio, Abrams, and Meyerowitz-Katz reported no financial disclosures. Shah is principle investigator on the NUTRIVENTION trial and reported receiving research funding and/or personal fees from Celgene/BMS, Janssen, and Sanofi.

A version of this article first appeared on Medscape.com.

Diets heavy in ultraprocessed foods (UPFs) are associated with earlier death in cancer survivors, a new study finds — though issues with the research design suggest that the findings should be taken with a grain of salt.

The study, published on February 4 in Cancer Epidemiology, Biomarkers & Prevention, is among the latest to point to health hazards from eating too many foods full of preservatives, dyes, and other industrially made ingredients.

These so-called UPFs have been linked to an increased risk for cancer, but whether they have any relationship to long-term survival after cancer has been unclear.

In the new study, of 802 adults with a previous cancer diagnosis, those in the top third for UPF consumption had a 48% higher rate of death from any cause over 15 years than those in the bottom third. Similarly, heavier UPF consumers had a 57% higher rate of death from cancer.

Those excess risks were seen after adjustment for numerous variables, including age, physical activity, BMI, smoking status, and socioeconomic indicators.

“Clinicians should encourage a shift toward fresh, minimally processed foods, [and] away from heavily industrially processed products,” said lead author Marialaura Bonaccio, PhD, of the Research Unit of Epidemiology and Prevention at IRCCS Neuromed in Pozzilli, Italy.

Oncologists not involved in the work said the findings support what researchers have suspected.

“UPFs have been linked to increased risk of obesity, diabetes, inflammation, cardiovascular disease, and...all-cause mortality and cardiovascular mortality,” said Urvi A. Shah, MD, a myeloma specialist who conducts nutrition research at Memorial Sloan Kettering Cancer Center in New York City. “However, there was limited data on cancer-specific mortality to date until this study.”

The findings also dovetail with recommendations on cancer prevention that emphasize diets rich in plant foods and low in processed foods, particularly those loaded with sugar, starch, and fat.

The study “may make oncologists think twice before assuring patients to ‘eat whatever you want, it doesn’t really matter’ because these investigators show that it does,” said Donald I. Abrams, MD, an integrative oncologist at the UCSF Osher Center for Integrative Health.

However, Gideon Meyerowitz-Katz, PhD, an epidemiologist at the University of Wollongong in Wollongong, Australia, was not impressed by the analysis.

He pointed to several sources of potential bias and noted that the crude results actually showed that cancer survivors with the lowest UPF consumption had a higher rate of death than the heaviest consumers.

“The story of UPFs being bad is consistent with this data, but so is the story of UPFs being fine,” said Meyerowitz-Katz, who has written about prior research on the subject.

The broad questions of whether and how UPFs might be harming human health have been gaining research interest, partly because of their ubiquity. The foods reportedly make up about 60% of the typical American diet.

There’s no universal agreement on the precise definition of “ultraprocessed,” but researchers generally use the NOVA classification system, which assigns foods into one of four groups based on the level and purpose of processing. UPFs contain ingredients not found in the standard home kitchen (such as high-fructose corn syrup) and often have artificial flavors, colors, and other additives.

Examples of UPFs include the usual “junk food,” such as candy, soda, and processed meat, but many healthy-sounding products, such as flavored yogurts and plant-based milk, also qualify.

For their study, Bonaccio and her colleagues identified 802 cancer survivors from the Moli-sani cohort study (476 women and 326 men) who completed food-frequency questionnaires an average of 8 years postdiagnosis.

Using the NOVA system, the team calculated the amount of UPF in participants’ diets as both weight and energy ratios.

Over a median follow-up of nearly 15 years, there were 281 deaths. In the lowest third of UPF consumption (4.3% mean intake by weight), there were 3.3 deaths per 100 patient-years, compared with 2.4 per 100 patient-years in the highest UPF tertile (16.7% mean intake by weight). For cancer-specific deaths, those numbers were 1.5 and 1.4, respectively.

However, after adjustment for age and total energy intake, the top UPF-intake group showed significantly higher death rates. In the final model, which adjusted for > 20 variables, the hazard ratios for the highest versus lowest UPF consumption were 1.48 (95% CI, 1.07-2.03) for all-cause mortality and 1.57 (95% CI, 1.00-2.47) for cancer mortality.

To explore potential biological mechanisms, the researchers also analyzed certain biomarkers. They found that adjustment for inflammatory markers and resting heart rate at baseline attenuated the association between UPF and all-cause deaths by nearly 40%.

The authors acknowledged some limitations of their study, including its use of self-report and potential survivor bias.

But Meyerowitz-Katz found additional weak points. For one, he said the authors “downplayed” the impact of their analysis controlling for inflammation and heart rate.

“Inflammation and heart rate are both strong markers of future cancer risk,” Meyerowitz-Katz said. “In this cohort, there would be people who were already experiencing cancer recurrence, which is important to control for at baseline.”

He also highlighted a little-known but important issue in observational research called collider bias, which can create a false association between an exposure and outcome. In this study, he said, the researchers introduced “a huge potential for collider bias” by controlling for energy intake, because both UPF consumption and cancer recurrence are causally associated with energy intake.

Bonaccio called that particular critique “a fair methodological question” but defended her work.

She pointed out that study participants were long-term survivors, which reduces the chance that their calorie intake was mainly driven by active cancer or treatment side effects.

“And,” she said, “our models include a wide set of baseline covariates that capture major determinants of both mortality and dietary intake.”

For Bonaccio, the take-home message for patients remains the same: “Emphasizing simple, home-cooked meals and traditional dietary patterns might be especially beneficial during the survivorship phase.”

The two US experts agreed that overall diet quality is key, with limits on UPFs being part of that. They also noted that the average American’s diet contains substantially more UPFs than what was seen in this Italian study.

“I spend 20 minutes of my 60-minute new patient consult in integrative oncology advising patients to eat an organic, plant-based, antioxidant-rich, anti-inflammatory, real and whole-foods diet,” Abrams said.

For her part, Shah said that cancer survivors should aim to get at least 25-30 grams of dietary fiber daily. She also suggested they avoid particular types of UPF with little to no nutritional value, such as processed meats, sugar-laden beverages, and fast food.

The study received no commercial funding. Bonaccio, Abrams, and Meyerowitz-Katz reported no financial disclosures. Shah is principle investigator on the NUTRIVENTION trial and reported receiving research funding and/or personal fees from Celgene/BMS, Janssen, and Sanofi.

A version of this article first appeared on Medscape.com.

TOPLINE:

Exposure to Agent Orange, the defoliant used by the US Air Force during the Vietnam War, was one of the factors associated with increased odds of acral melanoma (AM), a rare melanoma subtype affecting palms, soles, and nail units.

METHODOLOGY:

• Researchers conducted a nested case-control study in the Veterans Affairs healthcare system, and identified 1292 veterans (median age, 70.13 years; 94.0% men; 73.4% White, 14.6% Black) with AM through the Veterans Affairs Cancer Registry and a validated natural language processing pipeline from 2000 to 2024.
• Researchers matched each case of AM to 4 individuals with nonacral cutaneous melanoma (CM) and 4 control individuals without melanoma diagnoses, based on diagnosis year and outpatient visit frequency.
• Exposures included age, sex, race, ethnicity, rurality, region, military branch, comorbidities, smoking status, alcohol use, BMI, Agent Orange exposure, prior photosensitizing medications, nevi, and keratinocyte carcinoma.

TAKEAWAY:

• Veterans exposed to Agent Orange had higher odds of AM than individuals with CM (adjusted odds ratio [AOR], 1.31; 95% CI, 1.06-1.62) and control individuals without melanoma (AOR, 1.27; 95% CI, 1.04-1.56).
• Individuals with current smoking habit had lower odds of AM than those with CM (AOR, 0.65; 95% CI, 0.52-0.81) and control individuals without melanoma (AOR, 0.50; 95% CI, 0.40-0.62).
• Patients with prior keratinocyte carcinoma and actinic keratosis had higher odds of AM than control individuals without melanoma but lower odds than those with CM.
• History of nevus was associated with higher odds of acral melanoma compared with individuals without melanoma (AOR, 2.11; 95% CI, 1.49-2.98).

IN PRACTICE:

“Our results support the need for continued investigation of AM as a distinct entity from CM and may inform future evaluations of the associations between [Agent Orange exposure] in veteran populations, as well as those between other environmental exposures in different populations," the study authors wrote. Referring to the “continued search for a better understanding of a potential link” between Agent Orange and melanoma, as well as AM, and other possible etiologic factors for AM, this study “provides a strong impetus to further these research goals and contribute to the investigation of the legacy of the Vietnam War and honor a commitment to the veterans community,” Andrew F. Olshan, PhD, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, wrote in an accompanying editorial.

SOURCE:

The study was led by Jonathan C. Hwang, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, and was published online on February 4 in JAMA Dermatology.

LIMITATIONS:

The case-control design limits causal inference and the findings might not be generalized outside US veterans. Exposure misclassification could be present.

DISCLOSURES:

The study was supported by the Department of Defense and the Department of Veterans Affairs. Several authors reported receiving grants from CU Anschutz Medical Center, Department of Defense, CDMRP Melanoma Research Program, and Merck, Bayer, and Department of Veteran Affairs. They also reported receiving royalty from UpToDate, and being shareholder in many companies, including Apple. NVIDIA, Amazon, Gilead, AstraZeneca, BioNTech, and Moderna. Olshan declared being a member of the National Academies of Sciences, Engineering, and Medicine Veterans and Agent Orange review committee.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

Exposure to Agent Orange, the defoliant used by the US Air Force during the Vietnam War, was one of the factors associated with increased odds of acral melanoma (AM), a rare melanoma subtype affecting palms, soles, and nail units.

METHODOLOGY:

• Researchers conducted a nested case-control study in the Veterans Affairs healthcare system, and identified 1292 veterans (median age, 70.13 years; 94.0% men; 73.4% White, 14.6% Black) with AM through the Veterans Affairs Cancer Registry and a validated natural language processing pipeline from 2000 to 2024.
• Researchers matched each case of AM to 4 individuals with nonacral cutaneous melanoma (CM) and 4 control individuals without melanoma diagnoses, based on diagnosis year and outpatient visit frequency.
• Exposures included age, sex, race, ethnicity, rurality, region, military branch, comorbidities, smoking status, alcohol use, BMI, Agent Orange exposure, prior photosensitizing medications, nevi, and keratinocyte carcinoma.

TAKEAWAY:

• Veterans exposed to Agent Orange had higher odds of AM than individuals with CM (adjusted odds ratio [AOR], 1.31; 95% CI, 1.06-1.62) and control individuals without melanoma (AOR, 1.27; 95% CI, 1.04-1.56).
• Individuals with current smoking habit had lower odds of AM than those with CM (AOR, 0.65; 95% CI, 0.52-0.81) and control individuals without melanoma (AOR, 0.50; 95% CI, 0.40-0.62).
• Patients with prior keratinocyte carcinoma and actinic keratosis had higher odds of AM than control individuals without melanoma but lower odds than those with CM.
• History of nevus was associated with higher odds of acral melanoma compared with individuals without melanoma (AOR, 2.11; 95% CI, 1.49-2.98).

IN PRACTICE:

“Our results support the need for continued investigation of AM as a distinct entity from CM and may inform future evaluations of the associations between [Agent Orange exposure] in veteran populations, as well as those between other environmental exposures in different populations," the study authors wrote. Referring to the “continued search for a better understanding of a potential link” between Agent Orange and melanoma, as well as AM, and other possible etiologic factors for AM, this study “provides a strong impetus to further these research goals and contribute to the investigation of the legacy of the Vietnam War and honor a commitment to the veterans community,” Andrew F. Olshan, PhD, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, wrote in an accompanying editorial.

SOURCE:

The study was led by Jonathan C. Hwang, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, and was published online on February 4 in JAMA Dermatology.

LIMITATIONS:

The case-control design limits causal inference and the findings might not be generalized outside US veterans. Exposure misclassification could be present.

DISCLOSURES:

The study was supported by the Department of Defense and the Department of Veterans Affairs. Several authors reported receiving grants from CU Anschutz Medical Center, Department of Defense, CDMRP Melanoma Research Program, and Merck, Bayer, and Department of Veteran Affairs. They also reported receiving royalty from UpToDate, and being shareholder in many companies, including Apple. NVIDIA, Amazon, Gilead, AstraZeneca, BioNTech, and Moderna. Olshan declared being a member of the National Academies of Sciences, Engineering, and Medicine Veterans and Agent Orange review committee.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

Exposure to Agent Orange, the defoliant used by the US Air Force during the Vietnam War, was one of the factors associated with increased odds of acral melanoma (AM), a rare melanoma subtype affecting palms, soles, and nail units.

METHODOLOGY:

• Researchers conducted a nested case-control study in the Veterans Affairs healthcare system, and identified 1292 veterans (median age, 70.13 years; 94.0% men; 73.4% White, 14.6% Black) with AM through the Veterans Affairs Cancer Registry and a validated natural language processing pipeline from 2000 to 2024.
• Researchers matched each case of AM to 4 individuals with nonacral cutaneous melanoma (CM) and 4 control individuals without melanoma diagnoses, based on diagnosis year and outpatient visit frequency.
• Exposures included age, sex, race, ethnicity, rurality, region, military branch, comorbidities, smoking status, alcohol use, BMI, Agent Orange exposure, prior photosensitizing medications, nevi, and keratinocyte carcinoma.

TAKEAWAY:

• Veterans exposed to Agent Orange had higher odds of AM than individuals with CM (adjusted odds ratio [AOR], 1.31; 95% CI, 1.06-1.62) and control individuals without melanoma (AOR, 1.27; 95% CI, 1.04-1.56).
• Individuals with current smoking habit had lower odds of AM than those with CM (AOR, 0.65; 95% CI, 0.52-0.81) and control individuals without melanoma (AOR, 0.50; 95% CI, 0.40-0.62).
• Patients with prior keratinocyte carcinoma and actinic keratosis had higher odds of AM than control individuals without melanoma but lower odds than those with CM.
• History of nevus was associated with higher odds of acral melanoma compared with individuals without melanoma (AOR, 2.11; 95% CI, 1.49-2.98).

IN PRACTICE:

“Our results support the need for continued investigation of AM as a distinct entity from CM and may inform future evaluations of the associations between [Agent Orange exposure] in veteran populations, as well as those between other environmental exposures in different populations," the study authors wrote. Referring to the “continued search for a better understanding of a potential link” between Agent Orange and melanoma, as well as AM, and other possible etiologic factors for AM, this study “provides a strong impetus to further these research goals and contribute to the investigation of the legacy of the Vietnam War and honor a commitment to the veterans community,” Andrew F. Olshan, PhD, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, wrote in an accompanying editorial.

SOURCE:

The study was led by Jonathan C. Hwang, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, and was published online on February 4 in JAMA Dermatology.

LIMITATIONS:

The case-control design limits causal inference and the findings might not be generalized outside US veterans. Exposure misclassification could be present.

DISCLOSURES:

The study was supported by the Department of Defense and the Department of Veterans Affairs. Several authors reported receiving grants from CU Anschutz Medical Center, Department of Defense, CDMRP Melanoma Research Program, and Merck, Bayer, and Department of Veteran Affairs. They also reported receiving royalty from UpToDate, and being shareholder in many companies, including Apple. NVIDIA, Amazon, Gilead, AstraZeneca, BioNTech, and Moderna. Olshan declared being a member of the National Academies of Sciences, Engineering, and Medicine Veterans and Agent Orange review committee.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

A history of tuberculosis (TB) and a history of chronic bronchitis were associated with an increased risk for lung cancer in individuals who had never smoked, whereas asthma had a positive, nonsignificant association overall and a significant association in women.

METHODOLOGY:

• Researchers conducted a systematic review and meta-analysis of clinical databases from inception to July 2025, to assess the association between asthma, TB, and/or chronic bronchitis and the risk for lung cancer among participants aged 18 years or older who had never smoked.
• They included data from 20 case-control studies involving 54,135 participants and five cohort studies involving 377,983 participants.
• The primary outcome was the risk for lung cancer among participants with a history of TB, asthma, or chronic bronchitis.
• Participants were labeled as “never smokers” if they were explicitly described in the manuscripts as having “never smoked” or reported smoking < 100 cigarettes in their lifetime.

TAKEAWAY:

• In case-control studies, TB (16 studies) and chronic bronchitis (9 studies) were significantly associated with an increased risk for lung cancer (odds ratio [OR], 1.76; P < .001 and OR, 1.36; P = .012, respectively).
• In four case-cohort studies, TB was associated with an increased but nonsignificant risk for lung cancer (hazard ratio, 1.64).
• Eleven case-control studies demonstrated a positive but nonsignificant association between asthma and the risk for lung cancer (OR, 1.34). However, a significant association emerged when analyses were limited to women (five studies; OR, 1.61; P < .01).

IN PRACTICE:

History of TB was especially associated with increased LC [lung cancer] risk, meriting particular attention for prospective CT screening studies,” the authors of the study wrote.

SOURCE:

This study was led by Nishwant Swami, MD, Hospital of the University of Pennsylvania, Philadelphia. It was published online on January 11, 2026, in Chest.

LIMITATIONS:

Most studies lacked uniform adjustment for key confounders, increasing the risk for residual confounding. The inclusion of few cohort studies in the analysis may have limited the assessment of temporality and precision. Additionally, differences in covariate adjustment, variable definitions, and language restrictions may have limited comparability and generalizability.

DISCLOSURES:

No specific funding was reported for this study. One author reported serving as a consultant or advisor for various companies, including AstraZeneca, Merck, and Pfizer. Another author reported receiving funding, in part, through the Prostate Cancer Foundation Young Investigator Award and through the Cancer Center Support Grant from the National Cancer Institute.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

A history of tuberculosis (TB) and a history of chronic bronchitis were associated with an increased risk for lung cancer in individuals who had never smoked, whereas asthma had a positive, nonsignificant association overall and a significant association in women.

METHODOLOGY:

• Researchers conducted a systematic review and meta-analysis of clinical databases from inception to July 2025, to assess the association between asthma, TB, and/or chronic bronchitis and the risk for lung cancer among participants aged 18 years or older who had never smoked.
• They included data from 20 case-control studies involving 54,135 participants and five cohort studies involving 377,983 participants.
• The primary outcome was the risk for lung cancer among participants with a history of TB, asthma, or chronic bronchitis.
• Participants were labeled as “never smokers” if they were explicitly described in the manuscripts as having “never smoked” or reported smoking < 100 cigarettes in their lifetime.

TAKEAWAY:

• In case-control studies, TB (16 studies) and chronic bronchitis (9 studies) were significantly associated with an increased risk for lung cancer (odds ratio [OR], 1.76; P < .001 and OR, 1.36; P = .012, respectively).
• In four case-cohort studies, TB was associated with an increased but nonsignificant risk for lung cancer (hazard ratio, 1.64).
• Eleven case-control studies demonstrated a positive but nonsignificant association between asthma and the risk for lung cancer (OR, 1.34). However, a significant association emerged when analyses were limited to women (five studies; OR, 1.61; P < .01).

IN PRACTICE:

History of TB was especially associated with increased LC [lung cancer] risk, meriting particular attention for prospective CT screening studies,” the authors of the study wrote.

SOURCE:

This study was led by Nishwant Swami, MD, Hospital of the University of Pennsylvania, Philadelphia. It was published online on January 11, 2026, in Chest.

LIMITATIONS:

Most studies lacked uniform adjustment for key confounders, increasing the risk for residual confounding. The inclusion of few cohort studies in the analysis may have limited the assessment of temporality and precision. Additionally, differences in covariate adjustment, variable definitions, and language restrictions may have limited comparability and generalizability.

DISCLOSURES:

No specific funding was reported for this study. One author reported serving as a consultant or advisor for various companies, including AstraZeneca, Merck, and Pfizer. Another author reported receiving funding, in part, through the Prostate Cancer Foundation Young Investigator Award and through the Cancer Center Support Grant from the National Cancer Institute.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

A history of tuberculosis (TB) and a history of chronic bronchitis were associated with an increased risk for lung cancer in individuals who had never smoked, whereas asthma had a positive, nonsignificant association overall and a significant association in women.

METHODOLOGY:

• Researchers conducted a systematic review and meta-analysis of clinical databases from inception to July 2025, to assess the association between asthma, TB, and/or chronic bronchitis and the risk for lung cancer among participants aged 18 years or older who had never smoked.
• They included data from 20 case-control studies involving 54,135 participants and five cohort studies involving 377,983 participants.
• The primary outcome was the risk for lung cancer among participants with a history of TB, asthma, or chronic bronchitis.
• Participants were labeled as “never smokers” if they were explicitly described in the manuscripts as having “never smoked” or reported smoking < 100 cigarettes in their lifetime.

TAKEAWAY:

• In case-control studies, TB (16 studies) and chronic bronchitis (9 studies) were significantly associated with an increased risk for lung cancer (odds ratio [OR], 1.76; P < .001 and OR, 1.36; P = .012, respectively).
• In four case-cohort studies, TB was associated with an increased but nonsignificant risk for lung cancer (hazard ratio, 1.64).
• Eleven case-control studies demonstrated a positive but nonsignificant association between asthma and the risk for lung cancer (OR, 1.34). However, a significant association emerged when analyses were limited to women (five studies; OR, 1.61; P < .01).

IN PRACTICE:

History of TB was especially associated with increased LC [lung cancer] risk, meriting particular attention for prospective CT screening studies,” the authors of the study wrote.

SOURCE:

This study was led by Nishwant Swami, MD, Hospital of the University of Pennsylvania, Philadelphia. It was published online on January 11, 2026, in Chest.

LIMITATIONS:

Most studies lacked uniform adjustment for key confounders, increasing the risk for residual confounding. The inclusion of few cohort studies in the analysis may have limited the assessment of temporality and precision. Additionally, differences in covariate adjustment, variable definitions, and language restrictions may have limited comparability and generalizability.

DISCLOSURES:

No specific funding was reported for this study. One author reported serving as a consultant or advisor for various companies, including AstraZeneca, Merck, and Pfizer. Another author reported receiving funding, in part, through the Prostate Cancer Foundation Young Investigator Award and through the Cancer Center Support Grant from the National Cancer Institute.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

Healthy donor fecal microbiota transplantation (FMT) combined with immune checkpoint inhibitors (ICI) in metastatic renal cell carcinoma demonstrated safety with a 50% objective response rate and no grade 4-5 toxicities. Successful engraftment of diverse, anti-inflammatory microbiota correlated with improved clinical response and reduced immune-related adverse events.

METHODOLOGY:

• Many patients with metastatic renal cell carcinoma who take ICI experience immune-related adverse events that may require treatment interruption. Recent studies have provided proof of concept for microbiome modulation as a therapeutic adjunct in metastatic renal cell carcinoma, with FMT showing efficacy in resolving TKI-induced toxicities. However, the safety and clinical activity of healthy donor FMT in metastatic renal cell carcinoma remained unexplored, and its mechanism of action was unclear prior to this study.
• The new phase 1 trial enrolled 20 treatment-naive patients with metastatic renal cell carcinoma classified as intermediate-risk or poor-risk disease, who received encapsulated healthy donor FMT (LND101) combined with ipilimumab plus nivolumab (n = 16), pembrolizumab plus axitinib (n = 3), or pembrolizumab plus lenvatinib (n = 1).
• Participants underwent polyethylene glycol bowel preparation before receiving one full dose (36-40 capsules containing 80-100 g of stool) and two half-doses (20-25 capsules each containing 50-60 g of stool) of FMT from rigorously screened healthy donors.
• The primary endpoint was safety assessed through incidence and severity of immune-related adverse events, while secondary endpoints included objective response rate by response evaluation criteria in solid tumors version 1.1, gut microbiome changes, immune correlates, and quality of life.
• Analysis included longitudinal monitoring of stool and blood samples at five timepoints: baseline, week 1 post-FMT, week 4, week 7, and week 10, with a median follow-up of 21.9 months.

TAKEAWAY:

• The safety endpoint was met, with half (10 of 20) of patients experiencing grade 3 immune-related adverse events and no serious FMT-related toxicities or grade 4-5 immune-related adverse events. One patient (5%) reported experiencing an FMT-related grade 1 gastrointestinal event.
• Among evaluable patients (n = 18), the objective response rate was 50% (9 of 18), including two complete responses (11%; 2 of 18), while 67% (12 of 18) achieved clinical benefit defined as complete response, partial response, or stable disease for at least 6 months.
• Higher alpha diversity and greater functional engraftment of short-chain fatty acid-producing and anti-inflammatory taxa correlated with protection from severe immune-related adverse events (P = .041) and improved therapeutic response (P = .006).
• Expansion of Segatella copri above 10 counts per million at 10 weeks post-FMT predicted severe toxicity in patients receiving ipilimumab plus nivolumab, regardless of donor or recipient microbiota origin.

IN PRACTICE:

These findings demonstrate the safety and potential for functional microbiome engraftment to optimize response and minimize toxicity in ICI-treated [metastatic renal cell carcinoma]. Together, our results underscore the importance of functional donor screening and targeted modulation of the microbiome in optimizing the safety and efficacy of next-generation immune-based therapies,” wrote the authors of the study.

SOURCE:

The study was led by Ricardo Fernandes, Behnam Jabbarizadeh, and Adnan Rajeh, London Health Sciences Centre, London, Ontario, Canada. It was published online on January 28 in Nature Medicine.

LIMITATIONS:

According to the authors, the study’s primary limitation was its small sample size, which was not powered to define the ideal donor microbiome composition for enhancing immunotherapy efficacy without additional toxicities. The single-center design and highly selected patient population may limit external generalizability, requiring validation in larger, multicenter trials to refine donor selection criteria and clarify microbiome-immunity mechanisms.

DISCLOSURES:

The clinical trial was primarily funded through philanthropic donations to co-authors Saman Maleki Vareki and Fernandes through the London Health Sciences Foundation clinical trials program. Vareki and Michael Silverman, another co-author, reported having US Patent application no. 63/913,940 related to FMT donor screening. Vareki reported receiving grants from the Lotte and John Hecht Memorial Foundation, the Weston Family Foundation, and the Canadian Institutes of Health Research. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

Healthy donor fecal microbiota transplantation (FMT) combined with immune checkpoint inhibitors (ICI) in metastatic renal cell carcinoma demonstrated safety with a 50% objective response rate and no grade 4-5 toxicities. Successful engraftment of diverse, anti-inflammatory microbiota correlated with improved clinical response and reduced immune-related adverse events.

METHODOLOGY:

• Many patients with metastatic renal cell carcinoma who take ICI experience immune-related adverse events that may require treatment interruption. Recent studies have provided proof of concept for microbiome modulation as a therapeutic adjunct in metastatic renal cell carcinoma, with FMT showing efficacy in resolving TKI-induced toxicities. However, the safety and clinical activity of healthy donor FMT in metastatic renal cell carcinoma remained unexplored, and its mechanism of action was unclear prior to this study.
• The new phase 1 trial enrolled 20 treatment-naive patients with metastatic renal cell carcinoma classified as intermediate-risk or poor-risk disease, who received encapsulated healthy donor FMT (LND101) combined with ipilimumab plus nivolumab (n = 16), pembrolizumab plus axitinib (n = 3), or pembrolizumab plus lenvatinib (n = 1).
• Participants underwent polyethylene glycol bowel preparation before receiving one full dose (36-40 capsules containing 80-100 g of stool) and two half-doses (20-25 capsules each containing 50-60 g of stool) of FMT from rigorously screened healthy donors.
• The primary endpoint was safety assessed through incidence and severity of immune-related adverse events, while secondary endpoints included objective response rate by response evaluation criteria in solid tumors version 1.1, gut microbiome changes, immune correlates, and quality of life.
• Analysis included longitudinal monitoring of stool and blood samples at five timepoints: baseline, week 1 post-FMT, week 4, week 7, and week 10, with a median follow-up of 21.9 months.

TAKEAWAY:

• The safety endpoint was met, with half (10 of 20) of patients experiencing grade 3 immune-related adverse events and no serious FMT-related toxicities or grade 4-5 immune-related adverse events. One patient (5%) reported experiencing an FMT-related grade 1 gastrointestinal event.
• Among evaluable patients (n = 18), the objective response rate was 50% (9 of 18), including two complete responses (11%; 2 of 18), while 67% (12 of 18) achieved clinical benefit defined as complete response, partial response, or stable disease for at least 6 months.
• Higher alpha diversity and greater functional engraftment of short-chain fatty acid-producing and anti-inflammatory taxa correlated with protection from severe immune-related adverse events (P = .041) and improved therapeutic response (P = .006).
• Expansion of Segatella copri above 10 counts per million at 10 weeks post-FMT predicted severe toxicity in patients receiving ipilimumab plus nivolumab, regardless of donor or recipient microbiota origin.

IN PRACTICE:

These findings demonstrate the safety and potential for functional microbiome engraftment to optimize response and minimize toxicity in ICI-treated [metastatic renal cell carcinoma]. Together, our results underscore the importance of functional donor screening and targeted modulation of the microbiome in optimizing the safety and efficacy of next-generation immune-based therapies,” wrote the authors of the study.

SOURCE:

The study was led by Ricardo Fernandes, Behnam Jabbarizadeh, and Adnan Rajeh, London Health Sciences Centre, London, Ontario, Canada. It was published online on January 28 in Nature Medicine.

LIMITATIONS:

According to the authors, the study’s primary limitation was its small sample size, which was not powered to define the ideal donor microbiome composition for enhancing immunotherapy efficacy without additional toxicities. The single-center design and highly selected patient population may limit external generalizability, requiring validation in larger, multicenter trials to refine donor selection criteria and clarify microbiome-immunity mechanisms.

DISCLOSURES:

The clinical trial was primarily funded through philanthropic donations to co-authors Saman Maleki Vareki and Fernandes through the London Health Sciences Foundation clinical trials program. Vareki and Michael Silverman, another co-author, reported having US Patent application no. 63/913,940 related to FMT donor screening. Vareki reported receiving grants from the Lotte and John Hecht Memorial Foundation, the Weston Family Foundation, and the Canadian Institutes of Health Research. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

Healthy donor fecal microbiota transplantation (FMT) combined with immune checkpoint inhibitors (ICI) in metastatic renal cell carcinoma demonstrated safety with a 50% objective response rate and no grade 4-5 toxicities. Successful engraftment of diverse, anti-inflammatory microbiota correlated with improved clinical response and reduced immune-related adverse events.

METHODOLOGY:

• Many patients with metastatic renal cell carcinoma who take ICI experience immune-related adverse events that may require treatment interruption. Recent studies have provided proof of concept for microbiome modulation as a therapeutic adjunct in metastatic renal cell carcinoma, with FMT showing efficacy in resolving TKI-induced toxicities. However, the safety and clinical activity of healthy donor FMT in metastatic renal cell carcinoma remained unexplored, and its mechanism of action was unclear prior to this study.
• The new phase 1 trial enrolled 20 treatment-naive patients with metastatic renal cell carcinoma classified as intermediate-risk or poor-risk disease, who received encapsulated healthy donor FMT (LND101) combined with ipilimumab plus nivolumab (n = 16), pembrolizumab plus axitinib (n = 3), or pembrolizumab plus lenvatinib (n = 1).
• Participants underwent polyethylene glycol bowel preparation before receiving one full dose (36-40 capsules containing 80-100 g of stool) and two half-doses (20-25 capsules each containing 50-60 g of stool) of FMT from rigorously screened healthy donors.
• The primary endpoint was safety assessed through incidence and severity of immune-related adverse events, while secondary endpoints included objective response rate by response evaluation criteria in solid tumors version 1.1, gut microbiome changes, immune correlates, and quality of life.
• Analysis included longitudinal monitoring of stool and blood samples at five timepoints: baseline, week 1 post-FMT, week 4, week 7, and week 10, with a median follow-up of 21.9 months.

TAKEAWAY:

• The safety endpoint was met, with half (10 of 20) of patients experiencing grade 3 immune-related adverse events and no serious FMT-related toxicities or grade 4-5 immune-related adverse events. One patient (5%) reported experiencing an FMT-related grade 1 gastrointestinal event.
• Among evaluable patients (n = 18), the objective response rate was 50% (9 of 18), including two complete responses (11%; 2 of 18), while 67% (12 of 18) achieved clinical benefit defined as complete response, partial response, or stable disease for at least 6 months.
• Higher alpha diversity and greater functional engraftment of short-chain fatty acid-producing and anti-inflammatory taxa correlated with protection from severe immune-related adverse events (P = .041) and improved therapeutic response (P = .006).
• Expansion of Segatella copri above 10 counts per million at 10 weeks post-FMT predicted severe toxicity in patients receiving ipilimumab plus nivolumab, regardless of donor or recipient microbiota origin.

IN PRACTICE:

These findings demonstrate the safety and potential for functional microbiome engraftment to optimize response and minimize toxicity in ICI-treated [metastatic renal cell carcinoma]. Together, our results underscore the importance of functional donor screening and targeted modulation of the microbiome in optimizing the safety and efficacy of next-generation immune-based therapies,” wrote the authors of the study.

SOURCE:

The study was led by Ricardo Fernandes, Behnam Jabbarizadeh, and Adnan Rajeh, London Health Sciences Centre, London, Ontario, Canada. It was published online on January 28 in Nature Medicine.

LIMITATIONS:

According to the authors, the study’s primary limitation was its small sample size, which was not powered to define the ideal donor microbiome composition for enhancing immunotherapy efficacy without additional toxicities. The single-center design and highly selected patient population may limit external generalizability, requiring validation in larger, multicenter trials to refine donor selection criteria and clarify microbiome-immunity mechanisms.

DISCLOSURES:

The clinical trial was primarily funded through philanthropic donations to co-authors Saman Maleki Vareki and Fernandes through the London Health Sciences Foundation clinical trials program. Vareki and Michael Silverman, another co-author, reported having US Patent application no. 63/913,940 related to FMT donor screening. Vareki reported receiving grants from the Lotte and John Hecht Memorial Foundation, the Weston Family Foundation, and the Canadian Institutes of Health Research. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

A new analysis found that high-deductible health plans were associated with worse overall survival and cancer-specific survival among cancer survivors. High-deductible plans, however, were not associated with worse overall survival among adults without a history of cancer.

METHODOLOGY:

• Previous studies have linked high-deductible health plans with decreased or delayed health utilization among cancer survivors and higher out-of-pocket costs. However, it’s not clear whether these plans influence cancer outcomes.
• In a cross-sectional study, researchers analyzed data from 147,254 respondents (aged 18 to 84 years) in the National Health Interview Survey from 2011 to 2018 and identified individuals with high-deductible plans — 2331 cancer survivors and 37,473 people without a history of cancer.
• The researchers acquired linked mortality files from the National Death Index, which included data on mortality events through the end of 2019.
• High-deductible health plans were identified through survey responses and defined as plans with yearly deductibles of at least $1200-$1350 for individuals or at least $2400-$2700 for families.
• The primary endpoints included overall survival and cancer-specific survival. Researchers adjusted for insurance status, marital status, sex, comorbidities, education, household income, geographic region, cancer site, and time since diagnosis.

TAKEAWAY:

• Among cancer survivors, having a high-deductible health plan was associated with worse overall survival (hazard ratio [HR], 1.46) and cancer-specific survival (HR, 1.34). However, sensitivity analyses incorporating time since diagnosis slightly attenuated the cancer-specific survival association (HR, 1.20; 95% CI, 0.92-1.55).
• Among adults without a history of cancer, having a high-deductible health plan was not associated with significantly worse overall survival (HR, 1.08; 95% CI, 0.96-1.21).
• General concerns over finances, worry about medical bills, cost-related delays, or forgone care, as well as cost-related underuse of medications were significant mediators of the associations between high-deductible health plan status and mortality outcomes among cancer survivors.
• High-deductible health plan status was also associated with worse cancer-specific survival among cancer survivors with incomes at least 400% of the federal poverty level (HR, 1.65; P for interaction = .03).

IN PRACTICE:

“These data suggest that insurance coverage that financially discourages medical care may financially discourage necessary care and ultimately worsen cancer outcomes,” the study authors wrote. “This danger appears to be unique to cancer survivors, as [high-deductible health plans] were not associated with survival among adults without a cancer history.”

SOURCE:

The study, led by Justin M. Barnes, MD, MS, Department of Radiation Oncology, Mayo Clinic in Rochester, Minnesota, was published online on January 29 in JAMA Network Open.

LIMITATIONS:

High-deductible health plan status was self-reported and may have been inaccurate for some individuals, with more than half of consumers being unsure about their annual deductible amount. The study lacked specific plan details and exact deductible amounts, and high-deductible health plan status was based on a single time point during survey participation. Additionally, researchers lacked information about cancer stage, cancer-directed therapies, recurrences, or complications, and cancer mortality could be from cancers diagnosed after survey participation.

DISCLOSURES:

Meera Ragavan, MD, MPH, disclosed receiving personal fees from Trial Library and AstraZeneca and grants from Merck, outside the submitted work. Other authors reported receiving personal fees from Costs of Care during the study. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

A new analysis found that high-deductible health plans were associated with worse overall survival and cancer-specific survival among cancer survivors. High-deductible plans, however, were not associated with worse overall survival among adults without a history of cancer.

METHODOLOGY:

• Previous studies have linked high-deductible health plans with decreased or delayed health utilization among cancer survivors and higher out-of-pocket costs. However, it’s not clear whether these plans influence cancer outcomes.
• In a cross-sectional study, researchers analyzed data from 147,254 respondents (aged 18 to 84 years) in the National Health Interview Survey from 2011 to 2018 and identified individuals with high-deductible plans — 2331 cancer survivors and 37,473 people without a history of cancer.
• The researchers acquired linked mortality files from the National Death Index, which included data on mortality events through the end of 2019.
• High-deductible health plans were identified through survey responses and defined as plans with yearly deductibles of at least $1200-$1350 for individuals or at least $2400-$2700 for families.
• The primary endpoints included overall survival and cancer-specific survival. Researchers adjusted for insurance status, marital status, sex, comorbidities, education, household income, geographic region, cancer site, and time since diagnosis.

TAKEAWAY:

• Among cancer survivors, having a high-deductible health plan was associated with worse overall survival (hazard ratio [HR], 1.46) and cancer-specific survival (HR, 1.34). However, sensitivity analyses incorporating time since diagnosis slightly attenuated the cancer-specific survival association (HR, 1.20; 95% CI, 0.92-1.55).
• Among adults without a history of cancer, having a high-deductible health plan was not associated with significantly worse overall survival (HR, 1.08; 95% CI, 0.96-1.21).
• General concerns over finances, worry about medical bills, cost-related delays, or forgone care, as well as cost-related underuse of medications were significant mediators of the associations between high-deductible health plan status and mortality outcomes among cancer survivors.
• High-deductible health plan status was also associated with worse cancer-specific survival among cancer survivors with incomes at least 400% of the federal poverty level (HR, 1.65; P for interaction = .03).

IN PRACTICE:

“These data suggest that insurance coverage that financially discourages medical care may financially discourage necessary care and ultimately worsen cancer outcomes,” the study authors wrote. “This danger appears to be unique to cancer survivors, as [high-deductible health plans] were not associated with survival among adults without a cancer history.”

SOURCE:

The study, led by Justin M. Barnes, MD, MS, Department of Radiation Oncology, Mayo Clinic in Rochester, Minnesota, was published online on January 29 in JAMA Network Open.

LIMITATIONS:

High-deductible health plan status was self-reported and may have been inaccurate for some individuals, with more than half of consumers being unsure about their annual deductible amount. The study lacked specific plan details and exact deductible amounts, and high-deductible health plan status was based on a single time point during survey participation. Additionally, researchers lacked information about cancer stage, cancer-directed therapies, recurrences, or complications, and cancer mortality could be from cancers diagnosed after survey participation.

DISCLOSURES:

Meera Ragavan, MD, MPH, disclosed receiving personal fees from Trial Library and AstraZeneca and grants from Merck, outside the submitted work. Other authors reported receiving personal fees from Costs of Care during the study. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

A new analysis found that high-deductible health plans were associated with worse overall survival and cancer-specific survival among cancer survivors. High-deductible plans, however, were not associated with worse overall survival among adults without a history of cancer.

METHODOLOGY:

• Previous studies have linked high-deductible health plans with decreased or delayed health utilization among cancer survivors and higher out-of-pocket costs. However, it’s not clear whether these plans influence cancer outcomes.
• In a cross-sectional study, researchers analyzed data from 147,254 respondents (aged 18 to 84 years) in the National Health Interview Survey from 2011 to 2018 and identified individuals with high-deductible plans — 2331 cancer survivors and 37,473 people without a history of cancer.
• The researchers acquired linked mortality files from the National Death Index, which included data on mortality events through the end of 2019.
• High-deductible health plans were identified through survey responses and defined as plans with yearly deductibles of at least $1200-$1350 for individuals or at least $2400-$2700 for families.
• The primary endpoints included overall survival and cancer-specific survival. Researchers adjusted for insurance status, marital status, sex, comorbidities, education, household income, geographic region, cancer site, and time since diagnosis.

TAKEAWAY:

• Among cancer survivors, having a high-deductible health plan was associated with worse overall survival (hazard ratio [HR], 1.46) and cancer-specific survival (HR, 1.34). However, sensitivity analyses incorporating time since diagnosis slightly attenuated the cancer-specific survival association (HR, 1.20; 95% CI, 0.92-1.55).
• Among adults without a history of cancer, having a high-deductible health plan was not associated with significantly worse overall survival (HR, 1.08; 95% CI, 0.96-1.21).
• General concerns over finances, worry about medical bills, cost-related delays, or forgone care, as well as cost-related underuse of medications were significant mediators of the associations between high-deductible health plan status and mortality outcomes among cancer survivors.
• High-deductible health plan status was also associated with worse cancer-specific survival among cancer survivors with incomes at least 400% of the federal poverty level (HR, 1.65; P for interaction = .03).

IN PRACTICE:

“These data suggest that insurance coverage that financially discourages medical care may financially discourage necessary care and ultimately worsen cancer outcomes,” the study authors wrote. “This danger appears to be unique to cancer survivors, as [high-deductible health plans] were not associated with survival among adults without a cancer history.”

SOURCE:

The study, led by Justin M. Barnes, MD, MS, Department of Radiation Oncology, Mayo Clinic in Rochester, Minnesota, was published online on January 29 in JAMA Network Open.

LIMITATIONS:

High-deductible health plan status was self-reported and may have been inaccurate for some individuals, with more than half of consumers being unsure about their annual deductible amount. The study lacked specific plan details and exact deductible amounts, and high-deductible health plan status was based on a single time point during survey participation. Additionally, researchers lacked information about cancer stage, cancer-directed therapies, recurrences, or complications, and cancer mortality could be from cancers diagnosed after survey participation.

DISCLOSURES:

Meera Ragavan, MD, MPH, disclosed receiving personal fees from Trial Library and AstraZeneca and grants from Merck, outside the submitted work. Other authors reported receiving personal fees from Costs of Care during the study. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

Adding aminopeptidase N and polymeric immunoglobin receptor to a plasma biomarker panel of carbohydrate antigen 19-9 (CA19-9) and thrombospondin 2 (THBS2) enhanced the detection of early-stage pancreatic ductal adenocarcinoma (PDAC). At 95% specificity, the four-marker panel achieved more than 87% sensitivity for early-stage and more than 91% sensitivity for disease at any stage in two independent phase II studies. But prospective validation is required to ascertain clinical applicability.

METHODOLOGY:

• PDAC is associated with high mortality, but markedly improved survival is observed with early detection. Biomarkers such as CA19-9 are widely used to monitor PDAC treatment response but lack sensitivity and specificity for early-stage disease and can be influenced by patients’ genetics. A phase 2 study found THBS2 complements CA19‑9, with higher THBS2 levels linked to poorer prognosis in late-stage disease. This study uses phase 1 and 2 analyses to identify additional plasma biomarkers to improve early detection of PDAC.
• In phase 1 discovery, researchers used pooled plasma from 2 centers (University of Pennsylvania [Penn] and Mayo Clinic [Mayo]) to create representative samples for healthy control, chronic pancreatitis, early-stage PDAC (stage I/II), mid-stage PDAC (stage III), and late-stage PDAC.
• Plasma pools underwent abundant-protein depletion and were analyzed by two complementary mass spectrometry workflows; proteins consistently elevated in early PDAC (aminopeptidase N and polymeric immunoglobin receptor) were prioritized.
• Phase 2 validation measured CA19-9, THBS2, aminopeptidase N, and polymeric immunoglobin receptor levels by enzyme-linked immunosorbent assay in two blinded retrospective cohorts (Penn, n = 135; Mayo, n = 537). Overall, the Penn cohort included 59 patients with PDAC, 47 healthy control individuals, and 29 control patients with diseases (chronic pancreatitis, pancreatic cysts, pancreatic intraepithelial neoplasia, and intraductal papillary mucinous neoplasms). The Mayo cohort included 197 patients with PDAC, 140 healthy control individuals, and 200 control patients with diseases (intraductal papillary mucinous neoplasms, pancreatic neuroendocrine tumors, and chronic pancreatitis).
• Investigators developed univariate and multivariable logistic regression models to evaluate each marker alone and in combinations (2-, 3-, and 4-marker panels) for discriminating patients with PDAC from healthy control individuals and from control patients with diseases. Model performance was assessed using receiver-operating characteristic (ROC) curves and area under the ROC curve (AUC), and bootstrap methods were used to estimate 95% CIs.

TAKEAWAY:

• Comparing the performances of single markers for patients with stage I/II PDAC vs healthy control individuals, no single marker could outperform CA19-9 alone (AUC = 0.90 in both Penn and Mayo cohorts). Two-marker models (CA19-9 plus one marker) vs CA19-9 alone improved AUCs for both early- and all-stage PDACs in both cohorts.
• Looking at multivariable panels for patients with stage I/II PDAC vs healthy control individuals, the 3-marker panel of CA19-9/THBS2/ aminopeptidase N outperformed the other three-marker models, with AUCs of 0.96 (Penn) and 0.97 (Mayo). The 4-marker panel of CA19-9/THBS2/aminopeptidase N /polymeric immunoglobin receptor was the strongest performing panel with AUCs of 0.96 (Penn) and 0.97 (Mayo).
• In the Mayo cohort, the 4-marker panel (CA19-9/THBS2/aminopeptidase N/polymeric immunoglobin receptor) achieved AUCs of 0.87 and 0.91 for patients with stage I/II PDAC vs control patients with diseases and patients with stages I-IV PDAC vs control patients with diseases, respectively.
• At a specificity of 95%, “a plasma biomarker panel composed of CA19-9 (≥ 35 U/mL), THBS2 (≥ 42 ng/mL), aminopeptidase N (≥ 2995 ng/mL), and polymeric immunoglobin receptor (≥ 1800 ng/mL) yielded a sensitivity of 91.94% for all stages and 87.53% for early stage I/II PDAC detection,” the authors wrote.

IN PRACTICE:

“A panel composed of CA19-9/THBS2/aminopeptidase N/polymeric immunoglobin receptor may be suitable for early detection of PDAC based on results showing a high sensitivity and specificity in the larger Mayo phase II cohort but would require prediagnostic cohorts for verification,” the authors of the study wrote.

SOURCE:

The study, led by Brianna M. Krusen, Institute for Regenerative Medicine, Perelman School of Medicine at Penn, Philadelphia, was published online in Clinical Cancer Research.

LIMITATIONS:

The biomarker panel was evaluated on samples drawn at the time of diagnosis and has not yet been assessed in prediagnostic or high‑risk surveillance cohorts, which are necessary to establish its clinical performance.

DISCLOSURES:

The study was supported by the Penn Pancreatic Cancer Research Center, A Love for Life, and National Institutes of Health (NIH) Grant. Several authors reported receiving grants and other support from the NIH and various other sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

Adding aminopeptidase N and polymeric immunoglobin receptor to a plasma biomarker panel of carbohydrate antigen 19-9 (CA19-9) and thrombospondin 2 (THBS2) enhanced the detection of early-stage pancreatic ductal adenocarcinoma (PDAC). At 95% specificity, the four-marker panel achieved more than 87% sensitivity for early-stage and more than 91% sensitivity for disease at any stage in two independent phase II studies. But prospective validation is required to ascertain clinical applicability.

METHODOLOGY:

• PDAC is associated with high mortality, but markedly improved survival is observed with early detection. Biomarkers such as CA19-9 are widely used to monitor PDAC treatment response but lack sensitivity and specificity for early-stage disease and can be influenced by patients’ genetics. A phase 2 study found THBS2 complements CA19‑9, with higher THBS2 levels linked to poorer prognosis in late-stage disease. This study uses phase 1 and 2 analyses to identify additional plasma biomarkers to improve early detection of PDAC.
• In phase 1 discovery, researchers used pooled plasma from 2 centers (University of Pennsylvania [Penn] and Mayo Clinic [Mayo]) to create representative samples for healthy control, chronic pancreatitis, early-stage PDAC (stage I/II), mid-stage PDAC (stage III), and late-stage PDAC.
• Plasma pools underwent abundant-protein depletion and were analyzed by two complementary mass spectrometry workflows; proteins consistently elevated in early PDAC (aminopeptidase N and polymeric immunoglobin receptor) were prioritized.
• Phase 2 validation measured CA19-9, THBS2, aminopeptidase N, and polymeric immunoglobin receptor levels by enzyme-linked immunosorbent assay in two blinded retrospective cohorts (Penn, n = 135; Mayo, n = 537). Overall, the Penn cohort included 59 patients with PDAC, 47 healthy control individuals, and 29 control patients with diseases (chronic pancreatitis, pancreatic cysts, pancreatic intraepithelial neoplasia, and intraductal papillary mucinous neoplasms). The Mayo cohort included 197 patients with PDAC, 140 healthy control individuals, and 200 control patients with diseases (intraductal papillary mucinous neoplasms, pancreatic neuroendocrine tumors, and chronic pancreatitis).
• Investigators developed univariate and multivariable logistic regression models to evaluate each marker alone and in combinations (2-, 3-, and 4-marker panels) for discriminating patients with PDAC from healthy control individuals and from control patients with diseases. Model performance was assessed using receiver-operating characteristic (ROC) curves and area under the ROC curve (AUC), and bootstrap methods were used to estimate 95% CIs.

TAKEAWAY:

• Comparing the performances of single markers for patients with stage I/II PDAC vs healthy control individuals, no single marker could outperform CA19-9 alone (AUC = 0.90 in both Penn and Mayo cohorts). Two-marker models (CA19-9 plus one marker) vs CA19-9 alone improved AUCs for both early- and all-stage PDACs in both cohorts.
• Looking at multivariable panels for patients with stage I/II PDAC vs healthy control individuals, the 3-marker panel of CA19-9/THBS2/ aminopeptidase N outperformed the other three-marker models, with AUCs of 0.96 (Penn) and 0.97 (Mayo). The 4-marker panel of CA19-9/THBS2/aminopeptidase N /polymeric immunoglobin receptor was the strongest performing panel with AUCs of 0.96 (Penn) and 0.97 (Mayo).
• In the Mayo cohort, the 4-marker panel (CA19-9/THBS2/aminopeptidase N/polymeric immunoglobin receptor) achieved AUCs of 0.87 and 0.91 for patients with stage I/II PDAC vs control patients with diseases and patients with stages I-IV PDAC vs control patients with diseases, respectively.
• At a specificity of 95%, “a plasma biomarker panel composed of CA19-9 (≥ 35 U/mL), THBS2 (≥ 42 ng/mL), aminopeptidase N (≥ 2995 ng/mL), and polymeric immunoglobin receptor (≥ 1800 ng/mL) yielded a sensitivity of 91.94% for all stages and 87.53% for early stage I/II PDAC detection,” the authors wrote.

IN PRACTICE:

“A panel composed of CA19-9/THBS2/aminopeptidase N/polymeric immunoglobin receptor may be suitable for early detection of PDAC based on results showing a high sensitivity and specificity in the larger Mayo phase II cohort but would require prediagnostic cohorts for verification,” the authors of the study wrote.

SOURCE:

The study, led by Brianna M. Krusen, Institute for Regenerative Medicine, Perelman School of Medicine at Penn, Philadelphia, was published online in Clinical Cancer Research.

LIMITATIONS:

The biomarker panel was evaluated on samples drawn at the time of diagnosis and has not yet been assessed in prediagnostic or high‑risk surveillance cohorts, which are necessary to establish its clinical performance.

DISCLOSURES:

The study was supported by the Penn Pancreatic Cancer Research Center, A Love for Life, and National Institutes of Health (NIH) Grant. Several authors reported receiving grants and other support from the NIH and various other sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

Adding aminopeptidase N and polymeric immunoglobin receptor to a plasma biomarker panel of carbohydrate antigen 19-9 (CA19-9) and thrombospondin 2 (THBS2) enhanced the detection of early-stage pancreatic ductal adenocarcinoma (PDAC). At 95% specificity, the four-marker panel achieved more than 87% sensitivity for early-stage and more than 91% sensitivity for disease at any stage in two independent phase II studies. But prospective validation is required to ascertain clinical applicability.

METHODOLOGY:

• PDAC is associated with high mortality, but markedly improved survival is observed with early detection. Biomarkers such as CA19-9 are widely used to monitor PDAC treatment response but lack sensitivity and specificity for early-stage disease and can be influenced by patients’ genetics. A phase 2 study found THBS2 complements CA19‑9, with higher THBS2 levels linked to poorer prognosis in late-stage disease. This study uses phase 1 and 2 analyses to identify additional plasma biomarkers to improve early detection of PDAC.
• In phase 1 discovery, researchers used pooled plasma from 2 centers (University of Pennsylvania [Penn] and Mayo Clinic [Mayo]) to create representative samples for healthy control, chronic pancreatitis, early-stage PDAC (stage I/II), mid-stage PDAC (stage III), and late-stage PDAC.
• Plasma pools underwent abundant-protein depletion and were analyzed by two complementary mass spectrometry workflows; proteins consistently elevated in early PDAC (aminopeptidase N and polymeric immunoglobin receptor) were prioritized.
• Phase 2 validation measured CA19-9, THBS2, aminopeptidase N, and polymeric immunoglobin receptor levels by enzyme-linked immunosorbent assay in two blinded retrospective cohorts (Penn, n = 135; Mayo, n = 537). Overall, the Penn cohort included 59 patients with PDAC, 47 healthy control individuals, and 29 control patients with diseases (chronic pancreatitis, pancreatic cysts, pancreatic intraepithelial neoplasia, and intraductal papillary mucinous neoplasms). The Mayo cohort included 197 patients with PDAC, 140 healthy control individuals, and 200 control patients with diseases (intraductal papillary mucinous neoplasms, pancreatic neuroendocrine tumors, and chronic pancreatitis).
• Investigators developed univariate and multivariable logistic regression models to evaluate each marker alone and in combinations (2-, 3-, and 4-marker panels) for discriminating patients with PDAC from healthy control individuals and from control patients with diseases. Model performance was assessed using receiver-operating characteristic (ROC) curves and area under the ROC curve (AUC), and bootstrap methods were used to estimate 95% CIs.

TAKEAWAY:

• Comparing the performances of single markers for patients with stage I/II PDAC vs healthy control individuals, no single marker could outperform CA19-9 alone (AUC = 0.90 in both Penn and Mayo cohorts). Two-marker models (CA19-9 plus one marker) vs CA19-9 alone improved AUCs for both early- and all-stage PDACs in both cohorts.
• Looking at multivariable panels for patients with stage I/II PDAC vs healthy control individuals, the 3-marker panel of CA19-9/THBS2/ aminopeptidase N outperformed the other three-marker models, with AUCs of 0.96 (Penn) and 0.97 (Mayo). The 4-marker panel of CA19-9/THBS2/aminopeptidase N /polymeric immunoglobin receptor was the strongest performing panel with AUCs of 0.96 (Penn) and 0.97 (Mayo).
• In the Mayo cohort, the 4-marker panel (CA19-9/THBS2/aminopeptidase N/polymeric immunoglobin receptor) achieved AUCs of 0.87 and 0.91 for patients with stage I/II PDAC vs control patients with diseases and patients with stages I-IV PDAC vs control patients with diseases, respectively.
• At a specificity of 95%, “a plasma biomarker panel composed of CA19-9 (≥ 35 U/mL), THBS2 (≥ 42 ng/mL), aminopeptidase N (≥ 2995 ng/mL), and polymeric immunoglobin receptor (≥ 1800 ng/mL) yielded a sensitivity of 91.94% for all stages and 87.53% for early stage I/II PDAC detection,” the authors wrote.

IN PRACTICE:

“A panel composed of CA19-9/THBS2/aminopeptidase N/polymeric immunoglobin receptor may be suitable for early detection of PDAC based on results showing a high sensitivity and specificity in the larger Mayo phase II cohort but would require prediagnostic cohorts for verification,” the authors of the study wrote.

SOURCE:

The study, led by Brianna M. Krusen, Institute for Regenerative Medicine, Perelman School of Medicine at Penn, Philadelphia, was published online in Clinical Cancer Research.

LIMITATIONS:

The biomarker panel was evaluated on samples drawn at the time of diagnosis and has not yet been assessed in prediagnostic or high‑risk surveillance cohorts, which are necessary to establish its clinical performance.

DISCLOSURES:

The study was supported by the Penn Pancreatic Cancer Research Center, A Love for Life, and National Institutes of Health (NIH) Grant. Several authors reported receiving grants and other support from the NIH and various other sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

New research examining recreational physical activity’s relationship with breast tissue composition, oxidative stress, and inflammation in adolescent girls revealed potential pathways for cancer risk reduction.

METHODOLOGY:

• Recent research shows 12-22% lower risk for breast cancer among highly active women, but the biological mechanisms explaining this remain unclear. Breast tissue composition, particularly mammographic density, is one of the strongest predictors of breast cancer risk, and breast tissue composition tracks across the life course.
• Researchers analyzed data from a population-based urban cohort of 191 Black/African American and Hispanic (Dominican) adolescent girls aged 11-20 years.
• Participants reported organized and unorganized recreational physical activity in the past week, categorized as none, < 2 hours, or ≥ 2 hours.
• Optical spectroscopy measured breast tissue composition through chromophores that are positively (percent water content and percent collagen content) or negatively (percent lipid content) correlated with mammographic breast density.
• Analysis included urinary concentrations of 15-F2-isoprostane for oxidative stress and blood biomarkers of inflammation including TNF-alpha, interleukin-6, and high-sensitivity C-reactive protein.

TAKEAWAY:

• Fifty-one percent of adolescent girls reported no past-week engagement in any type of recreational physical activity, with 73% reporting no participation in organized activities and 66% reporting no participation in unorganized activities.
• Girls engaging in at least 2 hours of organized recreational physical activity vs none showed lower percent water content in breast tissue (beta coefficient, -0.41; 95% CI, -0.77 to -0.05) and lower urinary concentrations of 15-F2-isoprostane (beta coefficient, -0.50; 95% CI, -0.95 to -0.05).
• Higher urinary concentrations of 15-F2-isoprostane were associated with higher percent collagen content in breast tissue (beta coefficient, 0.15; 95% CI, 0.00-0.31).
• No associations were found between recreational physical activity and inflammatory biomarkers, and these biomarkers showed no association with breast tissue composition after adjusting for percent body fat.

IN PRACTICE:

“These findings support that recreational physical activity is associated with breast tissue composition and oxidative stress in adolescent girls, independent of body fat. Additional longitudinal research is needed to understand the implications of these findings regarding subsequent breast cancer risk,” the authors of the study wrote.

SOURCE:

The study was led by Rebecca D. Kehm, PhD, Department of Epidemiology, Mailman School of Public Health, Columbia University, New York City. It was published online in Breast Cancer Research.

LIMITATIONS:

Recreational physical activity was assessed using self-reported data capturing only a 1-week timeframe, which may not fully reflect habitual patterns and is susceptible to measurement error. The cross-sectional nature of the analysis prevented establishing temporal relationships or causal inferences. The relatively small sample size limited statistical power, though researchers were able to detect modest associations. The findings may not be generalizable to populations with different demographics or higher levels of physical activity because recreational physical activity was notably low in this cohort. Additionally, while several validated biomarkers were examined, other mechanisms such as hormonal regulation and insulin sensitivity may also be important for understanding the relationship between adolescent physical activity and breast cancer risk.

DISCLOSURES:

The study received support from the National Institute of Environmental Health Sciences through grants U01ES026122 and P30ES009089, as well as grant ROICA263024 from the National Cancer Institute.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

New research examining recreational physical activity’s relationship with breast tissue composition, oxidative stress, and inflammation in adolescent girls revealed potential pathways for cancer risk reduction.

METHODOLOGY:

• Recent research shows 12-22% lower risk for breast cancer among highly active women, but the biological mechanisms explaining this remain unclear. Breast tissue composition, particularly mammographic density, is one of the strongest predictors of breast cancer risk, and breast tissue composition tracks across the life course.
• Researchers analyzed data from a population-based urban cohort of 191 Black/African American and Hispanic (Dominican) adolescent girls aged 11-20 years.
• Participants reported organized and unorganized recreational physical activity in the past week, categorized as none, < 2 hours, or ≥ 2 hours.
• Optical spectroscopy measured breast tissue composition through chromophores that are positively (percent water content and percent collagen content) or negatively (percent lipid content) correlated with mammographic breast density.
• Analysis included urinary concentrations of 15-F2-isoprostane for oxidative stress and blood biomarkers of inflammation including TNF-alpha, interleukin-6, and high-sensitivity C-reactive protein.

TAKEAWAY:

• Fifty-one percent of adolescent girls reported no past-week engagement in any type of recreational physical activity, with 73% reporting no participation in organized activities and 66% reporting no participation in unorganized activities.
• Girls engaging in at least 2 hours of organized recreational physical activity vs none showed lower percent water content in breast tissue (beta coefficient, -0.41; 95% CI, -0.77 to -0.05) and lower urinary concentrations of 15-F2-isoprostane (beta coefficient, -0.50; 95% CI, -0.95 to -0.05).
• Higher urinary concentrations of 15-F2-isoprostane were associated with higher percent collagen content in breast tissue (beta coefficient, 0.15; 95% CI, 0.00-0.31).
• No associations were found between recreational physical activity and inflammatory biomarkers, and these biomarkers showed no association with breast tissue composition after adjusting for percent body fat.

IN PRACTICE:

“These findings support that recreational physical activity is associated with breast tissue composition and oxidative stress in adolescent girls, independent of body fat. Additional longitudinal research is needed to understand the implications of these findings regarding subsequent breast cancer risk,” the authors of the study wrote.

SOURCE:

The study was led by Rebecca D. Kehm, PhD, Department of Epidemiology, Mailman School of Public Health, Columbia University, New York City. It was published online in Breast Cancer Research.

LIMITATIONS:

Recreational physical activity was assessed using self-reported data capturing only a 1-week timeframe, which may not fully reflect habitual patterns and is susceptible to measurement error. The cross-sectional nature of the analysis prevented establishing temporal relationships or causal inferences. The relatively small sample size limited statistical power, though researchers were able to detect modest associations. The findings may not be generalizable to populations with different demographics or higher levels of physical activity because recreational physical activity was notably low in this cohort. Additionally, while several validated biomarkers were examined, other mechanisms such as hormonal regulation and insulin sensitivity may also be important for understanding the relationship between adolescent physical activity and breast cancer risk.

DISCLOSURES:

The study received support from the National Institute of Environmental Health Sciences through grants U01ES026122 and P30ES009089, as well as grant ROICA263024 from the National Cancer Institute.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

New research examining recreational physical activity’s relationship with breast tissue composition, oxidative stress, and inflammation in adolescent girls revealed potential pathways for cancer risk reduction.

METHODOLOGY:

• Recent research shows 12-22% lower risk for breast cancer among highly active women, but the biological mechanisms explaining this remain unclear. Breast tissue composition, particularly mammographic density, is one of the strongest predictors of breast cancer risk, and breast tissue composition tracks across the life course.
• Researchers analyzed data from a population-based urban cohort of 191 Black/African American and Hispanic (Dominican) adolescent girls aged 11-20 years.
• Participants reported organized and unorganized recreational physical activity in the past week, categorized as none, < 2 hours, or ≥ 2 hours.
• Optical spectroscopy measured breast tissue composition through chromophores that are positively (percent water content and percent collagen content) or negatively (percent lipid content) correlated with mammographic breast density.
• Analysis included urinary concentrations of 15-F2-isoprostane for oxidative stress and blood biomarkers of inflammation including TNF-alpha, interleukin-6, and high-sensitivity C-reactive protein.

TAKEAWAY:

• Fifty-one percent of adolescent girls reported no past-week engagement in any type of recreational physical activity, with 73% reporting no participation in organized activities and 66% reporting no participation in unorganized activities.
• Girls engaging in at least 2 hours of organized recreational physical activity vs none showed lower percent water content in breast tissue (beta coefficient, -0.41; 95% CI, -0.77 to -0.05) and lower urinary concentrations of 15-F2-isoprostane (beta coefficient, -0.50; 95% CI, -0.95 to -0.05).
• Higher urinary concentrations of 15-F2-isoprostane were associated with higher percent collagen content in breast tissue (beta coefficient, 0.15; 95% CI, 0.00-0.31).
• No associations were found between recreational physical activity and inflammatory biomarkers, and these biomarkers showed no association with breast tissue composition after adjusting for percent body fat.

IN PRACTICE:

“These findings support that recreational physical activity is associated with breast tissue composition and oxidative stress in adolescent girls, independent of body fat. Additional longitudinal research is needed to understand the implications of these findings regarding subsequent breast cancer risk,” the authors of the study wrote.

SOURCE:

The study was led by Rebecca D. Kehm, PhD, Department of Epidemiology, Mailman School of Public Health, Columbia University, New York City. It was published online in Breast Cancer Research.

LIMITATIONS:

Recreational physical activity was assessed using self-reported data capturing only a 1-week timeframe, which may not fully reflect habitual patterns and is susceptible to measurement error. The cross-sectional nature of the analysis prevented establishing temporal relationships or causal inferences. The relatively small sample size limited statistical power, though researchers were able to detect modest associations. The findings may not be generalizable to populations with different demographics or higher levels of physical activity because recreational physical activity was notably low in this cohort. Additionally, while several validated biomarkers were examined, other mechanisms such as hormonal regulation and insulin sensitivity may also be important for understanding the relationship between adolescent physical activity and breast cancer risk.

DISCLOSURES:

The study received support from the National Institute of Environmental Health Sciences through grants U01ES026122 and P30ES009089, as well as grant ROICA263024 from the National Cancer Institute.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

Insights from phase 3 trials presented at the 2025 American Society of Hematology Annual Meeting may expand treatment options for veterans with chronic lymphocytic leukemia (CLL), as discussed by Dr Nicholas Burwick from University of Washington, Seattle.

Dr Burwick begins with the CLL17 trial examining continuous treatment vs fixed-duration therapy in previously untreated patients. The fixed-duration therapy showed noninferior results. Research pertaining to the veterans population in the phase 2 Benefit VA study may offer further insight on these results.

He next discusses the first study comparing the noncovalent BTKi pirtobrutinib to covalent ibrutinib in both treatment-naive patients and those with relapsed/refractory CLL. Pirtobrutinib demonstrated noninferiority in each subgroup. 

Pirtobrutinib was compared to bendamustine plus rituximab in the treatment-naive setting in the next study, showing favorable progression-free survival and a notable trend in overall survival. These two trials could lead to use of a noncovalent BTKi as frontline therapy.

Dr Burwick then turns to 6-year follow-up in the SEQUOIA trial, in which zanubrutinib showed sustained superiority over bendamustine and rituximab. He notes that acalabrutinib is currently the preferred BTKi therapy for veterans with CLL.

Finally, he discusses a study examining combination acalabrutinib and venetoclax, to which obinutuzumab was added either early or late. The rate of infections was significantly higher in the early group, an issue of particular concern in the veterans population.

--

Nicholas R. Burwick, MD, VA Puget Sound Health Care System; Associate Professor, Department of Medicine, Division of Hematology, University of Washington, Seattle; President, AVAHO - Association of VA Hematology/Oncology

Nicholas R. Burwick, MD, has disclosed no relevant financial relationships.

Insights from phase 3 trials presented at the 2025 American Society of Hematology Annual Meeting may expand treatment options for veterans with chronic lymphocytic leukemia (CLL), as discussed by Dr Nicholas Burwick from University of Washington, Seattle.

Dr Burwick begins with the CLL17 trial examining continuous treatment vs fixed-duration therapy in previously untreated patients. The fixed-duration therapy showed noninferior results. Research pertaining to the veterans population in the phase 2 Benefit VA study may offer further insight on these results.

He next discusses the first study comparing the noncovalent BTKi pirtobrutinib to covalent ibrutinib in both treatment-naive patients and those with relapsed/refractory CLL. Pirtobrutinib demonstrated noninferiority in each subgroup. 

Pirtobrutinib was compared to bendamustine plus rituximab in the treatment-naive setting in the next study, showing favorable progression-free survival and a notable trend in overall survival. These two trials could lead to use of a noncovalent BTKi as frontline therapy.

Dr Burwick then turns to 6-year follow-up in the SEQUOIA trial, in which zanubrutinib showed sustained superiority over bendamustine and rituximab. He notes that acalabrutinib is currently the preferred BTKi therapy for veterans with CLL.

Finally, he discusses a study examining combination acalabrutinib and venetoclax, to which obinutuzumab was added either early or late. The rate of infections was significantly higher in the early group, an issue of particular concern in the veterans population.

--

Nicholas R. Burwick, MD, VA Puget Sound Health Care System; Associate Professor, Department of Medicine, Division of Hematology, University of Washington, Seattle; President, AVAHO - Association of VA Hematology/Oncology

Nicholas R. Burwick, MD, has disclosed no relevant financial relationships.

Insights from phase 3 trials presented at the 2025 American Society of Hematology Annual Meeting may expand treatment options for veterans with chronic lymphocytic leukemia (CLL), as discussed by Dr Nicholas Burwick from University of Washington, Seattle.

Dr Burwick begins with the CLL17 trial examining continuous treatment vs fixed-duration therapy in previously untreated patients. The fixed-duration therapy showed noninferior results. Research pertaining to the veterans population in the phase 2 Benefit VA study may offer further insight on these results.

He next discusses the first study comparing the noncovalent BTKi pirtobrutinib to covalent ibrutinib in both treatment-naive patients and those with relapsed/refractory CLL. Pirtobrutinib demonstrated noninferiority in each subgroup. 

Pirtobrutinib was compared to bendamustine plus rituximab in the treatment-naive setting in the next study, showing favorable progression-free survival and a notable trend in overall survival. These two trials could lead to use of a noncovalent BTKi as frontline therapy.

Dr Burwick then turns to 6-year follow-up in the SEQUOIA trial, in which zanubrutinib showed sustained superiority over bendamustine and rituximab. He notes that acalabrutinib is currently the preferred BTKi therapy for veterans with CLL.

Finally, he discusses a study examining combination acalabrutinib and venetoclax, to which obinutuzumab was added either early or late. The rate of infections was significantly higher in the early group, an issue of particular concern in the veterans population.

--

Nicholas R. Burwick, MD, VA Puget Sound Health Care System; Associate Professor, Department of Medicine, Division of Hematology, University of Washington, Seattle; President, AVAHO - Association of VA Hematology/Oncology

Nicholas R. Burwick, MD, has disclosed no relevant financial relationships.

TOPLINE:

A systematic review of 69 economic evaluations revealed that adjuvant immunotherapy was cost-effective in 58% of studies, with higher Quality-Adjusted Life-Year gains reported in 91% of cases. Cost-effectiveness varied significantly by cancer type, treatment strategy, and healthcare system context, with industry-funded studies more likely to report favorable outcomes.

METHODOLOGY:

• Multiple phase 3 trials have shown improved survival and reduced recurrence with adjuvant immunotherapy in various cancers. But the high cost of immunotherapy treatments, often exceeding $100,000 per patient, has raised questions about their economic value and affordability across different healthcare systems.
• Researchers conducted a systematic review of 69 economic evaluations published between January 2015 and January 2025, focusing on adjuvant immunotherapy across various cancer types.
• Analysis included studies from PubMed, Embase, Scopus, Web of Science, and Cochrane Library, with most evaluations conducted in the US (26 studies) and China (20 studies).
• Quality assessment utilized the Criteria for Health Economic Quality Evaluation tool, evaluating 48 attributes across methodologic and reporting quality dimensions.
• Markov modeling dominated the analytical approach (46 studies [67%]), with EuroQol Five-Dimensions being the most commonly used health utility instrument (56 studies [81%]).

TAKEAWAY:

• Of 69 studies analyzed, 58% concluded that adjuvant immunotherapy was cost-effective, with stronger evidence in non-small cell lung cancer and melanoma, particularly in early-stage and high-risk populations.
• Industry-funded studies more frequently reported cost-effective outcomes (17 of 20 studies [85%]) than nonindustry funded studies (13 of 28 studies [46%]).
• Higher Quality-Adjusted Life-Year/Life-Year gains were consistently reported in the adjuvant immunotherapy group (63 studies [91%]), especially for non-small cell lung cancer and combination regimens.
• Cost-effectiveness results varied significantly by cancer type, model assumptions, drug pricing, funding organizations, and country-specific willingness-to-pay thresholds.

IN PRACTICE:

“From a policy standpoint, the findings of this systematic review support the use of structured, context-specific health technology assessment frameworks to evaluate adjuvant immunotherapies. For health systems under financial constraints, prioritizing subgroups with the highest absolute benefit may be a viable approach to ensure sustainable access,” the authors of the review wrote.

SOURCE:

The systematic review was led by Rashidul Alam Mahumud, PhD, MCncrSc, MPH, MSc, Health Economics and Health Technology Assessment Unit, National Health and Medical Research Council Clinical Trials Centre, The University of Sydney in Camperdown, Australia. It was published online on January 22 in JAMA Oncology.

LIMITATIONS:

The methodologic heterogeneity across studies presents a significant limitation, with variations in time horizons, discounting methods, survival data extrapolation, and health utility measurements affecting result comparability. Geographic distribution primarily focused on high-income countries, limiting generalizability to low- and middle-income settings. Few evaluations incorporated adaptive pricing schemes or managed entry agreements that increasingly influence clinical reimbursement decisions.

DISCLOSURES:

Mahumud had full access to all study data and takes responsibility for data integrity and analysis accuracy. The authors reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

A systematic review of 69 economic evaluations revealed that adjuvant immunotherapy was cost-effective in 58% of studies, with higher Quality-Adjusted Life-Year gains reported in 91% of cases. Cost-effectiveness varied significantly by cancer type, treatment strategy, and healthcare system context, with industry-funded studies more likely to report favorable outcomes.

METHODOLOGY:

• Multiple phase 3 trials have shown improved survival and reduced recurrence with adjuvant immunotherapy in various cancers. But the high cost of immunotherapy treatments, often exceeding $100,000 per patient, has raised questions about their economic value and affordability across different healthcare systems.
• Researchers conducted a systematic review of 69 economic evaluations published between January 2015 and January 2025, focusing on adjuvant immunotherapy across various cancer types.
• Analysis included studies from PubMed, Embase, Scopus, Web of Science, and Cochrane Library, with most evaluations conducted in the US (26 studies) and China (20 studies).
• Quality assessment utilized the Criteria for Health Economic Quality Evaluation tool, evaluating 48 attributes across methodologic and reporting quality dimensions.
• Markov modeling dominated the analytical approach (46 studies [67%]), with EuroQol Five-Dimensions being the most commonly used health utility instrument (56 studies [81%]).

TAKEAWAY:

• Of 69 studies analyzed, 58% concluded that adjuvant immunotherapy was cost-effective, with stronger evidence in non-small cell lung cancer and melanoma, particularly in early-stage and high-risk populations.
• Industry-funded studies more frequently reported cost-effective outcomes (17 of 20 studies [85%]) than nonindustry funded studies (13 of 28 studies [46%]).
• Higher Quality-Adjusted Life-Year/Life-Year gains were consistently reported in the adjuvant immunotherapy group (63 studies [91%]), especially for non-small cell lung cancer and combination regimens.
• Cost-effectiveness results varied significantly by cancer type, model assumptions, drug pricing, funding organizations, and country-specific willingness-to-pay thresholds.

IN PRACTICE:

“From a policy standpoint, the findings of this systematic review support the use of structured, context-specific health technology assessment frameworks to evaluate adjuvant immunotherapies. For health systems under financial constraints, prioritizing subgroups with the highest absolute benefit may be a viable approach to ensure sustainable access,” the authors of the review wrote.

SOURCE:

The systematic review was led by Rashidul Alam Mahumud, PhD, MCncrSc, MPH, MSc, Health Economics and Health Technology Assessment Unit, National Health and Medical Research Council Clinical Trials Centre, The University of Sydney in Camperdown, Australia. It was published online on January 22 in JAMA Oncology.

LIMITATIONS:

The methodologic heterogeneity across studies presents a significant limitation, with variations in time horizons, discounting methods, survival data extrapolation, and health utility measurements affecting result comparability. Geographic distribution primarily focused on high-income countries, limiting generalizability to low- and middle-income settings. Few evaluations incorporated adaptive pricing schemes or managed entry agreements that increasingly influence clinical reimbursement decisions.

DISCLOSURES:

Mahumud had full access to all study data and takes responsibility for data integrity and analysis accuracy. The authors reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

A systematic review of 69 economic evaluations revealed that adjuvant immunotherapy was cost-effective in 58% of studies, with higher Quality-Adjusted Life-Year gains reported in 91% of cases. Cost-effectiveness varied significantly by cancer type, treatment strategy, and healthcare system context, with industry-funded studies more likely to report favorable outcomes.

METHODOLOGY:

• Multiple phase 3 trials have shown improved survival and reduced recurrence with adjuvant immunotherapy in various cancers. But the high cost of immunotherapy treatments, often exceeding $100,000 per patient, has raised questions about their economic value and affordability across different healthcare systems.
• Researchers conducted a systematic review of 69 economic evaluations published between January 2015 and January 2025, focusing on adjuvant immunotherapy across various cancer types.
• Analysis included studies from PubMed, Embase, Scopus, Web of Science, and Cochrane Library, with most evaluations conducted in the US (26 studies) and China (20 studies).
• Quality assessment utilized the Criteria for Health Economic Quality Evaluation tool, evaluating 48 attributes across methodologic and reporting quality dimensions.
• Markov modeling dominated the analytical approach (46 studies [67%]), with EuroQol Five-Dimensions being the most commonly used health utility instrument (56 studies [81%]).

TAKEAWAY:

• Of 69 studies analyzed, 58% concluded that adjuvant immunotherapy was cost-effective, with stronger evidence in non-small cell lung cancer and melanoma, particularly in early-stage and high-risk populations.
• Industry-funded studies more frequently reported cost-effective outcomes (17 of 20 studies [85%]) than nonindustry funded studies (13 of 28 studies [46%]).
• Higher Quality-Adjusted Life-Year/Life-Year gains were consistently reported in the adjuvant immunotherapy group (63 studies [91%]), especially for non-small cell lung cancer and combination regimens.
• Cost-effectiveness results varied significantly by cancer type, model assumptions, drug pricing, funding organizations, and country-specific willingness-to-pay thresholds.

IN PRACTICE:

“From a policy standpoint, the findings of this systematic review support the use of structured, context-specific health technology assessment frameworks to evaluate adjuvant immunotherapies. For health systems under financial constraints, prioritizing subgroups with the highest absolute benefit may be a viable approach to ensure sustainable access,” the authors of the review wrote.

SOURCE:

The systematic review was led by Rashidul Alam Mahumud, PhD, MCncrSc, MPH, MSc, Health Economics and Health Technology Assessment Unit, National Health and Medical Research Council Clinical Trials Centre, The University of Sydney in Camperdown, Australia. It was published online on January 22 in JAMA Oncology.

LIMITATIONS:

The methodologic heterogeneity across studies presents a significant limitation, with variations in time horizons, discounting methods, survival data extrapolation, and health utility measurements affecting result comparability. Geographic distribution primarily focused on high-income countries, limiting generalizability to low- and middle-income settings. Few evaluations incorporated adaptive pricing schemes or managed entry agreements that increasingly influence clinical reimbursement decisions.

DISCLOSURES:

Mahumud had full access to all study data and takes responsibility for data integrity and analysis accuracy. The authors reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.