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A retrospective cohort study links clomiphene citrate (CC) to significantly lower mortality rates when compared with testosterone replacement therapy (TRT) in male veterans with hypogonadism or infertility. CC is not approved by the US Food and Drug Administration (FDA) for hypogonadism but is often used off label. Patients taking clomiphene also had significantly lower risk of diseases of the circulatory system, brain, and bones. 

The study tracked matched cohorts of 2518 patients taking CC or TRT for a mean 3.5 years. All-cause mortality was lower in the CC group (1.83%) than the TRT group (10.13%, P < .001), reported researchers at the Kansas City Veterans Affairs Medical Center and University of Missouri-Kansas City School of Medicine, et al in Andrology.

The researchers also reported that outcomes were better in the CC group than the TRT group for new-onset hypertension (6.04% vs 10.48%, P < .001), cerebrovascular accident (0.52% vs 1.43%, P < .001), coronary artery disease (1.51% vs 2.26%, P < .048), polycythemia (1.07% vs 2.22%, P < .001), and osteoporosis (1.15% vs 2.07%, P = .009), respectively. 

“It seems like clomiphene is a good medication to be used long term, but we still need more investigation into this,” endocrinologist Mariana Garcia-Touza, MD said in an interview with Federal Practitioner. 

TRT is a common therapy for male hypogonadism, although the study notes it is linked to thickened blood, breast growth, infertility, fluid retention, obstructive sleep apnea, and cardiovascular and prostate problems. Guidelines recommend against its use in patients with prostate cancer, at high cardiovascular risk, and those trying to have children.

CC is a selective estrogen receptor modulator and used off-label to treat male hypogonadism because it can boost the production of testosterone. The study notes how many Veterans health Administration patients have low testosterone, with previous research reporting the rate among veterans aged ≥ 60 years at 34%. 

Garcia-Touza was especially interested in any effect clomiphene has on bones: “We’ve been hearing that it probably affects the bone and can cause osteoporosis, but no one has looked into it.”

The study tracked veterans from December 1990 to September 2024; follow-ups lasted up to 34 years. Patient mean ages were 46.5 and 47.5 years for the HRT and CC groups, respectively. Hypogonadism was the treatment indication for 98.4% and 64.5% and infertility was the indication for 1.6% and 35.5% for the HRT and CC groups, respectively. About 70% of both groups were White. 

There were no statistically significant gaps between the groups regarding hip fractures, pulmonary embolism, thrombosis, and vertebral fractures. Garcia-Touza said the all-cause mortality gap the study reported was surprising, although the study did not control for factors that may have differed between the groups.

“This needs to be more carefully examined to see if this is a real finding or if there is some bias in the study that is causing it,” she said.

Moving forward, Garcia-Touza said she hopes to launch a prospective study of TRT vs CC.

Parviz K. Kavoussi, MD, a reproductive urologist at the University of Texas at Austin who was not involved in the study, said in an interview the study’s findings highlight the importance of monitoring patients on TRT for an increase in hematocrit. 

“Not all testosterone replacement therapies are created equal from this standpoint,” he said, noting that risk depends on the delivery method. “There are multiple modalities — topical gels, patches, nasal gels, intramuscular injections, subcutaneous pellets, subcutaneous autoinjector pens, and oral testosterone pills. Each of these has a defined percentage risk of secondary erythrocytosis, with some being significantly higher than others.”

As for other potential risks from TRT such as a possible higher mortality rate, Kavoussi noted that a landmark 2023 trial of middle-aged and older men convinced the FDA to no longer require testosterone products to include a black-box warning about cardiovascular disease. 

Regarding the question of whether clomiphene works as well as testosterone, Kavoussi noted his group’s research has found clomiphene can normalize testosterone levels biochemically. However, “where clomiphene typically falls short in data and in clinical practice is the level of symptomatic improvement in testosterone deficiency symptoms that patients can achieve in comparison to exogenous testosterone replacement.” 

No funding was reported, and the authors – including Garcia-Touza – had no disclosures. Kavoussi discloses relationships with Halozyme and Verity.

A retrospective cohort study links clomiphene citrate (CC) to significantly lower mortality rates when compared with testosterone replacement therapy (TRT) in male veterans with hypogonadism or infertility. CC is not approved by the US Food and Drug Administration (FDA) for hypogonadism but is often used off label. Patients taking clomiphene also had significantly lower risk of diseases of the circulatory system, brain, and bones. 

The study tracked matched cohorts of 2518 patients taking CC or TRT for a mean 3.5 years. All-cause mortality was lower in the CC group (1.83%) than the TRT group (10.13%, P < .001), reported researchers at the Kansas City Veterans Affairs Medical Center and University of Missouri-Kansas City School of Medicine, et al in Andrology.

The researchers also reported that outcomes were better in the CC group than the TRT group for new-onset hypertension (6.04% vs 10.48%, P < .001), cerebrovascular accident (0.52% vs 1.43%, P < .001), coronary artery disease (1.51% vs 2.26%, P < .048), polycythemia (1.07% vs 2.22%, P < .001), and osteoporosis (1.15% vs 2.07%, P = .009), respectively. 

“It seems like clomiphene is a good medication to be used long term, but we still need more investigation into this,” endocrinologist Mariana Garcia-Touza, MD said in an interview with Federal Practitioner. 

TRT is a common therapy for male hypogonadism, although the study notes it is linked to thickened blood, breast growth, infertility, fluid retention, obstructive sleep apnea, and cardiovascular and prostate problems. Guidelines recommend against its use in patients with prostate cancer, at high cardiovascular risk, and those trying to have children.

CC is a selective estrogen receptor modulator and used off-label to treat male hypogonadism because it can boost the production of testosterone. The study notes how many Veterans health Administration patients have low testosterone, with previous research reporting the rate among veterans aged ≥ 60 years at 34%. 

Garcia-Touza was especially interested in any effect clomiphene has on bones: “We’ve been hearing that it probably affects the bone and can cause osteoporosis, but no one has looked into it.”

The study tracked veterans from December 1990 to September 2024; follow-ups lasted up to 34 years. Patient mean ages were 46.5 and 47.5 years for the HRT and CC groups, respectively. Hypogonadism was the treatment indication for 98.4% and 64.5% and infertility was the indication for 1.6% and 35.5% for the HRT and CC groups, respectively. About 70% of both groups were White. 

There were no statistically significant gaps between the groups regarding hip fractures, pulmonary embolism, thrombosis, and vertebral fractures. Garcia-Touza said the all-cause mortality gap the study reported was surprising, although the study did not control for factors that may have differed between the groups.

“This needs to be more carefully examined to see if this is a real finding or if there is some bias in the study that is causing it,” she said.

Moving forward, Garcia-Touza said she hopes to launch a prospective study of TRT vs CC.

Parviz K. Kavoussi, MD, a reproductive urologist at the University of Texas at Austin who was not involved in the study, said in an interview the study’s findings highlight the importance of monitoring patients on TRT for an increase in hematocrit. 

“Not all testosterone replacement therapies are created equal from this standpoint,” he said, noting that risk depends on the delivery method. “There are multiple modalities — topical gels, patches, nasal gels, intramuscular injections, subcutaneous pellets, subcutaneous autoinjector pens, and oral testosterone pills. Each of these has a defined percentage risk of secondary erythrocytosis, with some being significantly higher than others.”

As for other potential risks from TRT such as a possible higher mortality rate, Kavoussi noted that a landmark 2023 trial of middle-aged and older men convinced the FDA to no longer require testosterone products to include a black-box warning about cardiovascular disease. 

Regarding the question of whether clomiphene works as well as testosterone, Kavoussi noted his group’s research has found clomiphene can normalize testosterone levels biochemically. However, “where clomiphene typically falls short in data and in clinical practice is the level of symptomatic improvement in testosterone deficiency symptoms that patients can achieve in comparison to exogenous testosterone replacement.” 

No funding was reported, and the authors – including Garcia-Touza – had no disclosures. Kavoussi discloses relationships with Halozyme and Verity.

A retrospective cohort study links clomiphene citrate (CC) to significantly lower mortality rates when compared with testosterone replacement therapy (TRT) in male veterans with hypogonadism or infertility. CC is not approved by the US Food and Drug Administration (FDA) for hypogonadism but is often used off label. Patients taking clomiphene also had significantly lower risk of diseases of the circulatory system, brain, and bones. 

The study tracked matched cohorts of 2518 patients taking CC or TRT for a mean 3.5 years. All-cause mortality was lower in the CC group (1.83%) than the TRT group (10.13%, P < .001), reported researchers at the Kansas City Veterans Affairs Medical Center and University of Missouri-Kansas City School of Medicine, et al in Andrology.

The researchers also reported that outcomes were better in the CC group than the TRT group for new-onset hypertension (6.04% vs 10.48%, P < .001), cerebrovascular accident (0.52% vs 1.43%, P < .001), coronary artery disease (1.51% vs 2.26%, P < .048), polycythemia (1.07% vs 2.22%, P < .001), and osteoporosis (1.15% vs 2.07%, P = .009), respectively. 

“It seems like clomiphene is a good medication to be used long term, but we still need more investigation into this,” endocrinologist Mariana Garcia-Touza, MD said in an interview with Federal Practitioner. 

TRT is a common therapy for male hypogonadism, although the study notes it is linked to thickened blood, breast growth, infertility, fluid retention, obstructive sleep apnea, and cardiovascular and prostate problems. Guidelines recommend against its use in patients with prostate cancer, at high cardiovascular risk, and those trying to have children.

CC is a selective estrogen receptor modulator and used off-label to treat male hypogonadism because it can boost the production of testosterone. The study notes how many Veterans health Administration patients have low testosterone, with previous research reporting the rate among veterans aged ≥ 60 years at 34%. 

Garcia-Touza was especially interested in any effect clomiphene has on bones: “We’ve been hearing that it probably affects the bone and can cause osteoporosis, but no one has looked into it.”

The study tracked veterans from December 1990 to September 2024; follow-ups lasted up to 34 years. Patient mean ages were 46.5 and 47.5 years for the HRT and CC groups, respectively. Hypogonadism was the treatment indication for 98.4% and 64.5% and infertility was the indication for 1.6% and 35.5% for the HRT and CC groups, respectively. About 70% of both groups were White. 

There were no statistically significant gaps between the groups regarding hip fractures, pulmonary embolism, thrombosis, and vertebral fractures. Garcia-Touza said the all-cause mortality gap the study reported was surprising, although the study did not control for factors that may have differed between the groups.

“This needs to be more carefully examined to see if this is a real finding or if there is some bias in the study that is causing it,” she said.

Moving forward, Garcia-Touza said she hopes to launch a prospective study of TRT vs CC.

Parviz K. Kavoussi, MD, a reproductive urologist at the University of Texas at Austin who was not involved in the study, said in an interview the study’s findings highlight the importance of monitoring patients on TRT for an increase in hematocrit. 

“Not all testosterone replacement therapies are created equal from this standpoint,” he said, noting that risk depends on the delivery method. “There are multiple modalities — topical gels, patches, nasal gels, intramuscular injections, subcutaneous pellets, subcutaneous autoinjector pens, and oral testosterone pills. Each of these has a defined percentage risk of secondary erythrocytosis, with some being significantly higher than others.”

As for other potential risks from TRT such as a possible higher mortality rate, Kavoussi noted that a landmark 2023 trial of middle-aged and older men convinced the FDA to no longer require testosterone products to include a black-box warning about cardiovascular disease. 

Regarding the question of whether clomiphene works as well as testosterone, Kavoussi noted his group’s research has found clomiphene can normalize testosterone levels biochemically. However, “where clomiphene typically falls short in data and in clinical practice is the level of symptomatic improvement in testosterone deficiency symptoms that patients can achieve in comparison to exogenous testosterone replacement.” 

No funding was reported, and the authors – including Garcia-Touza – had no disclosures. Kavoussi discloses relationships with Halozyme and Verity.

The heart is one of the organs least likely to develop cancer, a long-standing biologic puzzle that may now have an explanation. A study published in Science found that the mechanical load generated by the beating heart suppresses tumor cell proliferation through a molecular pathway that alters gene expression, raising the possibility of new therapeutic targets.

Mechanical Protection

Tumors that originate directly in the myocardium are exceptionally rare, occurring in < 1% of autopsies. Even cardiac metastases, which have been reported in up to 18% of autopsies, are often small, asymptomatic, and incidentally discovered. Although this phenomenon has long been recognized, its biologic basis remains unclear.

The heart is notable for its limited capacity for regeneration. After birth, cardiomyocytes stop dividing and subsequently renew at a rate of about 1% per year. However, when the mechanical load is reduced, such as in patients supported by left ventricular assist devices, cardiomyocytes once again show signs of proliferation.

This observation prompted researchers to investigate whether the same mechanical load that restrains normal cardiac cells might also suppress cancer growth.

More Load, Less Growth

To investigate this question, researchers introduced two genetic alterations commonly found in human cancers, activation of the KRAS oncogene and loss of the TP53, into the liver, skeletal muscle, and hearts of mice. Tumors developed in multiple organs, but not in the heart.

The researchers then used a heterotopic heart transplant model in which a donor mouse’s heart is surgically connected to the neck (cervical) or abdominal vessels of a recipient mouse. The transplanted heart remained perfused but lost its normal mechanical loading (constant beating).

When researchers injected lung adenocarcinoma cells into 2 different hearts of the same animal, they observed entirely different outcomes. The cancer cells did not grow in the native mechanically loaded heart. However, the same cells grew rapidly and extensively in the mechanically unloaded transplanted heart.

Tumor cells had replaced nearly all normal tissue in the unloaded heart, whereas they occupied only approximately 20% of the ventricle in the native heart in 14 days. This difference could not be explained by differences in the initial tumor engraftment or cell death. Instead, the findings pointed to substantial differences in tumor cell proliferation.

Similar results were observed in bioengineered cardiac tissues exposed to varying degrees of mechanical stress. Tumor cells proliferated under conditions of low mechanical load but ceased proliferating as the mechanical load increased. Tumor growth was lowest in regions exposed to the greatest mechanical stimulation of cardiomyocytes in vitro.

However, the possibility of metabolic competition between cardiac and tumor cells for nutrition was ruled out.

From Mechanics to Genes

Next, we examined the influence of mechanical forces on tumor cell behavior.

Gene expression analyses of both human cardiac metastases and mouse tumor cells showed that mechanical stimulation altered chromatin accessibility through the activation of genes involved in chromatin remodeling. These changes promoted the expression of genes that suppress cell division.

The study also identified Nesprin-2, a part of the linker of the nucleoskeleton and cytoskeleton complex, which acts as a physical bridge. It is a multitasking protein that connects the cell’s outer structural network (cytoskeleton) to its inner genetic storage (nucleus) and appears to play a significant role in converting mechanical signals into changes in gene expression.

When Nesprin-2 was inactivated, cancer cells resumed proliferation despite exposure to a mechanical load, both in engineered tissues and animal models.

“Collectively, these results shed light on the role of mechanical forces in protecting the heart from cancer and may pave the way to cancer therapies based on mechanical stimulation,” concluded the authors.

An Actively Protected Organ

Speaking with Univadis Italy, part of the Medscape Professional Network, Giorgio Scita, PhD, director of the Mechanisms of Tumor Cell Migration research unit at AIRC Institute of Molecular Oncology and professor of general pathology at the University of Milan in Milan, Italy, said, “The study addressed a simple but fundamental question: Why is the heart largely resistant to cancer despite being highly vascularized and continuously exposed to circulating tumor cells?

These findings suggest that the heartbeat itself creates a mechanical environment that is hostile to tumor growth. The compressive forces generated by rhythmic myocardial contraction are sensed by cancer cells and translated into biochemical signals that limit their proliferation.

In this view, the heart is not simply an organ that is unfavorable for cancer growth but a tissue actively protected by its own mechanical forces.”

Speaking with Univadis Italy, Serena Zacchigna, PhD, study coauthor and head of the Cardiovascular Biology Laboratory at the International Centre for Genetic Engineering and Biotechnology, Trieste, Italy, said, “Until now, however, attention had focused primarily on signals from the extracellular matrix, such as tissue stiffness. Our study adds a new element: even forces generated directly by the movement of an organ — in this case, cardiac contraction — can influence the growth of cancer cells.”

Beyond the Heart

Scita said the findings have implications that extend well beyond the heart.

“The most significant aspect is that this work identifies tissue mechanics as an active regulator of tumor behavior,” he said. Stiffness, compression, tension, and confinement are not merely consequences of tumor growth, but factors capable of influencing proliferation, invasion, and dormancy.

The concept may apply to many solid tumors. Scita noted that cancer cells growing in confined environments, such as ductal carcinoma in situ of the breast, are exposed to substantial mechanical constraints. Understanding why some tumor cells remain susceptible to these forces whereas others evade them and become invasive remains a major unanswered question in cancer biology.

Research on these mechanisms is expanding internationally and in Italy as well. One example is the AIRC “5 per mille” (5 per thousand) research programs on metastatic disease, which includes projects designed to clarify how the mechanical properties of tumor tissue influence cancer initiation, metastatic spread, and disease progression.

Therapeutic Potential

According to Zacchigna, these findings open 2 principal avenues for future research.

“The first focuses on mechanical stimulation itself. In collaboration with engineers at the University of Siena, including a group led by Domenico Prattichizzo, researchers are developing wearable robotic devices designed to mimic the heartbeat and deliver mechanical stimulation to superficial solid tumors such as certain skin cancers.

The second approach is pharmacology. Researchers are investigating whether epigenetic therapies capable of modifying chromatin remodeling can reproduce the effects of cardiac contraction and suppress tumor cell proliferation.

However, Zacchigna cautioned that this work remains at an early experimental phase.”

However, before therapeutic applications can be pursued, important mechanistic questions remain unanswered.

Zacchigna noted that although the linker of nucleoskeleton and cytoskeleton (LINC) complex and Nesprin-2 are involved in signal transduction leading to chromatin reorganization and activation of cell cycle inhibitory loci, the molecular intermediates involved have yet to be fully defined.

Researchers also need to determine which genes are most critical, whether the mechanism operates across different tumor types, and whether it can be safely manipulated for therapeutic purposes.

In an accompanying commentary published in Science, Wyatt G. Paltzer, PhD, and James F. Martin, MD, from the Department of Integrative Physiology at the Baylor College of Medicine in Houston, noted that the findings suggest enhancing LINC complex activity could potentially suppress tumor growth.

However, because the complex has broad biologic functions, it may prove difficult to target therapeutically. The authors suggested that future studies should focus on identifying proteins that interact with Nesprin-2 or other components of the LINC complex and play a more specific role in inhibiting cancer cell proliferation.

Looking Ahead

Despite these challenges, Scita said that the study’s conceptual significance is already clear.

“Even if therapeutic applications remain years away, the findings suggest that cancer may one day be targeted by altering how tumor cells perceive and interpret physical forces.”

Scita and Zacchigna reported having no relevant conflicts of interest.

This story was translated from Univadis Italy.

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

The heart is one of the organs least likely to develop cancer, a long-standing biologic puzzle that may now have an explanation. A study published in Science found that the mechanical load generated by the beating heart suppresses tumor cell proliferation through a molecular pathway that alters gene expression, raising the possibility of new therapeutic targets.

Mechanical Protection

Tumors that originate directly in the myocardium are exceptionally rare, occurring in < 1% of autopsies. Even cardiac metastases, which have been reported in up to 18% of autopsies, are often small, asymptomatic, and incidentally discovered. Although this phenomenon has long been recognized, its biologic basis remains unclear.

The heart is notable for its limited capacity for regeneration. After birth, cardiomyocytes stop dividing and subsequently renew at a rate of about 1% per year. However, when the mechanical load is reduced, such as in patients supported by left ventricular assist devices, cardiomyocytes once again show signs of proliferation.

This observation prompted researchers to investigate whether the same mechanical load that restrains normal cardiac cells might also suppress cancer growth.

More Load, Less Growth

To investigate this question, researchers introduced two genetic alterations commonly found in human cancers, activation of the KRAS oncogene and loss of the TP53, into the liver, skeletal muscle, and hearts of mice. Tumors developed in multiple organs, but not in the heart.

The researchers then used a heterotopic heart transplant model in which a donor mouse’s heart is surgically connected to the neck (cervical) or abdominal vessels of a recipient mouse. The transplanted heart remained perfused but lost its normal mechanical loading (constant beating).

When researchers injected lung adenocarcinoma cells into 2 different hearts of the same animal, they observed entirely different outcomes. The cancer cells did not grow in the native mechanically loaded heart. However, the same cells grew rapidly and extensively in the mechanically unloaded transplanted heart.

Tumor cells had replaced nearly all normal tissue in the unloaded heart, whereas they occupied only approximately 20% of the ventricle in the native heart in 14 days. This difference could not be explained by differences in the initial tumor engraftment or cell death. Instead, the findings pointed to substantial differences in tumor cell proliferation.

Similar results were observed in bioengineered cardiac tissues exposed to varying degrees of mechanical stress. Tumor cells proliferated under conditions of low mechanical load but ceased proliferating as the mechanical load increased. Tumor growth was lowest in regions exposed to the greatest mechanical stimulation of cardiomyocytes in vitro.

However, the possibility of metabolic competition between cardiac and tumor cells for nutrition was ruled out.

From Mechanics to Genes

Next, we examined the influence of mechanical forces on tumor cell behavior.

Gene expression analyses of both human cardiac metastases and mouse tumor cells showed that mechanical stimulation altered chromatin accessibility through the activation of genes involved in chromatin remodeling. These changes promoted the expression of genes that suppress cell division.

The study also identified Nesprin-2, a part of the linker of the nucleoskeleton and cytoskeleton complex, which acts as a physical bridge. It is a multitasking protein that connects the cell’s outer structural network (cytoskeleton) to its inner genetic storage (nucleus) and appears to play a significant role in converting mechanical signals into changes in gene expression.

When Nesprin-2 was inactivated, cancer cells resumed proliferation despite exposure to a mechanical load, both in engineered tissues and animal models.

“Collectively, these results shed light on the role of mechanical forces in protecting the heart from cancer and may pave the way to cancer therapies based on mechanical stimulation,” concluded the authors.

An Actively Protected Organ

Speaking with Univadis Italy, part of the Medscape Professional Network, Giorgio Scita, PhD, director of the Mechanisms of Tumor Cell Migration research unit at AIRC Institute of Molecular Oncology and professor of general pathology at the University of Milan in Milan, Italy, said, “The study addressed a simple but fundamental question: Why is the heart largely resistant to cancer despite being highly vascularized and continuously exposed to circulating tumor cells?

These findings suggest that the heartbeat itself creates a mechanical environment that is hostile to tumor growth. The compressive forces generated by rhythmic myocardial contraction are sensed by cancer cells and translated into biochemical signals that limit their proliferation.

In this view, the heart is not simply an organ that is unfavorable for cancer growth but a tissue actively protected by its own mechanical forces.”

Speaking with Univadis Italy, Serena Zacchigna, PhD, study coauthor and head of the Cardiovascular Biology Laboratory at the International Centre for Genetic Engineering and Biotechnology, Trieste, Italy, said, “Until now, however, attention had focused primarily on signals from the extracellular matrix, such as tissue stiffness. Our study adds a new element: even forces generated directly by the movement of an organ — in this case, cardiac contraction — can influence the growth of cancer cells.”

Beyond the Heart

Scita said the findings have implications that extend well beyond the heart.

“The most significant aspect is that this work identifies tissue mechanics as an active regulator of tumor behavior,” he said. Stiffness, compression, tension, and confinement are not merely consequences of tumor growth, but factors capable of influencing proliferation, invasion, and dormancy.

The concept may apply to many solid tumors. Scita noted that cancer cells growing in confined environments, such as ductal carcinoma in situ of the breast, are exposed to substantial mechanical constraints. Understanding why some tumor cells remain susceptible to these forces whereas others evade them and become invasive remains a major unanswered question in cancer biology.

Research on these mechanisms is expanding internationally and in Italy as well. One example is the AIRC “5 per mille” (5 per thousand) research programs on metastatic disease, which includes projects designed to clarify how the mechanical properties of tumor tissue influence cancer initiation, metastatic spread, and disease progression.

Therapeutic Potential

According to Zacchigna, these findings open 2 principal avenues for future research.

“The first focuses on mechanical stimulation itself. In collaboration with engineers at the University of Siena, including a group led by Domenico Prattichizzo, researchers are developing wearable robotic devices designed to mimic the heartbeat and deliver mechanical stimulation to superficial solid tumors such as certain skin cancers.

The second approach is pharmacology. Researchers are investigating whether epigenetic therapies capable of modifying chromatin remodeling can reproduce the effects of cardiac contraction and suppress tumor cell proliferation.

However, Zacchigna cautioned that this work remains at an early experimental phase.”

However, before therapeutic applications can be pursued, important mechanistic questions remain unanswered.

Zacchigna noted that although the linker of nucleoskeleton and cytoskeleton (LINC) complex and Nesprin-2 are involved in signal transduction leading to chromatin reorganization and activation of cell cycle inhibitory loci, the molecular intermediates involved have yet to be fully defined.

Researchers also need to determine which genes are most critical, whether the mechanism operates across different tumor types, and whether it can be safely manipulated for therapeutic purposes.

In an accompanying commentary published in Science, Wyatt G. Paltzer, PhD, and James F. Martin, MD, from the Department of Integrative Physiology at the Baylor College of Medicine in Houston, noted that the findings suggest enhancing LINC complex activity could potentially suppress tumor growth.

However, because the complex has broad biologic functions, it may prove difficult to target therapeutically. The authors suggested that future studies should focus on identifying proteins that interact with Nesprin-2 or other components of the LINC complex and play a more specific role in inhibiting cancer cell proliferation.

Looking Ahead

Despite these challenges, Scita said that the study’s conceptual significance is already clear.

“Even if therapeutic applications remain years away, the findings suggest that cancer may one day be targeted by altering how tumor cells perceive and interpret physical forces.”

Scita and Zacchigna reported having no relevant conflicts of interest.

This story was translated from Univadis Italy.

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

The heart is one of the organs least likely to develop cancer, a long-standing biologic puzzle that may now have an explanation. A study published in Science found that the mechanical load generated by the beating heart suppresses tumor cell proliferation through a molecular pathway that alters gene expression, raising the possibility of new therapeutic targets.

Mechanical Protection

Tumors that originate directly in the myocardium are exceptionally rare, occurring in < 1% of autopsies. Even cardiac metastases, which have been reported in up to 18% of autopsies, are often small, asymptomatic, and incidentally discovered. Although this phenomenon has long been recognized, its biologic basis remains unclear.

The heart is notable for its limited capacity for regeneration. After birth, cardiomyocytes stop dividing and subsequently renew at a rate of about 1% per year. However, when the mechanical load is reduced, such as in patients supported by left ventricular assist devices, cardiomyocytes once again show signs of proliferation.

This observation prompted researchers to investigate whether the same mechanical load that restrains normal cardiac cells might also suppress cancer growth.

More Load, Less Growth

To investigate this question, researchers introduced two genetic alterations commonly found in human cancers, activation of the KRAS oncogene and loss of the TP53, into the liver, skeletal muscle, and hearts of mice. Tumors developed in multiple organs, but not in the heart.

The researchers then used a heterotopic heart transplant model in which a donor mouse’s heart is surgically connected to the neck (cervical) or abdominal vessels of a recipient mouse. The transplanted heart remained perfused but lost its normal mechanical loading (constant beating).

When researchers injected lung adenocarcinoma cells into 2 different hearts of the same animal, they observed entirely different outcomes. The cancer cells did not grow in the native mechanically loaded heart. However, the same cells grew rapidly and extensively in the mechanically unloaded transplanted heart.

Tumor cells had replaced nearly all normal tissue in the unloaded heart, whereas they occupied only approximately 20% of the ventricle in the native heart in 14 days. This difference could not be explained by differences in the initial tumor engraftment or cell death. Instead, the findings pointed to substantial differences in tumor cell proliferation.

Similar results were observed in bioengineered cardiac tissues exposed to varying degrees of mechanical stress. Tumor cells proliferated under conditions of low mechanical load but ceased proliferating as the mechanical load increased. Tumor growth was lowest in regions exposed to the greatest mechanical stimulation of cardiomyocytes in vitro.

However, the possibility of metabolic competition between cardiac and tumor cells for nutrition was ruled out.

From Mechanics to Genes

Next, we examined the influence of mechanical forces on tumor cell behavior.

Gene expression analyses of both human cardiac metastases and mouse tumor cells showed that mechanical stimulation altered chromatin accessibility through the activation of genes involved in chromatin remodeling. These changes promoted the expression of genes that suppress cell division.

The study also identified Nesprin-2, a part of the linker of the nucleoskeleton and cytoskeleton complex, which acts as a physical bridge. It is a multitasking protein that connects the cell’s outer structural network (cytoskeleton) to its inner genetic storage (nucleus) and appears to play a significant role in converting mechanical signals into changes in gene expression.

When Nesprin-2 was inactivated, cancer cells resumed proliferation despite exposure to a mechanical load, both in engineered tissues and animal models.

“Collectively, these results shed light on the role of mechanical forces in protecting the heart from cancer and may pave the way to cancer therapies based on mechanical stimulation,” concluded the authors.

An Actively Protected Organ

Speaking with Univadis Italy, part of the Medscape Professional Network, Giorgio Scita, PhD, director of the Mechanisms of Tumor Cell Migration research unit at AIRC Institute of Molecular Oncology and professor of general pathology at the University of Milan in Milan, Italy, said, “The study addressed a simple but fundamental question: Why is the heart largely resistant to cancer despite being highly vascularized and continuously exposed to circulating tumor cells?

These findings suggest that the heartbeat itself creates a mechanical environment that is hostile to tumor growth. The compressive forces generated by rhythmic myocardial contraction are sensed by cancer cells and translated into biochemical signals that limit their proliferation.

In this view, the heart is not simply an organ that is unfavorable for cancer growth but a tissue actively protected by its own mechanical forces.”

Speaking with Univadis Italy, Serena Zacchigna, PhD, study coauthor and head of the Cardiovascular Biology Laboratory at the International Centre for Genetic Engineering and Biotechnology, Trieste, Italy, said, “Until now, however, attention had focused primarily on signals from the extracellular matrix, such as tissue stiffness. Our study adds a new element: even forces generated directly by the movement of an organ — in this case, cardiac contraction — can influence the growth of cancer cells.”

Beyond the Heart

Scita said the findings have implications that extend well beyond the heart.

“The most significant aspect is that this work identifies tissue mechanics as an active regulator of tumor behavior,” he said. Stiffness, compression, tension, and confinement are not merely consequences of tumor growth, but factors capable of influencing proliferation, invasion, and dormancy.

The concept may apply to many solid tumors. Scita noted that cancer cells growing in confined environments, such as ductal carcinoma in situ of the breast, are exposed to substantial mechanical constraints. Understanding why some tumor cells remain susceptible to these forces whereas others evade them and become invasive remains a major unanswered question in cancer biology.

Research on these mechanisms is expanding internationally and in Italy as well. One example is the AIRC “5 per mille” (5 per thousand) research programs on metastatic disease, which includes projects designed to clarify how the mechanical properties of tumor tissue influence cancer initiation, metastatic spread, and disease progression.

Therapeutic Potential

According to Zacchigna, these findings open 2 principal avenues for future research.

“The first focuses on mechanical stimulation itself. In collaboration with engineers at the University of Siena, including a group led by Domenico Prattichizzo, researchers are developing wearable robotic devices designed to mimic the heartbeat and deliver mechanical stimulation to superficial solid tumors such as certain skin cancers.

The second approach is pharmacology. Researchers are investigating whether epigenetic therapies capable of modifying chromatin remodeling can reproduce the effects of cardiac contraction and suppress tumor cell proliferation.

However, Zacchigna cautioned that this work remains at an early experimental phase.”

However, before therapeutic applications can be pursued, important mechanistic questions remain unanswered.

Zacchigna noted that although the linker of nucleoskeleton and cytoskeleton (LINC) complex and Nesprin-2 are involved in signal transduction leading to chromatin reorganization and activation of cell cycle inhibitory loci, the molecular intermediates involved have yet to be fully defined.

Researchers also need to determine which genes are most critical, whether the mechanism operates across different tumor types, and whether it can be safely manipulated for therapeutic purposes.

In an accompanying commentary published in Science, Wyatt G. Paltzer, PhD, and James F. Martin, MD, from the Department of Integrative Physiology at the Baylor College of Medicine in Houston, noted that the findings suggest enhancing LINC complex activity could potentially suppress tumor growth.

However, because the complex has broad biologic functions, it may prove difficult to target therapeutically. The authors suggested that future studies should focus on identifying proteins that interact with Nesprin-2 or other components of the LINC complex and play a more specific role in inhibiting cancer cell proliferation.

Looking Ahead

Despite these challenges, Scita said that the study’s conceptual significance is already clear.

“Even if therapeutic applications remain years away, the findings suggest that cancer may one day be targeted by altering how tumor cells perceive and interpret physical forces.”

Scita and Zacchigna reported having no relevant conflicts of interest.

This story was translated from Univadis Italy.

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

Oral nicotinamide was cost-effective for reducing keratinocyte carcinoma (KC) risk in US veterans with a history of the disease, according to an economic analysis of Veterans Health Administration (VHA) data.

The findings, published online June 10 in JAMA Dermatology, “support strong consideration of nicotinamide for KC prevention in high-risk populations like veterans, particularly given its safety and tolerability,” wrote senior author Rebecca I. Hartman, MD, chief of the Dermatology Section at VA Boston and assistant professor of dermatology at Brigham and Women’s Hospital and Harvard Medical School, Boston, and co-authors.

Nicotinamide supplementation is “not only a cost-effective and patient-centric strategy for KC prevention, but it also remains economically favorable under a range of assumptions and may become even more cost-effective under higher procedure costs and frequency,” noted the authors.

The analysis included 33,822 individuals from the VHA database, all with a history of one or more KCs, including those with nicotinamide exposure for 30 or more days (n = 12,287) and those without that exposure (n = 21,535).

The mean ages in the unexposed and exposed cohorts were 76.9 and 77.2 years, respectively, and 98% were men. Procedural US VHA costs for KC treatment were estimated from previous research and adjusted for inflation. Nicotinamide pricing was obtained from the VHA.

KC incidence among nicotinamide-exposed and unexposed individuals was 0.204 and 0.255 events per person-year, respectively, reflecting an absolute risk reduction of 0.051 and 624 KCs prevented annually with nicotinamide supplementation.

With an estimated cost of $843 per KC, the yearly KC treatment expense was estimated at approximately $2.64 million, and the annual nicotinamide cost was estimated at $161,451, resulting in net savings of $364,581 — a 19.9% reduction in cohort-specific costs.

Assuming a quality-adjusted life-year (QALY) decrement of -0.01 per KC, nicotinamide use yielded an annual gain of 6.24 QALYs across the cohort and a savings of $58,426 per QALY gained.

A calculation of non-VHA cost-effectiveness, estimated with civilian prices and distributions, showed savings of $14,407 per QALY gained.

The authors concluded that oral nicotinamide was “a cost-effective and patient-centric preventive approach for KC, particularly in individuals with KC history at high risk of multiple primary KC.”

In an accompanying editorial, Ivo Abraham, PhD, JAMA Dermatology’s associate editor for quantitative methods and chief scientist at Matrix45, a health economics research and consulting group in Tucson, Arizona, and co-authors noted that although nicotinamide “is inexpensive, widely available, and mechanistically plausible for chemoprevention of actinic keratoses and KCs…stronger evidence remains required to support clinical recommendations.”

“Broader nicotinamide implementation might impart substantial population health benefits and cost savings to the VHA,” they wrote, while also asking, “do we truly know whether nicotinamide is effective for KC chemoprevention in broader populations?” They suggested that only an adequately powered randomized clinical trial in representative nonimmunosuppressed populations would provide the answer.

“Additional randomized controlled trials in non-VHA populations would provide further insight into generalizability beyond the VA healthcare system,” Hartman told Medscape Medical News.

“We are aiming to conduct a large [randomized controlled trial] in the VA to provide a more definitive answer,” added Lee Wheless, MD, one of Hartman’s coauthors, from Vanderbilt University Medical Center and the Tennessee Valley Healthcare System VA Medical Center, both in Nashville, Tennessee. “Doing so would also give a much better estimate of any potential side effects, though we and others have found no increased rate, and sometimes even a decreased rate, of major adverse cardiovascular events.”

Sarah Arron, MD, dermatologic surgeon with Palo Alto Foundation Medical Group in Palo Alto, California, and Premier Aesthetic Dermatology in San Carlos, California, who was not involved in the research, said, “It is gratifying to see that in the veteran population, nicotinamide affords protection against nonmelanoma skin cancer and is a cost-effective intervention. For a healthcare system such as the VHA, providing this over-the-counter vitamin through pharmacy benefits is an excellent method for reducing the overall cost of skin cancer treatment.”

Although Arron agreed that a randomized trial would offer a higher level of evidence for this intervention, she said the real-world obstacle is that nicotinamide is such an easily available, low-cost vitamin with a high safety profile. “Patients are not likely to sign up for a possible placebo when they can purchase nicotinamide online or at the drugstore,” she said. “This was reflected in Australia; once the positive data from the ONTRAC trial was publicized, investigators on the ONTRANS trial had difficulty enrolling patients because they were already taking the vitamin. The second study closed without meeting its enrollment goals and thus did not have power to show statistical significance.”

Hartman is supported by the US Department of Defense and the US Department of Veterans Affairs. Wheless is also supported by the US Department of Veterans Affairs. Arron is a speaker for Regeneron and Castle Biosciences; a consultant for Regeneron, Replimune, Castle, Lumenis, and Enspectra Health; an unpaid ambassador for HarkenDerm, which makes sunscreen as well as a sun and eye health supplement that includes nicotinamide as one of the ingredients.

The study authors reported having no conflicts of interest. Of the editorial authors, Abraham disclosed owning stock in Matrix45, which has received contract funding from companies outside this work, one author had disclosures not related to the work, and the third author had no disclosures.

Kate Johnson is a Montreal-based freelance medical journalist who has been writing for > 30 years about all areas of medicine.

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

Oral nicotinamide was cost-effective for reducing keratinocyte carcinoma (KC) risk in US veterans with a history of the disease, according to an economic analysis of Veterans Health Administration (VHA) data.

The findings, published online June 10 in JAMA Dermatology, “support strong consideration of nicotinamide for KC prevention in high-risk populations like veterans, particularly given its safety and tolerability,” wrote senior author Rebecca I. Hartman, MD, chief of the Dermatology Section at VA Boston and assistant professor of dermatology at Brigham and Women’s Hospital and Harvard Medical School, Boston, and co-authors.

Nicotinamide supplementation is “not only a cost-effective and patient-centric strategy for KC prevention, but it also remains economically favorable under a range of assumptions and may become even more cost-effective under higher procedure costs and frequency,” noted the authors.

The analysis included 33,822 individuals from the VHA database, all with a history of one or more KCs, including those with nicotinamide exposure for 30 or more days (n = 12,287) and those without that exposure (n = 21,535).

The mean ages in the unexposed and exposed cohorts were 76.9 and 77.2 years, respectively, and 98% were men. Procedural US VHA costs for KC treatment were estimated from previous research and adjusted for inflation. Nicotinamide pricing was obtained from the VHA.

KC incidence among nicotinamide-exposed and unexposed individuals was 0.204 and 0.255 events per person-year, respectively, reflecting an absolute risk reduction of 0.051 and 624 KCs prevented annually with nicotinamide supplementation.

With an estimated cost of $843 per KC, the yearly KC treatment expense was estimated at approximately $2.64 million, and the annual nicotinamide cost was estimated at $161,451, resulting in net savings of $364,581 — a 19.9% reduction in cohort-specific costs.

Assuming a quality-adjusted life-year (QALY) decrement of -0.01 per KC, nicotinamide use yielded an annual gain of 6.24 QALYs across the cohort and a savings of $58,426 per QALY gained.

A calculation of non-VHA cost-effectiveness, estimated with civilian prices and distributions, showed savings of $14,407 per QALY gained.

The authors concluded that oral nicotinamide was “a cost-effective and patient-centric preventive approach for KC, particularly in individuals with KC history at high risk of multiple primary KC.”

In an accompanying editorial, Ivo Abraham, PhD, JAMA Dermatology’s associate editor for quantitative methods and chief scientist at Matrix45, a health economics research and consulting group in Tucson, Arizona, and co-authors noted that although nicotinamide “is inexpensive, widely available, and mechanistically plausible for chemoprevention of actinic keratoses and KCs…stronger evidence remains required to support clinical recommendations.”

“Broader nicotinamide implementation might impart substantial population health benefits and cost savings to the VHA,” they wrote, while also asking, “do we truly know whether nicotinamide is effective for KC chemoprevention in broader populations?” They suggested that only an adequately powered randomized clinical trial in representative nonimmunosuppressed populations would provide the answer.

“Additional randomized controlled trials in non-VHA populations would provide further insight into generalizability beyond the VA healthcare system,” Hartman told Medscape Medical News.

“We are aiming to conduct a large [randomized controlled trial] in the VA to provide a more definitive answer,” added Lee Wheless, MD, one of Hartman’s coauthors, from Vanderbilt University Medical Center and the Tennessee Valley Healthcare System VA Medical Center, both in Nashville, Tennessee. “Doing so would also give a much better estimate of any potential side effects, though we and others have found no increased rate, and sometimes even a decreased rate, of major adverse cardiovascular events.”

Sarah Arron, MD, dermatologic surgeon with Palo Alto Foundation Medical Group in Palo Alto, California, and Premier Aesthetic Dermatology in San Carlos, California, who was not involved in the research, said, “It is gratifying to see that in the veteran population, nicotinamide affords protection against nonmelanoma skin cancer and is a cost-effective intervention. For a healthcare system such as the VHA, providing this over-the-counter vitamin through pharmacy benefits is an excellent method for reducing the overall cost of skin cancer treatment.”

Although Arron agreed that a randomized trial would offer a higher level of evidence for this intervention, she said the real-world obstacle is that nicotinamide is such an easily available, low-cost vitamin with a high safety profile. “Patients are not likely to sign up for a possible placebo when they can purchase nicotinamide online or at the drugstore,” she said. “This was reflected in Australia; once the positive data from the ONTRAC trial was publicized, investigators on the ONTRANS trial had difficulty enrolling patients because they were already taking the vitamin. The second study closed without meeting its enrollment goals and thus did not have power to show statistical significance.”

Hartman is supported by the US Department of Defense and the US Department of Veterans Affairs. Wheless is also supported by the US Department of Veterans Affairs. Arron is a speaker for Regeneron and Castle Biosciences; a consultant for Regeneron, Replimune, Castle, Lumenis, and Enspectra Health; an unpaid ambassador for HarkenDerm, which makes sunscreen as well as a sun and eye health supplement that includes nicotinamide as one of the ingredients.

The study authors reported having no conflicts of interest. Of the editorial authors, Abraham disclosed owning stock in Matrix45, which has received contract funding from companies outside this work, one author had disclosures not related to the work, and the third author had no disclosures.

Kate Johnson is a Montreal-based freelance medical journalist who has been writing for > 30 years about all areas of medicine.

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

Oral nicotinamide was cost-effective for reducing keratinocyte carcinoma (KC) risk in US veterans with a history of the disease, according to an economic analysis of Veterans Health Administration (VHA) data.

The findings, published online June 10 in JAMA Dermatology, “support strong consideration of nicotinamide for KC prevention in high-risk populations like veterans, particularly given its safety and tolerability,” wrote senior author Rebecca I. Hartman, MD, chief of the Dermatology Section at VA Boston and assistant professor of dermatology at Brigham and Women’s Hospital and Harvard Medical School, Boston, and co-authors.

Nicotinamide supplementation is “not only a cost-effective and patient-centric strategy for KC prevention, but it also remains economically favorable under a range of assumptions and may become even more cost-effective under higher procedure costs and frequency,” noted the authors.

The analysis included 33,822 individuals from the VHA database, all with a history of one or more KCs, including those with nicotinamide exposure for 30 or more days (n = 12,287) and those without that exposure (n = 21,535).

The mean ages in the unexposed and exposed cohorts were 76.9 and 77.2 years, respectively, and 98% were men. Procedural US VHA costs for KC treatment were estimated from previous research and adjusted for inflation. Nicotinamide pricing was obtained from the VHA.

KC incidence among nicotinamide-exposed and unexposed individuals was 0.204 and 0.255 events per person-year, respectively, reflecting an absolute risk reduction of 0.051 and 624 KCs prevented annually with nicotinamide supplementation.

With an estimated cost of $843 per KC, the yearly KC treatment expense was estimated at approximately $2.64 million, and the annual nicotinamide cost was estimated at $161,451, resulting in net savings of $364,581 — a 19.9% reduction in cohort-specific costs.

Assuming a quality-adjusted life-year (QALY) decrement of -0.01 per KC, nicotinamide use yielded an annual gain of 6.24 QALYs across the cohort and a savings of $58,426 per QALY gained.

A calculation of non-VHA cost-effectiveness, estimated with civilian prices and distributions, showed savings of $14,407 per QALY gained.

The authors concluded that oral nicotinamide was “a cost-effective and patient-centric preventive approach for KC, particularly in individuals with KC history at high risk of multiple primary KC.”

In an accompanying editorial, Ivo Abraham, PhD, JAMA Dermatology’s associate editor for quantitative methods and chief scientist at Matrix45, a health economics research and consulting group in Tucson, Arizona, and co-authors noted that although nicotinamide “is inexpensive, widely available, and mechanistically plausible for chemoprevention of actinic keratoses and KCs…stronger evidence remains required to support clinical recommendations.”

“Broader nicotinamide implementation might impart substantial population health benefits and cost savings to the VHA,” they wrote, while also asking, “do we truly know whether nicotinamide is effective for KC chemoprevention in broader populations?” They suggested that only an adequately powered randomized clinical trial in representative nonimmunosuppressed populations would provide the answer.

“Additional randomized controlled trials in non-VHA populations would provide further insight into generalizability beyond the VA healthcare system,” Hartman told Medscape Medical News.

“We are aiming to conduct a large [randomized controlled trial] in the VA to provide a more definitive answer,” added Lee Wheless, MD, one of Hartman’s coauthors, from Vanderbilt University Medical Center and the Tennessee Valley Healthcare System VA Medical Center, both in Nashville, Tennessee. “Doing so would also give a much better estimate of any potential side effects, though we and others have found no increased rate, and sometimes even a decreased rate, of major adverse cardiovascular events.”

Sarah Arron, MD, dermatologic surgeon with Palo Alto Foundation Medical Group in Palo Alto, California, and Premier Aesthetic Dermatology in San Carlos, California, who was not involved in the research, said, “It is gratifying to see that in the veteran population, nicotinamide affords protection against nonmelanoma skin cancer and is a cost-effective intervention. For a healthcare system such as the VHA, providing this over-the-counter vitamin through pharmacy benefits is an excellent method for reducing the overall cost of skin cancer treatment.”

Although Arron agreed that a randomized trial would offer a higher level of evidence for this intervention, she said the real-world obstacle is that nicotinamide is such an easily available, low-cost vitamin with a high safety profile. “Patients are not likely to sign up for a possible placebo when they can purchase nicotinamide online or at the drugstore,” she said. “This was reflected in Australia; once the positive data from the ONTRAC trial was publicized, investigators on the ONTRANS trial had difficulty enrolling patients because they were already taking the vitamin. The second study closed without meeting its enrollment goals and thus did not have power to show statistical significance.”

Hartman is supported by the US Department of Defense and the US Department of Veterans Affairs. Wheless is also supported by the US Department of Veterans Affairs. Arron is a speaker for Regeneron and Castle Biosciences; a consultant for Regeneron, Replimune, Castle, Lumenis, and Enspectra Health; an unpaid ambassador for HarkenDerm, which makes sunscreen as well as a sun and eye health supplement that includes nicotinamide as one of the ingredients.

The study authors reported having no conflicts of interest. Of the editorial authors, Abraham disclosed owning stock in Matrix45, which has received contract funding from companies outside this work, one author had disclosures not related to the work, and the third author had no disclosures.

Kate Johnson is a Montreal-based freelance medical journalist who has been writing for > 30 years about all areas of medicine.

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

Offering lung cancer screening to everyone with a 20-year smoking history could expand access to screening, identify more cancers, and reduce disparities, new research suggests.

In an analysis of nearly 1 million US veterans, researchers estimated that a simplified approach to lung cancer screening — based on smoking duration rather than pack-years — would expand screening eligibility by nearly 30% and reduce potentially missed lung cancers by over 70%.

Those shifts would be especially pronounced among women and Black individuals — 2 groups that are underserved by current screening criteria.

The results, presented at the American Society of Clinical Oncology (ASCO) 2026, come at a time when some groups are revisiting their lung cancer screening guidelines.

And they support smoking duration as a “simpler, more sensitive, and more equitable metric for screening eligibility,” researcher Brendan T. Heiden, MD, MPHS, Washington University School of Medicine in St. Louis, St. Louis, told meeting attendees.

Toward a Better Metric

Current guidelines from the US Preventive Services Task Force (USPSTF) recommend annual lung cancer screening with low-dose CT for adults aged 50-80 years who have at least a 20 pack-year smoking history and either currently smoke or quit within the past 15 years.

The 20 pack-year metric is equivalent to smoking a pack of cigarettes per day for 20 years. Because it requires patients to remember their smoking intensity over decades, it can be challenging to calculate and translate into care, Heiden said.

As it stands, few Americans who are eligible under current USPSTF guidelines actually undergo lung cancer screening, at about 15%-20%, Heiden noted. Meanwhile, mounting evidence suggests that many lung cancers occur in individuals who never meet those eligibility criteria.

Boosting screening uptake, Heiden said, is not enough: There’s a need to revisit eligibility itself to reach more high-risk individuals.

Some groups are already taking steps in that direction. Recently updated guidelines from the National Comprehensive Cancer Network (NCCN) added a category 2B recommendation supporting screening for individuals with at least a 20-year smoking history, regardless of pack-years. (The guidelines also say former smokers are eligible no matter how long ago they quit.)

For their study, Heiden’s team sought to estimate the performance of that smoking-duration metric against current USPSTF pack-year criteria. They used Veterans Health Administration data on over 980,000 veterans whose smoking histories were prospectively collected; lung cancer diagnoses were identified through the Veterans Affairs Central Cancer Registry.

Most of the included veterans (67%) had a smoking history; their mean age was 64 years, and 21% were Black.

Overall, the researchers found that basing eligibility on 20-year smoking duration would substantially expand access to screening: Among veterans with a smoking history, 68% qualified for screening under current USPSTF criteria compared with 87% using the smoking-duration approach.

The gains were especially pronounced among women and Black individuals (who, based on prior research, typically smoke less intensely than White males). Under USPSTF criteria, only about 55% of female and Black veterans qualified for screening compared with 83% for both groups under the smoking-duration criterion.

Importantly, Heiden said, people meeting the smoking-duration threshold remained at substantially elevated risk for lung cancer, suggesting the broader screening criteria were not merely capturing low-risk smokers.

The 5-year lung cancer incidence among veterans eligible under the smoking-duration approach was 1.59% — 11 times the rate of 0.14% among never smokers.

Perhaps most striking, Heiden said, the proportion of potentially missed cancers dropped from 13% with the pack-year metric to just 4% using the smoking-duration metric — a relative reduction of more than 70%.

Again, women and Black individuals would see the largest gains: Among Black veterans, potentially missed cancers fell from 25% to 6%, whereas among female veterans they declined from 22% to 7%.

Optimal Approach Still Unclear

The analysis had limitations, including a predominantly male veteran population whose smoking exposure was far greater than that of the general US population, indicating high inherent lung cancer risk.

But the results support what the NCCN has already done, according to Mary Reid, PhD, MSPH, BSN, a member of the group’s lung cancer screening guideline panel and chief of cancer screening, survivorship and mentorship at Roswell Park Comprehensive Cancer Center in Buffalo, New York.

“Doing the calculation for pack-years can be difficult,” Reid told Medscape Medical News. “Smoking duration is easier to calculate and really the way to go.”

The USPSTF does not comment on individual studies outside of its recommendation development process.

At the meeting, study discussant Katharine A. Rendle, PhD, called the work “impressive,” citing the size of the cohort and strength of the data.

It’s particularly noteworthy that the simpler screening criteria improved sensitivity for all veterans, while largely eliminating disparities, according to Rendle, of the Abramson Cancer Center at the University of Pennsylvania in Philadelphia.

Still, she said, further research could better define the optimal screening strategy.

“Smoking duration is a promising approach, but in my opinion, guidelines likely need to account for the underlying risk in the population,” Rendle said, noting that current smoking prevalence in the US population is about 10%.

She suggested future studies consider other smoking-duration thresholds, such as 30 or 40 years, and look at other outcomes, including life-years gained.

“It’s critical that we prioritize strategies that maximize potential benefit from screening — not just identify those at lung cancer risk — given downstream costs and burden on populations and health care systems,” Rendle said.

The study had no commercial funding. Heiden, Rendle, and Reid had no relevant disclosures.

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

Offering lung cancer screening to everyone with a 20-year smoking history could expand access to screening, identify more cancers, and reduce disparities, new research suggests.

In an analysis of nearly 1 million US veterans, researchers estimated that a simplified approach to lung cancer screening — based on smoking duration rather than pack-years — would expand screening eligibility by nearly 30% and reduce potentially missed lung cancers by over 70%.

Those shifts would be especially pronounced among women and Black individuals — 2 groups that are underserved by current screening criteria.

The results, presented at the American Society of Clinical Oncology (ASCO) 2026, come at a time when some groups are revisiting their lung cancer screening guidelines.

And they support smoking duration as a “simpler, more sensitive, and more equitable metric for screening eligibility,” researcher Brendan T. Heiden, MD, MPHS, Washington University School of Medicine in St. Louis, St. Louis, told meeting attendees.

Toward a Better Metric

Current guidelines from the US Preventive Services Task Force (USPSTF) recommend annual lung cancer screening with low-dose CT for adults aged 50-80 years who have at least a 20 pack-year smoking history and either currently smoke or quit within the past 15 years.

The 20 pack-year metric is equivalent to smoking a pack of cigarettes per day for 20 years. Because it requires patients to remember their smoking intensity over decades, it can be challenging to calculate and translate into care, Heiden said.

As it stands, few Americans who are eligible under current USPSTF guidelines actually undergo lung cancer screening, at about 15%-20%, Heiden noted. Meanwhile, mounting evidence suggests that many lung cancers occur in individuals who never meet those eligibility criteria.

Boosting screening uptake, Heiden said, is not enough: There’s a need to revisit eligibility itself to reach more high-risk individuals.

Some groups are already taking steps in that direction. Recently updated guidelines from the National Comprehensive Cancer Network (NCCN) added a category 2B recommendation supporting screening for individuals with at least a 20-year smoking history, regardless of pack-years. (The guidelines also say former smokers are eligible no matter how long ago they quit.)

For their study, Heiden’s team sought to estimate the performance of that smoking-duration metric against current USPSTF pack-year criteria. They used Veterans Health Administration data on over 980,000 veterans whose smoking histories were prospectively collected; lung cancer diagnoses were identified through the Veterans Affairs Central Cancer Registry.

Most of the included veterans (67%) had a smoking history; their mean age was 64 years, and 21% were Black.

Overall, the researchers found that basing eligibility on 20-year smoking duration would substantially expand access to screening: Among veterans with a smoking history, 68% qualified for screening under current USPSTF criteria compared with 87% using the smoking-duration approach.

The gains were especially pronounced among women and Black individuals (who, based on prior research, typically smoke less intensely than White males). Under USPSTF criteria, only about 55% of female and Black veterans qualified for screening compared with 83% for both groups under the smoking-duration criterion.

Importantly, Heiden said, people meeting the smoking-duration threshold remained at substantially elevated risk for lung cancer, suggesting the broader screening criteria were not merely capturing low-risk smokers.

The 5-year lung cancer incidence among veterans eligible under the smoking-duration approach was 1.59% — 11 times the rate of 0.14% among never smokers.

Perhaps most striking, Heiden said, the proportion of potentially missed cancers dropped from 13% with the pack-year metric to just 4% using the smoking-duration metric — a relative reduction of more than 70%.

Again, women and Black individuals would see the largest gains: Among Black veterans, potentially missed cancers fell from 25% to 6%, whereas among female veterans they declined from 22% to 7%.

Optimal Approach Still Unclear

The analysis had limitations, including a predominantly male veteran population whose smoking exposure was far greater than that of the general US population, indicating high inherent lung cancer risk.

But the results support what the NCCN has already done, according to Mary Reid, PhD, MSPH, BSN, a member of the group’s lung cancer screening guideline panel and chief of cancer screening, survivorship and mentorship at Roswell Park Comprehensive Cancer Center in Buffalo, New York.

“Doing the calculation for pack-years can be difficult,” Reid told Medscape Medical News. “Smoking duration is easier to calculate and really the way to go.”

The USPSTF does not comment on individual studies outside of its recommendation development process.

At the meeting, study discussant Katharine A. Rendle, PhD, called the work “impressive,” citing the size of the cohort and strength of the data.

It’s particularly noteworthy that the simpler screening criteria improved sensitivity for all veterans, while largely eliminating disparities, according to Rendle, of the Abramson Cancer Center at the University of Pennsylvania in Philadelphia.

Still, she said, further research could better define the optimal screening strategy.

“Smoking duration is a promising approach, but in my opinion, guidelines likely need to account for the underlying risk in the population,” Rendle said, noting that current smoking prevalence in the US population is about 10%.

She suggested future studies consider other smoking-duration thresholds, such as 30 or 40 years, and look at other outcomes, including life-years gained.

“It’s critical that we prioritize strategies that maximize potential benefit from screening — not just identify those at lung cancer risk — given downstream costs and burden on populations and health care systems,” Rendle said.

The study had no commercial funding. Heiden, Rendle, and Reid had no relevant disclosures.

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

Offering lung cancer screening to everyone with a 20-year smoking history could expand access to screening, identify more cancers, and reduce disparities, new research suggests.

In an analysis of nearly 1 million US veterans, researchers estimated that a simplified approach to lung cancer screening — based on smoking duration rather than pack-years — would expand screening eligibility by nearly 30% and reduce potentially missed lung cancers by over 70%.

Those shifts would be especially pronounced among women and Black individuals — 2 groups that are underserved by current screening criteria.

The results, presented at the American Society of Clinical Oncology (ASCO) 2026, come at a time when some groups are revisiting their lung cancer screening guidelines.

And they support smoking duration as a “simpler, more sensitive, and more equitable metric for screening eligibility,” researcher Brendan T. Heiden, MD, MPHS, Washington University School of Medicine in St. Louis, St. Louis, told meeting attendees.

Toward a Better Metric

Current guidelines from the US Preventive Services Task Force (USPSTF) recommend annual lung cancer screening with low-dose CT for adults aged 50-80 years who have at least a 20 pack-year smoking history and either currently smoke or quit within the past 15 years.

The 20 pack-year metric is equivalent to smoking a pack of cigarettes per day for 20 years. Because it requires patients to remember their smoking intensity over decades, it can be challenging to calculate and translate into care, Heiden said.

As it stands, few Americans who are eligible under current USPSTF guidelines actually undergo lung cancer screening, at about 15%-20%, Heiden noted. Meanwhile, mounting evidence suggests that many lung cancers occur in individuals who never meet those eligibility criteria.

Boosting screening uptake, Heiden said, is not enough: There’s a need to revisit eligibility itself to reach more high-risk individuals.

Some groups are already taking steps in that direction. Recently updated guidelines from the National Comprehensive Cancer Network (NCCN) added a category 2B recommendation supporting screening for individuals with at least a 20-year smoking history, regardless of pack-years. (The guidelines also say former smokers are eligible no matter how long ago they quit.)

For their study, Heiden’s team sought to estimate the performance of that smoking-duration metric against current USPSTF pack-year criteria. They used Veterans Health Administration data on over 980,000 veterans whose smoking histories were prospectively collected; lung cancer diagnoses were identified through the Veterans Affairs Central Cancer Registry.

Most of the included veterans (67%) had a smoking history; their mean age was 64 years, and 21% were Black.

Overall, the researchers found that basing eligibility on 20-year smoking duration would substantially expand access to screening: Among veterans with a smoking history, 68% qualified for screening under current USPSTF criteria compared with 87% using the smoking-duration approach.

The gains were especially pronounced among women and Black individuals (who, based on prior research, typically smoke less intensely than White males). Under USPSTF criteria, only about 55% of female and Black veterans qualified for screening compared with 83% for both groups under the smoking-duration criterion.

Importantly, Heiden said, people meeting the smoking-duration threshold remained at substantially elevated risk for lung cancer, suggesting the broader screening criteria were not merely capturing low-risk smokers.

The 5-year lung cancer incidence among veterans eligible under the smoking-duration approach was 1.59% — 11 times the rate of 0.14% among never smokers.

Perhaps most striking, Heiden said, the proportion of potentially missed cancers dropped from 13% with the pack-year metric to just 4% using the smoking-duration metric — a relative reduction of more than 70%.

Again, women and Black individuals would see the largest gains: Among Black veterans, potentially missed cancers fell from 25% to 6%, whereas among female veterans they declined from 22% to 7%.

Optimal Approach Still Unclear

The analysis had limitations, including a predominantly male veteran population whose smoking exposure was far greater than that of the general US population, indicating high inherent lung cancer risk.

But the results support what the NCCN has already done, according to Mary Reid, PhD, MSPH, BSN, a member of the group’s lung cancer screening guideline panel and chief of cancer screening, survivorship and mentorship at Roswell Park Comprehensive Cancer Center in Buffalo, New York.

“Doing the calculation for pack-years can be difficult,” Reid told Medscape Medical News. “Smoking duration is easier to calculate and really the way to go.”

The USPSTF does not comment on individual studies outside of its recommendation development process.

At the meeting, study discussant Katharine A. Rendle, PhD, called the work “impressive,” citing the size of the cohort and strength of the data.

It’s particularly noteworthy that the simpler screening criteria improved sensitivity for all veterans, while largely eliminating disparities, according to Rendle, of the Abramson Cancer Center at the University of Pennsylvania in Philadelphia.

Still, she said, further research could better define the optimal screening strategy.

“Smoking duration is a promising approach, but in my opinion, guidelines likely need to account for the underlying risk in the population,” Rendle said, noting that current smoking prevalence in the US population is about 10%.

She suggested future studies consider other smoking-duration thresholds, such as 30 or 40 years, and look at other outcomes, including life-years gained.

“It’s critical that we prioritize strategies that maximize potential benefit from screening — not just identify those at lung cancer risk — given downstream costs and burden on populations and health care systems,” Rendle said.

The study had no commercial funding. Heiden, Rendle, and Reid had no relevant disclosures.

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

A pharmacist-driven Veterans Health Administration (VHA) care program for veterans recovering from hospital visits for chronic obstructive pulmonary disease (COPD) is helping reduce symptom burden, a new retrospective cohort study finds. 

Of 286 patients with COPD who participated in the program and reported outcomes, 62.6% said their symptoms improved, 28.7% said they had no change, and 8.7% reported worsening symptoms, according to Edward Portillo, PharmD, and colleagues in Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation. Patients whose medications were changed by VHA pharmacists with prescribing authority were more likely to experience clinically meaningful improvement in symptoms compared to those without this medication change (66.3% vs. 46.6%, respectively, P < .001).

“If you had a debilitating lung disease that was affecting your ability to breathe all day, affected your ability to go to the grocery store, made it hard for you to see your grandkids, and all of a sudden you had this visit and a month to 2 months later reported feeling a heck of a lot better—that’s a really big deal,” Portillo said in an interview with Federal Practitioner. 

COPD, a progressive and irreversible lung disease that encompasses emphysema and chronic bronchitis, is the fifth-leading cause of death in the US according to the most recently available data. Research has suggested that many patients do not receive guidance-concordant care. 

“The prevalence of COPD among our veteran population is threefold greater than in the civilian population, and 1 in 4 veterans have a COPD diagnosis,” noted Portillo a pharmacist at the William S. Middleton Veterans Affairs (VA) Hospital and an associate professor at the University of Wisconsin, Madison School of Pharmacy.

In 2015, Portillo developed a program called COPD Coordinated Access to Reduce Exacerbations (COPD CARE). The program, now operating at 50 VA medical centers, allows pharmacists to optimize medication, order spirometry, assess symptoms, place referrals for pulmonary rehabilitation, and support inhaler adherence and tobacco cessation. The pharmacists work with other members of the patient care teams such as primary care physicians and nurses.

“It's integrated within the teams themselves that serve our veterans, which is very unique for a service like this,” Portillo said.

The program is especially beneficial for patients within their first 30 to 90 days posthospitalization when they may not normally be seen in the clinic, Portillo said.

“We use a national dashboard to identify patients who left the [emergency department] or hospital, and then we assess if they’d be appropriate candidates for the program,” he said. “Our goal is to see patients as fast as 30 days and as late as 90 days, but ideally within 30 to 60 days of discharge.”

An initial in-person visit of ≤ 30 minutes is followed by a 15-minute follow-up phone call in 30 days to see if interventions have been continued, he said. 

The study analyzed data from September 2020 to February 2024 from 28 VA medical centers that administer the COPD CARE program. All patients had an initial wellness visit within 90 days of hospitalization and 2 COPD Assessment Test (CAT) scores. Among 326 patients, the average age was 73.2 years; 95.7% were male; 77.9% were White, 15.6% were Black, and 2.1% had Hispanic ethnicity. 

At the time of the wellness visit, patients mean CAT score was 18.4. It improved to 15.2 by follow-up, with especially large improvements in limitations (2.5 to 2.0), tightness (1.7 to 1.2), cough (2.5 to 2.1), energy (2.9 to 2.5), phlegm (2.4 to 2.0), and sleep (1.9 to 1.5).

Pharmacists created 236 COPD action plans, changed 208 medications, provided 151 service referrals, identified 117 nonadherent patients, and identified 62 incorrect techniques. 

But only 1 intervention – medication change – was linked to clinically meaningful improvements in symptoms.

“This is not a disease that's easy to change symptomatically,” Portillo said. “My hope is that over time, and with multiple visits, those patients shift into a mode of ‘I am actually feeling much better now.’” 

Suzanne Bollmeier, PharmD, professor of Pharmacy Practice at the University of Health Sciences and Pharmacy in St. Louis, who is familiar with the study but did not take part in it, told Federal Practitioner that the results align with previous research.

Bollmeier mentioned several studies that link pharmacist interventions to better health outcomes, including inhalation technique and medication adherence.

“Pharmacists are well-positioned within the health care team to help care for patients with COPD,” she said. “Pharmacists can help with patient adherence, inhaler education, and reduction in disease risk but also identify drug-related problems and modify respiratory regimens to better optimize patient outcomes.”

Moving forward, she said, “it would be interesting to see what specific medication regimen changes were made in this present study that led to improvement in symptoms.”

The study was funded by the VA Office of Rural Health and the University of Wisconsin Institute for Clinical and Translational Research, which is supported by the National Center for Advancing Translational Sciences. The study authors and Bollmeier had no disclosures.

A pharmacist-driven Veterans Health Administration (VHA) care program for veterans recovering from hospital visits for chronic obstructive pulmonary disease (COPD) is helping reduce symptom burden, a new retrospective cohort study finds. 

Of 286 patients with COPD who participated in the program and reported outcomes, 62.6% said their symptoms improved, 28.7% said they had no change, and 8.7% reported worsening symptoms, according to Edward Portillo, PharmD, and colleagues in Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation. Patients whose medications were changed by VHA pharmacists with prescribing authority were more likely to experience clinically meaningful improvement in symptoms compared to those without this medication change (66.3% vs. 46.6%, respectively, P < .001).

“If you had a debilitating lung disease that was affecting your ability to breathe all day, affected your ability to go to the grocery store, made it hard for you to see your grandkids, and all of a sudden you had this visit and a month to 2 months later reported feeling a heck of a lot better—that’s a really big deal,” Portillo said in an interview with Federal Practitioner. 

COPD, a progressive and irreversible lung disease that encompasses emphysema and chronic bronchitis, is the fifth-leading cause of death in the US according to the most recently available data. Research has suggested that many patients do not receive guidance-concordant care. 

“The prevalence of COPD among our veteran population is threefold greater than in the civilian population, and 1 in 4 veterans have a COPD diagnosis,” noted Portillo a pharmacist at the William S. Middleton Veterans Affairs (VA) Hospital and an associate professor at the University of Wisconsin, Madison School of Pharmacy.

In 2015, Portillo developed a program called COPD Coordinated Access to Reduce Exacerbations (COPD CARE). The program, now operating at 50 VA medical centers, allows pharmacists to optimize medication, order spirometry, assess symptoms, place referrals for pulmonary rehabilitation, and support inhaler adherence and tobacco cessation. The pharmacists work with other members of the patient care teams such as primary care physicians and nurses.

“It's integrated within the teams themselves that serve our veterans, which is very unique for a service like this,” Portillo said.

The program is especially beneficial for patients within their first 30 to 90 days posthospitalization when they may not normally be seen in the clinic, Portillo said.

“We use a national dashboard to identify patients who left the [emergency department] or hospital, and then we assess if they’d be appropriate candidates for the program,” he said. “Our goal is to see patients as fast as 30 days and as late as 90 days, but ideally within 30 to 60 days of discharge.”

An initial in-person visit of ≤ 30 minutes is followed by a 15-minute follow-up phone call in 30 days to see if interventions have been continued, he said. 

The study analyzed data from September 2020 to February 2024 from 28 VA medical centers that administer the COPD CARE program. All patients had an initial wellness visit within 90 days of hospitalization and 2 COPD Assessment Test (CAT) scores. Among 326 patients, the average age was 73.2 years; 95.7% were male; 77.9% were White, 15.6% were Black, and 2.1% had Hispanic ethnicity. 

At the time of the wellness visit, patients mean CAT score was 18.4. It improved to 15.2 by follow-up, with especially large improvements in limitations (2.5 to 2.0), tightness (1.7 to 1.2), cough (2.5 to 2.1), energy (2.9 to 2.5), phlegm (2.4 to 2.0), and sleep (1.9 to 1.5).

Pharmacists created 236 COPD action plans, changed 208 medications, provided 151 service referrals, identified 117 nonadherent patients, and identified 62 incorrect techniques. 

But only 1 intervention – medication change – was linked to clinically meaningful improvements in symptoms.

“This is not a disease that's easy to change symptomatically,” Portillo said. “My hope is that over time, and with multiple visits, those patients shift into a mode of ‘I am actually feeling much better now.’” 

Suzanne Bollmeier, PharmD, professor of Pharmacy Practice at the University of Health Sciences and Pharmacy in St. Louis, who is familiar with the study but did not take part in it, told Federal Practitioner that the results align with previous research.

Bollmeier mentioned several studies that link pharmacist interventions to better health outcomes, including inhalation technique and medication adherence.

“Pharmacists are well-positioned within the health care team to help care for patients with COPD,” she said. “Pharmacists can help with patient adherence, inhaler education, and reduction in disease risk but also identify drug-related problems and modify respiratory regimens to better optimize patient outcomes.”

Moving forward, she said, “it would be interesting to see what specific medication regimen changes were made in this present study that led to improvement in symptoms.”

The study was funded by the VA Office of Rural Health and the University of Wisconsin Institute for Clinical and Translational Research, which is supported by the National Center for Advancing Translational Sciences. The study authors and Bollmeier had no disclosures.

A pharmacist-driven Veterans Health Administration (VHA) care program for veterans recovering from hospital visits for chronic obstructive pulmonary disease (COPD) is helping reduce symptom burden, a new retrospective cohort study finds. 

Of 286 patients with COPD who participated in the program and reported outcomes, 62.6% said their symptoms improved, 28.7% said they had no change, and 8.7% reported worsening symptoms, according to Edward Portillo, PharmD, and colleagues in Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation. Patients whose medications were changed by VHA pharmacists with prescribing authority were more likely to experience clinically meaningful improvement in symptoms compared to those without this medication change (66.3% vs. 46.6%, respectively, P < .001).

“If you had a debilitating lung disease that was affecting your ability to breathe all day, affected your ability to go to the grocery store, made it hard for you to see your grandkids, and all of a sudden you had this visit and a month to 2 months later reported feeling a heck of a lot better—that’s a really big deal,” Portillo said in an interview with Federal Practitioner. 

COPD, a progressive and irreversible lung disease that encompasses emphysema and chronic bronchitis, is the fifth-leading cause of death in the US according to the most recently available data. Research has suggested that many patients do not receive guidance-concordant care. 

“The prevalence of COPD among our veteran population is threefold greater than in the civilian population, and 1 in 4 veterans have a COPD diagnosis,” noted Portillo a pharmacist at the William S. Middleton Veterans Affairs (VA) Hospital and an associate professor at the University of Wisconsin, Madison School of Pharmacy.

In 2015, Portillo developed a program called COPD Coordinated Access to Reduce Exacerbations (COPD CARE). The program, now operating at 50 VA medical centers, allows pharmacists to optimize medication, order spirometry, assess symptoms, place referrals for pulmonary rehabilitation, and support inhaler adherence and tobacco cessation. The pharmacists work with other members of the patient care teams such as primary care physicians and nurses.

“It's integrated within the teams themselves that serve our veterans, which is very unique for a service like this,” Portillo said.

The program is especially beneficial for patients within their first 30 to 90 days posthospitalization when they may not normally be seen in the clinic, Portillo said.

“We use a national dashboard to identify patients who left the [emergency department] or hospital, and then we assess if they’d be appropriate candidates for the program,” he said. “Our goal is to see patients as fast as 30 days and as late as 90 days, but ideally within 30 to 60 days of discharge.”

An initial in-person visit of ≤ 30 minutes is followed by a 15-minute follow-up phone call in 30 days to see if interventions have been continued, he said. 

The study analyzed data from September 2020 to February 2024 from 28 VA medical centers that administer the COPD CARE program. All patients had an initial wellness visit within 90 days of hospitalization and 2 COPD Assessment Test (CAT) scores. Among 326 patients, the average age was 73.2 years; 95.7% were male; 77.9% were White, 15.6% were Black, and 2.1% had Hispanic ethnicity. 

At the time of the wellness visit, patients mean CAT score was 18.4. It improved to 15.2 by follow-up, with especially large improvements in limitations (2.5 to 2.0), tightness (1.7 to 1.2), cough (2.5 to 2.1), energy (2.9 to 2.5), phlegm (2.4 to 2.0), and sleep (1.9 to 1.5).

Pharmacists created 236 COPD action plans, changed 208 medications, provided 151 service referrals, identified 117 nonadherent patients, and identified 62 incorrect techniques. 

But only 1 intervention – medication change – was linked to clinically meaningful improvements in symptoms.

“This is not a disease that's easy to change symptomatically,” Portillo said. “My hope is that over time, and with multiple visits, those patients shift into a mode of ‘I am actually feeling much better now.’” 

Suzanne Bollmeier, PharmD, professor of Pharmacy Practice at the University of Health Sciences and Pharmacy in St. Louis, who is familiar with the study but did not take part in it, told Federal Practitioner that the results align with previous research.

Bollmeier mentioned several studies that link pharmacist interventions to better health outcomes, including inhalation technique and medication adherence.

“Pharmacists are well-positioned within the health care team to help care for patients with COPD,” she said. “Pharmacists can help with patient adherence, inhaler education, and reduction in disease risk but also identify drug-related problems and modify respiratory regimens to better optimize patient outcomes.”

Moving forward, she said, “it would be interesting to see what specific medication regimen changes were made in this present study that led to improvement in symptoms.”

The study was funded by the VA Office of Rural Health and the University of Wisconsin Institute for Clinical and Translational Research, which is supported by the National Center for Advancing Translational Sciences. The study authors and Bollmeier had no disclosures.

ORLANDO, Fla. — The Centers for Medicare & Medicaid Services (CMS) will not cover continuous positive airway pressure (CPAP) treatment for people who are nonadherent by 90 days. However, that requirement is too stringent, said researchers who found more than one third of adults who struggled with adherence initially still used the therapy 1 year later at levels associated with clinical benefit.

To test the requirement, investigators assessed 132,492 patients in the Kaiser Permanente Southern California system. The patients were issued CPAP devices to treat obstructive sleep apnea from 2015 to 2023. At 1 year, 36% who would have failed the CMS requirement were still using their CPAP.

The results counter CMS’ assumption that poor early CPAP use always leads to long-term abandonment, said Dennis Hwang, MD, co-chair of Sleep Medicine and medical director of the Sleep Disorders Center at Kaiser Permanente Southern California in Fontana, California.

"We should transition away from a one-size-fits-all definition of success," Hwang added at the American Thoracic Society (ATS) 2026 International Conference.

Background and Methodology

The 90-day adherence requirement does not only apply to Medicare or Medicaid recipients, Hwang said; many private insurers have adopted the same policy. In contrast, Kaiser Permanente Southern California does not restrict usage based on early adherence.

Hwang et al considered any Kaiser Permanente member with any CPAP usage during the 12 months after being issued a device an active user. They tracked mean nightly minutes of use and the percentage of nights with ≥ 2 and ≥ 4 hours of average use.

Overall, 49% would have met the CMS criteria and used the therapy ≥ 4 hours on average each night for 70% of nights during the first 90 days. Kaiser Permanente members aged ≥ 65 years were more compliant, with 54% meeting the CMS benchmarks. ATS guidelines recognize that even ≥ 2 hours of CPAP per night on average can confer some benefits.

The average age in the study was 55 years, and the mean apnea-hypopnea index was 32-33 events per hour, suggesting severe obstructive sleep apnea at baseline. The cohort was diverse, with 42% White, 35% Hispanic, 10% Black, 9% Asian, and 4% other race or ethnicity.

Key Findings

A total of 64,568 adults would have been CMS adherent at 90 days; investigators compared outcomes at 12 months with another 67,867 nonadherent adults.

There were some significant differences between groups. The mean age was 56.4 years vs 53.7 years in the adherent group vs the nonadherent group; men made up a greater proportion of the adherent group, 68.5% vs 62.6%; and the mean number of events per hour was 35 vs 30 (P < .001 for all).

Among the 90-day nonadherent group, about 21% met the 2-hour or greater adherence benchmark, and approximately 14% used CPAP an average of ≥ 4 hours.

“Still a substantial number of [non-CMS adherent] patients are using CPAP,” Hwang said.

Failure to meet CMS adherence was associated with younger age, female sex, non-White race or ethnicity, lower socioeconomic status, and lower severity of obstructive sleep apnea.

“There is also an equity dimension. Whites had better adherence rates during the first 90 days, so there is already a disparity here in terms of outcomes,” Hwang said. Policy changes could improve access to long-term therapy on a more equitable basis, he added. For example, a 2023 ATS policy statement calls for a more patient-centric approach and a focus on reducing inequities.

An Arbitrary Requirement

The 90-day requirement seems a little short, said session co-moderator Oren Cohen, MD, assistant professor in the Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine at Icahn School of Medicine at Mount Sinai in New York City, when asked to comment. “It can take longer to get a patient back into the clinic and go through a lot of the trial and error that it takes to do a mask fitting and adjust the pressures.”

If a patient is using their CPAP device for fewer than 4 hours a night in the early period, it doesn’t mean things are failing, Cohen said. “It’s just that you’ve got to keep trying and pushing forward.”

Nonetheless, there are some long-term noncompliant patients, Cohen said. “I certainly don’t think that somebody who’s not using the device for years should continue to hold on to it. That resource can be reallocated to somebody who would get more benefit from it. But I think setting a 90-day and 4-hour rule seems arbitrary…and there should be more leeway there.”

The study was independently supported.

Hwang and Cohen reported having no relevant financial disclosures.

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

ORLANDO, Fla. — The Centers for Medicare & Medicaid Services (CMS) will not cover continuous positive airway pressure (CPAP) treatment for people who are nonadherent by 90 days. However, that requirement is too stringent, said researchers who found more than one third of adults who struggled with adherence initially still used the therapy 1 year later at levels associated with clinical benefit.

To test the requirement, investigators assessed 132,492 patients in the Kaiser Permanente Southern California system. The patients were issued CPAP devices to treat obstructive sleep apnea from 2015 to 2023. At 1 year, 36% who would have failed the CMS requirement were still using their CPAP.

The results counter CMS’ assumption that poor early CPAP use always leads to long-term abandonment, said Dennis Hwang, MD, co-chair of Sleep Medicine and medical director of the Sleep Disorders Center at Kaiser Permanente Southern California in Fontana, California.

"We should transition away from a one-size-fits-all definition of success," Hwang added at the American Thoracic Society (ATS) 2026 International Conference.

Background and Methodology

The 90-day adherence requirement does not only apply to Medicare or Medicaid recipients, Hwang said; many private insurers have adopted the same policy. In contrast, Kaiser Permanente Southern California does not restrict usage based on early adherence.

Hwang et al considered any Kaiser Permanente member with any CPAP usage during the 12 months after being issued a device an active user. They tracked mean nightly minutes of use and the percentage of nights with ≥ 2 and ≥ 4 hours of average use.

Overall, 49% would have met the CMS criteria and used the therapy ≥ 4 hours on average each night for 70% of nights during the first 90 days. Kaiser Permanente members aged ≥ 65 years were more compliant, with 54% meeting the CMS benchmarks. ATS guidelines recognize that even ≥ 2 hours of CPAP per night on average can confer some benefits.

The average age in the study was 55 years, and the mean apnea-hypopnea index was 32-33 events per hour, suggesting severe obstructive sleep apnea at baseline. The cohort was diverse, with 42% White, 35% Hispanic, 10% Black, 9% Asian, and 4% other race or ethnicity.

Key Findings

A total of 64,568 adults would have been CMS adherent at 90 days; investigators compared outcomes at 12 months with another 67,867 nonadherent adults.

There were some significant differences between groups. The mean age was 56.4 years vs 53.7 years in the adherent group vs the nonadherent group; men made up a greater proportion of the adherent group, 68.5% vs 62.6%; and the mean number of events per hour was 35 vs 30 (P < .001 for all).

Among the 90-day nonadherent group, about 21% met the 2-hour or greater adherence benchmark, and approximately 14% used CPAP an average of ≥ 4 hours.

“Still a substantial number of [non-CMS adherent] patients are using CPAP,” Hwang said.

Failure to meet CMS adherence was associated with younger age, female sex, non-White race or ethnicity, lower socioeconomic status, and lower severity of obstructive sleep apnea.

“There is also an equity dimension. Whites had better adherence rates during the first 90 days, so there is already a disparity here in terms of outcomes,” Hwang said. Policy changes could improve access to long-term therapy on a more equitable basis, he added. For example, a 2023 ATS policy statement calls for a more patient-centric approach and a focus on reducing inequities.

An Arbitrary Requirement

The 90-day requirement seems a little short, said session co-moderator Oren Cohen, MD, assistant professor in the Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine at Icahn School of Medicine at Mount Sinai in New York City, when asked to comment. “It can take longer to get a patient back into the clinic and go through a lot of the trial and error that it takes to do a mask fitting and adjust the pressures.”

If a patient is using their CPAP device for fewer than 4 hours a night in the early period, it doesn’t mean things are failing, Cohen said. “It’s just that you’ve got to keep trying and pushing forward.”

Nonetheless, there are some long-term noncompliant patients, Cohen said. “I certainly don’t think that somebody who’s not using the device for years should continue to hold on to it. That resource can be reallocated to somebody who would get more benefit from it. But I think setting a 90-day and 4-hour rule seems arbitrary…and there should be more leeway there.”

The study was independently supported.

Hwang and Cohen reported having no relevant financial disclosures.

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

ORLANDO, Fla. — The Centers for Medicare & Medicaid Services (CMS) will not cover continuous positive airway pressure (CPAP) treatment for people who are nonadherent by 90 days. However, that requirement is too stringent, said researchers who found more than one third of adults who struggled with adherence initially still used the therapy 1 year later at levels associated with clinical benefit.

To test the requirement, investigators assessed 132,492 patients in the Kaiser Permanente Southern California system. The patients were issued CPAP devices to treat obstructive sleep apnea from 2015 to 2023. At 1 year, 36% who would have failed the CMS requirement were still using their CPAP.

The results counter CMS’ assumption that poor early CPAP use always leads to long-term abandonment, said Dennis Hwang, MD, co-chair of Sleep Medicine and medical director of the Sleep Disorders Center at Kaiser Permanente Southern California in Fontana, California.

"We should transition away from a one-size-fits-all definition of success," Hwang added at the American Thoracic Society (ATS) 2026 International Conference.

Background and Methodology

The 90-day adherence requirement does not only apply to Medicare or Medicaid recipients, Hwang said; many private insurers have adopted the same policy. In contrast, Kaiser Permanente Southern California does not restrict usage based on early adherence.

Hwang et al considered any Kaiser Permanente member with any CPAP usage during the 12 months after being issued a device an active user. They tracked mean nightly minutes of use and the percentage of nights with ≥ 2 and ≥ 4 hours of average use.

Overall, 49% would have met the CMS criteria and used the therapy ≥ 4 hours on average each night for 70% of nights during the first 90 days. Kaiser Permanente members aged ≥ 65 years were more compliant, with 54% meeting the CMS benchmarks. ATS guidelines recognize that even ≥ 2 hours of CPAP per night on average can confer some benefits.

The average age in the study was 55 years, and the mean apnea-hypopnea index was 32-33 events per hour, suggesting severe obstructive sleep apnea at baseline. The cohort was diverse, with 42% White, 35% Hispanic, 10% Black, 9% Asian, and 4% other race or ethnicity.

Key Findings

A total of 64,568 adults would have been CMS adherent at 90 days; investigators compared outcomes at 12 months with another 67,867 nonadherent adults.

There were some significant differences between groups. The mean age was 56.4 years vs 53.7 years in the adherent group vs the nonadherent group; men made up a greater proportion of the adherent group, 68.5% vs 62.6%; and the mean number of events per hour was 35 vs 30 (P < .001 for all).

Among the 90-day nonadherent group, about 21% met the 2-hour or greater adherence benchmark, and approximately 14% used CPAP an average of ≥ 4 hours.

“Still a substantial number of [non-CMS adherent] patients are using CPAP,” Hwang said.

Failure to meet CMS adherence was associated with younger age, female sex, non-White race or ethnicity, lower socioeconomic status, and lower severity of obstructive sleep apnea.

“There is also an equity dimension. Whites had better adherence rates during the first 90 days, so there is already a disparity here in terms of outcomes,” Hwang said. Policy changes could improve access to long-term therapy on a more equitable basis, he added. For example, a 2023 ATS policy statement calls for a more patient-centric approach and a focus on reducing inequities.

An Arbitrary Requirement

The 90-day requirement seems a little short, said session co-moderator Oren Cohen, MD, assistant professor in the Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine at Icahn School of Medicine at Mount Sinai in New York City, when asked to comment. “It can take longer to get a patient back into the clinic and go through a lot of the trial and error that it takes to do a mask fitting and adjust the pressures.”

If a patient is using their CPAP device for fewer than 4 hours a night in the early period, it doesn’t mean things are failing, Cohen said. “It’s just that you’ve got to keep trying and pushing forward.”

Nonetheless, there are some long-term noncompliant patients, Cohen said. “I certainly don’t think that somebody who’s not using the device for years should continue to hold on to it. That resource can be reallocated to somebody who would get more benefit from it. But I think setting a 90-day and 4-hour rule seems arbitrary…and there should be more leeway there.”

The study was independently supported.

Hwang and Cohen reported having no relevant financial disclosures.

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 a very interesting paper that appeared in Cancer, entitled, “Association of alcohol intake over the lifetime with colorectal adenoma and colorectal cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.”

This is an important paper. It is very clear, certainly to those in the public health community and cancer doctors, that there is an association with alcohol intake and the risk of cancer. However, in population-based surveys, there is a very large percentage of individuals who do not appear to see the risk of alcohol intake, particularly excessive alcohol intake, related to cancer, or an even larger segment of population simply doesn’t know. This analysis is important to help address this question.

The investigators looked at adults in the United States who were enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, which is a very important study that had been ongoing for many years. Individuals in this study reported at several timepoints during their participation what their current and past alcohol intake was.

What these investigators found is as follows. Among the 88,092 participants, there were a total of 1679 incident colorectal cancers that developed over 20 years of follow-up. Investigators demonstrated that current drinkers with an average lifetime alcohol intake of 14 or more drinks per week, or approximately 2 drinks per day, had a higher risk of colorectal cancer with a hazard ratio of 1.25, a 25% increase, compared to those individuals who had ≤ 1 drink per week.

Very importantly, individuals were characterized by their own information that they provided as consistent heavy drinking versus light drinking. This was associated with almost a doubling of the risk of the development of colorectal cancer over that 20-year period.

Clearly, heavy drinking and higher lifetime alcohol intake is associated with an increased risk of colorectal cancer. This is relevant information for public health officials, primary care doctors, and the public in general to understand that there is a risk if you drink often, particularly heavy drinking, with increased development of cancer in general — but in this case, we’re talking specifically about colorectal cancer.

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 a very interesting paper that appeared in Cancer, entitled, “Association of alcohol intake over the lifetime with colorectal adenoma and colorectal cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.”

This is an important paper. It is very clear, certainly to those in the public health community and cancer doctors, that there is an association with alcohol intake and the risk of cancer. However, in population-based surveys, there is a very large percentage of individuals who do not appear to see the risk of alcohol intake, particularly excessive alcohol intake, related to cancer, or an even larger segment of population simply doesn’t know. This analysis is important to help address this question.

The investigators looked at adults in the United States who were enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, which is a very important study that had been ongoing for many years. Individuals in this study reported at several timepoints during their participation what their current and past alcohol intake was.

What these investigators found is as follows. Among the 88,092 participants, there were a total of 1679 incident colorectal cancers that developed over 20 years of follow-up. Investigators demonstrated that current drinkers with an average lifetime alcohol intake of 14 or more drinks per week, or approximately 2 drinks per day, had a higher risk of colorectal cancer with a hazard ratio of 1.25, a 25% increase, compared to those individuals who had ≤ 1 drink per week.

Very importantly, individuals were characterized by their own information that they provided as consistent heavy drinking versus light drinking. This was associated with almost a doubling of the risk of the development of colorectal cancer over that 20-year period.

Clearly, heavy drinking and higher lifetime alcohol intake is associated with an increased risk of colorectal cancer. This is relevant information for public health officials, primary care doctors, and the public in general to understand that there is a risk if you drink often, particularly heavy drinking, with increased development of cancer in general — but in this case, we’re talking specifically about colorectal cancer.

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 a very interesting paper that appeared in Cancer, entitled, “Association of alcohol intake over the lifetime with colorectal adenoma and colorectal cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.”

This is an important paper. It is very clear, certainly to those in the public health community and cancer doctors, that there is an association with alcohol intake and the risk of cancer. However, in population-based surveys, there is a very large percentage of individuals who do not appear to see the risk of alcohol intake, particularly excessive alcohol intake, related to cancer, or an even larger segment of population simply doesn’t know. This analysis is important to help address this question.

The investigators looked at adults in the United States who were enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, which is a very important study that had been ongoing for many years. Individuals in this study reported at several timepoints during their participation what their current and past alcohol intake was.

What these investigators found is as follows. Among the 88,092 participants, there were a total of 1679 incident colorectal cancers that developed over 20 years of follow-up. Investigators demonstrated that current drinkers with an average lifetime alcohol intake of 14 or more drinks per week, or approximately 2 drinks per day, had a higher risk of colorectal cancer with a hazard ratio of 1.25, a 25% increase, compared to those individuals who had ≤ 1 drink per week.

Very importantly, individuals were characterized by their own information that they provided as consistent heavy drinking versus light drinking. This was associated with almost a doubling of the risk of the development of colorectal cancer over that 20-year period.

Clearly, heavy drinking and higher lifetime alcohol intake is associated with an increased risk of colorectal cancer. This is relevant information for public health officials, primary care doctors, and the public in general to understand that there is a risk if you drink often, particularly heavy drinking, with increased development of cancer in general — but in this case, we’re talking specifically about colorectal cancer.

I thank you for your attention.

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

Individuals with obesity without diabetes taking GLP-1 receptor agonists (RAs) may have a reduced risk for certain cancers, a new study suggests.

The target trial emulation of more than 160,000 patients found that individuals receiving the medications had a 41% lower risk for obesity-associated cancers (OACs), with an even more substantial 68% risk reduction among men.

“If confirmed in prospective studies, GLP-1 RAs may be associated with a broader clinical profile that extends beyond obesity management to include potential effects on cancer risk,” wrote lead author A.H.-C. Hsu, of Houston Methodist Neal Cancer Center, Houston, and colleagues in Annals of Oncology.

How Are GLP-1 RAs Linked to Reduced Cancer Risk?

According to the investigators, obesity is a recognized risk factor for 13 malignancies: breast, colorectal, endometrial, kidney, pancreatic, thyroid, ovarian, esophageal, gastric, liver, and gallbladder cancers, as well as multiple myeloma and meningioma. These conditions account for about 40% of cancers diagnosed in high-income countries, with incidence rising fastest among younger adults.

Preclinical work suggests GLP-1 receptor activation can suppress proliferation in cancer cells that express the receptor, although these mechanisms remain poorly understood. Observational clinical data have linked GLP-1 RAs to lower cancer risk, mainly in people with type 2 diabetes, but it has remained unclear whether the same association would hold among patients with obesity without diabetes.

How Was the New Study Designed?

The investigators first identified 229,467 adults with obesity without diabetes or a prior OAC in the TriNetX federated database. These patients were entered into a target trial emulation framework, which uses trial-like eligibility, treatment, and follow-up rules to approximate a randomized comparison from observational data.

The population was divided into two cohorts; the first comprised patients who filled at least two prescriptions for a GLP-1 RA and the second included patients who received only diet or exercise counseling. Groups were balanced using 1:1 propensity score matching, yielding 80,899 patients per group. The mean age was 47 years, and about 72% of the population were women.

The primary outcome was the cumulative incidence of OACs over 2 years. Further analyses characterized the same outcome based on sex, BMI, race, and the two most-used drugs, semaglutide and tirzepatide.

What Were the Key Findings?

GLP-1 RA use was associated with a 41% lower incidence of OACs overall (hazard ratio [HR], 0.59). The association held across most subgroups, with a more pronounced benefit among men (HR, 0.32) compared with women (HR, 0.65).

Taking tirzepatide (HR, 0.31) was also associated with a greater risk reduction than taking semaglutide (HR, 0.80); however, the investigators encouraged a cautious interpretation of these findings because the study was not designed for a head-to-head comparison between the agents.

In contrast with the above positive findings, no significant risk reduction was observed among Black patients (HR, 0.77; 95% CI, 0.58-1.03) vs a roughly 50% risk reduction among White patients (HR, 0.54; 95% CI, 0.47-0.62).

The reason for the lack of benefit among Black patients is unclear.

Among specific OACs, greatest risk reductions were reported for multiple myeloma (HR, 0.37), pancreatic cancer (HR, 0.40), endometrial cancer (HR, 0.42), and colorectal cancer (HR, 0.49).

No significant risk reductions were observed for breast cancer, ovarian cancer, or meningioma.

What Are the Clinical Implications?

The investigators emphasized that the study, being observational, is insufficient to confirm that GLP-1 RAs prevent cancer in this patient population. Still, the findings may be worth mentioning to patients considering GLP-1 RAs.

While using GLP-1 RAs specifically to lower cancer risk is “not ready for prime time yet,” the data may offer some reassurance for patients concerned about OACs who already have reason to be prescribed GLP-1 RAs, Michael D. Iglesia, MD, PhD, told Medscape Medical News.

Iglesia, who was not involved in the study, took a more cautious stance on the subgroup findings, first pointing out that women report higher rates of gastrointestinal side effects with GLP-1 RAs, so “the men in this study may have received more consistent GLP-1 RA exposure.”

Commenting on the negative findings among Black patients in the study, Iglesia, who is a medical oncologist at the UNC Lineberger Comprehensive Cancer Center pointed out that this subgroup comprised only 82 GLP-1 RA users and 106 people on diet or exercise.

“Issues related to structural inequality and access to care often affect this kind of study,” he said, adding that further work on social and structural factors is needed “before we posit any biological underpinnings for this observed difference.”

What Questions Remain?

Hsu and colleagues called for long-term prospective trials and postmarketing surveillance to track cancer outcomes among GLP-1 RA users, particularly younger patients.

Underlying mechanisms remain a key unknown, the investigators noted, as it remains unclear whether GLP-1 RAs lower cancer risk through weight loss, direct effects on cancer cells, or some combination thereof.

“Knowing the mechanism behind the association shown in this paper would be important for understanding which cancer types may be treated best with GLP-1 RAs,” Iglesia said.

The investigators and Iglesia reported having no conflicts of interest.

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

Individuals with obesity without diabetes taking GLP-1 receptor agonists (RAs) may have a reduced risk for certain cancers, a new study suggests.

The target trial emulation of more than 160,000 patients found that individuals receiving the medications had a 41% lower risk for obesity-associated cancers (OACs), with an even more substantial 68% risk reduction among men.

“If confirmed in prospective studies, GLP-1 RAs may be associated with a broader clinical profile that extends beyond obesity management to include potential effects on cancer risk,” wrote lead author A.H.-C. Hsu, of Houston Methodist Neal Cancer Center, Houston, and colleagues in Annals of Oncology.

How Are GLP-1 RAs Linked to Reduced Cancer Risk?

According to the investigators, obesity is a recognized risk factor for 13 malignancies: breast, colorectal, endometrial, kidney, pancreatic, thyroid, ovarian, esophageal, gastric, liver, and gallbladder cancers, as well as multiple myeloma and meningioma. These conditions account for about 40% of cancers diagnosed in high-income countries, with incidence rising fastest among younger adults.

Preclinical work suggests GLP-1 receptor activation can suppress proliferation in cancer cells that express the receptor, although these mechanisms remain poorly understood. Observational clinical data have linked GLP-1 RAs to lower cancer risk, mainly in people with type 2 diabetes, but it has remained unclear whether the same association would hold among patients with obesity without diabetes.

How Was the New Study Designed?

The investigators first identified 229,467 adults with obesity without diabetes or a prior OAC in the TriNetX federated database. These patients were entered into a target trial emulation framework, which uses trial-like eligibility, treatment, and follow-up rules to approximate a randomized comparison from observational data.

The population was divided into two cohorts; the first comprised patients who filled at least two prescriptions for a GLP-1 RA and the second included patients who received only diet or exercise counseling. Groups were balanced using 1:1 propensity score matching, yielding 80,899 patients per group. The mean age was 47 years, and about 72% of the population were women.

The primary outcome was the cumulative incidence of OACs over 2 years. Further analyses characterized the same outcome based on sex, BMI, race, and the two most-used drugs, semaglutide and tirzepatide.

What Were the Key Findings?

GLP-1 RA use was associated with a 41% lower incidence of OACs overall (hazard ratio [HR], 0.59). The association held across most subgroups, with a more pronounced benefit among men (HR, 0.32) compared with women (HR, 0.65).

Taking tirzepatide (HR, 0.31) was also associated with a greater risk reduction than taking semaglutide (HR, 0.80); however, the investigators encouraged a cautious interpretation of these findings because the study was not designed for a head-to-head comparison between the agents.

In contrast with the above positive findings, no significant risk reduction was observed among Black patients (HR, 0.77; 95% CI, 0.58-1.03) vs a roughly 50% risk reduction among White patients (HR, 0.54; 95% CI, 0.47-0.62).

The reason for the lack of benefit among Black patients is unclear.

Among specific OACs, greatest risk reductions were reported for multiple myeloma (HR, 0.37), pancreatic cancer (HR, 0.40), endometrial cancer (HR, 0.42), and colorectal cancer (HR, 0.49).

No significant risk reductions were observed for breast cancer, ovarian cancer, or meningioma.

What Are the Clinical Implications?

The investigators emphasized that the study, being observational, is insufficient to confirm that GLP-1 RAs prevent cancer in this patient population. Still, the findings may be worth mentioning to patients considering GLP-1 RAs.

While using GLP-1 RAs specifically to lower cancer risk is “not ready for prime time yet,” the data may offer some reassurance for patients concerned about OACs who already have reason to be prescribed GLP-1 RAs, Michael D. Iglesia, MD, PhD, told Medscape Medical News.

Iglesia, who was not involved in the study, took a more cautious stance on the subgroup findings, first pointing out that women report higher rates of gastrointestinal side effects with GLP-1 RAs, so “the men in this study may have received more consistent GLP-1 RA exposure.”

Commenting on the negative findings among Black patients in the study, Iglesia, who is a medical oncologist at the UNC Lineberger Comprehensive Cancer Center pointed out that this subgroup comprised only 82 GLP-1 RA users and 106 people on diet or exercise.

“Issues related to structural inequality and access to care often affect this kind of study,” he said, adding that further work on social and structural factors is needed “before we posit any biological underpinnings for this observed difference.”

What Questions Remain?

Hsu and colleagues called for long-term prospective trials and postmarketing surveillance to track cancer outcomes among GLP-1 RA users, particularly younger patients.

Underlying mechanisms remain a key unknown, the investigators noted, as it remains unclear whether GLP-1 RAs lower cancer risk through weight loss, direct effects on cancer cells, or some combination thereof.

“Knowing the mechanism behind the association shown in this paper would be important for understanding which cancer types may be treated best with GLP-1 RAs,” Iglesia said.

The investigators and Iglesia reported having no conflicts of interest.

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

Individuals with obesity without diabetes taking GLP-1 receptor agonists (RAs) may have a reduced risk for certain cancers, a new study suggests.

The target trial emulation of more than 160,000 patients found that individuals receiving the medications had a 41% lower risk for obesity-associated cancers (OACs), with an even more substantial 68% risk reduction among men.

“If confirmed in prospective studies, GLP-1 RAs may be associated with a broader clinical profile that extends beyond obesity management to include potential effects on cancer risk,” wrote lead author A.H.-C. Hsu, of Houston Methodist Neal Cancer Center, Houston, and colleagues in Annals of Oncology.

How Are GLP-1 RAs Linked to Reduced Cancer Risk?

According to the investigators, obesity is a recognized risk factor for 13 malignancies: breast, colorectal, endometrial, kidney, pancreatic, thyroid, ovarian, esophageal, gastric, liver, and gallbladder cancers, as well as multiple myeloma and meningioma. These conditions account for about 40% of cancers diagnosed in high-income countries, with incidence rising fastest among younger adults.

Preclinical work suggests GLP-1 receptor activation can suppress proliferation in cancer cells that express the receptor, although these mechanisms remain poorly understood. Observational clinical data have linked GLP-1 RAs to lower cancer risk, mainly in people with type 2 diabetes, but it has remained unclear whether the same association would hold among patients with obesity without diabetes.

How Was the New Study Designed?

The investigators first identified 229,467 adults with obesity without diabetes or a prior OAC in the TriNetX federated database. These patients were entered into a target trial emulation framework, which uses trial-like eligibility, treatment, and follow-up rules to approximate a randomized comparison from observational data.

The population was divided into two cohorts; the first comprised patients who filled at least two prescriptions for a GLP-1 RA and the second included patients who received only diet or exercise counseling. Groups were balanced using 1:1 propensity score matching, yielding 80,899 patients per group. The mean age was 47 years, and about 72% of the population were women.

The primary outcome was the cumulative incidence of OACs over 2 years. Further analyses characterized the same outcome based on sex, BMI, race, and the two most-used drugs, semaglutide and tirzepatide.

What Were the Key Findings?

GLP-1 RA use was associated with a 41% lower incidence of OACs overall (hazard ratio [HR], 0.59). The association held across most subgroups, with a more pronounced benefit among men (HR, 0.32) compared with women (HR, 0.65).

Taking tirzepatide (HR, 0.31) was also associated with a greater risk reduction than taking semaglutide (HR, 0.80); however, the investigators encouraged a cautious interpretation of these findings because the study was not designed for a head-to-head comparison between the agents.

In contrast with the above positive findings, no significant risk reduction was observed among Black patients (HR, 0.77; 95% CI, 0.58-1.03) vs a roughly 50% risk reduction among White patients (HR, 0.54; 95% CI, 0.47-0.62).

The reason for the lack of benefit among Black patients is unclear.

Among specific OACs, greatest risk reductions were reported for multiple myeloma (HR, 0.37), pancreatic cancer (HR, 0.40), endometrial cancer (HR, 0.42), and colorectal cancer (HR, 0.49).

No significant risk reductions were observed for breast cancer, ovarian cancer, or meningioma.

What Are the Clinical Implications?

The investigators emphasized that the study, being observational, is insufficient to confirm that GLP-1 RAs prevent cancer in this patient population. Still, the findings may be worth mentioning to patients considering GLP-1 RAs.

While using GLP-1 RAs specifically to lower cancer risk is “not ready for prime time yet,” the data may offer some reassurance for patients concerned about OACs who already have reason to be prescribed GLP-1 RAs, Michael D. Iglesia, MD, PhD, told Medscape Medical News.

Iglesia, who was not involved in the study, took a more cautious stance on the subgroup findings, first pointing out that women report higher rates of gastrointestinal side effects with GLP-1 RAs, so “the men in this study may have received more consistent GLP-1 RA exposure.”

Commenting on the negative findings among Black patients in the study, Iglesia, who is a medical oncologist at the UNC Lineberger Comprehensive Cancer Center pointed out that this subgroup comprised only 82 GLP-1 RA users and 106 people on diet or exercise.

“Issues related to structural inequality and access to care often affect this kind of study,” he said, adding that further work on social and structural factors is needed “before we posit any biological underpinnings for this observed difference.”

What Questions Remain?

Hsu and colleagues called for long-term prospective trials and postmarketing surveillance to track cancer outcomes among GLP-1 RA users, particularly younger patients.

Underlying mechanisms remain a key unknown, the investigators noted, as it remains unclear whether GLP-1 RAs lower cancer risk through weight loss, direct effects on cancer cells, or some combination thereof.

“Knowing the mechanism behind the association shown in this paper would be important for understanding which cancer types may be treated best with GLP-1 RAs,” Iglesia said.

The investigators and Iglesia reported having no conflicts of interest.

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

An investigational oral drug that targets RAS, the dominant oncogenic driver in pancreatic cancer, nearly doubled overall survival compared with common second-line chemotherapy regimens in patients with previously treated metastatic disease.

In the 500-patient phase 3 RASolute 302 trial, patients who received daraxonrasib, a RAS(ON) multi-selective inhibitor, lived a median of 13.2 months compared with 6.7 months for those who received chemotherapy. The drug also doubled progression-free survival, tripled the response rate, and delayed deterioration in both pain and quality of life.

“Results from RASolute 302 support daraxonrasib as a new standard of care for patients with previously treated metastatic pancreatic cancer,” said lead investigator Brian Wolpin, MD, MPH, director of the Hale Family Center for Pancreatic Cancer Research, Dana-Farber Cancer Institute in Boston, who presented the findings at the American Society of Clinical Oncology (ASCO) 2026. The study was also published simultaneously on May 31 in The New England Journal of Medicine.

Pancreatic ductal adenocarcinoma is one of the most lethal cancers, with most patients presenting with advanced disease at diagnosis. For those whose cancer progresses after first-line chemotherapy, no single standard second-line treatment has been established. Available regimens typically produce median progression-free survival of 3-4 months and a median overall survival of 6-7 months.

More than 90% of pancreatic cancers harbor activating RAS mutations — most commonly KRAS G12D and G12V — that drive tumor growth. The first approved KRAS inhibitors — sotorasib and adagrasib for certain lung and colorectal cancers — target KRAS G12C, which is rare in pancreatic cancer. So far, no RAS-targeted therapy has been approved for pancreatic cancer.

Daraxonrasib takes a broader approach. The oral agent can target a range of RAS variants, including mutant and wild-type RAS, by binding the active form of RAS and blocking downstream signaling.

In the phase 3 open-label RASolute 302 trial, researchers randomized 500 patients with previously treated metastatic pancreatic cancer 1:1 to receive daraxonrasib 300 mg orally once daily or investigator’s choice of chemotherapy. The most used regimens in the control arm were gemcitabine plus nab-paclitaxel (56.5%) and liposomal irinotecan plus fluorouracil and leucovorin (32.7%).

Patients were required to have an Eastern Cooperative Oncology Group performance status of 0 or 1. Documented RAS mutational status was required, and nearly 92% of patients had RAS G12 mutations.

The dual primary endpoints were overall survival and progression-free survival in the RAS G12 population. Key secondary endpoints included the same measures in the overall population as well as objective response rate and patient-reported quality of life. The median follow-up was 8.5 months.

In the RAS G12 population, daraxonrasib reduced the risk for death by 60% (hazard ratio [HR], 0.40; P < .001). The median overall survival was 13.2 months with daraxonrasib vs 6.6 months with chemotherapy. Results were nearly identical in the overall population: 13.2 vs 6.7 months (HR, 0.40; P < .001).

Progression-free survival in the RAS G12 population was 7.3 vs 3.5 months (HR, 0.45; P < .001). The objective response rate was 33.2% vs 11.8%.

Daraxonrasib significantly delayed deterioration in pain (median, 9.0 vs 3.7 months; HR, 0.51; P < .001) and global quality of life (5.6 vs 2.4 months; HR, 0.60; P < .001).

Treatment-related adverse events of grade ≥ 3 occurred in 43.6% of patients on daraxonrasib vs 57.5% of patients on chemotherapy. The most common high-grade events with daraxonrasib were rash (13.7%) and stomatitis (12.0%), whereas neutropenia (27.6%) and anemia (16.4%) were most common with chemotherapy.

One patient in the daraxonrasib arm died from treatment-related pneumonitis. Discontinuation due to adverse events occurred in 1.2% of patients on daraxonrasib vs 11.2% of patients on chemotherapy.

The median duration of treatment was 6.2 months with daraxonrasib vs 1.5-3.2 months across chemotherapy regimens, and 42% of patients on daraxonrasib remained on treatment at data cutoff, Wolpin said.

The open-label design is a limitation. About 15% of patients randomized to chemotherapy never received treatment, largely after learning their treatment assignment, although all were included in the intention-to-treat analysis.

Invited discussant Jennifer Knox, MD, a medical oncologist at Princess Margaret Cancer Center and professor of medicine at the University of Toronto in Toronto, Ontario, Canada, called daraxonrasib a game changer, describing the drug as “probably the most exciting strategy in five decades” for pancreatic cancer.

“It is an absolutely beautiful curve,” Knox said of the overall survival data, noting that the Kaplan-Meier curves separated early and continued to widen over time — a pattern rarely seen in pancreatic cancer trials where initial separation between treatment arms typically narrows as patients in both groups deteriorate.

Knox highlighted the pain and quality-of-life data as “the most important endpoints for our patients,” given the severity of the disease.

She pointed out, however, that the combination of rash and stomatitis will be “challenging” in practice, and called for improved supportive care and closer collaboration with dermatology as oncologists gain experience with this first-in-class drug.

Knox said RAS-targeted therapy “should dominate trials across the full spectrum of pancreatic cancer clinical presentations,” pointing to first-line combination trials already underway and noting that treating a larger, earlier population would have the greatest impact.

“This is the first glimpse at the real power of targeting RAS in pancreas cancer,” Knox said.

The study was funded by Revolution Medicines. Wolpin reported consulting or advisory roles with Revolution Medicines, Mirati Therapeutics, Ipsen, and others, and institutional research funding from Revolution Medicines, Agios, Amgen, AstraZeneca, Lilly, and Novartis. Knox reported receiving honoraria from Astellas Pharma, AstraZeneca, Incyte, and Ipsen, and consulting or advisory roles with AstraZeneca/MedImmune, Incyte, and Ipsen.

A version of this article was previously published on Medscape.com.

An investigational oral drug that targets RAS, the dominant oncogenic driver in pancreatic cancer, nearly doubled overall survival compared with common second-line chemotherapy regimens in patients with previously treated metastatic disease.

In the 500-patient phase 3 RASolute 302 trial, patients who received daraxonrasib, a RAS(ON) multi-selective inhibitor, lived a median of 13.2 months compared with 6.7 months for those who received chemotherapy. The drug also doubled progression-free survival, tripled the response rate, and delayed deterioration in both pain and quality of life.

“Results from RASolute 302 support daraxonrasib as a new standard of care for patients with previously treated metastatic pancreatic cancer,” said lead investigator Brian Wolpin, MD, MPH, director of the Hale Family Center for Pancreatic Cancer Research, Dana-Farber Cancer Institute in Boston, who presented the findings at the American Society of Clinical Oncology (ASCO) 2026. The study was also published simultaneously on May 31 in The New England Journal of Medicine.

Pancreatic ductal adenocarcinoma is one of the most lethal cancers, with most patients presenting with advanced disease at diagnosis. For those whose cancer progresses after first-line chemotherapy, no single standard second-line treatment has been established. Available regimens typically produce median progression-free survival of 3-4 months and a median overall survival of 6-7 months.

More than 90% of pancreatic cancers harbor activating RAS mutations — most commonly KRAS G12D and G12V — that drive tumor growth. The first approved KRAS inhibitors — sotorasib and adagrasib for certain lung and colorectal cancers — target KRAS G12C, which is rare in pancreatic cancer. So far, no RAS-targeted therapy has been approved for pancreatic cancer.

Daraxonrasib takes a broader approach. The oral agent can target a range of RAS variants, including mutant and wild-type RAS, by binding the active form of RAS and blocking downstream signaling.

In the phase 3 open-label RASolute 302 trial, researchers randomized 500 patients with previously treated metastatic pancreatic cancer 1:1 to receive daraxonrasib 300 mg orally once daily or investigator’s choice of chemotherapy. The most used regimens in the control arm were gemcitabine plus nab-paclitaxel (56.5%) and liposomal irinotecan plus fluorouracil and leucovorin (32.7%).

Patients were required to have an Eastern Cooperative Oncology Group performance status of 0 or 1. Documented RAS mutational status was required, and nearly 92% of patients had RAS G12 mutations.

The dual primary endpoints were overall survival and progression-free survival in the RAS G12 population. Key secondary endpoints included the same measures in the overall population as well as objective response rate and patient-reported quality of life. The median follow-up was 8.5 months.

In the RAS G12 population, daraxonrasib reduced the risk for death by 60% (hazard ratio [HR], 0.40; P < .001). The median overall survival was 13.2 months with daraxonrasib vs 6.6 months with chemotherapy. Results were nearly identical in the overall population: 13.2 vs 6.7 months (HR, 0.40; P < .001).

Progression-free survival in the RAS G12 population was 7.3 vs 3.5 months (HR, 0.45; P < .001). The objective response rate was 33.2% vs 11.8%.

Daraxonrasib significantly delayed deterioration in pain (median, 9.0 vs 3.7 months; HR, 0.51; P < .001) and global quality of life (5.6 vs 2.4 months; HR, 0.60; P < .001).

Treatment-related adverse events of grade ≥ 3 occurred in 43.6% of patients on daraxonrasib vs 57.5% of patients on chemotherapy. The most common high-grade events with daraxonrasib were rash (13.7%) and stomatitis (12.0%), whereas neutropenia (27.6%) and anemia (16.4%) were most common with chemotherapy.

One patient in the daraxonrasib arm died from treatment-related pneumonitis. Discontinuation due to adverse events occurred in 1.2% of patients on daraxonrasib vs 11.2% of patients on chemotherapy.

The median duration of treatment was 6.2 months with daraxonrasib vs 1.5-3.2 months across chemotherapy regimens, and 42% of patients on daraxonrasib remained on treatment at data cutoff, Wolpin said.

The open-label design is a limitation. About 15% of patients randomized to chemotherapy never received treatment, largely after learning their treatment assignment, although all were included in the intention-to-treat analysis.

Invited discussant Jennifer Knox, MD, a medical oncologist at Princess Margaret Cancer Center and professor of medicine at the University of Toronto in Toronto, Ontario, Canada, called daraxonrasib a game changer, describing the drug as “probably the most exciting strategy in five decades” for pancreatic cancer.

“It is an absolutely beautiful curve,” Knox said of the overall survival data, noting that the Kaplan-Meier curves separated early and continued to widen over time — a pattern rarely seen in pancreatic cancer trials where initial separation between treatment arms typically narrows as patients in both groups deteriorate.

Knox highlighted the pain and quality-of-life data as “the most important endpoints for our patients,” given the severity of the disease.

She pointed out, however, that the combination of rash and stomatitis will be “challenging” in practice, and called for improved supportive care and closer collaboration with dermatology as oncologists gain experience with this first-in-class drug.

Knox said RAS-targeted therapy “should dominate trials across the full spectrum of pancreatic cancer clinical presentations,” pointing to first-line combination trials already underway and noting that treating a larger, earlier population would have the greatest impact.

“This is the first glimpse at the real power of targeting RAS in pancreas cancer,” Knox said.

The study was funded by Revolution Medicines. Wolpin reported consulting or advisory roles with Revolution Medicines, Mirati Therapeutics, Ipsen, and others, and institutional research funding from Revolution Medicines, Agios, Amgen, AstraZeneca, Lilly, and Novartis. Knox reported receiving honoraria from Astellas Pharma, AstraZeneca, Incyte, and Ipsen, and consulting or advisory roles with AstraZeneca/MedImmune, Incyte, and Ipsen.

A version of this article was previously published on Medscape.com.

An investigational oral drug that targets RAS, the dominant oncogenic driver in pancreatic cancer, nearly doubled overall survival compared with common second-line chemotherapy regimens in patients with previously treated metastatic disease.

In the 500-patient phase 3 RASolute 302 trial, patients who received daraxonrasib, a RAS(ON) multi-selective inhibitor, lived a median of 13.2 months compared with 6.7 months for those who received chemotherapy. The drug also doubled progression-free survival, tripled the response rate, and delayed deterioration in both pain and quality of life.

“Results from RASolute 302 support daraxonrasib as a new standard of care for patients with previously treated metastatic pancreatic cancer,” said lead investigator Brian Wolpin, MD, MPH, director of the Hale Family Center for Pancreatic Cancer Research, Dana-Farber Cancer Institute in Boston, who presented the findings at the American Society of Clinical Oncology (ASCO) 2026. The study was also published simultaneously on May 31 in The New England Journal of Medicine.

Pancreatic ductal adenocarcinoma is one of the most lethal cancers, with most patients presenting with advanced disease at diagnosis. For those whose cancer progresses after first-line chemotherapy, no single standard second-line treatment has been established. Available regimens typically produce median progression-free survival of 3-4 months and a median overall survival of 6-7 months.

More than 90% of pancreatic cancers harbor activating RAS mutations — most commonly KRAS G12D and G12V — that drive tumor growth. The first approved KRAS inhibitors — sotorasib and adagrasib for certain lung and colorectal cancers — target KRAS G12C, which is rare in pancreatic cancer. So far, no RAS-targeted therapy has been approved for pancreatic cancer.

Daraxonrasib takes a broader approach. The oral agent can target a range of RAS variants, including mutant and wild-type RAS, by binding the active form of RAS and blocking downstream signaling.

In the phase 3 open-label RASolute 302 trial, researchers randomized 500 patients with previously treated metastatic pancreatic cancer 1:1 to receive daraxonrasib 300 mg orally once daily or investigator’s choice of chemotherapy. The most used regimens in the control arm were gemcitabine plus nab-paclitaxel (56.5%) and liposomal irinotecan plus fluorouracil and leucovorin (32.7%).

Patients were required to have an Eastern Cooperative Oncology Group performance status of 0 or 1. Documented RAS mutational status was required, and nearly 92% of patients had RAS G12 mutations.

The dual primary endpoints were overall survival and progression-free survival in the RAS G12 population. Key secondary endpoints included the same measures in the overall population as well as objective response rate and patient-reported quality of life. The median follow-up was 8.5 months.

In the RAS G12 population, daraxonrasib reduced the risk for death by 60% (hazard ratio [HR], 0.40; P < .001). The median overall survival was 13.2 months with daraxonrasib vs 6.6 months with chemotherapy. Results were nearly identical in the overall population: 13.2 vs 6.7 months (HR, 0.40; P < .001).

Progression-free survival in the RAS G12 population was 7.3 vs 3.5 months (HR, 0.45; P < .001). The objective response rate was 33.2% vs 11.8%.

Daraxonrasib significantly delayed deterioration in pain (median, 9.0 vs 3.7 months; HR, 0.51; P < .001) and global quality of life (5.6 vs 2.4 months; HR, 0.60; P < .001).

Treatment-related adverse events of grade ≥ 3 occurred in 43.6% of patients on daraxonrasib vs 57.5% of patients on chemotherapy. The most common high-grade events with daraxonrasib were rash (13.7%) and stomatitis (12.0%), whereas neutropenia (27.6%) and anemia (16.4%) were most common with chemotherapy.

One patient in the daraxonrasib arm died from treatment-related pneumonitis. Discontinuation due to adverse events occurred in 1.2% of patients on daraxonrasib vs 11.2% of patients on chemotherapy.

The median duration of treatment was 6.2 months with daraxonrasib vs 1.5-3.2 months across chemotherapy regimens, and 42% of patients on daraxonrasib remained on treatment at data cutoff, Wolpin said.

The open-label design is a limitation. About 15% of patients randomized to chemotherapy never received treatment, largely after learning their treatment assignment, although all were included in the intention-to-treat analysis.

Invited discussant Jennifer Knox, MD, a medical oncologist at Princess Margaret Cancer Center and professor of medicine at the University of Toronto in Toronto, Ontario, Canada, called daraxonrasib a game changer, describing the drug as “probably the most exciting strategy in five decades” for pancreatic cancer.

“It is an absolutely beautiful curve,” Knox said of the overall survival data, noting that the Kaplan-Meier curves separated early and continued to widen over time — a pattern rarely seen in pancreatic cancer trials where initial separation between treatment arms typically narrows as patients in both groups deteriorate.

Knox highlighted the pain and quality-of-life data as “the most important endpoints for our patients,” given the severity of the disease.

She pointed out, however, that the combination of rash and stomatitis will be “challenging” in practice, and called for improved supportive care and closer collaboration with dermatology as oncologists gain experience with this first-in-class drug.

Knox said RAS-targeted therapy “should dominate trials across the full spectrum of pancreatic cancer clinical presentations,” pointing to first-line combination trials already underway and noting that treating a larger, earlier population would have the greatest impact.

“This is the first glimpse at the real power of targeting RAS in pancreas cancer,” Knox said.

The study was funded by Revolution Medicines. Wolpin reported consulting or advisory roles with Revolution Medicines, Mirati Therapeutics, Ipsen, and others, and institutional research funding from Revolution Medicines, Agios, Amgen, AstraZeneca, Lilly, and Novartis. Knox reported receiving honoraria from Astellas Pharma, AstraZeneca, Incyte, and Ipsen, and consulting or advisory roles with AstraZeneca/MedImmune, Incyte, and Ipsen.

A version of this article was previously published on Medscape.com.

A US Department of Veterans Affairs (VA) Office of Inspector General (OIG) report has found that many patients who scored high on a screening for alcohol use are not receiving recommended counseling interventions.

The OIG report evaluated Veterans Health Administration (VHA) primary care staff adherence to the screening requirements and intervention interventions during fiscal year 2024 (October 1, 2023, to September 30, 2024). VHA primary care clinicians used the Alcohol Use Disorders Identification Test – Consumption (AUDIT-C), which produces a score of 0 to 12, to screen almost 4 million patients.

Based on sex-specific thresholds, the report found 8% of men and 11% of women screened positive for unhealthy alcohol use (AUDIT-C score ≥ 4 for men and ≥ 3 for women). However, because VHA electronic health record prompts clinicians to provide intervention for patients with scores ≥ 5, 54% of men and 75% of women who may have benefited from brief intervention did not.

A brief intervention with a clinician consists of a 5-minute counseling session, with individualized feedback and a discussion on strategies for the patient to reduce or abstain from alcohol.

Aligning with VHA guidance, clinicians provided brief intervention to 77% of men and 75% of women who recorded an AUDIT-C score ≥ 5. However, < 2% of patients with a score at the sex-specific threshold received brief intervention.  

Veterans have high rates of unhealthy alcohol use, which is associated with increased risk of interpersonal violence and poor health outcomes. In a May 2026 study, 44% of 3117 veterans met criteria for alcohol use disorder; 44% reported past 30-day alcohol use.

The VHA requires annual screening using the AUDIT-C. In a study of 63,397 VHA patients, 25% of women and 28% of men screened positive for unhealthy alcohol use. The prevalence of alcohol and other substance abuse disorders increased with increasing AUDIT-C scores, ranging as high as 82% for women and 69% for men. 

A 2018 analysis found that tailoring the AUDIT-C binge-drinking item, AUDIT-C scoring, or both increased detection of unhealthy alcohol use in women. In 2020, VHA adjusted the binge drinking item for women, reducing it to 4 drinks on an occasion from 6 to characterize binge drinking. Despite this adjustment, the VHA maintained an AUDIT-C score ≥ 5 to prompt brief intervention for both women and men.

A 2022 study of 4148 veterans found that 15% were not properly screened for alcohol despite 1 in 11 met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for alcohol abuse/dependence. A lack of screening may not be the issue, however. In the OIG report, VHA found 95% adherence to alcohol use screening in 2024 using a sample-based performance measure and 79% adherence after transitioning that year to a population-based measure. OIG determined that the population-based measure provides a more accurate representation of screening documentation.

Following the OIG recommendations, VA Under Secretary for Health John J. Bartrum, JD, MBA, provided an action plan to evaluate factors that affect screening, identify facilities for performance improvement, and evaluate the use of sex-specific alcohol use screening thresholds. 

A US Department of Veterans Affairs (VA) Office of Inspector General (OIG) report has found that many patients who scored high on a screening for alcohol use are not receiving recommended counseling interventions.

The OIG report evaluated Veterans Health Administration (VHA) primary care staff adherence to the screening requirements and intervention interventions during fiscal year 2024 (October 1, 2023, to September 30, 2024). VHA primary care clinicians used the Alcohol Use Disorders Identification Test – Consumption (AUDIT-C), which produces a score of 0 to 12, to screen almost 4 million patients.

Based on sex-specific thresholds, the report found 8% of men and 11% of women screened positive for unhealthy alcohol use (AUDIT-C score ≥ 4 for men and ≥ 3 for women). However, because VHA electronic health record prompts clinicians to provide intervention for patients with scores ≥ 5, 54% of men and 75% of women who may have benefited from brief intervention did not.

A brief intervention with a clinician consists of a 5-minute counseling session, with individualized feedback and a discussion on strategies for the patient to reduce or abstain from alcohol.

Aligning with VHA guidance, clinicians provided brief intervention to 77% of men and 75% of women who recorded an AUDIT-C score ≥ 5. However, < 2% of patients with a score at the sex-specific threshold received brief intervention.  

Veterans have high rates of unhealthy alcohol use, which is associated with increased risk of interpersonal violence and poor health outcomes. In a May 2026 study, 44% of 3117 veterans met criteria for alcohol use disorder; 44% reported past 30-day alcohol use.

The VHA requires annual screening using the AUDIT-C. In a study of 63,397 VHA patients, 25% of women and 28% of men screened positive for unhealthy alcohol use. The prevalence of alcohol and other substance abuse disorders increased with increasing AUDIT-C scores, ranging as high as 82% for women and 69% for men. 

A 2018 analysis found that tailoring the AUDIT-C binge-drinking item, AUDIT-C scoring, or both increased detection of unhealthy alcohol use in women. In 2020, VHA adjusted the binge drinking item for women, reducing it to 4 drinks on an occasion from 6 to characterize binge drinking. Despite this adjustment, the VHA maintained an AUDIT-C score ≥ 5 to prompt brief intervention for both women and men.

A 2022 study of 4148 veterans found that 15% were not properly screened for alcohol despite 1 in 11 met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for alcohol abuse/dependence. A lack of screening may not be the issue, however. In the OIG report, VHA found 95% adherence to alcohol use screening in 2024 using a sample-based performance measure and 79% adherence after transitioning that year to a population-based measure. OIG determined that the population-based measure provides a more accurate representation of screening documentation.

Following the OIG recommendations, VA Under Secretary for Health John J. Bartrum, JD, MBA, provided an action plan to evaluate factors that affect screening, identify facilities for performance improvement, and evaluate the use of sex-specific alcohol use screening thresholds. 

A US Department of Veterans Affairs (VA) Office of Inspector General (OIG) report has found that many patients who scored high on a screening for alcohol use are not receiving recommended counseling interventions.

The OIG report evaluated Veterans Health Administration (VHA) primary care staff adherence to the screening requirements and intervention interventions during fiscal year 2024 (October 1, 2023, to September 30, 2024). VHA primary care clinicians used the Alcohol Use Disorders Identification Test – Consumption (AUDIT-C), which produces a score of 0 to 12, to screen almost 4 million patients.

Based on sex-specific thresholds, the report found 8% of men and 11% of women screened positive for unhealthy alcohol use (AUDIT-C score ≥ 4 for men and ≥ 3 for women). However, because VHA electronic health record prompts clinicians to provide intervention for patients with scores ≥ 5, 54% of men and 75% of women who may have benefited from brief intervention did not.

A brief intervention with a clinician consists of a 5-minute counseling session, with individualized feedback and a discussion on strategies for the patient to reduce or abstain from alcohol.

Aligning with VHA guidance, clinicians provided brief intervention to 77% of men and 75% of women who recorded an AUDIT-C score ≥ 5. However, < 2% of patients with a score at the sex-specific threshold received brief intervention.  

Veterans have high rates of unhealthy alcohol use, which is associated with increased risk of interpersonal violence and poor health outcomes. In a May 2026 study, 44% of 3117 veterans met criteria for alcohol use disorder; 44% reported past 30-day alcohol use.

The VHA requires annual screening using the AUDIT-C. In a study of 63,397 VHA patients, 25% of women and 28% of men screened positive for unhealthy alcohol use. The prevalence of alcohol and other substance abuse disorders increased with increasing AUDIT-C scores, ranging as high as 82% for women and 69% for men. 

A 2018 analysis found that tailoring the AUDIT-C binge-drinking item, AUDIT-C scoring, or both increased detection of unhealthy alcohol use in women. In 2020, VHA adjusted the binge drinking item for women, reducing it to 4 drinks on an occasion from 6 to characterize binge drinking. Despite this adjustment, the VHA maintained an AUDIT-C score ≥ 5 to prompt brief intervention for both women and men.

A 2022 study of 4148 veterans found that 15% were not properly screened for alcohol despite 1 in 11 met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for alcohol abuse/dependence. A lack of screening may not be the issue, however. In the OIG report, VHA found 95% adherence to alcohol use screening in 2024 using a sample-based performance measure and 79% adherence after transitioning that year to a population-based measure. OIG determined that the population-based measure provides a more accurate representation of screening documentation.

Following the OIG recommendations, VA Under Secretary for Health John J. Bartrum, JD, MBA, provided an action plan to evaluate factors that affect screening, identify facilities for performance improvement, and evaluate the use of sex-specific alcohol use screening thresholds.