Cancer

Patients with advanced cancer treated with immune checkpoint inhibitors appear to have a survival benefit if they receive influenza vaccination, a new retrospective analysis found. The results also suggest no increase in the risk for immune-related adverse events (IRAEs) in these patients and that the improvement in survival outcomes may be stronger among those with cutaneous malignant melanoma.

“Our findings align with a growing body of evidence, mainly from retrospective studies, that suggest a potential association between influenza vaccination during immune checkpoint inhibitor treatment and improved survival among patients with cancer,” wrote senior author Antonis Valachis, MD, PhD, and colleagues in an article published in JCO Clinical Practice on February 9. “An additional clinically relevant observation is that the association between influenza vaccination and survival may vary by tumor type.”

The new research supports “current recommendations to offer influenza vaccination to all patients undergoing cancer therapy, including those receiving the drugs,” Valachis, of the Department of Oncology, Örebro University in Örebro, Sweden, and his coauthors wrote.

“What we observed is that influenza vaccination is safe for patients under immunotherapy treatment,” Valachis told Medscape Medical News. But “whether influenza vaccination can be used to boost immunotherapy effectiveness should be tested in a study with a different design,” such as a prospective interventional trial.

Discussing potential explanations for why influenza vaccination could affect immunotherapy outcomes without affecting rates of IRAEs, Valachis said that this “cannot be answered within the constraints of our study design, since all patients were treated with immunotherapy.”

It may nevertheless be hypothesized that “immune activation triggered by vaccination preferentially stimulates immune mechanisms that enhance immunotherapy efficacy, while sparing those that contribute to IRAEs.”

Steady Was 'Relatively Modestly Sized'

Question marks were raised over the study itself and, as a result, its findings.

Justin Jee, MD, PhD, a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center, New York City, told Medscape Medical News that there are “a lot of challenges when looking at retrospective data.”

“The authors did a very reasonable job of trying to control for confounders and certain time dependent issues, like immortality bias,” he said. “That said, it’s a relatively modestly sized retrospective study for looking at something that has enormous potential for confounding bias that really can’t be captured with any standard statistical method.”

Jee pointed to factors such as providers potentially being more likely to refer people for vaccination if they’re healthier “vs if the patient is in hospice care,” or individuals simply not getting vaccinated because it is not uppermost in their mind.

“Those things are very, very difficult to control for.”

Jee also said he believes the benefit with influenza vaccination being stronger in cutaneous malignant melanoma could be a study artifact, while the lack of difference in rates of IRAEs could be the result of selection bias, but “it’s just impossible to say with a study like this.”

“I’ve seen several studies looking at both COVID and flu vaccines and whether or not they improve immune checkpoint blockade efficacy,” he added, explaining that “some of them say COVID vaccine good, flu vaccine not as good; others say both flu and COVID vaccines good; others say flu vaccine good, COVID vaccine not as good.”

All Patients With Cancer Should Be Vaccinated

What is clear is that “patients with cancer are [at] especially high risk of developing complications from viral illnesses, including flu, including COVID, and vaccines are a very important part of reducing morbidity, mortality, and spread,” Jee said. The “big picture” is that everyone should get the influenza vaccine, especially patients with cancer, “so in that sense I agree with that part of the conclusion of the paper” and that’s “an important message.”

Mini Kamboj, MD, chief medical epidemiologist at Memorial Sloan Kettering Cancer Center, agreed, saying that the results are “consistent with other research showing that vaccines are safe and beneficial for patients on checkpoint inhibitors.”

“While vaccinated patients with melanoma showed the greatest survival benefit, the authors note small sample size and unrecognized differences between the groups as a potential explanation for their findings. This does not change vaccine recommendations as evidence already supports flu vaccine safety and effectiveness in people with lung cancer on checkpoint inhibitors.”

Nearly 600 Patients With Advanced Cancer

The researchers performed a retrospective cohort study of patients from three regions in Sweden who had advanced solid tumors and were treated with PD-1 or PD-L1 inhibitor monotherapy, or PD-1 combination therapy with a cytotoxic T-lymphocyte-associated protein 4 inhibitor, between January 1, 2016, until December 31, 2021. Treatment was given either routinely or as part of a clinical trial.

Electronic medical records were examined to gather data on a range of variables, including age at diagnosis, sex, Charlson Comorbidity Index, type of cancer, primary treatment at diagnosis, number of previous lines of treatment, best treatment response, IRAEs, influenza vaccination status, and date and cause of death.

In all, 587 patients were treated with immune checkpoint inhibition over the study period. They had a median age of 66 years, and 58.1% were men. The most common malignancies were nonsmall cell lung cancer (NSCLC), cutaneous malignant melanoma (32.5%), and renal cell carcinoma (14.7%).

The most commonly used immune checkpoint inhibitor was nivolumab, which was administered to 47.9% of patients, followed by pembrolizumab (34.6%), atezolizumab (9.4%), and nivolumab plus ipilimumab (6.8%).

Only Patients With Malignant Melanoma Benefit

Over the study period, 17.7% of patients underwent influenza vaccination, at a median time between initiation of immune checkpoint inhibition and vaccination of 2 months. Ninety per cent of patients received the vaccine within 9 months of starting treatment.

Time-dependent Cox regression analysis revealed that real-world progression-free survival (rwPFS) was significantly longer with vaccinated patients than unvaccinated patients at a hazard ratio of 0.59 (95% CI, 0.44-0.79), as was overall survival, at a hazard ratio of 0.56 (95% CI, 0.42-0.75).

There was no significant difference in rwPFS and overall survival between vaccinated and unvaccinated patients among those with NSCLC, but significant differences were seen in those with cutaneous malignant melanoma, at hazard ratios of 0.58 (95% CI, 0.36-0.96) and 0.58 (95% CI, 0.36-0.96), respectively.

Restricting the analysis to immune checkpoint inhibitor monotherapy indicated that vaccinated patients had significantly longer rwPFS and overall survival than unvaccinated patients, at hazard ratios of 0.58 (95% CI, 0.43-0.79) and 0.50 (95% CI, 0.38-0.76), respectively.

Finally, the team found that there were no significant differences in the rates of any grade IRAEs between vaccinated and unvaccinated patients, at 48.4% vs 51.2% (P = .455), or in rates of multiple IRAEs, at 15.1% vs 19.2% (P = .297). The therapeutic management and outcomes of IRAEs were also comparable.

No funding or relevant financial relationships were declared.

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

Patients with advanced cancer treated with immune checkpoint inhibitors appear to have a survival benefit if they receive influenza vaccination, a new retrospective analysis found. The results also suggest no increase in the risk for immune-related adverse events (IRAEs) in these patients and that the improvement in survival outcomes may be stronger among those with cutaneous malignant melanoma.

“Our findings align with a growing body of evidence, mainly from retrospective studies, that suggest a potential association between influenza vaccination during immune checkpoint inhibitor treatment and improved survival among patients with cancer,” wrote senior author Antonis Valachis, MD, PhD, and colleagues in an article published in JCO Clinical Practice on February 9. “An additional clinically relevant observation is that the association between influenza vaccination and survival may vary by tumor type.”

The new research supports “current recommendations to offer influenza vaccination to all patients undergoing cancer therapy, including those receiving the drugs,” Valachis, of the Department of Oncology, Örebro University in Örebro, Sweden, and his coauthors wrote.

“What we observed is that influenza vaccination is safe for patients under immunotherapy treatment,” Valachis told Medscape Medical News. But “whether influenza vaccination can be used to boost immunotherapy effectiveness should be tested in a study with a different design,” such as a prospective interventional trial.

Discussing potential explanations for why influenza vaccination could affect immunotherapy outcomes without affecting rates of IRAEs, Valachis said that this “cannot be answered within the constraints of our study design, since all patients were treated with immunotherapy.”

It may nevertheless be hypothesized that “immune activation triggered by vaccination preferentially stimulates immune mechanisms that enhance immunotherapy efficacy, while sparing those that contribute to IRAEs.”

Steady Was 'Relatively Modestly Sized'

Question marks were raised over the study itself and, as a result, its findings.

Justin Jee, MD, PhD, a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center, New York City, told Medscape Medical News that there are “a lot of challenges when looking at retrospective data.”

“The authors did a very reasonable job of trying to control for confounders and certain time dependent issues, like immortality bias,” he said. “That said, it’s a relatively modestly sized retrospective study for looking at something that has enormous potential for confounding bias that really can’t be captured with any standard statistical method.”

Jee pointed to factors such as providers potentially being more likely to refer people for vaccination if they’re healthier “vs if the patient is in hospice care,” or individuals simply not getting vaccinated because it is not uppermost in their mind.

“Those things are very, very difficult to control for.”

Jee also said he believes the benefit with influenza vaccination being stronger in cutaneous malignant melanoma could be a study artifact, while the lack of difference in rates of IRAEs could be the result of selection bias, but “it’s just impossible to say with a study like this.”

“I’ve seen several studies looking at both COVID and flu vaccines and whether or not they improve immune checkpoint blockade efficacy,” he added, explaining that “some of them say COVID vaccine good, flu vaccine not as good; others say both flu and COVID vaccines good; others say flu vaccine good, COVID vaccine not as good.”

All Patients With Cancer Should Be Vaccinated

What is clear is that “patients with cancer are [at] especially high risk of developing complications from viral illnesses, including flu, including COVID, and vaccines are a very important part of reducing morbidity, mortality, and spread,” Jee said. The “big picture” is that everyone should get the influenza vaccine, especially patients with cancer, “so in that sense I agree with that part of the conclusion of the paper” and that’s “an important message.”

Mini Kamboj, MD, chief medical epidemiologist at Memorial Sloan Kettering Cancer Center, agreed, saying that the results are “consistent with other research showing that vaccines are safe and beneficial for patients on checkpoint inhibitors.”

“While vaccinated patients with melanoma showed the greatest survival benefit, the authors note small sample size and unrecognized differences between the groups as a potential explanation for their findings. This does not change vaccine recommendations as evidence already supports flu vaccine safety and effectiveness in people with lung cancer on checkpoint inhibitors.”

Nearly 600 Patients With Advanced Cancer

The researchers performed a retrospective cohort study of patients from three regions in Sweden who had advanced solid tumors and were treated with PD-1 or PD-L1 inhibitor monotherapy, or PD-1 combination therapy with a cytotoxic T-lymphocyte-associated protein 4 inhibitor, between January 1, 2016, until December 31, 2021. Treatment was given either routinely or as part of a clinical trial.

Electronic medical records were examined to gather data on a range of variables, including age at diagnosis, sex, Charlson Comorbidity Index, type of cancer, primary treatment at diagnosis, number of previous lines of treatment, best treatment response, IRAEs, influenza vaccination status, and date and cause of death.

In all, 587 patients were treated with immune checkpoint inhibition over the study period. They had a median age of 66 years, and 58.1% were men. The most common malignancies were nonsmall cell lung cancer (NSCLC), cutaneous malignant melanoma (32.5%), and renal cell carcinoma (14.7%).

The most commonly used immune checkpoint inhibitor was nivolumab, which was administered to 47.9% of patients, followed by pembrolizumab (34.6%), atezolizumab (9.4%), and nivolumab plus ipilimumab (6.8%).

Only Patients With Malignant Melanoma Benefit

Over the study period, 17.7% of patients underwent influenza vaccination, at a median time between initiation of immune checkpoint inhibition and vaccination of 2 months. Ninety per cent of patients received the vaccine within 9 months of starting treatment.

Time-dependent Cox regression analysis revealed that real-world progression-free survival (rwPFS) was significantly longer with vaccinated patients than unvaccinated patients at a hazard ratio of 0.59 (95% CI, 0.44-0.79), as was overall survival, at a hazard ratio of 0.56 (95% CI, 0.42-0.75).

There was no significant difference in rwPFS and overall survival between vaccinated and unvaccinated patients among those with NSCLC, but significant differences were seen in those with cutaneous malignant melanoma, at hazard ratios of 0.58 (95% CI, 0.36-0.96) and 0.58 (95% CI, 0.36-0.96), respectively.

Restricting the analysis to immune checkpoint inhibitor monotherapy indicated that vaccinated patients had significantly longer rwPFS and overall survival than unvaccinated patients, at hazard ratios of 0.58 (95% CI, 0.43-0.79) and 0.50 (95% CI, 0.38-0.76), respectively.

Finally, the team found that there were no significant differences in the rates of any grade IRAEs between vaccinated and unvaccinated patients, at 48.4% vs 51.2% (P = .455), or in rates of multiple IRAEs, at 15.1% vs 19.2% (P = .297). The therapeutic management and outcomes of IRAEs were also comparable.

No funding or relevant financial relationships were declared.

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

Patients with advanced cancer treated with immune checkpoint inhibitors appear to have a survival benefit if they receive influenza vaccination, a new retrospective analysis found. The results also suggest no increase in the risk for immune-related adverse events (IRAEs) in these patients and that the improvement in survival outcomes may be stronger among those with cutaneous malignant melanoma.

“Our findings align with a growing body of evidence, mainly from retrospective studies, that suggest a potential association between influenza vaccination during immune checkpoint inhibitor treatment and improved survival among patients with cancer,” wrote senior author Antonis Valachis, MD, PhD, and colleagues in an article published in JCO Clinical Practice on February 9. “An additional clinically relevant observation is that the association between influenza vaccination and survival may vary by tumor type.”

The new research supports “current recommendations to offer influenza vaccination to all patients undergoing cancer therapy, including those receiving the drugs,” Valachis, of the Department of Oncology, Örebro University in Örebro, Sweden, and his coauthors wrote.

“What we observed is that influenza vaccination is safe for patients under immunotherapy treatment,” Valachis told Medscape Medical News. But “whether influenza vaccination can be used to boost immunotherapy effectiveness should be tested in a study with a different design,” such as a prospective interventional trial.

Discussing potential explanations for why influenza vaccination could affect immunotherapy outcomes without affecting rates of IRAEs, Valachis said that this “cannot be answered within the constraints of our study design, since all patients were treated with immunotherapy.”

It may nevertheless be hypothesized that “immune activation triggered by vaccination preferentially stimulates immune mechanisms that enhance immunotherapy efficacy, while sparing those that contribute to IRAEs.”

Steady Was 'Relatively Modestly Sized'

Question marks were raised over the study itself and, as a result, its findings.

Justin Jee, MD, PhD, a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center, New York City, told Medscape Medical News that there are “a lot of challenges when looking at retrospective data.”

“The authors did a very reasonable job of trying to control for confounders and certain time dependent issues, like immortality bias,” he said. “That said, it’s a relatively modestly sized retrospective study for looking at something that has enormous potential for confounding bias that really can’t be captured with any standard statistical method.”

Jee pointed to factors such as providers potentially being more likely to refer people for vaccination if they’re healthier “vs if the patient is in hospice care,” or individuals simply not getting vaccinated because it is not uppermost in their mind.

“Those things are very, very difficult to control for.”

Jee also said he believes the benefit with influenza vaccination being stronger in cutaneous malignant melanoma could be a study artifact, while the lack of difference in rates of IRAEs could be the result of selection bias, but “it’s just impossible to say with a study like this.”

“I’ve seen several studies looking at both COVID and flu vaccines and whether or not they improve immune checkpoint blockade efficacy,” he added, explaining that “some of them say COVID vaccine good, flu vaccine not as good; others say both flu and COVID vaccines good; others say flu vaccine good, COVID vaccine not as good.”

All Patients With Cancer Should Be Vaccinated

What is clear is that “patients with cancer are [at] especially high risk of developing complications from viral illnesses, including flu, including COVID, and vaccines are a very important part of reducing morbidity, mortality, and spread,” Jee said. The “big picture” is that everyone should get the influenza vaccine, especially patients with cancer, “so in that sense I agree with that part of the conclusion of the paper” and that’s “an important message.”

Mini Kamboj, MD, chief medical epidemiologist at Memorial Sloan Kettering Cancer Center, agreed, saying that the results are “consistent with other research showing that vaccines are safe and beneficial for patients on checkpoint inhibitors.”

“While vaccinated patients with melanoma showed the greatest survival benefit, the authors note small sample size and unrecognized differences between the groups as a potential explanation for their findings. This does not change vaccine recommendations as evidence already supports flu vaccine safety and effectiveness in people with lung cancer on checkpoint inhibitors.”

Nearly 600 Patients With Advanced Cancer

The researchers performed a retrospective cohort study of patients from three regions in Sweden who had advanced solid tumors and were treated with PD-1 or PD-L1 inhibitor monotherapy, or PD-1 combination therapy with a cytotoxic T-lymphocyte-associated protein 4 inhibitor, between January 1, 2016, until December 31, 2021. Treatment was given either routinely or as part of a clinical trial.

Electronic medical records were examined to gather data on a range of variables, including age at diagnosis, sex, Charlson Comorbidity Index, type of cancer, primary treatment at diagnosis, number of previous lines of treatment, best treatment response, IRAEs, influenza vaccination status, and date and cause of death.

In all, 587 patients were treated with immune checkpoint inhibition over the study period. They had a median age of 66 years, and 58.1% were men. The most common malignancies were nonsmall cell lung cancer (NSCLC), cutaneous malignant melanoma (32.5%), and renal cell carcinoma (14.7%).

The most commonly used immune checkpoint inhibitor was nivolumab, which was administered to 47.9% of patients, followed by pembrolizumab (34.6%), atezolizumab (9.4%), and nivolumab plus ipilimumab (6.8%).

Only Patients With Malignant Melanoma Benefit

Over the study period, 17.7% of patients underwent influenza vaccination, at a median time between initiation of immune checkpoint inhibition and vaccination of 2 months. Ninety per cent of patients received the vaccine within 9 months of starting treatment.

Time-dependent Cox regression analysis revealed that real-world progression-free survival (rwPFS) was significantly longer with vaccinated patients than unvaccinated patients at a hazard ratio of 0.59 (95% CI, 0.44-0.79), as was overall survival, at a hazard ratio of 0.56 (95% CI, 0.42-0.75).

There was no significant difference in rwPFS and overall survival between vaccinated and unvaccinated patients among those with NSCLC, but significant differences were seen in those with cutaneous malignant melanoma, at hazard ratios of 0.58 (95% CI, 0.36-0.96) and 0.58 (95% CI, 0.36-0.96), respectively.

Restricting the analysis to immune checkpoint inhibitor monotherapy indicated that vaccinated patients had significantly longer rwPFS and overall survival than unvaccinated patients, at hazard ratios of 0.58 (95% CI, 0.43-0.79) and 0.50 (95% CI, 0.38-0.76), respectively.

Finally, the team found that there were no significant differences in the rates of any grade IRAEs between vaccinated and unvaccinated patients, at 48.4% vs 51.2% (P = .455), or in rates of multiple IRAEs, at 15.1% vs 19.2% (P = .297). The therapeutic management and outcomes of IRAEs were also comparable.

No funding or relevant financial relationships were declared.

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

One of the most common questions my patients ask is, “What diet can help me beat this cancer?” It is a profoundly important question that is worthy of our efforts to answer. In this brief essay, I will take a deep dive into this question in depth and explore the broader clinical and scientific themes it brings into play.

Low-Hanging Fruit: Nutrition Science

A cancer diagnosis can be a deeply disempowering experience. Although I have not lived with cancer myself, I have seen this play out repeatedly over the past 5 years in my role as an oncologist treating patients with hematologic malignancies.

Our diet is an important part of our personal identity, culturally and spiritually. If lifestyle changes, such as a modified diet or more exercise, can contribute to cancer treatment, it may help us regain a sense of control over our lives, one that cancer so often cruelly strips away. I hypothesize that, among other factors, this is why diet is so important to our patients.

Another factor is exposure to a compelling diet-cancer narrative. Nearly every day, a media headline appears claiming that eating a particular food, or drinking coffee, can either increase or decrease your risk for a certain disease.

These claims, however, are often based on studies of large observational datasets where individuals fill out surveys about their dietary habits and are subsequently assessed for disease outcomes. In these studies, people aren’t asked to eat a particular diet; instead, their dietary habits are analyzed by researchers who have endless permutations to explore. This, in a nutshell, is the field of nutritional epidemiology.

In my opinion, nutritional epidemiology represents the collision of the well-intentioned effort to answer clinically meaningful questions with the ease — and near-infinite permutations — of dietary questions that can be asked from an increasingly larger number of different datasets.

Now, factor in the never-ending appetite (pun intended) of journalism and the public’s desire for dietary studies, and you create the perfect storm of incentives that drives a flood of low-quality nutritional science. These studies are highly malleable to analytical choices and can essentially produce results consistent with your prior beliefs, regardless of the philosophical inclination you have (pro keto-diet, pro-vegan, etc.). I love quoting this study to my trainees that, depending on what variables are included and how the analysis is conducted, the same dataset could be used to show that red meat either increases, decreases, or has no effect on all-cause mortality. Unfortunately, much of the evidence base for diet in cancer comes from similarly confounded, low-quality studies.

Diet and Cancer

So, what do randomized trials show for diet and cancer?

The highest-quality evidence is generated from randomized controlled trials. One of their key advantages is the ability to control both measured and unmeasured confounders.

Unfortunately, the evidence supporting diet as an anticancer modality in randomized trials in patients with cancer is bleak. We did a systematic review of all randomized trials of dietary intervention ever done in patients with cancer. Most of the trials measured outcomes such as feasibility (often small pilot studies that measure variables such as weight changes or lab values). The trials that measure clinical endpoints, such as survival, were largely negative and demonstrated no meaningful effect of diet on outcomes. Take trials exploring whether a Mediterranean diet helps prevent breast cancer recurrence, or whether a diet rich in fruits and vegetables improves prostate cancer outcomes. Although these diets may offer benefits, these studies found that specific diets did not change the natural history of cancer.

Myeloma and Diet

In my specialty, multiple myeloma, I am thankful that some trials are beginning to shed light on whether diet influences cancer outcomes.

One study, which was recently published in Cancer Discovery, explored whether a high-fiber, plant-based diet could potentially slow or delay progression from myeloma precursor conditions toward full-blown multiple myeloma. The trial enrolled 23 participants, with the primary endpoints of dietary adherence and changes to BMI. Measures of progression to multiple myeloma were exploratory at best. Yet, the media coverage, as well as the majority of the discussion and results sections of this study manuscript, claimed that the diet changes can prevent progression to myeloma.

However, the study design and conclusions were flawed. The paper focused on two patients who had some improvement in disease trajectory, while descriptions of patients who had an increase in their bone marrow plasma cell percentage were relegated to the supplemental section.

As a primary investigator of a trial in smoldering myeloma where we use advanced imaging as an alternative to pharmacologic treatment, I frequently see myeloma markers fluctuate and often decrease. I attribute these changes to random variation, or possibly regression to the mean, rather than the effect of any intervention.

Future randomized studies by this group used primary endpoints of stool butyrate level and implement dietary interventions for a limited period— 2 weeks in one study and 12 weeks in another — to again assess the impact of a high-fiber, plant-based diet on progression to myeloma. Although there are no data yet, the limited timeframes in these studies severely limits generalizability for outcomes that would truly matter, such as cancer control and longevity. There is also no evidence that changes in stool butyrate levels influence patient outcomes.

High-quality science — whether it is evaluating diet or other interventions—requires high-quality data, effort, funding, and time. It is not impossible.

We can draw inspiration from the CHALLENGE trial. This large, randomized trial, which took over a decade to complete, assessed the benefit of a structured exercise program in the adjuvant setting for colon cancer. The endpoint of this study was disease-free survival, and the intervention was deployed over a much longer period: 3 years, as opposed to a 2-week intervention. This trial took years from inception to completion, but it yielded a conclusive result and will probably lead to more dedicated efforts to facilitate exercise programs for patients with cancer.

Our patients deserve the same effort as the CHALLENGE trial to answer their important dietary questions. Until such trials are completed, we must acknowledge, with humility, that despite the common sense and feel-good factor that many diets offer us, their impact on cancer remains uncertain.

Conversely, we must recognize that even if diet does not cure or alter the course of a certain cancer, it can still impact quality of life, treatment tolerance, and other supportive care outcomes, making it an important factor in patient care.

This is what I tell my patients that it is unlikely any one diet will change the trajectory of your cancer. Focus on eating healthy, and remember that most things in moderation are fine. Your diet remains an important risk factor and determinant for health outcomes beyond cancer. Eat what makes you happy. You are going through a tough time, and this is not the moment to impose stringent restrictions on yourself.

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

One of the most common questions my patients ask is, “What diet can help me beat this cancer?” It is a profoundly important question that is worthy of our efforts to answer. In this brief essay, I will take a deep dive into this question in depth and explore the broader clinical and scientific themes it brings into play.

Low-Hanging Fruit: Nutrition Science

A cancer diagnosis can be a deeply disempowering experience. Although I have not lived with cancer myself, I have seen this play out repeatedly over the past 5 years in my role as an oncologist treating patients with hematologic malignancies.

Our diet is an important part of our personal identity, culturally and spiritually. If lifestyle changes, such as a modified diet or more exercise, can contribute to cancer treatment, it may help us regain a sense of control over our lives, one that cancer so often cruelly strips away. I hypothesize that, among other factors, this is why diet is so important to our patients.

Another factor is exposure to a compelling diet-cancer narrative. Nearly every day, a media headline appears claiming that eating a particular food, or drinking coffee, can either increase or decrease your risk for a certain disease.

These claims, however, are often based on studies of large observational datasets where individuals fill out surveys about their dietary habits and are subsequently assessed for disease outcomes. In these studies, people aren’t asked to eat a particular diet; instead, their dietary habits are analyzed by researchers who have endless permutations to explore. This, in a nutshell, is the field of nutritional epidemiology.

In my opinion, nutritional epidemiology represents the collision of the well-intentioned effort to answer clinically meaningful questions with the ease — and near-infinite permutations — of dietary questions that can be asked from an increasingly larger number of different datasets.

Now, factor in the never-ending appetite (pun intended) of journalism and the public’s desire for dietary studies, and you create the perfect storm of incentives that drives a flood of low-quality nutritional science. These studies are highly malleable to analytical choices and can essentially produce results consistent with your prior beliefs, regardless of the philosophical inclination you have (pro keto-diet, pro-vegan, etc.). I love quoting this study to my trainees that, depending on what variables are included and how the analysis is conducted, the same dataset could be used to show that red meat either increases, decreases, or has no effect on all-cause mortality. Unfortunately, much of the evidence base for diet in cancer comes from similarly confounded, low-quality studies.

Diet and Cancer

So, what do randomized trials show for diet and cancer?

The highest-quality evidence is generated from randomized controlled trials. One of their key advantages is the ability to control both measured and unmeasured confounders.

Unfortunately, the evidence supporting diet as an anticancer modality in randomized trials in patients with cancer is bleak. We did a systematic review of all randomized trials of dietary intervention ever done in patients with cancer. Most of the trials measured outcomes such as feasibility (often small pilot studies that measure variables such as weight changes or lab values). The trials that measure clinical endpoints, such as survival, were largely negative and demonstrated no meaningful effect of diet on outcomes. Take trials exploring whether a Mediterranean diet helps prevent breast cancer recurrence, or whether a diet rich in fruits and vegetables improves prostate cancer outcomes. Although these diets may offer benefits, these studies found that specific diets did not change the natural history of cancer.

Myeloma and Diet

In my specialty, multiple myeloma, I am thankful that some trials are beginning to shed light on whether diet influences cancer outcomes.

One study, which was recently published in Cancer Discovery, explored whether a high-fiber, plant-based diet could potentially slow or delay progression from myeloma precursor conditions toward full-blown multiple myeloma. The trial enrolled 23 participants, with the primary endpoints of dietary adherence and changes to BMI. Measures of progression to multiple myeloma were exploratory at best. Yet, the media coverage, as well as the majority of the discussion and results sections of this study manuscript, claimed that the diet changes can prevent progression to myeloma.

However, the study design and conclusions were flawed. The paper focused on two patients who had some improvement in disease trajectory, while descriptions of patients who had an increase in their bone marrow plasma cell percentage were relegated to the supplemental section.

As a primary investigator of a trial in smoldering myeloma where we use advanced imaging as an alternative to pharmacologic treatment, I frequently see myeloma markers fluctuate and often decrease. I attribute these changes to random variation, or possibly regression to the mean, rather than the effect of any intervention.

Future randomized studies by this group used primary endpoints of stool butyrate level and implement dietary interventions for a limited period— 2 weeks in one study and 12 weeks in another — to again assess the impact of a high-fiber, plant-based diet on progression to myeloma. Although there are no data yet, the limited timeframes in these studies severely limits generalizability for outcomes that would truly matter, such as cancer control and longevity. There is also no evidence that changes in stool butyrate levels influence patient outcomes.

High-quality science — whether it is evaluating diet or other interventions—requires high-quality data, effort, funding, and time. It is not impossible.

We can draw inspiration from the CHALLENGE trial. This large, randomized trial, which took over a decade to complete, assessed the benefit of a structured exercise program in the adjuvant setting for colon cancer. The endpoint of this study was disease-free survival, and the intervention was deployed over a much longer period: 3 years, as opposed to a 2-week intervention. This trial took years from inception to completion, but it yielded a conclusive result and will probably lead to more dedicated efforts to facilitate exercise programs for patients with cancer.

Our patients deserve the same effort as the CHALLENGE trial to answer their important dietary questions. Until such trials are completed, we must acknowledge, with humility, that despite the common sense and feel-good factor that many diets offer us, their impact on cancer remains uncertain.

Conversely, we must recognize that even if diet does not cure or alter the course of a certain cancer, it can still impact quality of life, treatment tolerance, and other supportive care outcomes, making it an important factor in patient care.

This is what I tell my patients that it is unlikely any one diet will change the trajectory of your cancer. Focus on eating healthy, and remember that most things in moderation are fine. Your diet remains an important risk factor and determinant for health outcomes beyond cancer. Eat what makes you happy. You are going through a tough time, and this is not the moment to impose stringent restrictions on yourself.

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

One of the most common questions my patients ask is, “What diet can help me beat this cancer?” It is a profoundly important question that is worthy of our efforts to answer. In this brief essay, I will take a deep dive into this question in depth and explore the broader clinical and scientific themes it brings into play.

Low-Hanging Fruit: Nutrition Science

A cancer diagnosis can be a deeply disempowering experience. Although I have not lived with cancer myself, I have seen this play out repeatedly over the past 5 years in my role as an oncologist treating patients with hematologic malignancies.

Our diet is an important part of our personal identity, culturally and spiritually. If lifestyle changes, such as a modified diet or more exercise, can contribute to cancer treatment, it may help us regain a sense of control over our lives, one that cancer so often cruelly strips away. I hypothesize that, among other factors, this is why diet is so important to our patients.

Another factor is exposure to a compelling diet-cancer narrative. Nearly every day, a media headline appears claiming that eating a particular food, or drinking coffee, can either increase or decrease your risk for a certain disease.

These claims, however, are often based on studies of large observational datasets where individuals fill out surveys about their dietary habits and are subsequently assessed for disease outcomes. In these studies, people aren’t asked to eat a particular diet; instead, their dietary habits are analyzed by researchers who have endless permutations to explore. This, in a nutshell, is the field of nutritional epidemiology.

In my opinion, nutritional epidemiology represents the collision of the well-intentioned effort to answer clinically meaningful questions with the ease — and near-infinite permutations — of dietary questions that can be asked from an increasingly larger number of different datasets.

Now, factor in the never-ending appetite (pun intended) of journalism and the public’s desire for dietary studies, and you create the perfect storm of incentives that drives a flood of low-quality nutritional science. These studies are highly malleable to analytical choices and can essentially produce results consistent with your prior beliefs, regardless of the philosophical inclination you have (pro keto-diet, pro-vegan, etc.). I love quoting this study to my trainees that, depending on what variables are included and how the analysis is conducted, the same dataset could be used to show that red meat either increases, decreases, or has no effect on all-cause mortality. Unfortunately, much of the evidence base for diet in cancer comes from similarly confounded, low-quality studies.

Diet and Cancer

So, what do randomized trials show for diet and cancer?

The highest-quality evidence is generated from randomized controlled trials. One of their key advantages is the ability to control both measured and unmeasured confounders.

Unfortunately, the evidence supporting diet as an anticancer modality in randomized trials in patients with cancer is bleak. We did a systematic review of all randomized trials of dietary intervention ever done in patients with cancer. Most of the trials measured outcomes such as feasibility (often small pilot studies that measure variables such as weight changes or lab values). The trials that measure clinical endpoints, such as survival, were largely negative and demonstrated no meaningful effect of diet on outcomes. Take trials exploring whether a Mediterranean diet helps prevent breast cancer recurrence, or whether a diet rich in fruits and vegetables improves prostate cancer outcomes. Although these diets may offer benefits, these studies found that specific diets did not change the natural history of cancer.

Myeloma and Diet

In my specialty, multiple myeloma, I am thankful that some trials are beginning to shed light on whether diet influences cancer outcomes.

One study, which was recently published in Cancer Discovery, explored whether a high-fiber, plant-based diet could potentially slow or delay progression from myeloma precursor conditions toward full-blown multiple myeloma. The trial enrolled 23 participants, with the primary endpoints of dietary adherence and changes to BMI. Measures of progression to multiple myeloma were exploratory at best. Yet, the media coverage, as well as the majority of the discussion and results sections of this study manuscript, claimed that the diet changes can prevent progression to myeloma.

However, the study design and conclusions were flawed. The paper focused on two patients who had some improvement in disease trajectory, while descriptions of patients who had an increase in their bone marrow plasma cell percentage were relegated to the supplemental section.

As a primary investigator of a trial in smoldering myeloma where we use advanced imaging as an alternative to pharmacologic treatment, I frequently see myeloma markers fluctuate and often decrease. I attribute these changes to random variation, or possibly regression to the mean, rather than the effect of any intervention.

Future randomized studies by this group used primary endpoints of stool butyrate level and implement dietary interventions for a limited period— 2 weeks in one study and 12 weeks in another — to again assess the impact of a high-fiber, plant-based diet on progression to myeloma. Although there are no data yet, the limited timeframes in these studies severely limits generalizability for outcomes that would truly matter, such as cancer control and longevity. There is also no evidence that changes in stool butyrate levels influence patient outcomes.

High-quality science — whether it is evaluating diet or other interventions—requires high-quality data, effort, funding, and time. It is not impossible.

We can draw inspiration from the CHALLENGE trial. This large, randomized trial, which took over a decade to complete, assessed the benefit of a structured exercise program in the adjuvant setting for colon cancer. The endpoint of this study was disease-free survival, and the intervention was deployed over a much longer period: 3 years, as opposed to a 2-week intervention. This trial took years from inception to completion, but it yielded a conclusive result and will probably lead to more dedicated efforts to facilitate exercise programs for patients with cancer.

Our patients deserve the same effort as the CHALLENGE trial to answer their important dietary questions. Until such trials are completed, we must acknowledge, with humility, that despite the common sense and feel-good factor that many diets offer us, their impact on cancer remains uncertain.

Conversely, we must recognize that even if diet does not cure or alter the course of a certain cancer, it can still impact quality of life, treatment tolerance, and other supportive care outcomes, making it an important factor in patient care.

This is what I tell my patients that it is unlikely any one diet will change the trajectory of your cancer. Focus on eating healthy, and remember that most things in moderation are fine. Your diet remains an important risk factor and determinant for health outcomes beyond cancer. Eat what makes you happy. You are going through a tough time, and this is not the moment to impose stringent restrictions on yourself.

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

The FDA has granted traditional approval to encorafenib (Braftovi, Pfizer) in combination with cetuximab (Erbitux, Eli Lilly) and fluorouracil-based chemotherapy for treatment of adults with metastatic colorectal cancer with a BRAF V600E mutation, as detected by an FDA-authorized test.

Encorafenib received accelerated approval for use with cetuximab plus mFOLFOX6 in this patient population in 2024, based on results from the BREAKWATER trial showing improved objective response rates. The conversion to full approval is supported by progression-free and overall survival outcomes.

As reported previously by Medscape Medical News, the combination of encorafenib/cetuximab/mFOLFOX6 doubled median overall survival compared with standard chemotherapy with or without bevacizumab. At a median follow-up of 22 months, overall survival was 30 months with the encorafenib regimen vs 15 months with standard chemotherapy (hazard ratio [HR], 0.49; P < .0001).

At median follow up of 16.8 months, median progression-free survival was 12.8 in the encorafenib group vs 7.1 months in the standard chemotherapy group (HR, 0.53; P < .0001).

The survival results are “unprecedented” and “practice changing” for these patients, who historically have a poor prognosis, lead investigator Elena Élez, MD, PhD, of Vall d’Hebron University Hospital in Barcelona, Spain, said in presenting the findings at the American Society of Clinical Oncology (ASCO) 2025 annual meeting.

The results were simultaneously published in The New England Journal of Medicine.

Speaking at the ASCO meeting, study discussant Andrea Sartore-Bianchi, MD, of the University of Milan, Italy, called the results “striking” and said the encorafenib combination should be considered the first-line standard of care.

As for safety, the rate of treatment-related grade 3/4 adverse events in the trial was 76% with encorafenib vs 59% with standard chemotherapy. Patients receiving encorafenib also had higher rates of anemia, arthralgia, rash, and pyrexia, but there was no substantial increase in treatment discontinuation.

The recommended encorafenib dose is 300 mg (four 75 mg capsules) once daily, in combination with cetuximab and mFOLFOX6 or in combination with cetuximab and FOLFIRI until disease progression or unacceptable toxicity, the FDA said in its approval announcement.

Prescribing information includes warnings and precautions for new primary malignancies (cutaneous and noncutaneous), tumor promotion in BRAF-wild-type tumors, cardiomyopathy, hepatotoxicity, hemorrhage, uveitis, QT prolongation, and embryo-fetal toxicity.

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

The FDA has granted traditional approval to encorafenib (Braftovi, Pfizer) in combination with cetuximab (Erbitux, Eli Lilly) and fluorouracil-based chemotherapy for treatment of adults with metastatic colorectal cancer with a BRAF V600E mutation, as detected by an FDA-authorized test.

Encorafenib received accelerated approval for use with cetuximab plus mFOLFOX6 in this patient population in 2024, based on results from the BREAKWATER trial showing improved objective response rates. The conversion to full approval is supported by progression-free and overall survival outcomes.

As reported previously by Medscape Medical News, the combination of encorafenib/cetuximab/mFOLFOX6 doubled median overall survival compared with standard chemotherapy with or without bevacizumab. At a median follow-up of 22 months, overall survival was 30 months with the encorafenib regimen vs 15 months with standard chemotherapy (hazard ratio [HR], 0.49; P < .0001).

At median follow up of 16.8 months, median progression-free survival was 12.8 in the encorafenib group vs 7.1 months in the standard chemotherapy group (HR, 0.53; P < .0001).

The survival results are “unprecedented” and “practice changing” for these patients, who historically have a poor prognosis, lead investigator Elena Élez, MD, PhD, of Vall d’Hebron University Hospital in Barcelona, Spain, said in presenting the findings at the American Society of Clinical Oncology (ASCO) 2025 annual meeting.

The results were simultaneously published in The New England Journal of Medicine.

Speaking at the ASCO meeting, study discussant Andrea Sartore-Bianchi, MD, of the University of Milan, Italy, called the results “striking” and said the encorafenib combination should be considered the first-line standard of care.

As for safety, the rate of treatment-related grade 3/4 adverse events in the trial was 76% with encorafenib vs 59% with standard chemotherapy. Patients receiving encorafenib also had higher rates of anemia, arthralgia, rash, and pyrexia, but there was no substantial increase in treatment discontinuation.

The recommended encorafenib dose is 300 mg (four 75 mg capsules) once daily, in combination with cetuximab and mFOLFOX6 or in combination with cetuximab and FOLFIRI until disease progression or unacceptable toxicity, the FDA said in its approval announcement.

Prescribing information includes warnings and precautions for new primary malignancies (cutaneous and noncutaneous), tumor promotion in BRAF-wild-type tumors, cardiomyopathy, hepatotoxicity, hemorrhage, uveitis, QT prolongation, and embryo-fetal toxicity.

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

The FDA has granted traditional approval to encorafenib (Braftovi, Pfizer) in combination with cetuximab (Erbitux, Eli Lilly) and fluorouracil-based chemotherapy for treatment of adults with metastatic colorectal cancer with a BRAF V600E mutation, as detected by an FDA-authorized test.

Encorafenib received accelerated approval for use with cetuximab plus mFOLFOX6 in this patient population in 2024, based on results from the BREAKWATER trial showing improved objective response rates. The conversion to full approval is supported by progression-free and overall survival outcomes.

As reported previously by Medscape Medical News, the combination of encorafenib/cetuximab/mFOLFOX6 doubled median overall survival compared with standard chemotherapy with or without bevacizumab. At a median follow-up of 22 months, overall survival was 30 months with the encorafenib regimen vs 15 months with standard chemotherapy (hazard ratio [HR], 0.49; P < .0001).

At median follow up of 16.8 months, median progression-free survival was 12.8 in the encorafenib group vs 7.1 months in the standard chemotherapy group (HR, 0.53; P < .0001).

The survival results are “unprecedented” and “practice changing” for these patients, who historically have a poor prognosis, lead investigator Elena Élez, MD, PhD, of Vall d’Hebron University Hospital in Barcelona, Spain, said in presenting the findings at the American Society of Clinical Oncology (ASCO) 2025 annual meeting.

The results were simultaneously published in The New England Journal of Medicine.

Speaking at the ASCO meeting, study discussant Andrea Sartore-Bianchi, MD, of the University of Milan, Italy, called the results “striking” and said the encorafenib combination should be considered the first-line standard of care.

As for safety, the rate of treatment-related grade 3/4 adverse events in the trial was 76% with encorafenib vs 59% with standard chemotherapy. Patients receiving encorafenib also had higher rates of anemia, arthralgia, rash, and pyrexia, but there was no substantial increase in treatment discontinuation.

The recommended encorafenib dose is 300 mg (four 75 mg capsules) once daily, in combination with cetuximab and mFOLFOX6 or in combination with cetuximab and FOLFIRI until disease progression or unacceptable toxicity, the FDA said in its approval announcement.

Prescribing information includes warnings and precautions for new primary malignancies (cutaneous and noncutaneous), tumor promotion in BRAF-wild-type tumors, cardiomyopathy, hepatotoxicity, hemorrhage, uveitis, QT prolongation, and embryo-fetal toxicity.

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

TOPLINE:

In patients with 5-20 brain metastases, stereotactic radiation improved symptoms and reduced interference with daily functioning compared to hippocampal-avoidance whole brain radiation. The weighted composite MD Anderson Symptom Inventory-Brain Tumor score changed from 2.69 to 2.37 with stereotactic radiation compared with 2.29 to 3.03 with hippocampal-avoidance whole brain radiation.

METHODOLOGY:

• Randomized trials have shown stereotactic radiation preserves neurocognitive function and patient-reported outcomes compared with whole brain radiation in patients with four or less brain metastases. For patients with more than four brain metastases, published randomized comparisons of stereotactic radiation vs whole brain radiation were lacking prior to this study.
• Researchers conducted a phase 3, open-label, randomized clinical trial at four US-based centers, enrolling 196 patients between April 2017 and May 2024, with final follow-up in March 2025.
• Participants included patients with 5-20 brain metastases and no prior brain-directed radiation, with a median of 14 brain metastases per patient and 25% having undergone prior neurosurgical resection.
• The primary outcome was the mean weighted patient-reported symptom severity and interference score change over 6 months. The researchers used the MD Anderson Symptom Inventory-Brain Tumor instrument, with scores ranging from 0-10 and change range of -10 to 10, to measure outcomes.
• Stereotactic radiation was delivered in either 1 day (20 Gy) or five daily fractions (30 Gy, or 25 Gy for surgically removed tumors), while hippocampal-avoidance whole brain radiation was administered as 30 Gy in 10 daily fractions with memantine.

TAKEAWAY:

• Primary outcome analysis showed that stereotactic radiation was linked to a change in the weighted composite MD Anderson Symptom Inventory-Brain Tumor score of 2.69 to 2.37 (mean change, -0.32) compared with 2.29 to 3.03 (mean change, 0.74) with hippocampal-avoidance whole brain radiation (mean difference, -1.06; 95% CI, -1.54 to -0.58; P < .001).
• Functional independence via the Barthel Index was better in the stereotactic radiation group at 4 months (mean difference, 6.79; 95% CI, 1.19-12.38; P = .02) and 12 months (mean difference, 7.92; 95% CI, 1.34-14.49; P = .02).
• New brain metastases were more frequent with stereotactic radiation (1-year cumulative incidence, 45.4% vs 24.2%; P = .003), while local recurrence was lower (3.2% vs 39.5%; P < .001).
• Grade 3-5 adverse events occurred in 12% of stereotactic radiation patients vs 13% in the hippocampal-avoidance whole brain radiation group, with fatigue being most common (28% vs 44%).

IN PRACTICE:

“While [the trial] clearly demonstrates that patients with 5-20 brain metastases have improved symptom burden and lowered interference with daily functioning, there are questions that remain for stereotactic radiosurgery in this population. Patients receiving stereotactic radiosurgery for brain metastases have a higher need for future salvage procedures, and this rate of salvage procedures is higher for patients with an increased number of brain metastases at diagnosis… Moreover, it has been shown that the upfront decision between stereotactic radiosurgery and whole brain radiotherapy is the single decision that contributes most to the cost of care of a patient with brain metastases,” said Michael Chan, MD, in an accompanying editorial published in JAMA.

SOURCE:

The study was led by Ayal A. Aizer, MD, MHS, Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston. It was published online on February 19 in JAMA.

LIMITATIONS:

According to the authors, the study was not blinded, and the primary outcome was subjective. High mortality limited long-term data collection, reducing precision and biasing outcomes toward survivors. Additionally, randomization was not stratified by treating center, allowing possible unmeasured imbalances. The minimal clinically important difference had not been defined for many study outcome measures.

DISCLOSURES:

The trial was supported by Varian, a Siemens Healthineers Company. Aizer disclosed receiving grants from NH TherAguix Research outside the submitted work. 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:

In patients with 5-20 brain metastases, stereotactic radiation improved symptoms and reduced interference with daily functioning compared to hippocampal-avoidance whole brain radiation. The weighted composite MD Anderson Symptom Inventory-Brain Tumor score changed from 2.69 to 2.37 with stereotactic radiation compared with 2.29 to 3.03 with hippocampal-avoidance whole brain radiation.

METHODOLOGY:

• Randomized trials have shown stereotactic radiation preserves neurocognitive function and patient-reported outcomes compared with whole brain radiation in patients with four or less brain metastases. For patients with more than four brain metastases, published randomized comparisons of stereotactic radiation vs whole brain radiation were lacking prior to this study.
• Researchers conducted a phase 3, open-label, randomized clinical trial at four US-based centers, enrolling 196 patients between April 2017 and May 2024, with final follow-up in March 2025.
• Participants included patients with 5-20 brain metastases and no prior brain-directed radiation, with a median of 14 brain metastases per patient and 25% having undergone prior neurosurgical resection.
• The primary outcome was the mean weighted patient-reported symptom severity and interference score change over 6 months. The researchers used the MD Anderson Symptom Inventory-Brain Tumor instrument, with scores ranging from 0-10 and change range of -10 to 10, to measure outcomes.
• Stereotactic radiation was delivered in either 1 day (20 Gy) or five daily fractions (30 Gy, or 25 Gy for surgically removed tumors), while hippocampal-avoidance whole brain radiation was administered as 30 Gy in 10 daily fractions with memantine.

TAKEAWAY:

• Primary outcome analysis showed that stereotactic radiation was linked to a change in the weighted composite MD Anderson Symptom Inventory-Brain Tumor score of 2.69 to 2.37 (mean change, -0.32) compared with 2.29 to 3.03 (mean change, 0.74) with hippocampal-avoidance whole brain radiation (mean difference, -1.06; 95% CI, -1.54 to -0.58; P < .001).
• Functional independence via the Barthel Index was better in the stereotactic radiation group at 4 months (mean difference, 6.79; 95% CI, 1.19-12.38; P = .02) and 12 months (mean difference, 7.92; 95% CI, 1.34-14.49; P = .02).
• New brain metastases were more frequent with stereotactic radiation (1-year cumulative incidence, 45.4% vs 24.2%; P = .003), while local recurrence was lower (3.2% vs 39.5%; P < .001).
• Grade 3-5 adverse events occurred in 12% of stereotactic radiation patients vs 13% in the hippocampal-avoidance whole brain radiation group, with fatigue being most common (28% vs 44%).

IN PRACTICE:

“While [the trial] clearly demonstrates that patients with 5-20 brain metastases have improved symptom burden and lowered interference with daily functioning, there are questions that remain for stereotactic radiosurgery in this population. Patients receiving stereotactic radiosurgery for brain metastases have a higher need for future salvage procedures, and this rate of salvage procedures is higher for patients with an increased number of brain metastases at diagnosis… Moreover, it has been shown that the upfront decision between stereotactic radiosurgery and whole brain radiotherapy is the single decision that contributes most to the cost of care of a patient with brain metastases,” said Michael Chan, MD, in an accompanying editorial published in JAMA.

SOURCE:

The study was led by Ayal A. Aizer, MD, MHS, Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston. It was published online on February 19 in JAMA.

LIMITATIONS:

According to the authors, the study was not blinded, and the primary outcome was subjective. High mortality limited long-term data collection, reducing precision and biasing outcomes toward survivors. Additionally, randomization was not stratified by treating center, allowing possible unmeasured imbalances. The minimal clinically important difference had not been defined for many study outcome measures.

DISCLOSURES:

The trial was supported by Varian, a Siemens Healthineers Company. Aizer disclosed receiving grants from NH TherAguix Research outside the submitted work. 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:

In patients with 5-20 brain metastases, stereotactic radiation improved symptoms and reduced interference with daily functioning compared to hippocampal-avoidance whole brain radiation. The weighted composite MD Anderson Symptom Inventory-Brain Tumor score changed from 2.69 to 2.37 with stereotactic radiation compared with 2.29 to 3.03 with hippocampal-avoidance whole brain radiation.

METHODOLOGY:

• Randomized trials have shown stereotactic radiation preserves neurocognitive function and patient-reported outcomes compared with whole brain radiation in patients with four or less brain metastases. For patients with more than four brain metastases, published randomized comparisons of stereotactic radiation vs whole brain radiation were lacking prior to this study.
• Researchers conducted a phase 3, open-label, randomized clinical trial at four US-based centers, enrolling 196 patients between April 2017 and May 2024, with final follow-up in March 2025.
• Participants included patients with 5-20 brain metastases and no prior brain-directed radiation, with a median of 14 brain metastases per patient and 25% having undergone prior neurosurgical resection.
• The primary outcome was the mean weighted patient-reported symptom severity and interference score change over 6 months. The researchers used the MD Anderson Symptom Inventory-Brain Tumor instrument, with scores ranging from 0-10 and change range of -10 to 10, to measure outcomes.
• Stereotactic radiation was delivered in either 1 day (20 Gy) or five daily fractions (30 Gy, or 25 Gy for surgically removed tumors), while hippocampal-avoidance whole brain radiation was administered as 30 Gy in 10 daily fractions with memantine.

TAKEAWAY:

• Primary outcome analysis showed that stereotactic radiation was linked to a change in the weighted composite MD Anderson Symptom Inventory-Brain Tumor score of 2.69 to 2.37 (mean change, -0.32) compared with 2.29 to 3.03 (mean change, 0.74) with hippocampal-avoidance whole brain radiation (mean difference, -1.06; 95% CI, -1.54 to -0.58; P < .001).
• Functional independence via the Barthel Index was better in the stereotactic radiation group at 4 months (mean difference, 6.79; 95% CI, 1.19-12.38; P = .02) and 12 months (mean difference, 7.92; 95% CI, 1.34-14.49; P = .02).
• New brain metastases were more frequent with stereotactic radiation (1-year cumulative incidence, 45.4% vs 24.2%; P = .003), while local recurrence was lower (3.2% vs 39.5%; P < .001).
• Grade 3-5 adverse events occurred in 12% of stereotactic radiation patients vs 13% in the hippocampal-avoidance whole brain radiation group, with fatigue being most common (28% vs 44%).

IN PRACTICE:

“While [the trial] clearly demonstrates that patients with 5-20 brain metastases have improved symptom burden and lowered interference with daily functioning, there are questions that remain for stereotactic radiosurgery in this population. Patients receiving stereotactic radiosurgery for brain metastases have a higher need for future salvage procedures, and this rate of salvage procedures is higher for patients with an increased number of brain metastases at diagnosis… Moreover, it has been shown that the upfront decision between stereotactic radiosurgery and whole brain radiotherapy is the single decision that contributes most to the cost of care of a patient with brain metastases,” said Michael Chan, MD, in an accompanying editorial published in JAMA.

SOURCE:

The study was led by Ayal A. Aizer, MD, MHS, Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston. It was published online on February 19 in JAMA.

LIMITATIONS:

According to the authors, the study was not blinded, and the primary outcome was subjective. High mortality limited long-term data collection, reducing precision and biasing outcomes toward survivors. Additionally, randomization was not stratified by treating center, allowing possible unmeasured imbalances. The minimal clinically important difference had not been defined for many study outcome measures.

DISCLOSURES:

The trial was supported by Varian, a Siemens Healthineers Company. Aizer disclosed receiving grants from NH TherAguix Research outside the submitted work. 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.

Transcript generated from video captions.

Hello. I'm Dr Maurie Markman, from City of Hope. I'd like to discuss over the next few minutes an absolutely provocative — and I don't use that term loosely — report that I would humbly suggest may, or perhaps even should, change standard of practice in the care of patients with breast cancer. The paper was published in the Journal of the National Cancer Institute, entitled, “Aprepitant Use During Chemotherapy and Association With Survival in Women With Early Breast Cancer.”

This is a very complex, important, and provocative topic, and I'm only going to have a short time to summarize these results, but again, I would suggest this is a topic worthy of very serious consideration in terms of the implications.

Aprepitant, as many of you know, is a standard antiemetic that has been used for many years. It’s very effective and very well tolerated. There’s not any question about that. It’s a supportive-care medication that may be used or not used; a variety of drugs might be used in its place.

However, there are preclinical data —I cannot go into any kind of detail here—that have revealed that aprepitant in these preclinical settings will slow breast cancer growth and progression.

What we're looking at in this report is retrospective data linking a nationwide registry of 13,811 women diagnosed with early breast cancer between 2008 and 2020 in Norway. These are population-based data that were very well documented because that's how things work in Scandinavian countries in general, but in Norway in particular. They know what patients receive nationally, over time, and there's follow-up.

The point is that they had knowledge of the diagnoses and the therapy. These women that I'm referring to had received chemotherapy and antiemetics, which, of course, is standard of care and has been for decades. These women were followed for the development of metastatic disease and death from 1 year after diagnosis to the end of 2021, which was the duration of this particular report.

During this period of time, of these 13,811 women, 7047 were given aprepitant, which is, interestingly, 51% or about half of the population. Here's the bottom line: Aprepitant use resulted in superior distant disease-free survival, with a hazard ratio of 0.89, and breast cancer-specific survival, with a hazard ratio of 0.83.

Increasingly interesting, only nonluminal breast cancer had this demonstrated benefit, with a hazard ratio of 0.69. Again, that's a hazard ratio for metastatic disease or death of 0.69 if aprepitant was used. It was strongest in triple-negative breast cancer, with a hazard ratio of 0.66. Let me repeat that: a hazard ratio of 0.66 for the reduction in the risk of distant disease or death. This was a difference that was able to be documented with the use of aprepitant or not.

Finally, in this analysis, survival outcomes were not observed with any other class of antiemetics, only aprepitant. In the nonluminal breast cancer population, the longer duration of aprepitant use — presumably multiple cycles over time — was associated with increasingly favorable survival outcomes. This was a trend analysis, so the longer it was used, the more superior the outcomes.

I’m not surprised. To get this paper published in a high-impact journal, the authors had to conclude that clinical trials are required to confirm these findings. Really?

If you're a patient, a family member, or an oncologist caring for a woman with triple-negative breast cancer, you are going to wait for a phase 3, randomized trial to be conducted and reported maybe in 5 or 10 years? When you're talking about a drug that is widely used and is safe, you're going to make a decision to wait for the clinical trial before you conclude that aprepitant should be used in this setting, based upon these excellent data?

I would challenge that and ask, on average today, certainly in patients that I'm seeing or counseling, aprepitant should become a component of the standard of care unless there's a contraindication to the use of the drug, based upon these excellent registry and population-based data.

We don't have to wait for randomized phase 3 trials to answer every question if what we see here makes sense, based on a plausible biological explanation and well-analyzed data. Obviously, other databases can look at this and see if they come up with different answers, but we do not need to wait for a phase 3, randomized trial before we incorporate something that we believe the data support as having a favorable impact on the outcome of patients we are seeing today.

I thank you for your attention.

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

Transcript generated from video captions.

Hello. I'm Dr Maurie Markman, from City of Hope. I'd like to discuss over the next few minutes an absolutely provocative — and I don't use that term loosely — report that I would humbly suggest may, or perhaps even should, change standard of practice in the care of patients with breast cancer. The paper was published in the Journal of the National Cancer Institute, entitled, “Aprepitant Use During Chemotherapy and Association With Survival in Women With Early Breast Cancer.”

This is a very complex, important, and provocative topic, and I'm only going to have a short time to summarize these results, but again, I would suggest this is a topic worthy of very serious consideration in terms of the implications.

Aprepitant, as many of you know, is a standard antiemetic that has been used for many years. It’s very effective and very well tolerated. There’s not any question about that. It’s a supportive-care medication that may be used or not used; a variety of drugs might be used in its place.

However, there are preclinical data —I cannot go into any kind of detail here—that have revealed that aprepitant in these preclinical settings will slow breast cancer growth and progression.

What we're looking at in this report is retrospective data linking a nationwide registry of 13,811 women diagnosed with early breast cancer between 2008 and 2020 in Norway. These are population-based data that were very well documented because that's how things work in Scandinavian countries in general, but in Norway in particular. They know what patients receive nationally, over time, and there's follow-up.

The point is that they had knowledge of the diagnoses and the therapy. These women that I'm referring to had received chemotherapy and antiemetics, which, of course, is standard of care and has been for decades. These women were followed for the development of metastatic disease and death from 1 year after diagnosis to the end of 2021, which was the duration of this particular report.

During this period of time, of these 13,811 women, 7047 were given aprepitant, which is, interestingly, 51% or about half of the population. Here's the bottom line: Aprepitant use resulted in superior distant disease-free survival, with a hazard ratio of 0.89, and breast cancer-specific survival, with a hazard ratio of 0.83.

Increasingly interesting, only nonluminal breast cancer had this demonstrated benefit, with a hazard ratio of 0.69. Again, that's a hazard ratio for metastatic disease or death of 0.69 if aprepitant was used. It was strongest in triple-negative breast cancer, with a hazard ratio of 0.66. Let me repeat that: a hazard ratio of 0.66 for the reduction in the risk of distant disease or death. This was a difference that was able to be documented with the use of aprepitant or not.

Finally, in this analysis, survival outcomes were not observed with any other class of antiemetics, only aprepitant. In the nonluminal breast cancer population, the longer duration of aprepitant use — presumably multiple cycles over time — was associated with increasingly favorable survival outcomes. This was a trend analysis, so the longer it was used, the more superior the outcomes.

I’m not surprised. To get this paper published in a high-impact journal, the authors had to conclude that clinical trials are required to confirm these findings. Really?

If you're a patient, a family member, or an oncologist caring for a woman with triple-negative breast cancer, you are going to wait for a phase 3, randomized trial to be conducted and reported maybe in 5 or 10 years? When you're talking about a drug that is widely used and is safe, you're going to make a decision to wait for the clinical trial before you conclude that aprepitant should be used in this setting, based upon these excellent data?

I would challenge that and ask, on average today, certainly in patients that I'm seeing or counseling, aprepitant should become a component of the standard of care unless there's a contraindication to the use of the drug, based upon these excellent registry and population-based data.

We don't have to wait for randomized phase 3 trials to answer every question if what we see here makes sense, based on a plausible biological explanation and well-analyzed data. Obviously, other databases can look at this and see if they come up with different answers, but we do not need to wait for a phase 3, randomized trial before we incorporate something that we believe the data support as having a favorable impact on the outcome of patients we are seeing today.

I thank you for your attention.

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

Transcript generated from video captions.

Hello. I'm Dr Maurie Markman, from City of Hope. I'd like to discuss over the next few minutes an absolutely provocative — and I don't use that term loosely — report that I would humbly suggest may, or perhaps even should, change standard of practice in the care of patients with breast cancer. The paper was published in the Journal of the National Cancer Institute, entitled, “Aprepitant Use During Chemotherapy and Association With Survival in Women With Early Breast Cancer.”

This is a very complex, important, and provocative topic, and I'm only going to have a short time to summarize these results, but again, I would suggest this is a topic worthy of very serious consideration in terms of the implications.

Aprepitant, as many of you know, is a standard antiemetic that has been used for many years. It’s very effective and very well tolerated. There’s not any question about that. It’s a supportive-care medication that may be used or not used; a variety of drugs might be used in its place.

However, there are preclinical data —I cannot go into any kind of detail here—that have revealed that aprepitant in these preclinical settings will slow breast cancer growth and progression.

What we're looking at in this report is retrospective data linking a nationwide registry of 13,811 women diagnosed with early breast cancer between 2008 and 2020 in Norway. These are population-based data that were very well documented because that's how things work in Scandinavian countries in general, but in Norway in particular. They know what patients receive nationally, over time, and there's follow-up.

The point is that they had knowledge of the diagnoses and the therapy. These women that I'm referring to had received chemotherapy and antiemetics, which, of course, is standard of care and has been for decades. These women were followed for the development of metastatic disease and death from 1 year after diagnosis to the end of 2021, which was the duration of this particular report.

During this period of time, of these 13,811 women, 7047 were given aprepitant, which is, interestingly, 51% or about half of the population. Here's the bottom line: Aprepitant use resulted in superior distant disease-free survival, with a hazard ratio of 0.89, and breast cancer-specific survival, with a hazard ratio of 0.83.

Increasingly interesting, only nonluminal breast cancer had this demonstrated benefit, with a hazard ratio of 0.69. Again, that's a hazard ratio for metastatic disease or death of 0.69 if aprepitant was used. It was strongest in triple-negative breast cancer, with a hazard ratio of 0.66. Let me repeat that: a hazard ratio of 0.66 for the reduction in the risk of distant disease or death. This was a difference that was able to be documented with the use of aprepitant or not.

Finally, in this analysis, survival outcomes were not observed with any other class of antiemetics, only aprepitant. In the nonluminal breast cancer population, the longer duration of aprepitant use — presumably multiple cycles over time — was associated with increasingly favorable survival outcomes. This was a trend analysis, so the longer it was used, the more superior the outcomes.

I’m not surprised. To get this paper published in a high-impact journal, the authors had to conclude that clinical trials are required to confirm these findings. Really?

If you're a patient, a family member, or an oncologist caring for a woman with triple-negative breast cancer, you are going to wait for a phase 3, randomized trial to be conducted and reported maybe in 5 or 10 years? When you're talking about a drug that is widely used and is safe, you're going to make a decision to wait for the clinical trial before you conclude that aprepitant should be used in this setting, based upon these excellent data?

I would challenge that and ask, on average today, certainly in patients that I'm seeing or counseling, aprepitant should become a component of the standard of care unless there's a contraindication to the use of the drug, based upon these excellent registry and population-based data.

We don't have to wait for randomized phase 3 trials to answer every question if what we see here makes sense, based on a plausible biological explanation and well-analyzed data. Obviously, other databases can look at this and see if they come up with different answers, but we do not need to wait for a phase 3, randomized trial before we incorporate something that we believe the data support as having a favorable impact on the outcome of patients we are seeing today.

I thank you for your attention.

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

DNA methylation-derived biomarkers called Protein EpiScores may improve the accuracy of disease-free and overall survival prediction in patients with colorectal cancer (CRC), compared with traditional clinical risk factors alone, suggest results of a prospective study.

Although Protein EpiScores require further validation before they are ready for clinical use, the present data offer insights into the underlying processes shaping CRC outcomes, lead author Alicia R. Richards, PhD, of Moffitt Cancer Center, Tampa, Florida, and colleagues wrote in Clinical Epigenetics.

“The immediate value of our findings is highlighting biological pathways like immune suppression and coagulation as drivers of poor outcomes,” senior author Jacob K. Kresovich, PhD, of Moffitt Cancer Center, told Medscape Medical News.

What Are Protein EpiScores?

Previous studies have evaluated epigenetic clocks, which are derived from DNA methylation profiles, as markers for CRC risk. However, these clocks cannot pinpoint specific biological drivers of cancer progression, the investigators wrote.

Protein EpiScores may fill this gap; they were developed based on previous work suggesting that DNA methylation profiles may improve disease prediction based on circulating proteins (eg, C-reactive protein) and physiologic traits (eg, smoking status) beyond directly measuring those same variables.

“Protein EpiScores may therefore represent a complementary class of biomarker to direct measurements,” the investigators wrote.

Although Protein EpiScores have helped uncover biological processes driving various conditions such as cardiovascular disease and cancer, this is the first study to evaluate them specifically in the context of cancer survival.

How Did This Study Evaluate Protein EpiScores in Patients With CRC?

The present study involved 136 patients with newly diagnosed CRC from the prospective ColoCare Study.

For each patient, the investigators recorded 107 Protein EpiScores from pretreatment whole blood samples. Disease-free and overall survival were monitored over a median follow-up of 7.3 years and as long as 13.8 years. During follow-up, 26% of patients experienced disease recurrence, and 35% died.

With these data, the investigators compared the predictive power of the Protein EpiScores vs traditional clinical risk factors for disease-free and overall survival. “We used the standard factors doctors routinely collect before treatment starts to assess prognosis, including tumor stage, age at cancer diagnosis, sex, body mass index, race, and tumor location,” Kresovich said. “These are well-established predictors readily available from medical records.”

What Were the Key Findings?

Adding specific Protein EpiScores to the standard clinical risk factors significantly improved prognostic accuracy for survival.

After adjusting for confounding variables, the HCII, VEGFA, CCL17, and LGALS3BP Protein EpiScores were each independently associated with worse disease-free survival, with hazard ratios ranging from 1.62 to 1.71. Adding these scores to the clinical model improved the concordance index (C-index) from 0.64 to 0.70.

The LGALS3BP Protein EpiScore was also independently linked to overall survival, with a hazard ratio of 1.80. Adding this score to the model raised the C-index from 0.70 to 0.75.

Finally, the HCII, LGALS3BP, MMP12, and VEGFA Protein EpiScores were tied to both disease-free and overall survival with hazard ratios above 1.50.

Are These Findings Practice-Changing?

“The improvements [in prognostic accuracy] are modest but potentially meaningful and comparable to gains from other established biomarkers,” Kresovich said. “The 6-point improvement for recurrence (C-index 0.64 to 0.70) resulted in 34% of patients being reclassified into more accurate risk categories.”

In theory, this could have a meaningful clinical impact.

“In cancer care, even incremental gains matter if they prevent undertreating high-risk patients or overtreating low-risk ones,” Kresovich said.

Despite this potential, he was clear that more work is needed.

“If our findings are validated in other epidemiologic settings, these Protein EpiScores could eventually complement existing risk tools, but we’re realistically several years from clinical implementation,” Kresovich said. “We see these current findings more as a research tool that requires validation in larger cohorts before clinical use.”

How Might These Findings Shape Future Research?

Although more studies are needed before clinical rollout, the present findings point to key biological pathways, such as those involving immune suppression and coagulation, which may be driving worse outcomes in patients with CRC.

“This information can guide basic scientists and mechanistic studies to identify potential therapeutic targets,” Kresovich said.

Beyond evaluating Protein EpiScores in larger patient populations, future studies may also need to recruit a more diverse patient population, given the present cohort was 93% White.

Although the investigators noted that “the racial homogeneity reduced potential confounding by ancestry,” they also explained that “Protein EpiScores were developed in European populations, and their translation to individuals with different ancestries has not been closely examined.”

The study was supported by the Miles for Moffitt Team Science Mechanism. The investigators reported no relevant conflicts of interest.

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

DNA methylation-derived biomarkers called Protein EpiScores may improve the accuracy of disease-free and overall survival prediction in patients with colorectal cancer (CRC), compared with traditional clinical risk factors alone, suggest results of a prospective study.

Although Protein EpiScores require further validation before they are ready for clinical use, the present data offer insights into the underlying processes shaping CRC outcomes, lead author Alicia R. Richards, PhD, of Moffitt Cancer Center, Tampa, Florida, and colleagues wrote in Clinical Epigenetics.

“The immediate value of our findings is highlighting biological pathways like immune suppression and coagulation as drivers of poor outcomes,” senior author Jacob K. Kresovich, PhD, of Moffitt Cancer Center, told Medscape Medical News.

What Are Protein EpiScores?

Previous studies have evaluated epigenetic clocks, which are derived from DNA methylation profiles, as markers for CRC risk. However, these clocks cannot pinpoint specific biological drivers of cancer progression, the investigators wrote.

Protein EpiScores may fill this gap; they were developed based on previous work suggesting that DNA methylation profiles may improve disease prediction based on circulating proteins (eg, C-reactive protein) and physiologic traits (eg, smoking status) beyond directly measuring those same variables.

“Protein EpiScores may therefore represent a complementary class of biomarker to direct measurements,” the investigators wrote.

Although Protein EpiScores have helped uncover biological processes driving various conditions such as cardiovascular disease and cancer, this is the first study to evaluate them specifically in the context of cancer survival.

How Did This Study Evaluate Protein EpiScores in Patients With CRC?

The present study involved 136 patients with newly diagnosed CRC from the prospective ColoCare Study.

For each patient, the investigators recorded 107 Protein EpiScores from pretreatment whole blood samples. Disease-free and overall survival were monitored over a median follow-up of 7.3 years and as long as 13.8 years. During follow-up, 26% of patients experienced disease recurrence, and 35% died.

With these data, the investigators compared the predictive power of the Protein EpiScores vs traditional clinical risk factors for disease-free and overall survival. “We used the standard factors doctors routinely collect before treatment starts to assess prognosis, including tumor stage, age at cancer diagnosis, sex, body mass index, race, and tumor location,” Kresovich said. “These are well-established predictors readily available from medical records.”

What Were the Key Findings?

Adding specific Protein EpiScores to the standard clinical risk factors significantly improved prognostic accuracy for survival.

After adjusting for confounding variables, the HCII, VEGFA, CCL17, and LGALS3BP Protein EpiScores were each independently associated with worse disease-free survival, with hazard ratios ranging from 1.62 to 1.71. Adding these scores to the clinical model improved the concordance index (C-index) from 0.64 to 0.70.

The LGALS3BP Protein EpiScore was also independently linked to overall survival, with a hazard ratio of 1.80. Adding this score to the model raised the C-index from 0.70 to 0.75.

Finally, the HCII, LGALS3BP, MMP12, and VEGFA Protein EpiScores were tied to both disease-free and overall survival with hazard ratios above 1.50.

Are These Findings Practice-Changing?

“The improvements [in prognostic accuracy] are modest but potentially meaningful and comparable to gains from other established biomarkers,” Kresovich said. “The 6-point improvement for recurrence (C-index 0.64 to 0.70) resulted in 34% of patients being reclassified into more accurate risk categories.”

In theory, this could have a meaningful clinical impact.

“In cancer care, even incremental gains matter if they prevent undertreating high-risk patients or overtreating low-risk ones,” Kresovich said.

Despite this potential, he was clear that more work is needed.

“If our findings are validated in other epidemiologic settings, these Protein EpiScores could eventually complement existing risk tools, but we’re realistically several years from clinical implementation,” Kresovich said. “We see these current findings more as a research tool that requires validation in larger cohorts before clinical use.”

How Might These Findings Shape Future Research?

Although more studies are needed before clinical rollout, the present findings point to key biological pathways, such as those involving immune suppression and coagulation, which may be driving worse outcomes in patients with CRC.

“This information can guide basic scientists and mechanistic studies to identify potential therapeutic targets,” Kresovich said.

Beyond evaluating Protein EpiScores in larger patient populations, future studies may also need to recruit a more diverse patient population, given the present cohort was 93% White.

Although the investigators noted that “the racial homogeneity reduced potential confounding by ancestry,” they also explained that “Protein EpiScores were developed in European populations, and their translation to individuals with different ancestries has not been closely examined.”

The study was supported by the Miles for Moffitt Team Science Mechanism. The investigators reported no relevant conflicts of interest.

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

DNA methylation-derived biomarkers called Protein EpiScores may improve the accuracy of disease-free and overall survival prediction in patients with colorectal cancer (CRC), compared with traditional clinical risk factors alone, suggest results of a prospective study.

Although Protein EpiScores require further validation before they are ready for clinical use, the present data offer insights into the underlying processes shaping CRC outcomes, lead author Alicia R. Richards, PhD, of Moffitt Cancer Center, Tampa, Florida, and colleagues wrote in Clinical Epigenetics.

“The immediate value of our findings is highlighting biological pathways like immune suppression and coagulation as drivers of poor outcomes,” senior author Jacob K. Kresovich, PhD, of Moffitt Cancer Center, told Medscape Medical News.

What Are Protein EpiScores?

Previous studies have evaluated epigenetic clocks, which are derived from DNA methylation profiles, as markers for CRC risk. However, these clocks cannot pinpoint specific biological drivers of cancer progression, the investigators wrote.

Protein EpiScores may fill this gap; they were developed based on previous work suggesting that DNA methylation profiles may improve disease prediction based on circulating proteins (eg, C-reactive protein) and physiologic traits (eg, smoking status) beyond directly measuring those same variables.

“Protein EpiScores may therefore represent a complementary class of biomarker to direct measurements,” the investigators wrote.

Although Protein EpiScores have helped uncover biological processes driving various conditions such as cardiovascular disease and cancer, this is the first study to evaluate them specifically in the context of cancer survival.

How Did This Study Evaluate Protein EpiScores in Patients With CRC?

The present study involved 136 patients with newly diagnosed CRC from the prospective ColoCare Study.

For each patient, the investigators recorded 107 Protein EpiScores from pretreatment whole blood samples. Disease-free and overall survival were monitored over a median follow-up of 7.3 years and as long as 13.8 years. During follow-up, 26% of patients experienced disease recurrence, and 35% died.

With these data, the investigators compared the predictive power of the Protein EpiScores vs traditional clinical risk factors for disease-free and overall survival. “We used the standard factors doctors routinely collect before treatment starts to assess prognosis, including tumor stage, age at cancer diagnosis, sex, body mass index, race, and tumor location,” Kresovich said. “These are well-established predictors readily available from medical records.”

What Were the Key Findings?

Adding specific Protein EpiScores to the standard clinical risk factors significantly improved prognostic accuracy for survival.

After adjusting for confounding variables, the HCII, VEGFA, CCL17, and LGALS3BP Protein EpiScores were each independently associated with worse disease-free survival, with hazard ratios ranging from 1.62 to 1.71. Adding these scores to the clinical model improved the concordance index (C-index) from 0.64 to 0.70.

The LGALS3BP Protein EpiScore was also independently linked to overall survival, with a hazard ratio of 1.80. Adding this score to the model raised the C-index from 0.70 to 0.75.

Finally, the HCII, LGALS3BP, MMP12, and VEGFA Protein EpiScores were tied to both disease-free and overall survival with hazard ratios above 1.50.

Are These Findings Practice-Changing?

“The improvements [in prognostic accuracy] are modest but potentially meaningful and comparable to gains from other established biomarkers,” Kresovich said. “The 6-point improvement for recurrence (C-index 0.64 to 0.70) resulted in 34% of patients being reclassified into more accurate risk categories.”

In theory, this could have a meaningful clinical impact.

“In cancer care, even incremental gains matter if they prevent undertreating high-risk patients or overtreating low-risk ones,” Kresovich said.

Despite this potential, he was clear that more work is needed.

“If our findings are validated in other epidemiologic settings, these Protein EpiScores could eventually complement existing risk tools, but we’re realistically several years from clinical implementation,” Kresovich said. “We see these current findings more as a research tool that requires validation in larger cohorts before clinical use.”

How Might These Findings Shape Future Research?

Although more studies are needed before clinical rollout, the present findings point to key biological pathways, such as those involving immune suppression and coagulation, which may be driving worse outcomes in patients with CRC.

“This information can guide basic scientists and mechanistic studies to identify potential therapeutic targets,” Kresovich said.

Beyond evaluating Protein EpiScores in larger patient populations, future studies may also need to recruit a more diverse patient population, given the present cohort was 93% White.

Although the investigators noted that “the racial homogeneity reduced potential confounding by ancestry,” they also explained that “Protein EpiScores were developed in European populations, and their translation to individuals with different ancestries has not been closely examined.”

The study was supported by the Miles for Moffitt Team Science Mechanism. The investigators reported no relevant conflicts of interest.

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

The National Cancer Institute (NCI), the federal research agency charged with leading the war against the nation’s second-largest killer, is studying ivermectin as a potential cancer treatment, according to its top official.

“There are enough reports of it, enough interest in it, that we actually did — ivermectin, in particular — did engage in sort of a better preclinical study of its properties and its ability to kill cancer cells,” said Anthony Letai, a physician the Trump administration appointed as NCI director in September.

Letai did not cite new evidence that might have prompted the institute to research the effectiveness of the antiparasitic drug against cancer. The drug, largely used to treat people or animals for infections caused by parasites, is a popular dewormer for horses.

“We’ll probably have those results in a few months,” Letai said. “So we are taking it seriously.”

He spoke about ivermectin at a January 30 event, “Reclaiming Science: The People’s NIH,” with National Institutes of Health (NIH) Director Jay Bhattacharya and other senior agency officials at Washington, DC’s Willard Hotel. The MAHA Institute hosted the discussion, framed by the “Make America Healthy Again” agenda of Health and Human Services (HSS) Secretary Robert F. Kennedy Jr. The National Cancer Institute is the largest of the NIH’s 27 branches.

During the COVID pandemic, ivermectin’s popularity surged as fringe medical groups promoted it as an effective treatment. Clinical trials have found it isn’t effective against COVID.

Ivermectin has become a symbol of resistance against the medical establishment among MAHA adherents and conservatives. Like-minded commentators and wellness and other online influencers have hyped — without evidence — ivermectin as a miracle cure for a host of diseases, including cancer. Trump officials have pointed to research on ivermectin as an example of the administration’s receptiveness to ideas the scientific establishment has rejected.

“If lots of people believe it and it’s moving public health, we as NIH have an obligation, again, to treat it seriously,” Bhattacharya said at the event. According to The Chronicle at Duke University, Bhattacharya recently said he wants the NIH to be “the research arm of MAHA.”

The decision by the world’s premier cancer research institute to study ivermectin as a cancer treatment has alarmed career scientists at the agency.

“I am shocked and appalled,” one NCI scientist said. “We are moving funds away from so much promising research in order to do a preclinical study based on nonscientific ideas. It’s absurd.”

KFF Health News granted the scientist and other NCI workers anonymity because they are not authorized to speak to the press and fear retaliation.

HHS and the National Cancer Institute did not answer KFF Health News’ questions on the amount of money the cancer institute is spending on the study, who is carrying it out, and whether there was new evidence that prompted NCI to look into ivermectin as an anticancer therapy. Emily Hilliard, an HHS spokesperson, said NIH is dedicated to “rigorous, gold-standard research,” something the administration has repeatedly professed.

A preclinical study is an early phase of research conducted in a lab to test whether a drug or treatment may be useful and to assess potential harms. These studies take place before human clinical trials.

The scientist questioned whether there is enough initial evidence to warrant NCI’s spending of taxpayer funds to investigate the drug’s potential as a cancer treatment.

The FDA has approved ivermectin for certain uses in humans and animals. Tablets are used to treat conditions caused by parasitic worms, and the FDA has approved ivermectin lotions to treat lice and rosacea. Two scientists involved in its discovery won the Nobel Prize in 2015, tied to the drug’s success in treating certain parasitic diseases.

The FDA has warned that large doses of ivermectin can be dangerous. Overdoses can cause seizures, comas, or death.

Kennedy, supporters of the MAHA movement, and some conservative commentators have promoted the idea that the government and pharmaceutical companies quashed ivermectin and other inexpensive, off-patent drugs because they’re not profitable for the drug industry.

“FDA’s war on public health is about to end,” Kennedy wrote in an October 2024 X post that has since gone viral. “This includes its aggressive suppression of psychedelics, peptides, stem cells, raw milk, hyperbaric therapies, chelating compounds, ivermectin, hydroxychloroquine, vitamins, clean foods, sunshine, exercise, nutraceuticals and anything else that advances human health and can’t be patented by Pharma.”

Previous laboratory research has shown that ivermectin could have anticancer effects because it promotes cell death and inhibits the growth of tumor cells. “It actually has been studied both with NIH funds and outside of NIH funds,” Letai said.

However, there is no evidence that ivermectin is safe and effective in treating cancer in humans. Preliminary data from a small clinical trial that gave ivermectin to patients with one type of metastatic breast cancer, in combination with immunotherapy, found no significant benefit from the addition of ivermectin.

Some physicians are concerned that patients will delay or forgo effective cancer treatments, or be harmed in other ways, if they believe unfounded claims that ivermectin can treat their disease.

“Many, many, many things work in a test tube. Quite a few things work in a mouse or a monkey. It still doesn’t mean it’s going to work in people,” said Jeffery Edenfield, executive medical director of oncology for the South Carolina-based Prisma Health Cancer Institute.

Edenfield said cancer patients ask him about ivermectin “regularly,” mostly because of what they see on social media. He said he persuaded a patient to stop using it, and a colleague recently had a patient who decided “to forgo highly effective standard therapy in favor of ivermectin.”

“People come to the discussion having largely already made up their mind,” Edenfield said. “We’re in this delicate time when there’s sort of a fundamental mistrust of medicine,” he added. “Some people are just not going to believe me. I just have to keep trying.”

A June letter by clinicians at Cincinnati Children’s Hospital Medical Center in Ohio detailed how an adolescent patient with metastatic bone cancer started taking ivermectin “after encountering social media posts touting its benefits.” The patient — who hadn’t been given a prescription by a clinician — experienced ivermectin-related neurotoxicity and had to seek emergency care because of nausea, fatigue, and other symptoms.

“We urge the pediatric oncology community to advocate for sensible health policy that prioritizes the well-being of our patients,” the clinicians wrote. The lack of evidence about ivermectin and cancer hasn’t stopped celebrities and online influencers from promoting the notion that the drug is a cure-all. On a January 2025 episode of Joe Rogan’s podcast, actor Mel Gibson claimed that a combination of drugs that included ivermectin cured 3friends with stage IV cancer. The episode has been viewed > 12 million times.

Lawmakers in a handful of states have made the drug available over the counter. And Florida — which, under Republican Governor Ron DeSantis, has become a hotbed for anti-vaccine policies and the spread of public health misinformation — announced last fall that the state plans to fund research to study the drug as a potential cancer treatment.

The Florida Department of Health did not respond to questions about that effort.

Letai, previously a Dana-Farber Cancer Institute oncologist, started at the National Cancer Institute after months of upheaval caused by Trump administration policies.

“What you’re hearing at the NIH now is an openness to ideas — even ideas that scientists would say, ‘Oh, there’s no way it could work’ — but nevertheless applying rigorous scientific methods to those ideas,” Bhattacharya said at the January 30 event.

A second NCI scientist, who was granted anonymity due to fear of retaliation, said the notion that NIH was not open to investigating the value of off-label drugs in cancer is “ridiculous.”

“This is not a new idea they came up with,” the scientist said.

Letai didn’t elaborate on whether NCI scientists are conducting the research or if it has directed funding to an outside institution. Three-fourths of the cancer institute’s research dollars go to outside scientists.

He also aimed to temper expectations.

“At least on a population level,” Letai said, “it’s not going to be a cure-all for cancer.”

The National Cancer Institute (NCI), the federal research agency charged with leading the war against the nation’s second-largest killer, is studying ivermectin as a potential cancer treatment, according to its top official.

“There are enough reports of it, enough interest in it, that we actually did — ivermectin, in particular — did engage in sort of a better preclinical study of its properties and its ability to kill cancer cells,” said Anthony Letai, a physician the Trump administration appointed as NCI director in September.

Letai did not cite new evidence that might have prompted the institute to research the effectiveness of the antiparasitic drug against cancer. The drug, largely used to treat people or animals for infections caused by parasites, is a popular dewormer for horses.

“We’ll probably have those results in a few months,” Letai said. “So we are taking it seriously.”

He spoke about ivermectin at a January 30 event, “Reclaiming Science: The People’s NIH,” with National Institutes of Health (NIH) Director Jay Bhattacharya and other senior agency officials at Washington, DC’s Willard Hotel. The MAHA Institute hosted the discussion, framed by the “Make America Healthy Again” agenda of Health and Human Services (HSS) Secretary Robert F. Kennedy Jr. The National Cancer Institute is the largest of the NIH’s 27 branches.

During the COVID pandemic, ivermectin’s popularity surged as fringe medical groups promoted it as an effective treatment. Clinical trials have found it isn’t effective against COVID.

Ivermectin has become a symbol of resistance against the medical establishment among MAHA adherents and conservatives. Like-minded commentators and wellness and other online influencers have hyped — without evidence — ivermectin as a miracle cure for a host of diseases, including cancer. Trump officials have pointed to research on ivermectin as an example of the administration’s receptiveness to ideas the scientific establishment has rejected.

“If lots of people believe it and it’s moving public health, we as NIH have an obligation, again, to treat it seriously,” Bhattacharya said at the event. According to The Chronicle at Duke University, Bhattacharya recently said he wants the NIH to be “the research arm of MAHA.”

The decision by the world’s premier cancer research institute to study ivermectin as a cancer treatment has alarmed career scientists at the agency.

“I am shocked and appalled,” one NCI scientist said. “We are moving funds away from so much promising research in order to do a preclinical study based on nonscientific ideas. It’s absurd.”

KFF Health News granted the scientist and other NCI workers anonymity because they are not authorized to speak to the press and fear retaliation.

HHS and the National Cancer Institute did not answer KFF Health News’ questions on the amount of money the cancer institute is spending on the study, who is carrying it out, and whether there was new evidence that prompted NCI to look into ivermectin as an anticancer therapy. Emily Hilliard, an HHS spokesperson, said NIH is dedicated to “rigorous, gold-standard research,” something the administration has repeatedly professed.

A preclinical study is an early phase of research conducted in a lab to test whether a drug or treatment may be useful and to assess potential harms. These studies take place before human clinical trials.

The scientist questioned whether there is enough initial evidence to warrant NCI’s spending of taxpayer funds to investigate the drug’s potential as a cancer treatment.

The FDA has approved ivermectin for certain uses in humans and animals. Tablets are used to treat conditions caused by parasitic worms, and the FDA has approved ivermectin lotions to treat lice and rosacea. Two scientists involved in its discovery won the Nobel Prize in 2015, tied to the drug’s success in treating certain parasitic diseases.

The FDA has warned that large doses of ivermectin can be dangerous. Overdoses can cause seizures, comas, or death.

Kennedy, supporters of the MAHA movement, and some conservative commentators have promoted the idea that the government and pharmaceutical companies quashed ivermectin and other inexpensive, off-patent drugs because they’re not profitable for the drug industry.

“FDA’s war on public health is about to end,” Kennedy wrote in an October 2024 X post that has since gone viral. “This includes its aggressive suppression of psychedelics, peptides, stem cells, raw milk, hyperbaric therapies, chelating compounds, ivermectin, hydroxychloroquine, vitamins, clean foods, sunshine, exercise, nutraceuticals and anything else that advances human health and can’t be patented by Pharma.”

Previous laboratory research has shown that ivermectin could have anticancer effects because it promotes cell death and inhibits the growth of tumor cells. “It actually has been studied both with NIH funds and outside of NIH funds,” Letai said.

However, there is no evidence that ivermectin is safe and effective in treating cancer in humans. Preliminary data from a small clinical trial that gave ivermectin to patients with one type of metastatic breast cancer, in combination with immunotherapy, found no significant benefit from the addition of ivermectin.

Some physicians are concerned that patients will delay or forgo effective cancer treatments, or be harmed in other ways, if they believe unfounded claims that ivermectin can treat their disease.

“Many, many, many things work in a test tube. Quite a few things work in a mouse or a monkey. It still doesn’t mean it’s going to work in people,” said Jeffery Edenfield, executive medical director of oncology for the South Carolina-based Prisma Health Cancer Institute.

Edenfield said cancer patients ask him about ivermectin “regularly,” mostly because of what they see on social media. He said he persuaded a patient to stop using it, and a colleague recently had a patient who decided “to forgo highly effective standard therapy in favor of ivermectin.”

“People come to the discussion having largely already made up their mind,” Edenfield said. “We’re in this delicate time when there’s sort of a fundamental mistrust of medicine,” he added. “Some people are just not going to believe me. I just have to keep trying.”

A June letter by clinicians at Cincinnati Children’s Hospital Medical Center in Ohio detailed how an adolescent patient with metastatic bone cancer started taking ivermectin “after encountering social media posts touting its benefits.” The patient — who hadn’t been given a prescription by a clinician — experienced ivermectin-related neurotoxicity and had to seek emergency care because of nausea, fatigue, and other symptoms.

“We urge the pediatric oncology community to advocate for sensible health policy that prioritizes the well-being of our patients,” the clinicians wrote. The lack of evidence about ivermectin and cancer hasn’t stopped celebrities and online influencers from promoting the notion that the drug is a cure-all. On a January 2025 episode of Joe Rogan’s podcast, actor Mel Gibson claimed that a combination of drugs that included ivermectin cured 3friends with stage IV cancer. The episode has been viewed > 12 million times.

Lawmakers in a handful of states have made the drug available over the counter. And Florida — which, under Republican Governor Ron DeSantis, has become a hotbed for anti-vaccine policies and the spread of public health misinformation — announced last fall that the state plans to fund research to study the drug as a potential cancer treatment.

The Florida Department of Health did not respond to questions about that effort.

Letai, previously a Dana-Farber Cancer Institute oncologist, started at the National Cancer Institute after months of upheaval caused by Trump administration policies.

“What you’re hearing at the NIH now is an openness to ideas — even ideas that scientists would say, ‘Oh, there’s no way it could work’ — but nevertheless applying rigorous scientific methods to those ideas,” Bhattacharya said at the January 30 event.

A second NCI scientist, who was granted anonymity due to fear of retaliation, said the notion that NIH was not open to investigating the value of off-label drugs in cancer is “ridiculous.”

“This is not a new idea they came up with,” the scientist said.

Letai didn’t elaborate on whether NCI scientists are conducting the research or if it has directed funding to an outside institution. Three-fourths of the cancer institute’s research dollars go to outside scientists.

He also aimed to temper expectations.

“At least on a population level,” Letai said, “it’s not going to be a cure-all for cancer.”

The National Cancer Institute (NCI), the federal research agency charged with leading the war against the nation’s second-largest killer, is studying ivermectin as a potential cancer treatment, according to its top official.

“There are enough reports of it, enough interest in it, that we actually did — ivermectin, in particular — did engage in sort of a better preclinical study of its properties and its ability to kill cancer cells,” said Anthony Letai, a physician the Trump administration appointed as NCI director in September.

Letai did not cite new evidence that might have prompted the institute to research the effectiveness of the antiparasitic drug against cancer. The drug, largely used to treat people or animals for infections caused by parasites, is a popular dewormer for horses.

“We’ll probably have those results in a few months,” Letai said. “So we are taking it seriously.”

He spoke about ivermectin at a January 30 event, “Reclaiming Science: The People’s NIH,” with National Institutes of Health (NIH) Director Jay Bhattacharya and other senior agency officials at Washington, DC’s Willard Hotel. The MAHA Institute hosted the discussion, framed by the “Make America Healthy Again” agenda of Health and Human Services (HSS) Secretary Robert F. Kennedy Jr. The National Cancer Institute is the largest of the NIH’s 27 branches.

During the COVID pandemic, ivermectin’s popularity surged as fringe medical groups promoted it as an effective treatment. Clinical trials have found it isn’t effective against COVID.

Ivermectin has become a symbol of resistance against the medical establishment among MAHA adherents and conservatives. Like-minded commentators and wellness and other online influencers have hyped — without evidence — ivermectin as a miracle cure for a host of diseases, including cancer. Trump officials have pointed to research on ivermectin as an example of the administration’s receptiveness to ideas the scientific establishment has rejected.

“If lots of people believe it and it’s moving public health, we as NIH have an obligation, again, to treat it seriously,” Bhattacharya said at the event. According to The Chronicle at Duke University, Bhattacharya recently said he wants the NIH to be “the research arm of MAHA.”

The decision by the world’s premier cancer research institute to study ivermectin as a cancer treatment has alarmed career scientists at the agency.

“I am shocked and appalled,” one NCI scientist said. “We are moving funds away from so much promising research in order to do a preclinical study based on nonscientific ideas. It’s absurd.”

KFF Health News granted the scientist and other NCI workers anonymity because they are not authorized to speak to the press and fear retaliation.

HHS and the National Cancer Institute did not answer KFF Health News’ questions on the amount of money the cancer institute is spending on the study, who is carrying it out, and whether there was new evidence that prompted NCI to look into ivermectin as an anticancer therapy. Emily Hilliard, an HHS spokesperson, said NIH is dedicated to “rigorous, gold-standard research,” something the administration has repeatedly professed.

A preclinical study is an early phase of research conducted in a lab to test whether a drug or treatment may be useful and to assess potential harms. These studies take place before human clinical trials.

The scientist questioned whether there is enough initial evidence to warrant NCI’s spending of taxpayer funds to investigate the drug’s potential as a cancer treatment.

The FDA has approved ivermectin for certain uses in humans and animals. Tablets are used to treat conditions caused by parasitic worms, and the FDA has approved ivermectin lotions to treat lice and rosacea. Two scientists involved in its discovery won the Nobel Prize in 2015, tied to the drug’s success in treating certain parasitic diseases.

The FDA has warned that large doses of ivermectin can be dangerous. Overdoses can cause seizures, comas, or death.

Kennedy, supporters of the MAHA movement, and some conservative commentators have promoted the idea that the government and pharmaceutical companies quashed ivermectin and other inexpensive, off-patent drugs because they’re not profitable for the drug industry.

“FDA’s war on public health is about to end,” Kennedy wrote in an October 2024 X post that has since gone viral. “This includes its aggressive suppression of psychedelics, peptides, stem cells, raw milk, hyperbaric therapies, chelating compounds, ivermectin, hydroxychloroquine, vitamins, clean foods, sunshine, exercise, nutraceuticals and anything else that advances human health and can’t be patented by Pharma.”

Previous laboratory research has shown that ivermectin could have anticancer effects because it promotes cell death and inhibits the growth of tumor cells. “It actually has been studied both with NIH funds and outside of NIH funds,” Letai said.

However, there is no evidence that ivermectin is safe and effective in treating cancer in humans. Preliminary data from a small clinical trial that gave ivermectin to patients with one type of metastatic breast cancer, in combination with immunotherapy, found no significant benefit from the addition of ivermectin.

Some physicians are concerned that patients will delay or forgo effective cancer treatments, or be harmed in other ways, if they believe unfounded claims that ivermectin can treat their disease.

“Many, many, many things work in a test tube. Quite a few things work in a mouse or a monkey. It still doesn’t mean it’s going to work in people,” said Jeffery Edenfield, executive medical director of oncology for the South Carolina-based Prisma Health Cancer Institute.

Edenfield said cancer patients ask him about ivermectin “regularly,” mostly because of what they see on social media. He said he persuaded a patient to stop using it, and a colleague recently had a patient who decided “to forgo highly effective standard therapy in favor of ivermectin.”

“People come to the discussion having largely already made up their mind,” Edenfield said. “We’re in this delicate time when there’s sort of a fundamental mistrust of medicine,” he added. “Some people are just not going to believe me. I just have to keep trying.”

A June letter by clinicians at Cincinnati Children’s Hospital Medical Center in Ohio detailed how an adolescent patient with metastatic bone cancer started taking ivermectin “after encountering social media posts touting its benefits.” The patient — who hadn’t been given a prescription by a clinician — experienced ivermectin-related neurotoxicity and had to seek emergency care because of nausea, fatigue, and other symptoms.

“We urge the pediatric oncology community to advocate for sensible health policy that prioritizes the well-being of our patients,” the clinicians wrote. The lack of evidence about ivermectin and cancer hasn’t stopped celebrities and online influencers from promoting the notion that the drug is a cure-all. On a January 2025 episode of Joe Rogan’s podcast, actor Mel Gibson claimed that a combination of drugs that included ivermectin cured 3friends with stage IV cancer. The episode has been viewed > 12 million times.

Lawmakers in a handful of states have made the drug available over the counter. And Florida — which, under Republican Governor Ron DeSantis, has become a hotbed for anti-vaccine policies and the spread of public health misinformation — announced last fall that the state plans to fund research to study the drug as a potential cancer treatment.

The Florida Department of Health did not respond to questions about that effort.

Letai, previously a Dana-Farber Cancer Institute oncologist, started at the National Cancer Institute after months of upheaval caused by Trump administration policies.

“What you’re hearing at the NIH now is an openness to ideas — even ideas that scientists would say, ‘Oh, there’s no way it could work’ — but nevertheless applying rigorous scientific methods to those ideas,” Bhattacharya said at the January 30 event.

A second NCI scientist, who was granted anonymity due to fear of retaliation, said the notion that NIH was not open to investigating the value of off-label drugs in cancer is “ridiculous.”

“This is not a new idea they came up with,” the scientist said.

Letai didn’t elaborate on whether NCI scientists are conducting the research or if it has directed funding to an outside institution. Three-fourths of the cancer institute’s research dollars go to outside scientists.

He also aimed to temper expectations.

“At least on a population level,” Letai said, “it’s not going to be a cure-all for cancer.”

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:

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.