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PHOENIX — Patients with head and neck cancer face high rates of malnutrition during treatment, and oral supplements are often recommended. But they are not the entire answer, a dietician told colleagues at the Association of Veterans Affairs (VA) Hematology/Oncology annual meeting.

“Patients should consume the most liberal diet possible throughout treatment,” said advanced practice oncology dietician Brittany Leneweaver, RD, CSO, CES, at the VA Washington DC Healthcare System. “This means not solely relying on oral nutrition supplements like Ensure if possible.”

While Leneweaver said many patients will need supplements, she stressed these products “are meant to supplement the diet and not be the sole source of nutrition, ideally.” Encouraging the intake of whole foods “is really key to make the transition back to solid foods after they’re done with treatment. This makes it so much easier when they’re already swallowing those thicker textures, rather than just liquid the entire time.”

Malnutrition: Common and Damaging

As Leneweaver noted, malnutrition is common in patients with head and neck cancer, and can lead to “increased treatment toxicity, increased risk of infection, decreased survival, increased surgical complication, delayed healing, decreased physical function, and decreased quality of life.”

Malnutrition data in patients with head and neck cancer in the US is sparse. However, a 2024 study found malnutrition in 20% of patients undergoing head and neck cancer surgery and linked the condition to increased length of stay (β, 5.20 additional days), higher costs (β, $15,722) higher odds of potentially preventable complications (adjusted odds ratio [aOR], 2.04), and lower odds of discharge to home (aOR, 0.34).

Leneweaver said her role involves addressing “nutrition impact symptoms” that reduce veteran food intake such as difficulty swallowing, taste disorders, dry mouth, and inflammation of the mucus membranes.

“I can’t tell you how much time I spend just talking to the patient about their medication regimens, making sure they have antiemetics on board, letting the radiation oncologist know, ‘Hey, it’s probably time for medicine,’” she said. “We’re constantly looking at side effects and addressing to alert the team as quickly as possible so that we can prevent further weight loss.”

Better Diets Lead to Better Outcomes

Leneweaver noted that “many times, patients will continue to rely on oral supplements as their primary source of nutrition over the long term. They may be missing out on several health benefits as a result.”

Research shows that high-quality diets matter in this patient group, she said. They’re associated with “decreased symptoms during treatment, reduced head and neck cancer risk, and reduced risk of those chronic nutrition impact symptoms,” Leneweaver said.

Diets before and after cancer diagnosis can make a difference. A 2019 study examined patient diets prior to diagnosis of head and neck cancer. It found that patients with better diet quality were less likely to experience overall nutrition impact symptoms (OR 0.45). However, “studies have found that the majority of our patients with head and neck cancer have an inadequate diet prior to diagnosis,” Leneweaver said. 

As for postdiagnosis nutrition, a 2022 study linked healthier diets in patients with head and neck cancer to 93% lower 3-year risk of all-cause mortality and 85% lower risk of cancer-specific mortality. 

What’s in a High-Quality Diet?

Regarding specific food recommendations, Leneweaver prefers the American Institute for Cancer Research (AICR) nutrition guidelines over the US Department of Agriculture’s Dietary Guidelines for Americans. The AICR “more clearly recommends plant-based diet with at least two-thirds of each meal coming from a variety of plant sources” and recommends avoiding alcohol entirely and limiting red meat, she said. 

Leneweaver said she recognizes that dietary change can be gradual.

“It’s not going to happen overnight,” she said. “We know that lifestyle change takes a lot of work.”

Basic interventions can be effective, she said: “This can be just as simple as recommending a plant-based diet to your patient or recommending they eat the rainbow. And I don’t mean Skittles, I mean actual plants. If you just mention these couple of things to the patients, this can really go a long way, especially if they’re hearing that consistent messaging.”

Team-Based Follow-Up Is Key

Leneweaver emphasized the importance of following up over time even if patients do not initially accept referrals to nutritional services. Dieticians ideally see patients before or during initial treatment and then weekly during radiation therapy. Posttreatment follow-up continues “until they’re nutritionally stable. This can be anywhere from weekly to monthly.”

Leneweaver emphasized collaborating with other team members. For example, she works with a speech pathologist at joint visits, either weekly or monthly, “so that they can get off of that feeding tube or get back to a solid consistency diet, typically before that 3-month PET scan.”

It is also important to understand barriers to healthy eating in the veteran population, including transportation challenges and poor access to healthy food, Leneweaver said.

“Make sure you’re utilizing your social worker, your psychologist, other resources, and food pantries, if you have them.” 

Even when the most ideal choices are not available, she said, “if they only have access to canned vegetables, I’d much rather them eat that than have nothing.”

No disclosures for Leneweaver were provided. 

PHOENIX — Patients with head and neck cancer face high rates of malnutrition during treatment, and oral supplements are often recommended. But they are not the entire answer, a dietician told colleagues at the Association of Veterans Affairs (VA) Hematology/Oncology annual meeting.

“Patients should consume the most liberal diet possible throughout treatment,” said advanced practice oncology dietician Brittany Leneweaver, RD, CSO, CES, at the VA Washington DC Healthcare System. “This means not solely relying on oral nutrition supplements like Ensure if possible.”

While Leneweaver said many patients will need supplements, she stressed these products “are meant to supplement the diet and not be the sole source of nutrition, ideally.” Encouraging the intake of whole foods “is really key to make the transition back to solid foods after they’re done with treatment. This makes it so much easier when they’re already swallowing those thicker textures, rather than just liquid the entire time.”

Malnutrition: Common and Damaging

As Leneweaver noted, malnutrition is common in patients with head and neck cancer, and can lead to “increased treatment toxicity, increased risk of infection, decreased survival, increased surgical complication, delayed healing, decreased physical function, and decreased quality of life.”

Malnutrition data in patients with head and neck cancer in the US is sparse. However, a 2024 study found malnutrition in 20% of patients undergoing head and neck cancer surgery and linked the condition to increased length of stay (β, 5.20 additional days), higher costs (β, $15,722) higher odds of potentially preventable complications (adjusted odds ratio [aOR], 2.04), and lower odds of discharge to home (aOR, 0.34).

Leneweaver said her role involves addressing “nutrition impact symptoms” that reduce veteran food intake such as difficulty swallowing, taste disorders, dry mouth, and inflammation of the mucus membranes.

“I can’t tell you how much time I spend just talking to the patient about their medication regimens, making sure they have antiemetics on board, letting the radiation oncologist know, ‘Hey, it’s probably time for medicine,’” she said. “We’re constantly looking at side effects and addressing to alert the team as quickly as possible so that we can prevent further weight loss.”

Better Diets Lead to Better Outcomes

Leneweaver noted that “many times, patients will continue to rely on oral supplements as their primary source of nutrition over the long term. They may be missing out on several health benefits as a result.”

Research shows that high-quality diets matter in this patient group, she said. They’re associated with “decreased symptoms during treatment, reduced head and neck cancer risk, and reduced risk of those chronic nutrition impact symptoms,” Leneweaver said.

Diets before and after cancer diagnosis can make a difference. A 2019 study examined patient diets prior to diagnosis of head and neck cancer. It found that patients with better diet quality were less likely to experience overall nutrition impact symptoms (OR 0.45). However, “studies have found that the majority of our patients with head and neck cancer have an inadequate diet prior to diagnosis,” Leneweaver said. 

As for postdiagnosis nutrition, a 2022 study linked healthier diets in patients with head and neck cancer to 93% lower 3-year risk of all-cause mortality and 85% lower risk of cancer-specific mortality. 

What’s in a High-Quality Diet?

Regarding specific food recommendations, Leneweaver prefers the American Institute for Cancer Research (AICR) nutrition guidelines over the US Department of Agriculture’s Dietary Guidelines for Americans. The AICR “more clearly recommends plant-based diet with at least two-thirds of each meal coming from a variety of plant sources” and recommends avoiding alcohol entirely and limiting red meat, she said. 

Leneweaver said she recognizes that dietary change can be gradual.

“It’s not going to happen overnight,” she said. “We know that lifestyle change takes a lot of work.”

Basic interventions can be effective, she said: “This can be just as simple as recommending a plant-based diet to your patient or recommending they eat the rainbow. And I don’t mean Skittles, I mean actual plants. If you just mention these couple of things to the patients, this can really go a long way, especially if they’re hearing that consistent messaging.”

Team-Based Follow-Up Is Key

Leneweaver emphasized the importance of following up over time even if patients do not initially accept referrals to nutritional services. Dieticians ideally see patients before or during initial treatment and then weekly during radiation therapy. Posttreatment follow-up continues “until they’re nutritionally stable. This can be anywhere from weekly to monthly.”

Leneweaver emphasized collaborating with other team members. For example, she works with a speech pathologist at joint visits, either weekly or monthly, “so that they can get off of that feeding tube or get back to a solid consistency diet, typically before that 3-month PET scan.”

It is also important to understand barriers to healthy eating in the veteran population, including transportation challenges and poor access to healthy food, Leneweaver said.

“Make sure you’re utilizing your social worker, your psychologist, other resources, and food pantries, if you have them.” 

Even when the most ideal choices are not available, she said, “if they only have access to canned vegetables, I’d much rather them eat that than have nothing.”

No disclosures for Leneweaver were provided. 

PHOENIX — Patients with head and neck cancer face high rates of malnutrition during treatment, and oral supplements are often recommended. But they are not the entire answer, a dietician told colleagues at the Association of Veterans Affairs (VA) Hematology/Oncology annual meeting.

“Patients should consume the most liberal diet possible throughout treatment,” said advanced practice oncology dietician Brittany Leneweaver, RD, CSO, CES, at the VA Washington DC Healthcare System. “This means not solely relying on oral nutrition supplements like Ensure if possible.”

While Leneweaver said many patients will need supplements, she stressed these products “are meant to supplement the diet and not be the sole source of nutrition, ideally.” Encouraging the intake of whole foods “is really key to make the transition back to solid foods after they’re done with treatment. This makes it so much easier when they’re already swallowing those thicker textures, rather than just liquid the entire time.”

Malnutrition: Common and Damaging

As Leneweaver noted, malnutrition is common in patients with head and neck cancer, and can lead to “increased treatment toxicity, increased risk of infection, decreased survival, increased surgical complication, delayed healing, decreased physical function, and decreased quality of life.”

Malnutrition data in patients with head and neck cancer in the US is sparse. However, a 2024 study found malnutrition in 20% of patients undergoing head and neck cancer surgery and linked the condition to increased length of stay (β, 5.20 additional days), higher costs (β, $15,722) higher odds of potentially preventable complications (adjusted odds ratio [aOR], 2.04), and lower odds of discharge to home (aOR, 0.34).

Leneweaver said her role involves addressing “nutrition impact symptoms” that reduce veteran food intake such as difficulty swallowing, taste disorders, dry mouth, and inflammation of the mucus membranes.

“I can’t tell you how much time I spend just talking to the patient about their medication regimens, making sure they have antiemetics on board, letting the radiation oncologist know, ‘Hey, it’s probably time for medicine,’” she said. “We’re constantly looking at side effects and addressing to alert the team as quickly as possible so that we can prevent further weight loss.”

Better Diets Lead to Better Outcomes

Leneweaver noted that “many times, patients will continue to rely on oral supplements as their primary source of nutrition over the long term. They may be missing out on several health benefits as a result.”

Research shows that high-quality diets matter in this patient group, she said. They’re associated with “decreased symptoms during treatment, reduced head and neck cancer risk, and reduced risk of those chronic nutrition impact symptoms,” Leneweaver said.

Diets before and after cancer diagnosis can make a difference. A 2019 study examined patient diets prior to diagnosis of head and neck cancer. It found that patients with better diet quality were less likely to experience overall nutrition impact symptoms (OR 0.45). However, “studies have found that the majority of our patients with head and neck cancer have an inadequate diet prior to diagnosis,” Leneweaver said. 

As for postdiagnosis nutrition, a 2022 study linked healthier diets in patients with head and neck cancer to 93% lower 3-year risk of all-cause mortality and 85% lower risk of cancer-specific mortality. 

What’s in a High-Quality Diet?

Regarding specific food recommendations, Leneweaver prefers the American Institute for Cancer Research (AICR) nutrition guidelines over the US Department of Agriculture’s Dietary Guidelines for Americans. The AICR “more clearly recommends plant-based diet with at least two-thirds of each meal coming from a variety of plant sources” and recommends avoiding alcohol entirely and limiting red meat, she said. 

Leneweaver said she recognizes that dietary change can be gradual.

“It’s not going to happen overnight,” she said. “We know that lifestyle change takes a lot of work.”

Basic interventions can be effective, she said: “This can be just as simple as recommending a plant-based diet to your patient or recommending they eat the rainbow. And I don’t mean Skittles, I mean actual plants. If you just mention these couple of things to the patients, this can really go a long way, especially if they’re hearing that consistent messaging.”

Team-Based Follow-Up Is Key

Leneweaver emphasized the importance of following up over time even if patients do not initially accept referrals to nutritional services. Dieticians ideally see patients before or during initial treatment and then weekly during radiation therapy. Posttreatment follow-up continues “until they’re nutritionally stable. This can be anywhere from weekly to monthly.”

Leneweaver emphasized collaborating with other team members. For example, she works with a speech pathologist at joint visits, either weekly or monthly, “so that they can get off of that feeding tube or get back to a solid consistency diet, typically before that 3-month PET scan.”

It is also important to understand barriers to healthy eating in the veteran population, including transportation challenges and poor access to healthy food, Leneweaver said.

“Make sure you’re utilizing your social worker, your psychologist, other resources, and food pantries, if you have them.” 

Even when the most ideal choices are not available, she said, “if they only have access to canned vegetables, I’d much rather them eat that than have nothing.”

No disclosures for Leneweaver were provided. 

US endoscopists frequently stray from established best practices when removing colon polyps smaller than 1 cm, with fewer than 60% of procedures using the recommended cold snare technique, an analysis of more than 1.8 million colonoscopies found. 

“We expected to find some variations in polypectomy technique, but the results were surprising; overall, cold snare usage was much lower than expected, given that this is the recommended method for removing most small polyps,” Seth Crockett, MD, MPH, AGAF, professor of medicine, Division of Gastroenterology and Hepatology, Oregon Health & Science University, Portland, told GI & Hepatology News. 

The study was published in the October issue of The American Journal of Gastroenterology.

Using Gastroenterology Quality Improvement Consortium Registry data, Crockett and colleagues analyzed more than 1.8 million colonoscopies performed by 4601 endoscopists between 2019 and 2022 across 702 sites. All colonoscopies involved removal of polyps < 1 cm; lesions of this size are commonly found in screening colonoscopies, and detection is crucial to early cancer prevention.

The researchers found striking variation in polypectomy technique. Guideline-based cold snare polypectomy (CSP) was used in only 58% of cases (and as a single device in only 51%), whereas cold forceps polypectomy (CFP) accounted for 35% and hot snare polypectomy (HSP) for 11%. 

The fact that CSP was used in fewer than 60% of cases represents “an important quality gap,” the authors wrote, adding that the fact that more than 10% of colonoscopies used HSP suggests that “some patients harboring low-risk lesions may be exposed to excess risk related to these practice variations.” 

And while recommendations around the use of CFP are more nuanced (based largely on forceps type and polyp size), the “high frequency of CFP also suggests nonadherence to best practices,” they noted. 
 

Gastroenterologists More Apt to Follow Guidance 

Polypectomy technique varied by polyp type. CFP was more common in cases where only hyperplastic polyps were removed compared with cases with tubular adenomas (45% vs 30%, respectively). CSP use was highest in cases where only sessile serrated lesions were removed (66%) compared with cases with only tubular adenomas (61%) or hyperplastic polyps (37%). 

There was also considerable variation by provider specialty.

Gastroenterologists (compared with non-GI specialists) used HSP less (4% vs 8%) and CSP more (40% vs 34%). Colonoscopies performed with GI fellows were more likely to use CFP (31% vs 21%) and less likely to use HSP (1% vs 5%) compared with colonoscopies without fellows.

“It was somewhat reassuring that colonoscopies performed by gastroenterologists were more likely to adhere to guideline recommendations, which suggests that dedicated endoscopy training is likely an important factor driving high-quality colonoscopy,” Crockett told GI & Hepatology News. 

“Unexpectedly,” polypectomy technique also differed dramatically by geographic region, he said. CFP was used more than twice as often in the Northeast (31%) as in the Midwest (14%), whereas CSP was used more frequently in the Midwest (52%) than in the Northeast (32%).

“We suspect that much of the variation is related to differences in training, preferences, habits, and evolution of colonoscopy practice over time,” Crockett said. “More research is needed on the underlying drivers of this variation, and how differences in polypectomy technique impact both the safety and efficacy of colonoscopy to prevent colorectal cancer,” he said.

“As a specialty, we need to continue to work on disseminating guideline recommendations regarding colonoscopy quality, monitoring adherence to evidence-based practices, and working to address gaps in quality where they exist,” he added. 
 

‘Concerning, Surprising, and Disappointing’

David Johnson, MD, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School and Old Dominion University in Norfolk, called the results “concerning, surprising, and disappointing” and not consistent with the most current quality recommendations that advocate cold snare for most polyps less than 1 cm in size. 

“Cold snare polypectomy has been shown not only to be more effective but also takes less time to perform, relative to cold biopsy,” said Johnson, who wasn’t involved in the study. 

Johnson told GI & Hepatology News, “Inadequate lesion resection and variation in resection quality are major issues for colonoscopy quality. Those who perform colonoscopies need to be up-to-date with evidence-based quality standards — as well as held accountable if [there is] discordant practice — if we are to optimize the cancer prevention benefits of quality colonoscopy.”

Limitations of the current analysis include lack of extensive patient information and inability to further stratify polyps < 1 cm by size. 

The study had no commercial funding. Crockett had no disclosures. Johnson disclosed serving as a director, officer, partner, employee, advisor, consultant, or trustee for ISOThrive.

A version of this article appeared on Medscape.com.

US endoscopists frequently stray from established best practices when removing colon polyps smaller than 1 cm, with fewer than 60% of procedures using the recommended cold snare technique, an analysis of more than 1.8 million colonoscopies found. 

“We expected to find some variations in polypectomy technique, but the results were surprising; overall, cold snare usage was much lower than expected, given that this is the recommended method for removing most small polyps,” Seth Crockett, MD, MPH, AGAF, professor of medicine, Division of Gastroenterology and Hepatology, Oregon Health & Science University, Portland, told GI & Hepatology News. 

The study was published in the October issue of The American Journal of Gastroenterology.

Using Gastroenterology Quality Improvement Consortium Registry data, Crockett and colleagues analyzed more than 1.8 million colonoscopies performed by 4601 endoscopists between 2019 and 2022 across 702 sites. All colonoscopies involved removal of polyps < 1 cm; lesions of this size are commonly found in screening colonoscopies, and detection is crucial to early cancer prevention.

The researchers found striking variation in polypectomy technique. Guideline-based cold snare polypectomy (CSP) was used in only 58% of cases (and as a single device in only 51%), whereas cold forceps polypectomy (CFP) accounted for 35% and hot snare polypectomy (HSP) for 11%. 

The fact that CSP was used in fewer than 60% of cases represents “an important quality gap,” the authors wrote, adding that the fact that more than 10% of colonoscopies used HSP suggests that “some patients harboring low-risk lesions may be exposed to excess risk related to these practice variations.” 

And while recommendations around the use of CFP are more nuanced (based largely on forceps type and polyp size), the “high frequency of CFP also suggests nonadherence to best practices,” they noted. 
 

Gastroenterologists More Apt to Follow Guidance 

Polypectomy technique varied by polyp type. CFP was more common in cases where only hyperplastic polyps were removed compared with cases with tubular adenomas (45% vs 30%, respectively). CSP use was highest in cases where only sessile serrated lesions were removed (66%) compared with cases with only tubular adenomas (61%) or hyperplastic polyps (37%). 

There was also considerable variation by provider specialty.

Gastroenterologists (compared with non-GI specialists) used HSP less (4% vs 8%) and CSP more (40% vs 34%). Colonoscopies performed with GI fellows were more likely to use CFP (31% vs 21%) and less likely to use HSP (1% vs 5%) compared with colonoscopies without fellows.

“It was somewhat reassuring that colonoscopies performed by gastroenterologists were more likely to adhere to guideline recommendations, which suggests that dedicated endoscopy training is likely an important factor driving high-quality colonoscopy,” Crockett told GI & Hepatology News. 

“Unexpectedly,” polypectomy technique also differed dramatically by geographic region, he said. CFP was used more than twice as often in the Northeast (31%) as in the Midwest (14%), whereas CSP was used more frequently in the Midwest (52%) than in the Northeast (32%).

“We suspect that much of the variation is related to differences in training, preferences, habits, and evolution of colonoscopy practice over time,” Crockett said. “More research is needed on the underlying drivers of this variation, and how differences in polypectomy technique impact both the safety and efficacy of colonoscopy to prevent colorectal cancer,” he said.

“As a specialty, we need to continue to work on disseminating guideline recommendations regarding colonoscopy quality, monitoring adherence to evidence-based practices, and working to address gaps in quality where they exist,” he added. 
 

‘Concerning, Surprising, and Disappointing’

David Johnson, MD, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School and Old Dominion University in Norfolk, called the results “concerning, surprising, and disappointing” and not consistent with the most current quality recommendations that advocate cold snare for most polyps less than 1 cm in size. 

“Cold snare polypectomy has been shown not only to be more effective but also takes less time to perform, relative to cold biopsy,” said Johnson, who wasn’t involved in the study. 

Johnson told GI & Hepatology News, “Inadequate lesion resection and variation in resection quality are major issues for colonoscopy quality. Those who perform colonoscopies need to be up-to-date with evidence-based quality standards — as well as held accountable if [there is] discordant practice — if we are to optimize the cancer prevention benefits of quality colonoscopy.”

Limitations of the current analysis include lack of extensive patient information and inability to further stratify polyps < 1 cm by size. 

The study had no commercial funding. Crockett had no disclosures. Johnson disclosed serving as a director, officer, partner, employee, advisor, consultant, or trustee for ISOThrive.

A version of this article appeared on Medscape.com.

US endoscopists frequently stray from established best practices when removing colon polyps smaller than 1 cm, with fewer than 60% of procedures using the recommended cold snare technique, an analysis of more than 1.8 million colonoscopies found. 

“We expected to find some variations in polypectomy technique, but the results were surprising; overall, cold snare usage was much lower than expected, given that this is the recommended method for removing most small polyps,” Seth Crockett, MD, MPH, AGAF, professor of medicine, Division of Gastroenterology and Hepatology, Oregon Health & Science University, Portland, told GI & Hepatology News. 

The study was published in the October issue of The American Journal of Gastroenterology.

Using Gastroenterology Quality Improvement Consortium Registry data, Crockett and colleagues analyzed more than 1.8 million colonoscopies performed by 4601 endoscopists between 2019 and 2022 across 702 sites. All colonoscopies involved removal of polyps < 1 cm; lesions of this size are commonly found in screening colonoscopies, and detection is crucial to early cancer prevention.

The researchers found striking variation in polypectomy technique. Guideline-based cold snare polypectomy (CSP) was used in only 58% of cases (and as a single device in only 51%), whereas cold forceps polypectomy (CFP) accounted for 35% and hot snare polypectomy (HSP) for 11%. 

The fact that CSP was used in fewer than 60% of cases represents “an important quality gap,” the authors wrote, adding that the fact that more than 10% of colonoscopies used HSP suggests that “some patients harboring low-risk lesions may be exposed to excess risk related to these practice variations.” 

And while recommendations around the use of CFP are more nuanced (based largely on forceps type and polyp size), the “high frequency of CFP also suggests nonadherence to best practices,” they noted. 
 

Gastroenterologists More Apt to Follow Guidance 

Polypectomy technique varied by polyp type. CFP was more common in cases where only hyperplastic polyps were removed compared with cases with tubular adenomas (45% vs 30%, respectively). CSP use was highest in cases where only sessile serrated lesions were removed (66%) compared with cases with only tubular adenomas (61%) or hyperplastic polyps (37%). 

There was also considerable variation by provider specialty.

Gastroenterologists (compared with non-GI specialists) used HSP less (4% vs 8%) and CSP more (40% vs 34%). Colonoscopies performed with GI fellows were more likely to use CFP (31% vs 21%) and less likely to use HSP (1% vs 5%) compared with colonoscopies without fellows.

“It was somewhat reassuring that colonoscopies performed by gastroenterologists were more likely to adhere to guideline recommendations, which suggests that dedicated endoscopy training is likely an important factor driving high-quality colonoscopy,” Crockett told GI & Hepatology News. 

“Unexpectedly,” polypectomy technique also differed dramatically by geographic region, he said. CFP was used more than twice as often in the Northeast (31%) as in the Midwest (14%), whereas CSP was used more frequently in the Midwest (52%) than in the Northeast (32%).

“We suspect that much of the variation is related to differences in training, preferences, habits, and evolution of colonoscopy practice over time,” Crockett said. “More research is needed on the underlying drivers of this variation, and how differences in polypectomy technique impact both the safety and efficacy of colonoscopy to prevent colorectal cancer,” he said.

“As a specialty, we need to continue to work on disseminating guideline recommendations regarding colonoscopy quality, monitoring adherence to evidence-based practices, and working to address gaps in quality where they exist,” he added. 
 

‘Concerning, Surprising, and Disappointing’

David Johnson, MD, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School and Old Dominion University in Norfolk, called the results “concerning, surprising, and disappointing” and not consistent with the most current quality recommendations that advocate cold snare for most polyps less than 1 cm in size. 

“Cold snare polypectomy has been shown not only to be more effective but also takes less time to perform, relative to cold biopsy,” said Johnson, who wasn’t involved in the study. 

Johnson told GI & Hepatology News, “Inadequate lesion resection and variation in resection quality are major issues for colonoscopy quality. Those who perform colonoscopies need to be up-to-date with evidence-based quality standards — as well as held accountable if [there is] discordant practice — if we are to optimize the cancer prevention benefits of quality colonoscopy.”

Limitations of the current analysis include lack of extensive patient information and inability to further stratify polyps < 1 cm by size. 

The study had no commercial funding. Crockett had no disclosures. Johnson disclosed serving as a director, officer, partner, employee, advisor, consultant, or trustee for ISOThrive.

A version of this article appeared on Medscape.com.

Social media is rife with content promoting colon cleansing as a way to shed toxins and fix everything from chronic fatigue and overweight to weak immunity and skin problems.

Even doctors who aren’t hip to the latest TikTok trends may not be able to avoid the hype. That’s because patients are bringing up colon cleansing during their office visit.

“Patients often raise questions about colonics or detox teas, especially when these gain traction on social media platforms like TikTok,” said Tauseef Ali, MD, AGAF, medical executive director of SSM Health Digestive Care at St. Anthony Hospital in Oklahoma City. “Interest typically comes in waves, closely tied to the latest online trends.”

That means gastroenterologists need to be prepared when they’re asked if the latest product — whether it’s colon hydrotherapy, a detox drink or pill, or an enema — being touted by influencers is good for their health. And it’s not just patients who are asking.

“Sometimes we’ll get a message from primary care,” Mohammad Bilal, MD, associate professor of medicine and director of Bariatric and Third Space Endoscopy at the University of Colorado Anschutz Medical Campus in Aurora, Colorado, told GI & Hepatology News. They’re getting the same questions from patients, and they want to know if colon cleansing that’s not connected with a colonoscopy exam has any benefits for overall health or specific health conditions.

The answer is no, and patients are more likely to believe that when physicians explain it using good information. Here is how Ali, Bilal, and professional organizations advise doctors to approach the issue.

 

What Exactly Is a Colon Cleanse?

Colon cleanses come in a variety of forms. Colonic irrigation, also called colon hydrotherapy, involves inserting a tube into the rectum and flushing out the colon with a large amount of fluid. Enemas do the same but use a small amount of liquid, and some product instructions tell the user to “hold it” for a designated amount of time before expelling colon contents.

Other cleanses, often called detoxing cleanses, are laxatives or herbal teas that users drink — and then stay close to the bathroom. Detox regimens and diets also are mentioned as a way to remove toxins from the body, improve health, and promote well-being.

 

Why Do Patients Use Them?

“Many patients describe a desire for ‘cleanliness,’ ‘detoxification,’ or to ‘feel lighter,’” Ali told GI & Hepatology News.

The claims on social media promote all of this and more — and well-known influencers make it all sound even more attractive.

“These motivations are often rooted in the cultural belief that the colon accumulates harmful toxins that must be flushed out,” Ali said. “This idea is not supported by scientific evidence. The body’s natural detox systems, primarily the liver and kidneys, already perform this function effectively.”

Bilal said that in recent years, he has noticed more awareness in general about the importance of gut health. “When there’s awareness, people often go to the other extreme,” he said.

Where Is the Evidence?

The National Center for Complementary and Integrative Health (NCCIH), part of the National Institutes of Health, warns on an information page that both cleansing and detox programs can be unsafe and falsely advertised.

While searches of medical literature turn up few studies, the NCCIH information points to a 2014 review that concluded that there is no compelling research to support the use of detox diets for managing weight or eliminating toxins. A 2017 review found juicing and detox regimens can cause weight loss initially but then lead to weight gain once a normal diet is resumed.

A systematic review of research on the safety and effectiveness of self-administered coffee enemas found nine case reports describing adverse events: seven reported colitis after the enema, and two reported more critical adverse events. All nine reports warned against the procedure. The researchers found no study reporting the effectiveness of coffee enemas.

The NCCIH information also notes that there is “limited clinical evidence validating colonic irrigation and insufficient evidence for its prescribed uses.”

 

Are Cleanses Regulated?

Some over-the-counter colon cleansing products are viewed as dietary supplements, giving the FDA authority to regulate them and take action under the Dietary Supplement Health and Education Act of 1994.

Certain products promoted as colon cleanses, such as laxatives, are regulated by the FDA as over-the-counter drugs and must meet safety and other requirements.

Colonic irrigation systems meant for cleansing before radiologic or endoscopic exams are class II devices — subject to 510(k) premarket notification requirements before marketing — whereas systems intended for other uses, such as routine colon cleansing for general well-being, are regarded as class III devices — subject to premarket approval requirements — according to an FDA spokesperson. To date, the FDA has not approved any colonic irrigation devices for the latter use, the spokesperson said.

For instance, the FDA warned consumers not to use a product promoted for colon cleansing after finding it contained tadalafil, the active ingredient in an FDA-approved drug for erectile dysfunction. The FDA has also issued numerous warning letters to the makers of colon cleansing devices, as they are not approved for this purpose.

The Federal Trade Commission can also take action specifically if the claims about the benefits and safety of products — including supplements, foods, over-the-counter drugs, or health equipment — are false, misleading, or not supported by science.

 

What Are the Dangers?

Cleanse and detox products come with many risks, including electrolyte imbalances, dehydration, and infections, Ali said. With colonic irrigation, there is a risk for rectal perforation. Products also may disrupt the gut microbiome, and some can interact with medications or worsen underlying health conditions, he added.

“It’s important for patients to be aware of these risks before considering nonmedical ‘cleaning’ methods,” he said.

At worst, patients risk fatality, Ali noted. He recalled a young patient who began using a vegetable enema as a detox. As it was being administered, the colon ruptured. The patient was admitted as a medical emergency and required surgery. Fortunately, the patient survived, but the incident could have proven fatal, Ali said.

 

Educating Patients

Because patients often don’t think of herbal cleanses, detox teas, and over-the-counter powders as supplements, Ali said it’s important to ask them about everything they take.

One way to frame this question is to ask if they are consuming any over-the-counter supplements or any other remedies, he said, and perhaps ask directly about any cleanses they are doing.

When patients ask him about colon cleanses, Ali explains the difference between evidence-based colonoscopy preparation and unregulated “cleanses.” Most patients respond to that approach, he said. Indeed, AGA and other GI societies updated their recommendations on optimizing bowel preparation quality for colonoscopy.

“Still, the appeal of quick fixes of social media trends can sometimes outweigh medical advice,” Ali said. He depends on building trusted relationships and reinforcing the message over time and finds that helps patients make informed and healthier choices.

Bilal, too, explains to patients that cleanses are unnecessary and educates them about what to do instead:

• Eat a  containing the recommended amount of  (22-34 g, depending on age and gender).
• For , follow a bowel regimen advised by your doctor.
• If gastrointestinal issues persist, get a medical checkup.
• Get any unexplained constipation or  checked out by a doctor.

Taking a careful history can pay off, Ali has found. He questioned a patient complaining of abdominal discomfort whose testing found unexpectedly elevated liver enzymes and found she had been using an herbal “cleanse tea” found online. Within 4 weeks of stopping it, her liver enzymes normalized. “Thankfully, she made a full recovery — and she never touched those remedies again,” he said.

Ali had no relevant disclosures. Bilal reported consulting for Boston Scientific, Cook Medical, and Steris.

 

A version of this article appeared on Medscape.com.

Social media is rife with content promoting colon cleansing as a way to shed toxins and fix everything from chronic fatigue and overweight to weak immunity and skin problems.

Even doctors who aren’t hip to the latest TikTok trends may not be able to avoid the hype. That’s because patients are bringing up colon cleansing during their office visit.

“Patients often raise questions about colonics or detox teas, especially when these gain traction on social media platforms like TikTok,” said Tauseef Ali, MD, AGAF, medical executive director of SSM Health Digestive Care at St. Anthony Hospital in Oklahoma City. “Interest typically comes in waves, closely tied to the latest online trends.”

That means gastroenterologists need to be prepared when they’re asked if the latest product — whether it’s colon hydrotherapy, a detox drink or pill, or an enema — being touted by influencers is good for their health. And it’s not just patients who are asking.

“Sometimes we’ll get a message from primary care,” Mohammad Bilal, MD, associate professor of medicine and director of Bariatric and Third Space Endoscopy at the University of Colorado Anschutz Medical Campus in Aurora, Colorado, told GI & Hepatology News. They’re getting the same questions from patients, and they want to know if colon cleansing that’s not connected with a colonoscopy exam has any benefits for overall health or specific health conditions.

The answer is no, and patients are more likely to believe that when physicians explain it using good information. Here is how Ali, Bilal, and professional organizations advise doctors to approach the issue.

 

What Exactly Is a Colon Cleanse?

Colon cleanses come in a variety of forms. Colonic irrigation, also called colon hydrotherapy, involves inserting a tube into the rectum and flushing out the colon with a large amount of fluid. Enemas do the same but use a small amount of liquid, and some product instructions tell the user to “hold it” for a designated amount of time before expelling colon contents.

Other cleanses, often called detoxing cleanses, are laxatives or herbal teas that users drink — and then stay close to the bathroom. Detox regimens and diets also are mentioned as a way to remove toxins from the body, improve health, and promote well-being.

 

Why Do Patients Use Them?

“Many patients describe a desire for ‘cleanliness,’ ‘detoxification,’ or to ‘feel lighter,’” Ali told GI & Hepatology News.

The claims on social media promote all of this and more — and well-known influencers make it all sound even more attractive.

“These motivations are often rooted in the cultural belief that the colon accumulates harmful toxins that must be flushed out,” Ali said. “This idea is not supported by scientific evidence. The body’s natural detox systems, primarily the liver and kidneys, already perform this function effectively.”

Bilal said that in recent years, he has noticed more awareness in general about the importance of gut health. “When there’s awareness, people often go to the other extreme,” he said.

Where Is the Evidence?

The National Center for Complementary and Integrative Health (NCCIH), part of the National Institutes of Health, warns on an information page that both cleansing and detox programs can be unsafe and falsely advertised.

While searches of medical literature turn up few studies, the NCCIH information points to a 2014 review that concluded that there is no compelling research to support the use of detox diets for managing weight or eliminating toxins. A 2017 review found juicing and detox regimens can cause weight loss initially but then lead to weight gain once a normal diet is resumed.

A systematic review of research on the safety and effectiveness of self-administered coffee enemas found nine case reports describing adverse events: seven reported colitis after the enema, and two reported more critical adverse events. All nine reports warned against the procedure. The researchers found no study reporting the effectiveness of coffee enemas.

The NCCIH information also notes that there is “limited clinical evidence validating colonic irrigation and insufficient evidence for its prescribed uses.”

 

Are Cleanses Regulated?

Some over-the-counter colon cleansing products are viewed as dietary supplements, giving the FDA authority to regulate them and take action under the Dietary Supplement Health and Education Act of 1994.

Certain products promoted as colon cleanses, such as laxatives, are regulated by the FDA as over-the-counter drugs and must meet safety and other requirements.

Colonic irrigation systems meant for cleansing before radiologic or endoscopic exams are class II devices — subject to 510(k) premarket notification requirements before marketing — whereas systems intended for other uses, such as routine colon cleansing for general well-being, are regarded as class III devices — subject to premarket approval requirements — according to an FDA spokesperson. To date, the FDA has not approved any colonic irrigation devices for the latter use, the spokesperson said.

For instance, the FDA warned consumers not to use a product promoted for colon cleansing after finding it contained tadalafil, the active ingredient in an FDA-approved drug for erectile dysfunction. The FDA has also issued numerous warning letters to the makers of colon cleansing devices, as they are not approved for this purpose.

The Federal Trade Commission can also take action specifically if the claims about the benefits and safety of products — including supplements, foods, over-the-counter drugs, or health equipment — are false, misleading, or not supported by science.

 

What Are the Dangers?

Cleanse and detox products come with many risks, including electrolyte imbalances, dehydration, and infections, Ali said. With colonic irrigation, there is a risk for rectal perforation. Products also may disrupt the gut microbiome, and some can interact with medications or worsen underlying health conditions, he added.

“It’s important for patients to be aware of these risks before considering nonmedical ‘cleaning’ methods,” he said.

At worst, patients risk fatality, Ali noted. He recalled a young patient who began using a vegetable enema as a detox. As it was being administered, the colon ruptured. The patient was admitted as a medical emergency and required surgery. Fortunately, the patient survived, but the incident could have proven fatal, Ali said.

 

Educating Patients

Because patients often don’t think of herbal cleanses, detox teas, and over-the-counter powders as supplements, Ali said it’s important to ask them about everything they take.

One way to frame this question is to ask if they are consuming any over-the-counter supplements or any other remedies, he said, and perhaps ask directly about any cleanses they are doing.

When patients ask him about colon cleanses, Ali explains the difference between evidence-based colonoscopy preparation and unregulated “cleanses.” Most patients respond to that approach, he said. Indeed, AGA and other GI societies updated their recommendations on optimizing bowel preparation quality for colonoscopy.

“Still, the appeal of quick fixes of social media trends can sometimes outweigh medical advice,” Ali said. He depends on building trusted relationships and reinforcing the message over time and finds that helps patients make informed and healthier choices.

Bilal, too, explains to patients that cleanses are unnecessary and educates them about what to do instead:

• Eat a  containing the recommended amount of  (22-34 g, depending on age and gender).
• For , follow a bowel regimen advised by your doctor.
• If gastrointestinal issues persist, get a medical checkup.
• Get any unexplained constipation or  checked out by a doctor.

Taking a careful history can pay off, Ali has found. He questioned a patient complaining of abdominal discomfort whose testing found unexpectedly elevated liver enzymes and found she had been using an herbal “cleanse tea” found online. Within 4 weeks of stopping it, her liver enzymes normalized. “Thankfully, she made a full recovery — and she never touched those remedies again,” he said.

Ali had no relevant disclosures. Bilal reported consulting for Boston Scientific, Cook Medical, and Steris.

 

A version of this article appeared on Medscape.com.

Social media is rife with content promoting colon cleansing as a way to shed toxins and fix everything from chronic fatigue and overweight to weak immunity and skin problems.

Even doctors who aren’t hip to the latest TikTok trends may not be able to avoid the hype. That’s because patients are bringing up colon cleansing during their office visit.

“Patients often raise questions about colonics or detox teas, especially when these gain traction on social media platforms like TikTok,” said Tauseef Ali, MD, AGAF, medical executive director of SSM Health Digestive Care at St. Anthony Hospital in Oklahoma City. “Interest typically comes in waves, closely tied to the latest online trends.”

That means gastroenterologists need to be prepared when they’re asked if the latest product — whether it’s colon hydrotherapy, a detox drink or pill, or an enema — being touted by influencers is good for their health. And it’s not just patients who are asking.

“Sometimes we’ll get a message from primary care,” Mohammad Bilal, MD, associate professor of medicine and director of Bariatric and Third Space Endoscopy at the University of Colorado Anschutz Medical Campus in Aurora, Colorado, told GI & Hepatology News. They’re getting the same questions from patients, and they want to know if colon cleansing that’s not connected with a colonoscopy exam has any benefits for overall health or specific health conditions.

The answer is no, and patients are more likely to believe that when physicians explain it using good information. Here is how Ali, Bilal, and professional organizations advise doctors to approach the issue.

 

What Exactly Is a Colon Cleanse?

Colon cleanses come in a variety of forms. Colonic irrigation, also called colon hydrotherapy, involves inserting a tube into the rectum and flushing out the colon with a large amount of fluid. Enemas do the same but use a small amount of liquid, and some product instructions tell the user to “hold it” for a designated amount of time before expelling colon contents.

Other cleanses, often called detoxing cleanses, are laxatives or herbal teas that users drink — and then stay close to the bathroom. Detox regimens and diets also are mentioned as a way to remove toxins from the body, improve health, and promote well-being.

 

Why Do Patients Use Them?

“Many patients describe a desire for ‘cleanliness,’ ‘detoxification,’ or to ‘feel lighter,’” Ali told GI & Hepatology News.

The claims on social media promote all of this and more — and well-known influencers make it all sound even more attractive.

“These motivations are often rooted in the cultural belief that the colon accumulates harmful toxins that must be flushed out,” Ali said. “This idea is not supported by scientific evidence. The body’s natural detox systems, primarily the liver and kidneys, already perform this function effectively.”

Bilal said that in recent years, he has noticed more awareness in general about the importance of gut health. “When there’s awareness, people often go to the other extreme,” he said.

Where Is the Evidence?

The National Center for Complementary and Integrative Health (NCCIH), part of the National Institutes of Health, warns on an information page that both cleansing and detox programs can be unsafe and falsely advertised.

While searches of medical literature turn up few studies, the NCCIH information points to a 2014 review that concluded that there is no compelling research to support the use of detox diets for managing weight or eliminating toxins. A 2017 review found juicing and detox regimens can cause weight loss initially but then lead to weight gain once a normal diet is resumed.

A systematic review of research on the safety and effectiveness of self-administered coffee enemas found nine case reports describing adverse events: seven reported colitis after the enema, and two reported more critical adverse events. All nine reports warned against the procedure. The researchers found no study reporting the effectiveness of coffee enemas.

The NCCIH information also notes that there is “limited clinical evidence validating colonic irrigation and insufficient evidence for its prescribed uses.”

 

Are Cleanses Regulated?

Some over-the-counter colon cleansing products are viewed as dietary supplements, giving the FDA authority to regulate them and take action under the Dietary Supplement Health and Education Act of 1994.

Certain products promoted as colon cleanses, such as laxatives, are regulated by the FDA as over-the-counter drugs and must meet safety and other requirements.

Colonic irrigation systems meant for cleansing before radiologic or endoscopic exams are class II devices — subject to 510(k) premarket notification requirements before marketing — whereas systems intended for other uses, such as routine colon cleansing for general well-being, are regarded as class III devices — subject to premarket approval requirements — according to an FDA spokesperson. To date, the FDA has not approved any colonic irrigation devices for the latter use, the spokesperson said.

For instance, the FDA warned consumers not to use a product promoted for colon cleansing after finding it contained tadalafil, the active ingredient in an FDA-approved drug for erectile dysfunction. The FDA has also issued numerous warning letters to the makers of colon cleansing devices, as they are not approved for this purpose.

The Federal Trade Commission can also take action specifically if the claims about the benefits and safety of products — including supplements, foods, over-the-counter drugs, or health equipment — are false, misleading, or not supported by science.

 

What Are the Dangers?

Cleanse and detox products come with many risks, including electrolyte imbalances, dehydration, and infections, Ali said. With colonic irrigation, there is a risk for rectal perforation. Products also may disrupt the gut microbiome, and some can interact with medications or worsen underlying health conditions, he added.

“It’s important for patients to be aware of these risks before considering nonmedical ‘cleaning’ methods,” he said.

At worst, patients risk fatality, Ali noted. He recalled a young patient who began using a vegetable enema as a detox. As it was being administered, the colon ruptured. The patient was admitted as a medical emergency and required surgery. Fortunately, the patient survived, but the incident could have proven fatal, Ali said.

 

Educating Patients

Because patients often don’t think of herbal cleanses, detox teas, and over-the-counter powders as supplements, Ali said it’s important to ask them about everything they take.

One way to frame this question is to ask if they are consuming any over-the-counter supplements or any other remedies, he said, and perhaps ask directly about any cleanses they are doing.

When patients ask him about colon cleanses, Ali explains the difference between evidence-based colonoscopy preparation and unregulated “cleanses.” Most patients respond to that approach, he said. Indeed, AGA and other GI societies updated their recommendations on optimizing bowel preparation quality for colonoscopy.

“Still, the appeal of quick fixes of social media trends can sometimes outweigh medical advice,” Ali said. He depends on building trusted relationships and reinforcing the message over time and finds that helps patients make informed and healthier choices.

Bilal, too, explains to patients that cleanses are unnecessary and educates them about what to do instead:

• Eat a  containing the recommended amount of  (22-34 g, depending on age and gender).
• For , follow a bowel regimen advised by your doctor.
• If gastrointestinal issues persist, get a medical checkup.
• Get any unexplained constipation or  checked out by a doctor.

Taking a careful history can pay off, Ali has found. He questioned a patient complaining of abdominal discomfort whose testing found unexpectedly elevated liver enzymes and found she had been using an herbal “cleanse tea” found online. Within 4 weeks of stopping it, her liver enzymes normalized. “Thankfully, she made a full recovery — and she never touched those remedies again,” he said.

Ali had no relevant disclosures. Bilal reported consulting for Boston Scientific, Cook Medical, and Steris.

 

A version of this article appeared on Medscape.com.

What does a successful military-to-civilian transition look like? How do we know if a veteran is sinking, treading water, or swimming? Two recent studies by the Penn State University Clearinghouse for Military Family Readiness sought to answer to those questions and more while determining how and when is the right time to step in to help a veteran in need.

The research analyzed The Veterans Metrics Initiative data (TVMI). This longitudinal study surveyed 9566 men and women who left active duty in 2016 over 3 years, answering questions about deployment histories, adverse childhood experiences (ACEs) and exposure to combat. They also reported whether they had symptoms related to anxiety and depression. 

The TVMI study found that ACEs predicted poor outcomes early on and when combined with warfare experience dramatically increased the likelihood of mental health issues, including posttraumatic stress disorder (PTSD), anxiety, and depression; moral injury impacted adjustment to civilian life (the degree varied by gender); and, many veterans have a “growth outlook” as a result of a trauma or crisis they experienced.

The TVMI study found that almost all veterans use transition resources in the first 2 years after military separation. Beyond that, however, those in high-risk categories (eg, PTSD and cumulative trauma experiences) need continued support. This may come in the form of a universal screener and linking it to a navigation infrastructure (eg, AmericaServes), “thereby identifying risk factors early and providing targeted supports, interventions, and components.”

Veterans often face a series of simultaneous challenges as they return to civilian life. Among them include getting used to family and friends again, finding jobs, losing their military identity, structure, and perhaps leaving military friends behind. In addition, veterans are likely dealing with physical and mental health challenges, which can significantly influence how well they readjust to civilian life and lead to inconsistency experiences for each individual.

A 2019 survey from the Pew Research Center found about 40% of veterans who suffered from PTSD said they frequently had difficulty dealing with the lack of structure in civilian life, compared with 5% of those who do not have PTSD. Another survey cited a large majority (78%) of pre-9/11 veterans said their readjustment was very or somewhat easy. However, 26% said adjusting to civilian life was difficult.

In 2011, 4 variables were identified that predicted easy civilian life re-entry: being an officer; having a consistently clear understanding of the missions while in the service; being a college graduate; and, for post-9/11 veterans, attending religious services frequently. Six variables were associated with a diminished probability of an easy transition: having had a traumatic experience; being seriously injured; serving in the post-9/11 era; serving in a combat zone; serving with someone who was killed or injured; and, for post-9/11 veterans, being married while in the service.

The probabilities of an easy re-entry dropped from 82% for those who did not experience a traumatic event to 56% for those who did—the largest change noted in the 2011 study.

The second Penn State study evaluated a model framework with a lifespan development perspective. The study surveyed veterans on their self-reported satisfaction or symptoms in 7 domains of well-being: employment, education, financial, legal problems, social, physical health, and mental health. Within 3 months of separation , 41% of respondents fell into the “problematic” category for the mental health domain. However, by 30 to 33 months postseparation, this proportion dropped to 34%. During the same period, the proportion of veterans in the at risk category increased from 28% at Wave 1 to 37% at Wave 6. About 30% of veterans fell into the successful category for symptoms across the 3 examined waves. Almost 60% were in the successful category across the 3 time points.

Both Penn State studies emphasize the importance of viewing veterans as individuals on their own timelines.

“These findings underscore that the transition to civilian life is not a single moment, but a process influenced by experiences across the life span,” said Mary M. Mitchell, research professor at the Clearinghouse and lead author on the predictors study. “By following veterans over 3 years, we were able to see how patterns emerge that would be invisible in a one-time survey.”

Current conceptualization “assumes that there are commonalities across veterans when evaluating the success of the transition to civilian life,” according to the authors of the framework study. “However, each veteran likely has his or her view of what a successful transition constitutes, and he or she may weigh domains differently when considering his or her own transition.”

The research highlights the need to find ways to encourage veterans to seek help—and not just in the first year, which is often the most stressful. The Pew Research Center survey identified a “significant break from the past,” in that nearly 70% of post-9/11 veterans said their superiors made them feel comfortable about seeking help with emotional issues resulting from their military service. 

However, ≤ 8% veterans in the TVMI study used any health programs, even when they screened positive for mental health problems. Veterans who did use counseling services, however, improved their depression symptoms. Engaging veterans at various time points could help keep mental health problems from worsening during—and beyond—the transition.

What does a successful military-to-civilian transition look like? How do we know if a veteran is sinking, treading water, or swimming? Two recent studies by the Penn State University Clearinghouse for Military Family Readiness sought to answer to those questions and more while determining how and when is the right time to step in to help a veteran in need.

The research analyzed The Veterans Metrics Initiative data (TVMI). This longitudinal study surveyed 9566 men and women who left active duty in 2016 over 3 years, answering questions about deployment histories, adverse childhood experiences (ACEs) and exposure to combat. They also reported whether they had symptoms related to anxiety and depression. 

The TVMI study found that ACEs predicted poor outcomes early on and when combined with warfare experience dramatically increased the likelihood of mental health issues, including posttraumatic stress disorder (PTSD), anxiety, and depression; moral injury impacted adjustment to civilian life (the degree varied by gender); and, many veterans have a “growth outlook” as a result of a trauma or crisis they experienced.

The TVMI study found that almost all veterans use transition resources in the first 2 years after military separation. Beyond that, however, those in high-risk categories (eg, PTSD and cumulative trauma experiences) need continued support. This may come in the form of a universal screener and linking it to a navigation infrastructure (eg, AmericaServes), “thereby identifying risk factors early and providing targeted supports, interventions, and components.”

Veterans often face a series of simultaneous challenges as they return to civilian life. Among them include getting used to family and friends again, finding jobs, losing their military identity, structure, and perhaps leaving military friends behind. In addition, veterans are likely dealing with physical and mental health challenges, which can significantly influence how well they readjust to civilian life and lead to inconsistency experiences for each individual.

A 2019 survey from the Pew Research Center found about 40% of veterans who suffered from PTSD said they frequently had difficulty dealing with the lack of structure in civilian life, compared with 5% of those who do not have PTSD. Another survey cited a large majority (78%) of pre-9/11 veterans said their readjustment was very or somewhat easy. However, 26% said adjusting to civilian life was difficult.

In 2011, 4 variables were identified that predicted easy civilian life re-entry: being an officer; having a consistently clear understanding of the missions while in the service; being a college graduate; and, for post-9/11 veterans, attending religious services frequently. Six variables were associated with a diminished probability of an easy transition: having had a traumatic experience; being seriously injured; serving in the post-9/11 era; serving in a combat zone; serving with someone who was killed or injured; and, for post-9/11 veterans, being married while in the service.

The probabilities of an easy re-entry dropped from 82% for those who did not experience a traumatic event to 56% for those who did—the largest change noted in the 2011 study.

The second Penn State study evaluated a model framework with a lifespan development perspective. The study surveyed veterans on their self-reported satisfaction or symptoms in 7 domains of well-being: employment, education, financial, legal problems, social, physical health, and mental health. Within 3 months of separation , 41% of respondents fell into the “problematic” category for the mental health domain. However, by 30 to 33 months postseparation, this proportion dropped to 34%. During the same period, the proportion of veterans in the at risk category increased from 28% at Wave 1 to 37% at Wave 6. About 30% of veterans fell into the successful category for symptoms across the 3 examined waves. Almost 60% were in the successful category across the 3 time points.

Both Penn State studies emphasize the importance of viewing veterans as individuals on their own timelines.

“These findings underscore that the transition to civilian life is not a single moment, but a process influenced by experiences across the life span,” said Mary M. Mitchell, research professor at the Clearinghouse and lead author on the predictors study. “By following veterans over 3 years, we were able to see how patterns emerge that would be invisible in a one-time survey.”

Current conceptualization “assumes that there are commonalities across veterans when evaluating the success of the transition to civilian life,” according to the authors of the framework study. “However, each veteran likely has his or her view of what a successful transition constitutes, and he or she may weigh domains differently when considering his or her own transition.”

The research highlights the need to find ways to encourage veterans to seek help—and not just in the first year, which is often the most stressful. The Pew Research Center survey identified a “significant break from the past,” in that nearly 70% of post-9/11 veterans said their superiors made them feel comfortable about seeking help with emotional issues resulting from their military service. 

However, ≤ 8% veterans in the TVMI study used any health programs, even when they screened positive for mental health problems. Veterans who did use counseling services, however, improved their depression symptoms. Engaging veterans at various time points could help keep mental health problems from worsening during—and beyond—the transition.

What does a successful military-to-civilian transition look like? How do we know if a veteran is sinking, treading water, or swimming? Two recent studies by the Penn State University Clearinghouse for Military Family Readiness sought to answer to those questions and more while determining how and when is the right time to step in to help a veteran in need.

The research analyzed The Veterans Metrics Initiative data (TVMI). This longitudinal study surveyed 9566 men and women who left active duty in 2016 over 3 years, answering questions about deployment histories, adverse childhood experiences (ACEs) and exposure to combat. They also reported whether they had symptoms related to anxiety and depression. 

The TVMI study found that ACEs predicted poor outcomes early on and when combined with warfare experience dramatically increased the likelihood of mental health issues, including posttraumatic stress disorder (PTSD), anxiety, and depression; moral injury impacted adjustment to civilian life (the degree varied by gender); and, many veterans have a “growth outlook” as a result of a trauma or crisis they experienced.

The TVMI study found that almost all veterans use transition resources in the first 2 years after military separation. Beyond that, however, those in high-risk categories (eg, PTSD and cumulative trauma experiences) need continued support. This may come in the form of a universal screener and linking it to a navigation infrastructure (eg, AmericaServes), “thereby identifying risk factors early and providing targeted supports, interventions, and components.”

Veterans often face a series of simultaneous challenges as they return to civilian life. Among them include getting used to family and friends again, finding jobs, losing their military identity, structure, and perhaps leaving military friends behind. In addition, veterans are likely dealing with physical and mental health challenges, which can significantly influence how well they readjust to civilian life and lead to inconsistency experiences for each individual.

A 2019 survey from the Pew Research Center found about 40% of veterans who suffered from PTSD said they frequently had difficulty dealing with the lack of structure in civilian life, compared with 5% of those who do not have PTSD. Another survey cited a large majority (78%) of pre-9/11 veterans said their readjustment was very or somewhat easy. However, 26% said adjusting to civilian life was difficult.

In 2011, 4 variables were identified that predicted easy civilian life re-entry: being an officer; having a consistently clear understanding of the missions while in the service; being a college graduate; and, for post-9/11 veterans, attending religious services frequently. Six variables were associated with a diminished probability of an easy transition: having had a traumatic experience; being seriously injured; serving in the post-9/11 era; serving in a combat zone; serving with someone who was killed or injured; and, for post-9/11 veterans, being married while in the service.

The probabilities of an easy re-entry dropped from 82% for those who did not experience a traumatic event to 56% for those who did—the largest change noted in the 2011 study.

The second Penn State study evaluated a model framework with a lifespan development perspective. The study surveyed veterans on their self-reported satisfaction or symptoms in 7 domains of well-being: employment, education, financial, legal problems, social, physical health, and mental health. Within 3 months of separation , 41% of respondents fell into the “problematic” category for the mental health domain. However, by 30 to 33 months postseparation, this proportion dropped to 34%. During the same period, the proportion of veterans in the at risk category increased from 28% at Wave 1 to 37% at Wave 6. About 30% of veterans fell into the successful category for symptoms across the 3 examined waves. Almost 60% were in the successful category across the 3 time points.

Both Penn State studies emphasize the importance of viewing veterans as individuals on their own timelines.

“These findings underscore that the transition to civilian life is not a single moment, but a process influenced by experiences across the life span,” said Mary M. Mitchell, research professor at the Clearinghouse and lead author on the predictors study. “By following veterans over 3 years, we were able to see how patterns emerge that would be invisible in a one-time survey.”

Current conceptualization “assumes that there are commonalities across veterans when evaluating the success of the transition to civilian life,” according to the authors of the framework study. “However, each veteran likely has his or her view of what a successful transition constitutes, and he or she may weigh domains differently when considering his or her own transition.”

The research highlights the need to find ways to encourage veterans to seek help—and not just in the first year, which is often the most stressful. The Pew Research Center survey identified a “significant break from the past,” in that nearly 70% of post-9/11 veterans said their superiors made them feel comfortable about seeking help with emotional issues resulting from their military service. 

However, ≤ 8% veterans in the TVMI study used any health programs, even when they screened positive for mental health problems. Veterans who did use counseling services, however, improved their depression symptoms. Engaging veterans at various time points could help keep mental health problems from worsening during—and beyond—the transition.

TOPLINE:

Energy insecurity, the inability to meet household energy needs, was associated with more than twice the odds of having depression and anxiety symptoms than energy security in US adults, a new cross-sectional study showed.

METHODOLOGY:

• Using data from the US Census Bureau's online Household Pulse Survey, administered between 2022 and 2024, researchers conducted a cross-sectional study with a weighted population of > 187 million US adults (51% women; 64% White, 16% Hispanic, 10% Black, and 5% Asian). About a quarter of the population was in each of 4 age groups: 18-34 years, 35-49 years, 50-64 years, and ≥ 65 years.
• Three indicators of energy insecurity—inability to pay energy bills, maintaining unsafe/unhealthy home temperatures, and forgoing expenses on basic necessities to pay energy bills—were assessed individually and as a composite measure.
• Mental health was assessed using modified versions of the 2-item Patient Health Questionnaire for depression and the 2-item Generalized Anxiety Disorder scale for anxiety.
• The analysis was adjusted for other social determinants of health, including unemployment, housing instability, and food insecurity. Covariates included a wide range of factors, such as age, educational level, sex, and annual household income.

TAKEAWAY:

• In all, > 43% of the population reported having ≥ 1 form of energy security; around 22% reported being unable to pay energy bills, 22% maintained unsafe home temperatures, and nearly 34% forewent spending on basic necessities to pay energy bills.
• Individuals who gave up spending on basic necessities to pay energy bills had higher odds of anxiety (adjusted odds ratio [aOR], 1.79) and depression (aOR, 1.74) than those who did not.
• Adults with energy insecurity on the composite measure had higher odds for anxiety (aOR, 2.29) and depression (aOR, 2.31) than those with energy security.
• Food insecurity was also associated with poorer mental health, with higher odds for symptoms of depression (aOR, 2.05) and anxiety (aOR, 2.07).

IN PRACTICE:

"Despite its high prevalence, energy insecurity remains underrecognized in public health and policy intervention strategies," the investigators wrote.

"These findings suggest that energy insecurity is a widespread and important factor associated with mental health symptoms and may warrant consideration in efforts to reduce adverse mental health outcomes," they added.

SOURCE:

This study was led by Michelle Graf, PhD, Carter School of Public Policy, Georgia Institute of Technology, Atlanta. It was published online on October 27 in JAMA Network Open.

LIMITATIONS:

The cross-sectional nature of the data limited causal interference and increased the possibility of reverse causality. The questionnaire captured subjective interpretations of unsafe and unhealthy indoor temperatures, which may have varied among respondents. Additionally, the recall periods for energy insecurity and mental health outcomes were different.

DISCLOSURES:

The investigators reported no relevant conflicts of interest.

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

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

TOPLINE:

Energy insecurity, the inability to meet household energy needs, was associated with more than twice the odds of having depression and anxiety symptoms than energy security in US adults, a new cross-sectional study showed.

METHODOLOGY:

• Using data from the US Census Bureau's online Household Pulse Survey, administered between 2022 and 2024, researchers conducted a cross-sectional study with a weighted population of > 187 million US adults (51% women; 64% White, 16% Hispanic, 10% Black, and 5% Asian). About a quarter of the population was in each of 4 age groups: 18-34 years, 35-49 years, 50-64 years, and ≥ 65 years.
• Three indicators of energy insecurity—inability to pay energy bills, maintaining unsafe/unhealthy home temperatures, and forgoing expenses on basic necessities to pay energy bills—were assessed individually and as a composite measure.
• Mental health was assessed using modified versions of the 2-item Patient Health Questionnaire for depression and the 2-item Generalized Anxiety Disorder scale for anxiety.
• The analysis was adjusted for other social determinants of health, including unemployment, housing instability, and food insecurity. Covariates included a wide range of factors, such as age, educational level, sex, and annual household income.

TAKEAWAY:

• In all, > 43% of the population reported having ≥ 1 form of energy security; around 22% reported being unable to pay energy bills, 22% maintained unsafe home temperatures, and nearly 34% forewent spending on basic necessities to pay energy bills.
• Individuals who gave up spending on basic necessities to pay energy bills had higher odds of anxiety (adjusted odds ratio [aOR], 1.79) and depression (aOR, 1.74) than those who did not.
• Adults with energy insecurity on the composite measure had higher odds for anxiety (aOR, 2.29) and depression (aOR, 2.31) than those with energy security.
• Food insecurity was also associated with poorer mental health, with higher odds for symptoms of depression (aOR, 2.05) and anxiety (aOR, 2.07).

IN PRACTICE:

"Despite its high prevalence, energy insecurity remains underrecognized in public health and policy intervention strategies," the investigators wrote.

"These findings suggest that energy insecurity is a widespread and important factor associated with mental health symptoms and may warrant consideration in efforts to reduce adverse mental health outcomes," they added.

SOURCE:

This study was led by Michelle Graf, PhD, Carter School of Public Policy, Georgia Institute of Technology, Atlanta. It was published online on October 27 in JAMA Network Open.

LIMITATIONS:

The cross-sectional nature of the data limited causal interference and increased the possibility of reverse causality. The questionnaire captured subjective interpretations of unsafe and unhealthy indoor temperatures, which may have varied among respondents. Additionally, the recall periods for energy insecurity and mental health outcomes were different.

DISCLOSURES:

The investigators reported no relevant conflicts of interest.

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

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

TOPLINE:

Energy insecurity, the inability to meet household energy needs, was associated with more than twice the odds of having depression and anxiety symptoms than energy security in US adults, a new cross-sectional study showed.

METHODOLOGY:

• Using data from the US Census Bureau's online Household Pulse Survey, administered between 2022 and 2024, researchers conducted a cross-sectional study with a weighted population of > 187 million US adults (51% women; 64% White, 16% Hispanic, 10% Black, and 5% Asian). About a quarter of the population was in each of 4 age groups: 18-34 years, 35-49 years, 50-64 years, and ≥ 65 years.
• Three indicators of energy insecurity—inability to pay energy bills, maintaining unsafe/unhealthy home temperatures, and forgoing expenses on basic necessities to pay energy bills—were assessed individually and as a composite measure.
• Mental health was assessed using modified versions of the 2-item Patient Health Questionnaire for depression and the 2-item Generalized Anxiety Disorder scale for anxiety.
• The analysis was adjusted for other social determinants of health, including unemployment, housing instability, and food insecurity. Covariates included a wide range of factors, such as age, educational level, sex, and annual household income.

TAKEAWAY:

• In all, > 43% of the population reported having ≥ 1 form of energy security; around 22% reported being unable to pay energy bills, 22% maintained unsafe home temperatures, and nearly 34% forewent spending on basic necessities to pay energy bills.
• Individuals who gave up spending on basic necessities to pay energy bills had higher odds of anxiety (adjusted odds ratio [aOR], 1.79) and depression (aOR, 1.74) than those who did not.
• Adults with energy insecurity on the composite measure had higher odds for anxiety (aOR, 2.29) and depression (aOR, 2.31) than those with energy security.
• Food insecurity was also associated with poorer mental health, with higher odds for symptoms of depression (aOR, 2.05) and anxiety (aOR, 2.07).

IN PRACTICE:

"Despite its high prevalence, energy insecurity remains underrecognized in public health and policy intervention strategies," the investigators wrote.

"These findings suggest that energy insecurity is a widespread and important factor associated with mental health symptoms and may warrant consideration in efforts to reduce adverse mental health outcomes," they added.

SOURCE:

This study was led by Michelle Graf, PhD, Carter School of Public Policy, Georgia Institute of Technology, Atlanta. It was published online on October 27 in JAMA Network Open.

LIMITATIONS:

The cross-sectional nature of the data limited causal interference and increased the possibility of reverse causality. The questionnaire captured subjective interpretations of unsafe and unhealthy indoor temperatures, which may have varied among respondents. Additionally, the recall periods for energy insecurity and mental health outcomes were different.

DISCLOSURES:

The investigators reported no relevant conflicts of interest.

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

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

TOPLINE:

A comprehensive review of 92 studies found that 15% to 20% of lung cancers occurred among nonsmokers and were associated with environmental and germline risk factors. These cancers frequently harbored actionable genomic drivers, and targeted EGFR and ALK therapies produced significant diseasefree survival (DFS) and overall survival benefits.

METHODOLOGY:

• Lung cancer continues to be the leading cause of cancer death worldwide, causing about 1.8 million deaths in 2022, with smoking remaining the predominant risk factor. However, the incidence of lung cancer among nonsmokers (those who have smoked less than 100 cigarettes in their lifetime) is rising, varies by sex and geography, and is linked to environmental exposures and family history. The misperception that lung cancer is almost invariably caused by smoking may delay assessment and diagnosis.
• Researchers conducted a review of 92 studies on lung cancer in nonsmokers: 6 meta-analyses or systematic reviews, 16 randomized clinical trials, eight prospective cohort studies, seven retrospective cohort studies, three cross-sectional studies, four observational or case-control studies, 13 genomic studies, and 35 other studies.
• Overall, lung cancer among nonsmokers accounted for 15% to 20% of all lung cancer cases. Most lung cancers in nonsmokers were adenocarcinomas (60% to 80%), with a median age at diagnosis of 67 years in this group compared with 70 years in people with a history of smoking.
• Data analysis from three US hospital networks showed that the proportion of lung cancer among nonsmokers increased from 8.0% to 14.9% between 1990 and 2013. A pooled analysis of seven Finnish cohorts reported an absolute increase in lung cancer among nonsmokers from 6.9 per 100,000 person-years in 1972 to 12.9 per 100,000 person-years in 2015.
• The age-adjusted incidence rate of lung cancer in the US between 2000 and 2013 was 17.5 per 100,000 individuals among Asian female nonsmokers compared with 10.1 per 100,000 among non-Hispanic White female nonsmokers.

TAKEAWAY:

• Environmental and occupational risk factors were secondhand smoke, residential radon, outdoor and household air pollution (PM_2.5), asbestos and silica exposure, and prior thoracic radiotherapy. Having a first-degree relative with lung cancer increased the risk of developing lung cancer, and genome-wide association studies identified susceptibility loci associated with lung cancer risk in nonsmokers.
• Family history and inherited susceptibility increased lung cancer risk in never smokers (odds ratio [OR] for lung cancer in those with a first–degree relative, 1.51), and clonal hematopoiesis was also associated with higher risk (OR, 1.43). Importantly, tumors in nonsmokers were frequently driven by actionable somatic alterations (EGFR mutations, 40% to 60% in nonsmokers compared with 10% in smokers) and enrichment of ALK/ROS1/RET/ERBB2/NTRK/NRG1 fusions; 78% to 92% of adenocarcinomas in nonsmokers harbored actionable drivers (compared with 49.5% in ever smokers), and nonsmokers had a substantially lower tumor mutational burden (10–fold lower).
• Similar to individuals with a history of smoking, nonsmokers with lung cancer presented with cough, pain, dyspnea, or weight loss or had disease detected incidentally. Surgical resection remained the preferred treatment for anatomically resectable lung cancer (stages I-III) in medically eligible patients, with follow-up CT screening recommended every 6 months for 2 to 3 years and then annually.
• Targeted adjuvant therapy substantially improved outcomes for resected EGFR–mutant or ALK–rearranged non-small cell lung cancer (NSCLC). Four-year DFS was increased to 70% with osimertinib compared with 29% with placebo (hazard ratio [HR], 0.23) and 5–year overall survival was increased to 85% compared with 73% (HR, 0.49). Two–year DFS was 93.8% with alectinib compared with 63% with placebo (HR, 0.24). In unresectable EGFR-mutated stage III NSCLC, median progression-free survival was 39.1 months with adjuvant osimertinib compared with 5.6 months with placebo. For resected ALKpositive disease, 2–year DFS was 93.8% with adjuvant alectinib compared with 63.0% with chemotherapy (HR, 0.24).
• However, singleagent single agent programmed cell death protein 1 inhibitors or programmed death-ligand 1 inhibitors demonstrated limited efficacy in EGFR or ALK–driven tumors, and benefit was attenuated in never smokers. Regarding screening and early detection, the US Preventive Services Task Force did not recommend lowdose CT screening for nonsmokers, whereas Taiwan implemented a biennial screening program for selected nonsmoking high–risk groups.

IN PRACTICE:

“Among patients with lung cancer, nonsmoking individuals are more likely to have genomic alterations, such as EGFR mutations or ALK gene rearrangements, and these patients have improved survival when treated with TKIs compared with chemotherapy,” the authors of the study wrote.

SOURCE:

The study, led by Cian Murphy, PhD, Cancer Evolution and Genome Instability Laboratory, Francis Crick Institute, London, England, was published online in JAMA.

LIMITATIONS:

Becausesmoking history was often not included in many databases, cancer registries, and trials, the incidence and prevalence of lung cancer in nonsmokers could not be accurately determined. Additionally, accurate quantification of environmental exposures, such as air pollution, presented significant challenges. The quality of the evidence was not formally evaluated, and some relevant articles may have been missed in the literature review.

DISCLOSURES:

The study received support from multiple organizations, including the Rosetrees Trust, Ruth Strauss Foundation, Cancer Research UK, and the National Health and Medical Research Council. Several authors reported receiving grants or personal fees from and having other ties with various sources. Full disclosures are noted in the original article.

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

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

TOPLINE:

A comprehensive review of 92 studies found that 15% to 20% of lung cancers occurred among nonsmokers and were associated with environmental and germline risk factors. These cancers frequently harbored actionable genomic drivers, and targeted EGFR and ALK therapies produced significant diseasefree survival (DFS) and overall survival benefits.

METHODOLOGY:

• Lung cancer continues to be the leading cause of cancer death worldwide, causing about 1.8 million deaths in 2022, with smoking remaining the predominant risk factor. However, the incidence of lung cancer among nonsmokers (those who have smoked less than 100 cigarettes in their lifetime) is rising, varies by sex and geography, and is linked to environmental exposures and family history. The misperception that lung cancer is almost invariably caused by smoking may delay assessment and diagnosis.
• Researchers conducted a review of 92 studies on lung cancer in nonsmokers: 6 meta-analyses or systematic reviews, 16 randomized clinical trials, eight prospective cohort studies, seven retrospective cohort studies, three cross-sectional studies, four observational or case-control studies, 13 genomic studies, and 35 other studies.
• Overall, lung cancer among nonsmokers accounted for 15% to 20% of all lung cancer cases. Most lung cancers in nonsmokers were adenocarcinomas (60% to 80%), with a median age at diagnosis of 67 years in this group compared with 70 years in people with a history of smoking.
• Data analysis from three US hospital networks showed that the proportion of lung cancer among nonsmokers increased from 8.0% to 14.9% between 1990 and 2013. A pooled analysis of seven Finnish cohorts reported an absolute increase in lung cancer among nonsmokers from 6.9 per 100,000 person-years in 1972 to 12.9 per 100,000 person-years in 2015.
• The age-adjusted incidence rate of lung cancer in the US between 2000 and 2013 was 17.5 per 100,000 individuals among Asian female nonsmokers compared with 10.1 per 100,000 among non-Hispanic White female nonsmokers.

TAKEAWAY:

• Environmental and occupational risk factors were secondhand smoke, residential radon, outdoor and household air pollution (PM_2.5), asbestos and silica exposure, and prior thoracic radiotherapy. Having a first-degree relative with lung cancer increased the risk of developing lung cancer, and genome-wide association studies identified susceptibility loci associated with lung cancer risk in nonsmokers.
• Family history and inherited susceptibility increased lung cancer risk in never smokers (odds ratio [OR] for lung cancer in those with a first–degree relative, 1.51), and clonal hematopoiesis was also associated with higher risk (OR, 1.43). Importantly, tumors in nonsmokers were frequently driven by actionable somatic alterations (EGFR mutations, 40% to 60% in nonsmokers compared with 10% in smokers) and enrichment of ALK/ROS1/RET/ERBB2/NTRK/NRG1 fusions; 78% to 92% of adenocarcinomas in nonsmokers harbored actionable drivers (compared with 49.5% in ever smokers), and nonsmokers had a substantially lower tumor mutational burden (10–fold lower).
• Similar to individuals with a history of smoking, nonsmokers with lung cancer presented with cough, pain, dyspnea, or weight loss or had disease detected incidentally. Surgical resection remained the preferred treatment for anatomically resectable lung cancer (stages I-III) in medically eligible patients, with follow-up CT screening recommended every 6 months for 2 to 3 years and then annually.
• Targeted adjuvant therapy substantially improved outcomes for resected EGFR–mutant or ALK–rearranged non-small cell lung cancer (NSCLC). Four-year DFS was increased to 70% with osimertinib compared with 29% with placebo (hazard ratio [HR], 0.23) and 5–year overall survival was increased to 85% compared with 73% (HR, 0.49). Two–year DFS was 93.8% with alectinib compared with 63% with placebo (HR, 0.24). In unresectable EGFR-mutated stage III NSCLC, median progression-free survival was 39.1 months with adjuvant osimertinib compared with 5.6 months with placebo. For resected ALKpositive disease, 2–year DFS was 93.8% with adjuvant alectinib compared with 63.0% with chemotherapy (HR, 0.24).
• However, singleagent single agent programmed cell death protein 1 inhibitors or programmed death-ligand 1 inhibitors demonstrated limited efficacy in EGFR or ALK–driven tumors, and benefit was attenuated in never smokers. Regarding screening and early detection, the US Preventive Services Task Force did not recommend lowdose CT screening for nonsmokers, whereas Taiwan implemented a biennial screening program for selected nonsmoking high–risk groups.

IN PRACTICE:

“Among patients with lung cancer, nonsmoking individuals are more likely to have genomic alterations, such as EGFR mutations or ALK gene rearrangements, and these patients have improved survival when treated with TKIs compared with chemotherapy,” the authors of the study wrote.

SOURCE:

The study, led by Cian Murphy, PhD, Cancer Evolution and Genome Instability Laboratory, Francis Crick Institute, London, England, was published online in JAMA.

LIMITATIONS:

Becausesmoking history was often not included in many databases, cancer registries, and trials, the incidence and prevalence of lung cancer in nonsmokers could not be accurately determined. Additionally, accurate quantification of environmental exposures, such as air pollution, presented significant challenges. The quality of the evidence was not formally evaluated, and some relevant articles may have been missed in the literature review.

DISCLOSURES:

The study received support from multiple organizations, including the Rosetrees Trust, Ruth Strauss Foundation, Cancer Research UK, and the National Health and Medical Research Council. Several authors reported receiving grants or personal fees from and having other ties with various sources. Full disclosures are noted in the original article.

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

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

TOPLINE:

A comprehensive review of 92 studies found that 15% to 20% of lung cancers occurred among nonsmokers and were associated with environmental and germline risk factors. These cancers frequently harbored actionable genomic drivers, and targeted EGFR and ALK therapies produced significant diseasefree survival (DFS) and overall survival benefits.

METHODOLOGY:

• Lung cancer continues to be the leading cause of cancer death worldwide, causing about 1.8 million deaths in 2022, with smoking remaining the predominant risk factor. However, the incidence of lung cancer among nonsmokers (those who have smoked less than 100 cigarettes in their lifetime) is rising, varies by sex and geography, and is linked to environmental exposures and family history. The misperception that lung cancer is almost invariably caused by smoking may delay assessment and diagnosis.
• Researchers conducted a review of 92 studies on lung cancer in nonsmokers: 6 meta-analyses or systematic reviews, 16 randomized clinical trials, eight prospective cohort studies, seven retrospective cohort studies, three cross-sectional studies, four observational or case-control studies, 13 genomic studies, and 35 other studies.
• Overall, lung cancer among nonsmokers accounted for 15% to 20% of all lung cancer cases. Most lung cancers in nonsmokers were adenocarcinomas (60% to 80%), with a median age at diagnosis of 67 years in this group compared with 70 years in people with a history of smoking.
• Data analysis from three US hospital networks showed that the proportion of lung cancer among nonsmokers increased from 8.0% to 14.9% between 1990 and 2013. A pooled analysis of seven Finnish cohorts reported an absolute increase in lung cancer among nonsmokers from 6.9 per 100,000 person-years in 1972 to 12.9 per 100,000 person-years in 2015.
• The age-adjusted incidence rate of lung cancer in the US between 2000 and 2013 was 17.5 per 100,000 individuals among Asian female nonsmokers compared with 10.1 per 100,000 among non-Hispanic White female nonsmokers.

TAKEAWAY:

• Environmental and occupational risk factors were secondhand smoke, residential radon, outdoor and household air pollution (PM_2.5), asbestos and silica exposure, and prior thoracic radiotherapy. Having a first-degree relative with lung cancer increased the risk of developing lung cancer, and genome-wide association studies identified susceptibility loci associated with lung cancer risk in nonsmokers.
• Family history and inherited susceptibility increased lung cancer risk in never smokers (odds ratio [OR] for lung cancer in those with a first–degree relative, 1.51), and clonal hematopoiesis was also associated with higher risk (OR, 1.43). Importantly, tumors in nonsmokers were frequently driven by actionable somatic alterations (EGFR mutations, 40% to 60% in nonsmokers compared with 10% in smokers) and enrichment of ALK/ROS1/RET/ERBB2/NTRK/NRG1 fusions; 78% to 92% of adenocarcinomas in nonsmokers harbored actionable drivers (compared with 49.5% in ever smokers), and nonsmokers had a substantially lower tumor mutational burden (10–fold lower).
• Similar to individuals with a history of smoking, nonsmokers with lung cancer presented with cough, pain, dyspnea, or weight loss or had disease detected incidentally. Surgical resection remained the preferred treatment for anatomically resectable lung cancer (stages I-III) in medically eligible patients, with follow-up CT screening recommended every 6 months for 2 to 3 years and then annually.
• Targeted adjuvant therapy substantially improved outcomes for resected EGFR–mutant or ALK–rearranged non-small cell lung cancer (NSCLC). Four-year DFS was increased to 70% with osimertinib compared with 29% with placebo (hazard ratio [HR], 0.23) and 5–year overall survival was increased to 85% compared with 73% (HR, 0.49). Two–year DFS was 93.8% with alectinib compared with 63% with placebo (HR, 0.24). In unresectable EGFR-mutated stage III NSCLC, median progression-free survival was 39.1 months with adjuvant osimertinib compared with 5.6 months with placebo. For resected ALKpositive disease, 2–year DFS was 93.8% with adjuvant alectinib compared with 63.0% with chemotherapy (HR, 0.24).
• However, singleagent single agent programmed cell death protein 1 inhibitors or programmed death-ligand 1 inhibitors demonstrated limited efficacy in EGFR or ALK–driven tumors, and benefit was attenuated in never smokers. Regarding screening and early detection, the US Preventive Services Task Force did not recommend lowdose CT screening for nonsmokers, whereas Taiwan implemented a biennial screening program for selected nonsmoking high–risk groups.

IN PRACTICE:

“Among patients with lung cancer, nonsmoking individuals are more likely to have genomic alterations, such as EGFR mutations or ALK gene rearrangements, and these patients have improved survival when treated with TKIs compared with chemotherapy,” the authors of the study wrote.

SOURCE:

The study, led by Cian Murphy, PhD, Cancer Evolution and Genome Instability Laboratory, Francis Crick Institute, London, England, was published online in JAMA.

LIMITATIONS:

Becausesmoking history was often not included in many databases, cancer registries, and trials, the incidence and prevalence of lung cancer in nonsmokers could not be accurately determined. Additionally, accurate quantification of environmental exposures, such as air pollution, presented significant challenges. The quality of the evidence was not formally evaluated, and some relevant articles may have been missed in the literature review.

DISCLOSURES:

The study received support from multiple organizations, including the Rosetrees Trust, Ruth Strauss Foundation, Cancer Research UK, and the National Health and Medical Research Council. Several authors reported receiving grants or personal fees from and having other ties with various sources. Full disclosures are noted in the original article.

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

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

BERLIN — Re-treatment with an antiepidermal growth factor receptor (EGFR) agent is effective in patients with chemorefractory metastatic colorectal cancer (mCRC) with RAS and BRAF wild-type tumors confirmed on circulating tumor DNA (ctDNA), although the sequencing of therapy does not seem to matter, suggest overall survival results from the crossover trial PARERE.

The findings nevertheless indicate that anti-EGFR rechallenge with panitumumab may prolong progression-free survival (PFS) over the multiple kinase inhibitor regorafenib. This suggests that “the most pragmatic choice” would be to give the anti-EGFR before regorafenib, said study presenter Marco Maria Germani, MD, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.

The caveat, however, is in patients who have an anti-EGFR interval since previously receiving the drugs of < 6 months. Those patients appeared to do better if they had regorafenib first and then anti-EGFR rechallenge.

Overall, Germani said that “since [trifluridine/tipiracil] plus bevacizumab is today the third-line standard of care” in this patient population, “anti-EGFR re-treatment might be considered after progression” on that combination.

Germani presented the research on October 18 at the European Society for Medical Oncology (ESMO) Annual Meeting 2025, which was simultaneously published in the Annals of Oncology.

Michel P. Ducreux, MD, PhD, head of the Digestive Cancer Committee at Gustave Roussy, Villejuif, France, and invited discussant for the results, said, despite the study being negative, it is “very important to continue to perform this kind of trial to evaluate the [ideal] sequence in the treatment of our patients.”

He continued that the secondary endpoints in the trial of PFS and objective response and disease control rates were “fairly in favor of the use of rechallenge before regorafenib, and in my opinion, this is really quite convincing.”

Ducreux, who was not involved in PARERE trail, also pointed to the sex difference seen in the study, which suggested that women responded much better to having anti-EGFR retreatment before regorafenib than did men.

Similar findings have been reported in a number of other trials, and previous work has suggested that there are sex differences in the pharmacokinetics of several anticancer drugs. However, while this is “very important,” he said that “we never consider it, because we are not able to really explain [it].”

Overall, he concluded that, on the basis of these results, he would agree with the notion that it is better to propose a rechallenge with anti-EGFR treatment as the fourth-line therapy in this patient population, before administering regorafenib.

Ducreux explained that, after a partial response, tumors acquire resistance to EGFR inhibitors through alterations and mutations that occur during treatment, via nongenetic mechanisms, and through treatment-induced selection for preexisting mutations.

Previous work has shown that mutations, such as in the RAS gene, are detectable early during EGFR inhibitor therapy, but that they then decay exponentially once the drugs are stopped, with the potential that tumors regain their sensitivity to them.

Germani said that this means that ctDNA-guided retreatment with anti-EGFR therapies is a “promising approach” in pretreated patients with RAS and BRAF wild-type mCRC, and that the sequencing of the drugs may be important. Indeed, the REVERCE trial showed that giving regorafenib followed by the anti-EGFR drug cetuzximab was associated with longer overall survival than the other way around in anti-EGFR medication-naive patients.

 

Methods and Results

For PARERE, the researchers enrolled patients aged at least 18 years with RAS and BRAF wild-type mCRC who were previously treated with a first-line anti-EGFR-containing regimen and had at least a partial response or stable disease for at least 6 months.

The patients were also required to have had at least one intervening anti-EGFR-free line of therapy, and to have previously received treatment with fluoropyrimidine, oxaliplatin, irinotecan, and anti-angiogenics. At least 4 months were required to have passed between the end of anti-EGFR administration and screening for the study.

In all, 428 patients were screened between December 2020 and December 2024, with 213 patients with RAS and BRAF wild-type mCRC, as detected on ctDNA, enrolled. They were randomized to panitumumab or regorafenib until first progression, followed by regorafenib, if they started on panitumumab, or panitumumab, if they started on regorafenib, until second progression.

The median age of the patients was 61 years among those who started on panitumumab and 64 years among those initially given regorafenib in the trial, and 63% and 57%, respectively, were male. The median number of prior lines of therapy was two in both groups, and 65% and 69%, respectively, had received pantitumumab as their first-line anti-EGFR.

Initial findings from the study presented at the 2025 ASCO Annual Meeting indicated that, after a median follow-up of 23.5 months, there was no significant difference in the median first PFS between the two treatment arms.

However, patients who started with panitumumab had a significant improvement in both the objective response and disease control rates (P < .001), as well as a signal for a potentially longer median second PFS, than those who started with regorafenib, particularly on the per-protocol analysis.

Presenting the overall survival results, Germani said that there was no significant difference between the groups on the intention-to-treat analysis, at a stratified hazard ratio of 1.13 (P = .440), or on the per-protocol analysis, at a hazard ratio of 1.07 (P = .730).

“We then ran a subgroup analysis,” he continued, “and we found out that an anti-EGFR-free interval before liquid biopsy shorter than 6 months was associated with less benefit from a panitumumab [first] sequence, which is biologically sound.”

It was also observed that women did significantly better when having panitumumab first, whereas men did not, for which “we do not have a clear biological explanation,” Germani added.

Confining the analysis to so-called “hyperselected” patients, who not only were RAS and BRAF wild type but also had no pathogenic mutations associated with anti-EGFR resistance, did not reveal any significant overall survival differences between the treatment groups.

However, Ducreux took issue with the way in which hyperselection, which is turning up more and more regularly in trials, is defined, as the choice of which mutations to include varies widely. He suggested that a consensus group be assembled to resolve this issue.

Looking more broadly, the researchers were able to show that, in this updated analysis, anti-EGFR re-treatment was superior to regorafenib regardless of the treatment sequence in terms of PFS, at 4.2 months vs 2.4 months (P = .103) when given first in the trial, and 3.9 months vs 2.7 months (P = .019) when given second in the trial, as well as in terms of objective response and disease control rates.

 

Adverse Events

In terms of safety, the results showed that, as expected, acneiform rash, fatigue, and hypomagnesemia were the most common adverse events associated with panitumumb, while those with regorafenib were fatigue, hand-foot skin reactions, and hypertension.

There were no notable differences in the number of patients receiving a post-study treatment nor in the post-study therapeutic choices, between the study arms.

The study was sponsored by GONO Foundation and partially supported by Amgen and Bayer. Germani declared having relationships with MSD and Amgen. Ducreux declared having relationships with Amgen, Bayer, BeiGene, Incyte, Jazz, Merck KGaA, Merck Serono, Merck Sharp & Dohme, Pierre Fabre, Roche, Servier, Keocyt, AbbVie, Abcely, Arcus, Bayer, BMS, Boehringer, GlaxoSmithKline, Sanofi, Scandion, and Zymeworks.

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

BERLIN — Re-treatment with an antiepidermal growth factor receptor (EGFR) agent is effective in patients with chemorefractory metastatic colorectal cancer (mCRC) with RAS and BRAF wild-type tumors confirmed on circulating tumor DNA (ctDNA), although the sequencing of therapy does not seem to matter, suggest overall survival results from the crossover trial PARERE.

The findings nevertheless indicate that anti-EGFR rechallenge with panitumumab may prolong progression-free survival (PFS) over the multiple kinase inhibitor regorafenib. This suggests that “the most pragmatic choice” would be to give the anti-EGFR before regorafenib, said study presenter Marco Maria Germani, MD, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.

The caveat, however, is in patients who have an anti-EGFR interval since previously receiving the drugs of < 6 months. Those patients appeared to do better if they had regorafenib first and then anti-EGFR rechallenge.

Overall, Germani said that “since [trifluridine/tipiracil] plus bevacizumab is today the third-line standard of care” in this patient population, “anti-EGFR re-treatment might be considered after progression” on that combination.

Germani presented the research on October 18 at the European Society for Medical Oncology (ESMO) Annual Meeting 2025, which was simultaneously published in the Annals of Oncology.

Michel P. Ducreux, MD, PhD, head of the Digestive Cancer Committee at Gustave Roussy, Villejuif, France, and invited discussant for the results, said, despite the study being negative, it is “very important to continue to perform this kind of trial to evaluate the [ideal] sequence in the treatment of our patients.”

He continued that the secondary endpoints in the trial of PFS and objective response and disease control rates were “fairly in favor of the use of rechallenge before regorafenib, and in my opinion, this is really quite convincing.”

Ducreux, who was not involved in PARERE trail, also pointed to the sex difference seen in the study, which suggested that women responded much better to having anti-EGFR retreatment before regorafenib than did men.

Similar findings have been reported in a number of other trials, and previous work has suggested that there are sex differences in the pharmacokinetics of several anticancer drugs. However, while this is “very important,” he said that “we never consider it, because we are not able to really explain [it].”

Overall, he concluded that, on the basis of these results, he would agree with the notion that it is better to propose a rechallenge with anti-EGFR treatment as the fourth-line therapy in this patient population, before administering regorafenib.

Ducreux explained that, after a partial response, tumors acquire resistance to EGFR inhibitors through alterations and mutations that occur during treatment, via nongenetic mechanisms, and through treatment-induced selection for preexisting mutations.

Previous work has shown that mutations, such as in the RAS gene, are detectable early during EGFR inhibitor therapy, but that they then decay exponentially once the drugs are stopped, with the potential that tumors regain their sensitivity to them.

Germani said that this means that ctDNA-guided retreatment with anti-EGFR therapies is a “promising approach” in pretreated patients with RAS and BRAF wild-type mCRC, and that the sequencing of the drugs may be important. Indeed, the REVERCE trial showed that giving regorafenib followed by the anti-EGFR drug cetuzximab was associated with longer overall survival than the other way around in anti-EGFR medication-naive patients.

 

Methods and Results

For PARERE, the researchers enrolled patients aged at least 18 years with RAS and BRAF wild-type mCRC who were previously treated with a first-line anti-EGFR-containing regimen and had at least a partial response or stable disease for at least 6 months.

The patients were also required to have had at least one intervening anti-EGFR-free line of therapy, and to have previously received treatment with fluoropyrimidine, oxaliplatin, irinotecan, and anti-angiogenics. At least 4 months were required to have passed between the end of anti-EGFR administration and screening for the study.

In all, 428 patients were screened between December 2020 and December 2024, with 213 patients with RAS and BRAF wild-type mCRC, as detected on ctDNA, enrolled. They were randomized to panitumumab or regorafenib until first progression, followed by regorafenib, if they started on panitumumab, or panitumumab, if they started on regorafenib, until second progression.

The median age of the patients was 61 years among those who started on panitumumab and 64 years among those initially given regorafenib in the trial, and 63% and 57%, respectively, were male. The median number of prior lines of therapy was two in both groups, and 65% and 69%, respectively, had received pantitumumab as their first-line anti-EGFR.

Initial findings from the study presented at the 2025 ASCO Annual Meeting indicated that, after a median follow-up of 23.5 months, there was no significant difference in the median first PFS between the two treatment arms.

However, patients who started with panitumumab had a significant improvement in both the objective response and disease control rates (P < .001), as well as a signal for a potentially longer median second PFS, than those who started with regorafenib, particularly on the per-protocol analysis.

Presenting the overall survival results, Germani said that there was no significant difference between the groups on the intention-to-treat analysis, at a stratified hazard ratio of 1.13 (P = .440), or on the per-protocol analysis, at a hazard ratio of 1.07 (P = .730).

“We then ran a subgroup analysis,” he continued, “and we found out that an anti-EGFR-free interval before liquid biopsy shorter than 6 months was associated with less benefit from a panitumumab [first] sequence, which is biologically sound.”

It was also observed that women did significantly better when having panitumumab first, whereas men did not, for which “we do not have a clear biological explanation,” Germani added.

Confining the analysis to so-called “hyperselected” patients, who not only were RAS and BRAF wild type but also had no pathogenic mutations associated with anti-EGFR resistance, did not reveal any significant overall survival differences between the treatment groups.

However, Ducreux took issue with the way in which hyperselection, which is turning up more and more regularly in trials, is defined, as the choice of which mutations to include varies widely. He suggested that a consensus group be assembled to resolve this issue.

Looking more broadly, the researchers were able to show that, in this updated analysis, anti-EGFR re-treatment was superior to regorafenib regardless of the treatment sequence in terms of PFS, at 4.2 months vs 2.4 months (P = .103) when given first in the trial, and 3.9 months vs 2.7 months (P = .019) when given second in the trial, as well as in terms of objective response and disease control rates.

 

Adverse Events

In terms of safety, the results showed that, as expected, acneiform rash, fatigue, and hypomagnesemia were the most common adverse events associated with panitumumb, while those with regorafenib were fatigue, hand-foot skin reactions, and hypertension.

There were no notable differences in the number of patients receiving a post-study treatment nor in the post-study therapeutic choices, between the study arms.

The study was sponsored by GONO Foundation and partially supported by Amgen and Bayer. Germani declared having relationships with MSD and Amgen. Ducreux declared having relationships with Amgen, Bayer, BeiGene, Incyte, Jazz, Merck KGaA, Merck Serono, Merck Sharp & Dohme, Pierre Fabre, Roche, Servier, Keocyt, AbbVie, Abcely, Arcus, Bayer, BMS, Boehringer, GlaxoSmithKline, Sanofi, Scandion, and Zymeworks.

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

BERLIN — Re-treatment with an antiepidermal growth factor receptor (EGFR) agent is effective in patients with chemorefractory metastatic colorectal cancer (mCRC) with RAS and BRAF wild-type tumors confirmed on circulating tumor DNA (ctDNA), although the sequencing of therapy does not seem to matter, suggest overall survival results from the crossover trial PARERE.

The findings nevertheless indicate that anti-EGFR rechallenge with panitumumab may prolong progression-free survival (PFS) over the multiple kinase inhibitor regorafenib. This suggests that “the most pragmatic choice” would be to give the anti-EGFR before regorafenib, said study presenter Marco Maria Germani, MD, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.

The caveat, however, is in patients who have an anti-EGFR interval since previously receiving the drugs of < 6 months. Those patients appeared to do better if they had regorafenib first and then anti-EGFR rechallenge.

Overall, Germani said that “since [trifluridine/tipiracil] plus bevacizumab is today the third-line standard of care” in this patient population, “anti-EGFR re-treatment might be considered after progression” on that combination.

Germani presented the research on October 18 at the European Society for Medical Oncology (ESMO) Annual Meeting 2025, which was simultaneously published in the Annals of Oncology.

Michel P. Ducreux, MD, PhD, head of the Digestive Cancer Committee at Gustave Roussy, Villejuif, France, and invited discussant for the results, said, despite the study being negative, it is “very important to continue to perform this kind of trial to evaluate the [ideal] sequence in the treatment of our patients.”

He continued that the secondary endpoints in the trial of PFS and objective response and disease control rates were “fairly in favor of the use of rechallenge before regorafenib, and in my opinion, this is really quite convincing.”

Ducreux, who was not involved in PARERE trail, also pointed to the sex difference seen in the study, which suggested that women responded much better to having anti-EGFR retreatment before regorafenib than did men.

Similar findings have been reported in a number of other trials, and previous work has suggested that there are sex differences in the pharmacokinetics of several anticancer drugs. However, while this is “very important,” he said that “we never consider it, because we are not able to really explain [it].”

Overall, he concluded that, on the basis of these results, he would agree with the notion that it is better to propose a rechallenge with anti-EGFR treatment as the fourth-line therapy in this patient population, before administering regorafenib.

Ducreux explained that, after a partial response, tumors acquire resistance to EGFR inhibitors through alterations and mutations that occur during treatment, via nongenetic mechanisms, and through treatment-induced selection for preexisting mutations.

Previous work has shown that mutations, such as in the RAS gene, are detectable early during EGFR inhibitor therapy, but that they then decay exponentially once the drugs are stopped, with the potential that tumors regain their sensitivity to them.

Germani said that this means that ctDNA-guided retreatment with anti-EGFR therapies is a “promising approach” in pretreated patients with RAS and BRAF wild-type mCRC, and that the sequencing of the drugs may be important. Indeed, the REVERCE trial showed that giving regorafenib followed by the anti-EGFR drug cetuzximab was associated with longer overall survival than the other way around in anti-EGFR medication-naive patients.

 

Methods and Results

For PARERE, the researchers enrolled patients aged at least 18 years with RAS and BRAF wild-type mCRC who were previously treated with a first-line anti-EGFR-containing regimen and had at least a partial response or stable disease for at least 6 months.

The patients were also required to have had at least one intervening anti-EGFR-free line of therapy, and to have previously received treatment with fluoropyrimidine, oxaliplatin, irinotecan, and anti-angiogenics. At least 4 months were required to have passed between the end of anti-EGFR administration and screening for the study.

In all, 428 patients were screened between December 2020 and December 2024, with 213 patients with RAS and BRAF wild-type mCRC, as detected on ctDNA, enrolled. They were randomized to panitumumab or regorafenib until first progression, followed by regorafenib, if they started on panitumumab, or panitumumab, if they started on regorafenib, until second progression.

The median age of the patients was 61 years among those who started on panitumumab and 64 years among those initially given regorafenib in the trial, and 63% and 57%, respectively, were male. The median number of prior lines of therapy was two in both groups, and 65% and 69%, respectively, had received pantitumumab as their first-line anti-EGFR.

Initial findings from the study presented at the 2025 ASCO Annual Meeting indicated that, after a median follow-up of 23.5 months, there was no significant difference in the median first PFS between the two treatment arms.

However, patients who started with panitumumab had a significant improvement in both the objective response and disease control rates (P < .001), as well as a signal for a potentially longer median second PFS, than those who started with regorafenib, particularly on the per-protocol analysis.

Presenting the overall survival results, Germani said that there was no significant difference between the groups on the intention-to-treat analysis, at a stratified hazard ratio of 1.13 (P = .440), or on the per-protocol analysis, at a hazard ratio of 1.07 (P = .730).

“We then ran a subgroup analysis,” he continued, “and we found out that an anti-EGFR-free interval before liquid biopsy shorter than 6 months was associated with less benefit from a panitumumab [first] sequence, which is biologically sound.”

It was also observed that women did significantly better when having panitumumab first, whereas men did not, for which “we do not have a clear biological explanation,” Germani added.

Confining the analysis to so-called “hyperselected” patients, who not only were RAS and BRAF wild type but also had no pathogenic mutations associated with anti-EGFR resistance, did not reveal any significant overall survival differences between the treatment groups.

However, Ducreux took issue with the way in which hyperselection, which is turning up more and more regularly in trials, is defined, as the choice of which mutations to include varies widely. He suggested that a consensus group be assembled to resolve this issue.

Looking more broadly, the researchers were able to show that, in this updated analysis, anti-EGFR re-treatment was superior to regorafenib regardless of the treatment sequence in terms of PFS, at 4.2 months vs 2.4 months (P = .103) when given first in the trial, and 3.9 months vs 2.7 months (P = .019) when given second in the trial, as well as in terms of objective response and disease control rates.

 

Adverse Events

In terms of safety, the results showed that, as expected, acneiform rash, fatigue, and hypomagnesemia were the most common adverse events associated with panitumumb, while those with regorafenib were fatigue, hand-foot skin reactions, and hypertension.

There were no notable differences in the number of patients receiving a post-study treatment nor in the post-study therapeutic choices, between the study arms.

The study was sponsored by GONO Foundation and partially supported by Amgen and Bayer. Germani declared having relationships with MSD and Amgen. Ducreux declared having relationships with Amgen, Bayer, BeiGene, Incyte, Jazz, Merck KGaA, Merck Serono, Merck Sharp & Dohme, Pierre Fabre, Roche, Servier, Keocyt, AbbVie, Abcely, Arcus, Bayer, BMS, Boehringer, GlaxoSmithKline, Sanofi, Scandion, and Zymeworks.

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