Both a standard and culturally tailored online intervention improved insomnia symptoms in Black women, compared with a non-Internet patient education intervention.

Data from previous studies suggest that women are up to 40% more likely to experience insomnia disorder compared with men, Eric S. Zhou, PhD, of Harvard Medical School, Boston, and colleagues wrote. The risk is even higher among Black women, but research on tailored treatments for this particular population has been limited.

In their study, published in JAMA Psychiatry, the researchers recruited women with elevated insomnia symptoms who were enrolled in the Black Women’s Health Study, an ongoing national, longitudinal research cohort in the United States. Participants were recruited between October 2019 and June 2020.The participants were randomized to an Internet-delivered behavior intervention (108 women), a stakeholder-informed Internet intervention tailored to Black women (110 women), or non-Internet patient education about sleep (115 women).

The Internet intervention, known as Sleep Healthy Using the Internet (SHUTi), was a 6-session program lasting 45-60 minutes per session and delivered over 6-9 weeks. The program included core elements of cognitive behavioral therapy and took into account information provided by patients about their baseline sleep function, treatment adherence, and sleep progress.

The tailored version of SHUTi for Black women (SHUTi-BWHS) was similar, but included Black actors for video vignettes and the inclusion of content about the cultural and social contexts in which insomnia often occurs for Black women, such while managing neighborhood noise and or living in crowded environments.

A third group received standard patient education material about sleep through a noninteractive website, and served as the control group.

The primary outcome of insomnia severity was measured using the Insomnia Severity Index (ISI), a 0- to 28-point scale. Scores for the ISI are based on responses to seven questions, including some that ask participants to rate the severity of their insomnia symptoms.

Clinically significant improvement in insomnia was defined as a reduction in score of more than 7 points. Patients were assessed at baseline, at 9 weeks, and again at approximately 6 months.
 

Significantly greater reductions in insomnia severity seen in intervention groups vs. control group

Overall, women randomized to SHUTi or SHUTi-BWHS) reported a significantly greater reduction in insomnia symptoms from baseline to 6 months, compared with the control group (P < .001), with ISI score decreases of 10.0, 9.3, and 3.6, respectively. No statistically significant differences in ISI score changes appeared between the between the SHUTi-BWHS and SHUTi groups.

Also, significantly more women in the SHUTi-BWHS group than in the SHUTi group completed the intervention (78.2% vs. 64.8%).

Treatment response was similar between the SHUTI-BWHS and SHUTi groups; 47.3% and 46.3%, respectively, had a decrease in ISI score of more than 7 points. In addition, 37% of women in the SHUTi-BWHS and 38% of women in the SHUTi groups reached ISI scores of less than 8 points, defined as full resolution of insomnia, by the last follow-up visit.

Both the SHUTi and SHUTi-BWHS interventions had dramatic effects on insomnia, but the increased number of women who completed the intervention in the SHUTi-BWHS group supports the value of tailored intervention, the researchers noted. “Similar to prior SHUTi trials, there was a direct association between the participant’s level of intervention engagement and their improvement in sleep.”

The average age of the participants was 60 years, 62% were single, and 44% had a graduate degree or higher. Approximately 5% were being actively treated for sleep apnea.

The study findings were limited by several factors including the relatively high socioeconomic status of the study participants, lack of data on medical mistrust, and inability to detect smaller differences between SHUTi and SHUTi-BWHS, the researchers noted.

 

Choose Internet-based CBT first for insomnia

“This was an excellent paper that sought to see the relative efficacy of standard version of Internet-delivered CBT-I [cognitive-behavioral therapy for insomnia] versus a culturally tailored version for Black women,” said Neil Skolnik, MD, professor of family and community medicine at Thomas Jefferson University, Philadelphia, in an interview. “The trial confirmed that, compared with sleep education, which was used as the control, Internet-delivered CBT-I is effective in the treatment of insomnia.”

“These results demonstrate two important things,” said Dr. Skolnik. “The most important is that Internet-delivered CBT-I works, and since it is both safe and effective, should be the first-line therapy for patients who want treatment for insomnia.”

Secondly, “the fact that more people completed culturally tailored versions suggests that, when culturally tailored versions are available, their use is preferable, as it might facilitate a higher proportion of patients being successful in their insomnia treatment,” he added.  

The study was supported by the Patient-Centered Outcomes Research Institute. The Black Women’s Health Study is supported by the National Cancer Institute. Dr. Zhou disclosed support from both PCORI and the NCI during the study. Dr. Skolnik, who was not involved in the study, disclosed serving on the advisory board for Idorsia Pharmaceuticals. He is also a member of the editorial advisory board of Family Practice News.

Both a standard and culturally tailored online intervention improved insomnia symptoms in Black women, compared with a non-Internet patient education intervention.

Data from previous studies suggest that women are up to 40% more likely to experience insomnia disorder compared with men, Eric S. Zhou, PhD, of Harvard Medical School, Boston, and colleagues wrote. The risk is even higher among Black women, but research on tailored treatments for this particular population has been limited.

In their study, published in JAMA Psychiatry, the researchers recruited women with elevated insomnia symptoms who were enrolled in the Black Women’s Health Study, an ongoing national, longitudinal research cohort in the United States. Participants were recruited between October 2019 and June 2020.The participants were randomized to an Internet-delivered behavior intervention (108 women), a stakeholder-informed Internet intervention tailored to Black women (110 women), or non-Internet patient education about sleep (115 women).

The Internet intervention, known as Sleep Healthy Using the Internet (SHUTi), was a 6-session program lasting 45-60 minutes per session and delivered over 6-9 weeks. The program included core elements of cognitive behavioral therapy and took into account information provided by patients about their baseline sleep function, treatment adherence, and sleep progress.

The tailored version of SHUTi for Black women (SHUTi-BWHS) was similar, but included Black actors for video vignettes and the inclusion of content about the cultural and social contexts in which insomnia often occurs for Black women, such while managing neighborhood noise and or living in crowded environments.

A third group received standard patient education material about sleep through a noninteractive website, and served as the control group.

The primary outcome of insomnia severity was measured using the Insomnia Severity Index (ISI), a 0- to 28-point scale. Scores for the ISI are based on responses to seven questions, including some that ask participants to rate the severity of their insomnia symptoms.

Clinically significant improvement in insomnia was defined as a reduction in score of more than 7 points. Patients were assessed at baseline, at 9 weeks, and again at approximately 6 months.
 

Significantly greater reductions in insomnia severity seen in intervention groups vs. control group

Overall, women randomized to SHUTi or SHUTi-BWHS) reported a significantly greater reduction in insomnia symptoms from baseline to 6 months, compared with the control group (P < .001), with ISI score decreases of 10.0, 9.3, and 3.6, respectively. No statistically significant differences in ISI score changes appeared between the between the SHUTi-BWHS and SHUTi groups.

Also, significantly more women in the SHUTi-BWHS group than in the SHUTi group completed the intervention (78.2% vs. 64.8%).

Treatment response was similar between the SHUTI-BWHS and SHUTi groups; 47.3% and 46.3%, respectively, had a decrease in ISI score of more than 7 points. In addition, 37% of women in the SHUTi-BWHS and 38% of women in the SHUTi groups reached ISI scores of less than 8 points, defined as full resolution of insomnia, by the last follow-up visit.

Both the SHUTi and SHUTi-BWHS interventions had dramatic effects on insomnia, but the increased number of women who completed the intervention in the SHUTi-BWHS group supports the value of tailored intervention, the researchers noted. “Similar to prior SHUTi trials, there was a direct association between the participant’s level of intervention engagement and their improvement in sleep.”

The average age of the participants was 60 years, 62% were single, and 44% had a graduate degree or higher. Approximately 5% were being actively treated for sleep apnea.

The study findings were limited by several factors including the relatively high socioeconomic status of the study participants, lack of data on medical mistrust, and inability to detect smaller differences between SHUTi and SHUTi-BWHS, the researchers noted.

 

Choose Internet-based CBT first for insomnia

“This was an excellent paper that sought to see the relative efficacy of standard version of Internet-delivered CBT-I [cognitive-behavioral therapy for insomnia] versus a culturally tailored version for Black women,” said Neil Skolnik, MD, professor of family and community medicine at Thomas Jefferson University, Philadelphia, in an interview. “The trial confirmed that, compared with sleep education, which was used as the control, Internet-delivered CBT-I is effective in the treatment of insomnia.”

“These results demonstrate two important things,” said Dr. Skolnik. “The most important is that Internet-delivered CBT-I works, and since it is both safe and effective, should be the first-line therapy for patients who want treatment for insomnia.”

Secondly, “the fact that more people completed culturally tailored versions suggests that, when culturally tailored versions are available, their use is preferable, as it might facilitate a higher proportion of patients being successful in their insomnia treatment,” he added.  

The study was supported by the Patient-Centered Outcomes Research Institute. The Black Women’s Health Study is supported by the National Cancer Institute. Dr. Zhou disclosed support from both PCORI and the NCI during the study. Dr. Skolnik, who was not involved in the study, disclosed serving on the advisory board for Idorsia Pharmaceuticals. He is also a member of the editorial advisory board of Family Practice News.

Both a standard and culturally tailored online intervention improved insomnia symptoms in Black women, compared with a non-Internet patient education intervention.

Data from previous studies suggest that women are up to 40% more likely to experience insomnia disorder compared with men, Eric S. Zhou, PhD, of Harvard Medical School, Boston, and colleagues wrote. The risk is even higher among Black women, but research on tailored treatments for this particular population has been limited.

In their study, published in JAMA Psychiatry, the researchers recruited women with elevated insomnia symptoms who were enrolled in the Black Women’s Health Study, an ongoing national, longitudinal research cohort in the United States. Participants were recruited between October 2019 and June 2020.The participants were randomized to an Internet-delivered behavior intervention (108 women), a stakeholder-informed Internet intervention tailored to Black women (110 women), or non-Internet patient education about sleep (115 women).

The Internet intervention, known as Sleep Healthy Using the Internet (SHUTi), was a 6-session program lasting 45-60 minutes per session and delivered over 6-9 weeks. The program included core elements of cognitive behavioral therapy and took into account information provided by patients about their baseline sleep function, treatment adherence, and sleep progress.

The tailored version of SHUTi for Black women (SHUTi-BWHS) was similar, but included Black actors for video vignettes and the inclusion of content about the cultural and social contexts in which insomnia often occurs for Black women, such while managing neighborhood noise and or living in crowded environments.

A third group received standard patient education material about sleep through a noninteractive website, and served as the control group.

The primary outcome of insomnia severity was measured using the Insomnia Severity Index (ISI), a 0- to 28-point scale. Scores for the ISI are based on responses to seven questions, including some that ask participants to rate the severity of their insomnia symptoms.

Clinically significant improvement in insomnia was defined as a reduction in score of more than 7 points. Patients were assessed at baseline, at 9 weeks, and again at approximately 6 months.
 

Significantly greater reductions in insomnia severity seen in intervention groups vs. control group

Overall, women randomized to SHUTi or SHUTi-BWHS) reported a significantly greater reduction in insomnia symptoms from baseline to 6 months, compared with the control group (P < .001), with ISI score decreases of 10.0, 9.3, and 3.6, respectively. No statistically significant differences in ISI score changes appeared between the between the SHUTi-BWHS and SHUTi groups.

Also, significantly more women in the SHUTi-BWHS group than in the SHUTi group completed the intervention (78.2% vs. 64.8%).

Treatment response was similar between the SHUTI-BWHS and SHUTi groups; 47.3% and 46.3%, respectively, had a decrease in ISI score of more than 7 points. In addition, 37% of women in the SHUTi-BWHS and 38% of women in the SHUTi groups reached ISI scores of less than 8 points, defined as full resolution of insomnia, by the last follow-up visit.

Both the SHUTi and SHUTi-BWHS interventions had dramatic effects on insomnia, but the increased number of women who completed the intervention in the SHUTi-BWHS group supports the value of tailored intervention, the researchers noted. “Similar to prior SHUTi trials, there was a direct association between the participant’s level of intervention engagement and their improvement in sleep.”

The average age of the participants was 60 years, 62% were single, and 44% had a graduate degree or higher. Approximately 5% were being actively treated for sleep apnea.

The study findings were limited by several factors including the relatively high socioeconomic status of the study participants, lack of data on medical mistrust, and inability to detect smaller differences between SHUTi and SHUTi-BWHS, the researchers noted.

 

Choose Internet-based CBT first for insomnia

“This was an excellent paper that sought to see the relative efficacy of standard version of Internet-delivered CBT-I [cognitive-behavioral therapy for insomnia] versus a culturally tailored version for Black women,” said Neil Skolnik, MD, professor of family and community medicine at Thomas Jefferson University, Philadelphia, in an interview. “The trial confirmed that, compared with sleep education, which was used as the control, Internet-delivered CBT-I is effective in the treatment of insomnia.”

“These results demonstrate two important things,” said Dr. Skolnik. “The most important is that Internet-delivered CBT-I works, and since it is both safe and effective, should be the first-line therapy for patients who want treatment for insomnia.”

Secondly, “the fact that more people completed culturally tailored versions suggests that, when culturally tailored versions are available, their use is preferable, as it might facilitate a higher proportion of patients being successful in their insomnia treatment,” he added.  

The study was supported by the Patient-Centered Outcomes Research Institute. The Black Women’s Health Study is supported by the National Cancer Institute. Dr. Zhou disclosed support from both PCORI and the NCI during the study. Dr. Skolnik, who was not involved in the study, disclosed serving on the advisory board for Idorsia Pharmaceuticals. He is also a member of the editorial advisory board of Family Practice News.

A Virginia physician assistant entered a plea of not guilty on April 21 to a murder charge in connection with a gruesome slaying of another PA in upstate New York.

Jacob L. Klein, 40, of Wirtz, Va., was charged with second-degree murder at the Town of New Scotland Court in New York following the discovery the previous week of 35-year-old Philip Rabadi, another PA. Mr. Rabadi was discovered on the garage floor of his New Scotland home, the Albany County Sheriff’s Office said in a press release.

Mr. Rabadi’s arms were bound and he suffered multiple stab wounds and body mutilation, authorities reported. Mr. Klein allegedly had been stalking Mr. Rabadi and his wife, Elana Z. Radin, for 3 days prior to the homicide after driving the 600 miles from Virginia to New Scotland. Ms. Radin had once been Mr. Klein’s girlfriend, according to a report in the Times Union in Albany, N.Y.

Mr. Klein was being held without bail in the Albany County Correctional Facility and a preliminary hearing was set for April 25. Mr. Klein had been extradited from Virginia April 20, the press release stated. He had been apprehended there April 15 as a fugitive on an arrest warrant, according to authorities.

Ms. Radin and Mr. Rabadi were married last September and worked as surgical PAs together at St. Peter’s Hospital in Albany, and “sincerely loved working with one another,” according to Mr. Rabadi’s obituary. They missed each other if they weren’t working together, the obituary stated. 

“I know an endless amount of love and strength is being sent my way,” Ms. Radin said in a Facebook post. “These words do not come close to completely encompassing Phil, but they are mine and I’d like to share them.” The obituary she created, reposted on Facebook, was accompanied by photos of the happy couple at their recent wedding.

“Philip was a shining bright light in this world. He was kind, endlessly charismatic, funny, intelligent, patient, and an immediate friend to all. His smile was breathtaking, and his laugh was infectious. Philip was simply a magnetic person. To have known him was a genuine gift in this lifetime.”

The Albany County Sheriff’s Office received a call to check the welfare of Mr. Rabadi after he failed to show up for work last week, according to the press release. Deputies and family members found Mr. Rabadi dead, the release stated.

Ms. Radin reportedly called 911 and arrived at the home with her father-in-law about the same time as the deputies, according to People magazine.

A St. Peter’s Health Partners spokesperson, in an email to this news organization, shared the health system’s reaction to the incident: “The news of Philip Rabadi’s passing leaves us with a deep sadness and heavy hearts...In a memo to colleagues, our senior leaders offered their condolences to Philip’s family and loved ones, mourning the tragic passing of our colleague and friend.”

The response continued, “As a healthcare organization, it is our mission to care for those in need. Right now, many of our own are struggling. Grief counseling services are being made available to colleagues should they need additional support.”

A scholarship was established for PA students in Mr. Rabadi’s name at his alma mater, Albany Medical College.

Meanwhile a search of Mr. Klein’s professional history shows he held a PA license in Syracuse, N.Y., until 2018 and his current license in Virginia was renewed in February.  

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

A Virginia physician assistant entered a plea of not guilty on April 21 to a murder charge in connection with a gruesome slaying of another PA in upstate New York.

Jacob L. Klein, 40, of Wirtz, Va., was charged with second-degree murder at the Town of New Scotland Court in New York following the discovery the previous week of 35-year-old Philip Rabadi, another PA. Mr. Rabadi was discovered on the garage floor of his New Scotland home, the Albany County Sheriff’s Office said in a press release.

Mr. Rabadi’s arms were bound and he suffered multiple stab wounds and body mutilation, authorities reported. Mr. Klein allegedly had been stalking Mr. Rabadi and his wife, Elana Z. Radin, for 3 days prior to the homicide after driving the 600 miles from Virginia to New Scotland. Ms. Radin had once been Mr. Klein’s girlfriend, according to a report in the Times Union in Albany, N.Y.

Mr. Klein was being held without bail in the Albany County Correctional Facility and a preliminary hearing was set for April 25. Mr. Klein had been extradited from Virginia April 20, the press release stated. He had been apprehended there April 15 as a fugitive on an arrest warrant, according to authorities.

Ms. Radin and Mr. Rabadi were married last September and worked as surgical PAs together at St. Peter’s Hospital in Albany, and “sincerely loved working with one another,” according to Mr. Rabadi’s obituary. They missed each other if they weren’t working together, the obituary stated. 

“I know an endless amount of love and strength is being sent my way,” Ms. Radin said in a Facebook post. “These words do not come close to completely encompassing Phil, but they are mine and I’d like to share them.” The obituary she created, reposted on Facebook, was accompanied by photos of the happy couple at their recent wedding.

“Philip was a shining bright light in this world. He was kind, endlessly charismatic, funny, intelligent, patient, and an immediate friend to all. His smile was breathtaking, and his laugh was infectious. Philip was simply a magnetic person. To have known him was a genuine gift in this lifetime.”

The Albany County Sheriff’s Office received a call to check the welfare of Mr. Rabadi after he failed to show up for work last week, according to the press release. Deputies and family members found Mr. Rabadi dead, the release stated.

Ms. Radin reportedly called 911 and arrived at the home with her father-in-law about the same time as the deputies, according to People magazine.

A St. Peter’s Health Partners spokesperson, in an email to this news organization, shared the health system’s reaction to the incident: “The news of Philip Rabadi’s passing leaves us with a deep sadness and heavy hearts...In a memo to colleagues, our senior leaders offered their condolences to Philip’s family and loved ones, mourning the tragic passing of our colleague and friend.”

The response continued, “As a healthcare organization, it is our mission to care for those in need. Right now, many of our own are struggling. Grief counseling services are being made available to colleagues should they need additional support.”

A scholarship was established for PA students in Mr. Rabadi’s name at his alma mater, Albany Medical College.

Meanwhile a search of Mr. Klein’s professional history shows he held a PA license in Syracuse, N.Y., until 2018 and his current license in Virginia was renewed in February.  

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

A Virginia physician assistant entered a plea of not guilty on April 21 to a murder charge in connection with a gruesome slaying of another PA in upstate New York.

Jacob L. Klein, 40, of Wirtz, Va., was charged with second-degree murder at the Town of New Scotland Court in New York following the discovery the previous week of 35-year-old Philip Rabadi, another PA. Mr. Rabadi was discovered on the garage floor of his New Scotland home, the Albany County Sheriff’s Office said in a press release.

Mr. Rabadi’s arms were bound and he suffered multiple stab wounds and body mutilation, authorities reported. Mr. Klein allegedly had been stalking Mr. Rabadi and his wife, Elana Z. Radin, for 3 days prior to the homicide after driving the 600 miles from Virginia to New Scotland. Ms. Radin had once been Mr. Klein’s girlfriend, according to a report in the Times Union in Albany, N.Y.

Mr. Klein was being held without bail in the Albany County Correctional Facility and a preliminary hearing was set for April 25. Mr. Klein had been extradited from Virginia April 20, the press release stated. He had been apprehended there April 15 as a fugitive on an arrest warrant, according to authorities.

Ms. Radin and Mr. Rabadi were married last September and worked as surgical PAs together at St. Peter’s Hospital in Albany, and “sincerely loved working with one another,” according to Mr. Rabadi’s obituary. They missed each other if they weren’t working together, the obituary stated. 

“I know an endless amount of love and strength is being sent my way,” Ms. Radin said in a Facebook post. “These words do not come close to completely encompassing Phil, but they are mine and I’d like to share them.” The obituary she created, reposted on Facebook, was accompanied by photos of the happy couple at their recent wedding.

“Philip was a shining bright light in this world. He was kind, endlessly charismatic, funny, intelligent, patient, and an immediate friend to all. His smile was breathtaking, and his laugh was infectious. Philip was simply a magnetic person. To have known him was a genuine gift in this lifetime.”

The Albany County Sheriff’s Office received a call to check the welfare of Mr. Rabadi after he failed to show up for work last week, according to the press release. Deputies and family members found Mr. Rabadi dead, the release stated.

Ms. Radin reportedly called 911 and arrived at the home with her father-in-law about the same time as the deputies, according to People magazine.

A St. Peter’s Health Partners spokesperson, in an email to this news organization, shared the health system’s reaction to the incident: “The news of Philip Rabadi’s passing leaves us with a deep sadness and heavy hearts...In a memo to colleagues, our senior leaders offered their condolences to Philip’s family and loved ones, mourning the tragic passing of our colleague and friend.”

The response continued, “As a healthcare organization, it is our mission to care for those in need. Right now, many of our own are struggling. Grief counseling services are being made available to colleagues should they need additional support.”

A scholarship was established for PA students in Mr. Rabadi’s name at his alma mater, Albany Medical College.

Meanwhile a search of Mr. Klein’s professional history shows he held a PA license in Syracuse, N.Y., until 2018 and his current license in Virginia was renewed in February.  

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

Did you hear the one about the TV host suggesting men get their testicles tanned?

The nutty idea dropped into the lexicon last weekend thanks to Fox News commentator Tucker Carlson.

He aired a promo for a show about an alleged decline of manhood. It featured shirtless, muscled men doing macho things like shooting automatic rifles and wrestling, and a naked man rather triumphantly exposing his crotch to a red-light device made to look like some sort of charging station.

Mr. Carlson then interviewed a “fitness professional,” and both enthused about the idea of exposing male genitalia to red light to raise testosterone levels.

The guest also said he’s heard of something he called “bromeopathy” for people who are suspicious of “mainstream” information. Yes, it’s a combination of the slang term “bro” and the practice of homeopathic medicine.

So, men of America, do you really need to start zapping your privates like Mr. Carlson seems to suggest?

Doctors say the answer is simple: Absolutely not.
 

‘No legitimate evidence’

“There is no legitimate evidence that this type of treatment is effective in improving testosterone levels,” says Petar Bajic MD, a urologist at the Cleveland Clinic who specializes in men’s health and testosterone.

The red light wouldn’t even be able to penetrate the body deep enough to reach the, uhm, targets, he said, citing “no scientific basis” for Mr. Tucker’s claims that we should be “open minded” about this kind of thing.

“It’s not only a waste of time but also a waste of money,” Dr. Bajic says. “There is a large amount of research and high-quality studies” into treating low testosterone, which is produced primarily in the testicles. “We have very effective and proven treatments available, and this is simply not one of them.”

Testosterone is an important hormone that contributes to masculine physical characteristics, “such as muscle mass and strength, and growth of facial and body hair,” according to the Mayo Clinic. It’s important for bone density, sperm production, erectile function, and more.

As men age, testosterone levels often drop, lowering energy and sexual function while causing weight gain and muscle loss.

If men experience some of these symptoms or become curious about their testosterone levels, they shouldn’t self-diagnose or rely on two guys promoting a TV show, Dr. Bajic says.

Instead, they should see their primary care doctor for a simple blood test, he says. Patient and doctor can decide on treatments, which commonly include:

• Topical gels
• Arm patches
• Injections into the muscle of the leg or the fatty tissue of the belly
• Pellets placed under the skin

Diet, exercise, sleep, and other factors play a role.
 

‘So much misinformation’

The men’s health consumer market is bloated with products promising to raise testosterone levels and help men boost their bedroom performance, among other claims.

But they’re usually based on nothing more than marketing, and erectile disfunction is more commonly caused by reduced blood flow than a lack of testosterone, Dr. Bajic says.

“It all comes down to looking at all of these as a consumer and as a patient ... with a critical eye. There’s always a new ‘cure all’ for whatever your ailment is,” he says.

Testosterone levels change throughout the day. It’s thought to be produced during REM sleep, which can be diminished by alcohol use and other factors.

“All these things are related,” Dr. Bajic said, so there’s no reason to flash a light where it’s usually not seen – especially since neither the safety nor efficacy of testicle tanning has been established.

Oregon urologist Ashley Winter, MD, got into the Twitter fray about Carlson’s comments.

“Also, by definition you CANNOT have data on testicle tanning because you cannot TAN an internal organ,” she said on the social media network. “Tanning your scrotal sack and calling it ‘testicle tanning,’ is like tanning your abdominal skin and calling it ‘liver tanning.’”
 

What advocates say

What do proponents of red light therapy say? A Men’s Health article claims red light “works to stimulate ATP production, increase energy available to the cell and in particular, increase the activity of the Leydig cells in your testes, which are the cells responsible for testosterone production.”

The article also helpfully points out: “It’s important to note that there are currently no light therapy devices on the market cleared by FDA for the enhanced production of testosterone LED-based therapy.” And many lamps sold for red light therapy can get so hot that they damage the skin.

The author ordered a Joovv device, which Mr. Carlson’s “fitness professional” guest name-dropped. They range from $600 to almost $10,000. He liked the way it felt and said it seemed to improve his sexual performance.
 

Still a hard sell

Atlanta dermatologist Emily de Golian, MD, says tanning genitalia can be dangerous to the skin.

“There is no such thing as a safe tan, all tanning is indicative of sun damage in the skin and is the body’s effort to shield the DNA from further damage, and tanning increases the risk of skin cancer,” she says. “Scrotal skin is particularly delicate and sensitive to sun exposure, and the risk of sunburn, which further increases the risk of skin cancer, is high.”

Mat Rezaei, founder and CEO of UPGUYS, which provides erectile disfunction medicine, says, “UV light has no negative or positive response to balancing testosterone deficiency.”

Even frequent Fox guest Kid Rock wasn’t buying into the idea.

“Dude, stop! Testicle tanning? Come on,” Mr. Rock said to Mr. Carlson. “I mean, I haven’t heard anything that good in a long time.”

“Open your mind,” said Mr. Carlson as he laughed along with the musician.

Kid Rock replied, “I’m starting a punk rock band and it’s called Testicle Tanning. That’s the end of it.”

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

Did you hear the one about the TV host suggesting men get their testicles tanned?

The nutty idea dropped into the lexicon last weekend thanks to Fox News commentator Tucker Carlson.

He aired a promo for a show about an alleged decline of manhood. It featured shirtless, muscled men doing macho things like shooting automatic rifles and wrestling, and a naked man rather triumphantly exposing his crotch to a red-light device made to look like some sort of charging station.

Mr. Carlson then interviewed a “fitness professional,” and both enthused about the idea of exposing male genitalia to red light to raise testosterone levels.

The guest also said he’s heard of something he called “bromeopathy” for people who are suspicious of “mainstream” information. Yes, it’s a combination of the slang term “bro” and the practice of homeopathic medicine.

So, men of America, do you really need to start zapping your privates like Mr. Carlson seems to suggest?

Doctors say the answer is simple: Absolutely not.
 

‘No legitimate evidence’

“There is no legitimate evidence that this type of treatment is effective in improving testosterone levels,” says Petar Bajic MD, a urologist at the Cleveland Clinic who specializes in men’s health and testosterone.

The red light wouldn’t even be able to penetrate the body deep enough to reach the, uhm, targets, he said, citing “no scientific basis” for Mr. Tucker’s claims that we should be “open minded” about this kind of thing.

“It’s not only a waste of time but also a waste of money,” Dr. Bajic says. “There is a large amount of research and high-quality studies” into treating low testosterone, which is produced primarily in the testicles. “We have very effective and proven treatments available, and this is simply not one of them.”

Testosterone is an important hormone that contributes to masculine physical characteristics, “such as muscle mass and strength, and growth of facial and body hair,” according to the Mayo Clinic. It’s important for bone density, sperm production, erectile function, and more.

As men age, testosterone levels often drop, lowering energy and sexual function while causing weight gain and muscle loss.

If men experience some of these symptoms or become curious about their testosterone levels, they shouldn’t self-diagnose or rely on two guys promoting a TV show, Dr. Bajic says.

Instead, they should see their primary care doctor for a simple blood test, he says. Patient and doctor can decide on treatments, which commonly include:

• Topical gels
• Arm patches
• Injections into the muscle of the leg or the fatty tissue of the belly
• Pellets placed under the skin

Diet, exercise, sleep, and other factors play a role.
 

‘So much misinformation’

The men’s health consumer market is bloated with products promising to raise testosterone levels and help men boost their bedroom performance, among other claims.

But they’re usually based on nothing more than marketing, and erectile disfunction is more commonly caused by reduced blood flow than a lack of testosterone, Dr. Bajic says.

“It all comes down to looking at all of these as a consumer and as a patient ... with a critical eye. There’s always a new ‘cure all’ for whatever your ailment is,” he says.

Testosterone levels change throughout the day. It’s thought to be produced during REM sleep, which can be diminished by alcohol use and other factors.

“All these things are related,” Dr. Bajic said, so there’s no reason to flash a light where it’s usually not seen – especially since neither the safety nor efficacy of testicle tanning has been established.

Oregon urologist Ashley Winter, MD, got into the Twitter fray about Carlson’s comments.

“Also, by definition you CANNOT have data on testicle tanning because you cannot TAN an internal organ,” she said on the social media network. “Tanning your scrotal sack and calling it ‘testicle tanning,’ is like tanning your abdominal skin and calling it ‘liver tanning.’”
 

What advocates say

What do proponents of red light therapy say? A Men’s Health article claims red light “works to stimulate ATP production, increase energy available to the cell and in particular, increase the activity of the Leydig cells in your testes, which are the cells responsible for testosterone production.”

The article also helpfully points out: “It’s important to note that there are currently no light therapy devices on the market cleared by FDA for the enhanced production of testosterone LED-based therapy.” And many lamps sold for red light therapy can get so hot that they damage the skin.

The author ordered a Joovv device, which Mr. Carlson’s “fitness professional” guest name-dropped. They range from $600 to almost $10,000. He liked the way it felt and said it seemed to improve his sexual performance.
 

Still a hard sell

Atlanta dermatologist Emily de Golian, MD, says tanning genitalia can be dangerous to the skin.

“There is no such thing as a safe tan, all tanning is indicative of sun damage in the skin and is the body’s effort to shield the DNA from further damage, and tanning increases the risk of skin cancer,” she says. “Scrotal skin is particularly delicate and sensitive to sun exposure, and the risk of sunburn, which further increases the risk of skin cancer, is high.”

Mat Rezaei, founder and CEO of UPGUYS, which provides erectile disfunction medicine, says, “UV light has no negative or positive response to balancing testosterone deficiency.”

Even frequent Fox guest Kid Rock wasn’t buying into the idea.

“Dude, stop! Testicle tanning? Come on,” Mr. Rock said to Mr. Carlson. “I mean, I haven’t heard anything that good in a long time.”

“Open your mind,” said Mr. Carlson as he laughed along with the musician.

Kid Rock replied, “I’m starting a punk rock band and it’s called Testicle Tanning. That’s the end of it.”

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

Did you hear the one about the TV host suggesting men get their testicles tanned?

The nutty idea dropped into the lexicon last weekend thanks to Fox News commentator Tucker Carlson.

He aired a promo for a show about an alleged decline of manhood. It featured shirtless, muscled men doing macho things like shooting automatic rifles and wrestling, and a naked man rather triumphantly exposing his crotch to a red-light device made to look like some sort of charging station.

Mr. Carlson then interviewed a “fitness professional,” and both enthused about the idea of exposing male genitalia to red light to raise testosterone levels.

The guest also said he’s heard of something he called “bromeopathy” for people who are suspicious of “mainstream” information. Yes, it’s a combination of the slang term “bro” and the practice of homeopathic medicine.

So, men of America, do you really need to start zapping your privates like Mr. Carlson seems to suggest?

Doctors say the answer is simple: Absolutely not.
 

‘No legitimate evidence’

“There is no legitimate evidence that this type of treatment is effective in improving testosterone levels,” says Petar Bajic MD, a urologist at the Cleveland Clinic who specializes in men’s health and testosterone.

The red light wouldn’t even be able to penetrate the body deep enough to reach the, uhm, targets, he said, citing “no scientific basis” for Mr. Tucker’s claims that we should be “open minded” about this kind of thing.

“It’s not only a waste of time but also a waste of money,” Dr. Bajic says. “There is a large amount of research and high-quality studies” into treating low testosterone, which is produced primarily in the testicles. “We have very effective and proven treatments available, and this is simply not one of them.”

Testosterone is an important hormone that contributes to masculine physical characteristics, “such as muscle mass and strength, and growth of facial and body hair,” according to the Mayo Clinic. It’s important for bone density, sperm production, erectile function, and more.

As men age, testosterone levels often drop, lowering energy and sexual function while causing weight gain and muscle loss.

If men experience some of these symptoms or become curious about their testosterone levels, they shouldn’t self-diagnose or rely on two guys promoting a TV show, Dr. Bajic says.

Instead, they should see their primary care doctor for a simple blood test, he says. Patient and doctor can decide on treatments, which commonly include:

• Topical gels
• Arm patches
• Injections into the muscle of the leg or the fatty tissue of the belly
• Pellets placed under the skin

Diet, exercise, sleep, and other factors play a role.
 

‘So much misinformation’

The men’s health consumer market is bloated with products promising to raise testosterone levels and help men boost their bedroom performance, among other claims.

But they’re usually based on nothing more than marketing, and erectile disfunction is more commonly caused by reduced blood flow than a lack of testosterone, Dr. Bajic says.

“It all comes down to looking at all of these as a consumer and as a patient ... with a critical eye. There’s always a new ‘cure all’ for whatever your ailment is,” he says.

Testosterone levels change throughout the day. It’s thought to be produced during REM sleep, which can be diminished by alcohol use and other factors.

“All these things are related,” Dr. Bajic said, so there’s no reason to flash a light where it’s usually not seen – especially since neither the safety nor efficacy of testicle tanning has been established.

Oregon urologist Ashley Winter, MD, got into the Twitter fray about Carlson’s comments.

“Also, by definition you CANNOT have data on testicle tanning because you cannot TAN an internal organ,” she said on the social media network. “Tanning your scrotal sack and calling it ‘testicle tanning,’ is like tanning your abdominal skin and calling it ‘liver tanning.’”
 

What advocates say

What do proponents of red light therapy say? A Men’s Health article claims red light “works to stimulate ATP production, increase energy available to the cell and in particular, increase the activity of the Leydig cells in your testes, which are the cells responsible for testosterone production.”

The article also helpfully points out: “It’s important to note that there are currently no light therapy devices on the market cleared by FDA for the enhanced production of testosterone LED-based therapy.” And many lamps sold for red light therapy can get so hot that they damage the skin.

The author ordered a Joovv device, which Mr. Carlson’s “fitness professional” guest name-dropped. They range from $600 to almost $10,000. He liked the way it felt and said it seemed to improve his sexual performance.
 

Still a hard sell

Atlanta dermatologist Emily de Golian, MD, says tanning genitalia can be dangerous to the skin.

“There is no such thing as a safe tan, all tanning is indicative of sun damage in the skin and is the body’s effort to shield the DNA from further damage, and tanning increases the risk of skin cancer,” she says. “Scrotal skin is particularly delicate and sensitive to sun exposure, and the risk of sunburn, which further increases the risk of skin cancer, is high.”

Mat Rezaei, founder and CEO of UPGUYS, which provides erectile disfunction medicine, says, “UV light has no negative or positive response to balancing testosterone deficiency.”

Even frequent Fox guest Kid Rock wasn’t buying into the idea.

“Dude, stop! Testicle tanning? Come on,” Mr. Rock said to Mr. Carlson. “I mean, I haven’t heard anything that good in a long time.”

“Open your mind,” said Mr. Carlson as he laughed along with the musician.

Kid Rock replied, “I’m starting a punk rock band and it’s called Testicle Tanning. That’s the end of it.”

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

Most National Cancer Institute–designated cancer centers fail to publicly disclose negotiated prices for cancer therapies, despite federal requirements to do so.

Among those that do provide this information, new research shows that hospitals substantially mark up prices for top-selling cancer therapies relative to acquisition costs. Median drug price markups across NCI centers and payers ranged from nearly 120% to more than 600%.

As a result, “the total price for an entire treatment course could vary on the order of hundreds of thousands of dollars,” Roy Xiao, MD, department of otolaryngology–head and neck surgery, Massachusetts Eye and Ear Infirmary, Boston, said in an interview.

The study was published online in JAMA Internal Medicine.

Manufacturers often price novel anticancer therapies at more than $100,000 per year, but less is known about how much hospitals mark up these prices for patients with private health insurance and how much negotiated prices vary across centers and payers.

Dr. Xiao and colleagues analyzed private payer-specific negotiated prices for the top 25 parenteral cancer therapies by Medicare Part B spending in 2019 using publicly available hospital price transparency files for 61 NCI-designated cancer centers.

Fewer than half of the centers (44.3%) disclosed payer-specific negotiated prices for at least one top-selling cancer drug. Disclosure rates for different drugs ranged from 21.3% (13 centers) for rituximab with hyaluronidase to 42.6% (26 centers) for rituximab, bevacizumab, or leuprolide.

The researchers also found a wide variation in negotiated prices for cancer therapies across hospitals. Across-center price ratios – defined as the ratio between the 90th and 10th percentile median price per unit – ranged from 2.2 ($16 vs. $36 for pembrolizumab 1 mg) and 15.8 ($247 vs. $3,914 for leuprolide 7.5 mg).

Payer-specific prices also varied considerably between payers at the same center. Among all centers, the median within-center price ratios for cancer therapies ranged from 1.8 (brentuximab) to 2.5 (bevacizumab).

As for the extent of cancer therapy markups, median price markups across centers and payers ranged from 118% (sipuleucel-T) to 634% (leuprolide) more than the estimated cost paid by hospitals.

Conservative estimates of acquisition costs and payer-specific prices yielded markups ranging from 42.1% (sipuleucel-T) to 234.1% (leuprolide).

The authors also provided examples of how these variations might affect the total cost of treatment. For instance, the median total price variation across centers to treat metastatic non–small cell lung cancer with pembrolizumab was $168,405. At one institution, the within-center median price variation for daratumumab as third-line therapy for multiple myeloma was $174,225.

To reduce the financial burden of cancer treatment for patients, the authors suggested implementing public policies “to discourage or prevent excessive hospital price markups on parenteral chemotherapeutics.”

To promote hospital compliance with transparency regulations, in January 2022, the Centers for Medicare & Medicare Services increased penalties for nondisclosure from a fixed maximum of $300 per day to up to $5,500 per day, based on hospital bed size, which would total over $2 million per year, Dr. Xiao said in an interview.

“We would expect that this significant financial penalty would encourage more consistent reporting,” he said.

The study had no specific funding. Dr. Xiao has disclosed no relevant disclosures.
 

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

Most National Cancer Institute–designated cancer centers fail to publicly disclose negotiated prices for cancer therapies, despite federal requirements to do so.

Among those that do provide this information, new research shows that hospitals substantially mark up prices for top-selling cancer therapies relative to acquisition costs. Median drug price markups across NCI centers and payers ranged from nearly 120% to more than 600%.

As a result, “the total price for an entire treatment course could vary on the order of hundreds of thousands of dollars,” Roy Xiao, MD, department of otolaryngology–head and neck surgery, Massachusetts Eye and Ear Infirmary, Boston, said in an interview.

The study was published online in JAMA Internal Medicine.

Manufacturers often price novel anticancer therapies at more than $100,000 per year, but less is known about how much hospitals mark up these prices for patients with private health insurance and how much negotiated prices vary across centers and payers.

Dr. Xiao and colleagues analyzed private payer-specific negotiated prices for the top 25 parenteral cancer therapies by Medicare Part B spending in 2019 using publicly available hospital price transparency files for 61 NCI-designated cancer centers.

Fewer than half of the centers (44.3%) disclosed payer-specific negotiated prices for at least one top-selling cancer drug. Disclosure rates for different drugs ranged from 21.3% (13 centers) for rituximab with hyaluronidase to 42.6% (26 centers) for rituximab, bevacizumab, or leuprolide.

The researchers also found a wide variation in negotiated prices for cancer therapies across hospitals. Across-center price ratios – defined as the ratio between the 90th and 10th percentile median price per unit – ranged from 2.2 ($16 vs. $36 for pembrolizumab 1 mg) and 15.8 ($247 vs. $3,914 for leuprolide 7.5 mg).

Payer-specific prices also varied considerably between payers at the same center. Among all centers, the median within-center price ratios for cancer therapies ranged from 1.8 (brentuximab) to 2.5 (bevacizumab).

As for the extent of cancer therapy markups, median price markups across centers and payers ranged from 118% (sipuleucel-T) to 634% (leuprolide) more than the estimated cost paid by hospitals.

Conservative estimates of acquisition costs and payer-specific prices yielded markups ranging from 42.1% (sipuleucel-T) to 234.1% (leuprolide).

The authors also provided examples of how these variations might affect the total cost of treatment. For instance, the median total price variation across centers to treat metastatic non–small cell lung cancer with pembrolizumab was $168,405. At one institution, the within-center median price variation for daratumumab as third-line therapy for multiple myeloma was $174,225.

To reduce the financial burden of cancer treatment for patients, the authors suggested implementing public policies “to discourage or prevent excessive hospital price markups on parenteral chemotherapeutics.”

To promote hospital compliance with transparency regulations, in January 2022, the Centers for Medicare & Medicare Services increased penalties for nondisclosure from a fixed maximum of $300 per day to up to $5,500 per day, based on hospital bed size, which would total over $2 million per year, Dr. Xiao said in an interview.

“We would expect that this significant financial penalty would encourage more consistent reporting,” he said.

The study had no specific funding. Dr. Xiao has disclosed no relevant disclosures.
 

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

Most National Cancer Institute–designated cancer centers fail to publicly disclose negotiated prices for cancer therapies, despite federal requirements to do so.

Among those that do provide this information, new research shows that hospitals substantially mark up prices for top-selling cancer therapies relative to acquisition costs. Median drug price markups across NCI centers and payers ranged from nearly 120% to more than 600%.

As a result, “the total price for an entire treatment course could vary on the order of hundreds of thousands of dollars,” Roy Xiao, MD, department of otolaryngology–head and neck surgery, Massachusetts Eye and Ear Infirmary, Boston, said in an interview.

The study was published online in JAMA Internal Medicine.

Manufacturers often price novel anticancer therapies at more than $100,000 per year, but less is known about how much hospitals mark up these prices for patients with private health insurance and how much negotiated prices vary across centers and payers.

Dr. Xiao and colleagues analyzed private payer-specific negotiated prices for the top 25 parenteral cancer therapies by Medicare Part B spending in 2019 using publicly available hospital price transparency files for 61 NCI-designated cancer centers.

Fewer than half of the centers (44.3%) disclosed payer-specific negotiated prices for at least one top-selling cancer drug. Disclosure rates for different drugs ranged from 21.3% (13 centers) for rituximab with hyaluronidase to 42.6% (26 centers) for rituximab, bevacizumab, or leuprolide.

The researchers also found a wide variation in negotiated prices for cancer therapies across hospitals. Across-center price ratios – defined as the ratio between the 90th and 10th percentile median price per unit – ranged from 2.2 ($16 vs. $36 for pembrolizumab 1 mg) and 15.8 ($247 vs. $3,914 for leuprolide 7.5 mg).

Payer-specific prices also varied considerably between payers at the same center. Among all centers, the median within-center price ratios for cancer therapies ranged from 1.8 (brentuximab) to 2.5 (bevacizumab).

As for the extent of cancer therapy markups, median price markups across centers and payers ranged from 118% (sipuleucel-T) to 634% (leuprolide) more than the estimated cost paid by hospitals.

Conservative estimates of acquisition costs and payer-specific prices yielded markups ranging from 42.1% (sipuleucel-T) to 234.1% (leuprolide).

The authors also provided examples of how these variations might affect the total cost of treatment. For instance, the median total price variation across centers to treat metastatic non–small cell lung cancer with pembrolizumab was $168,405. At one institution, the within-center median price variation for daratumumab as third-line therapy for multiple myeloma was $174,225.

To reduce the financial burden of cancer treatment for patients, the authors suggested implementing public policies “to discourage or prevent excessive hospital price markups on parenteral chemotherapeutics.”

To promote hospital compliance with transparency regulations, in January 2022, the Centers for Medicare & Medicare Services increased penalties for nondisclosure from a fixed maximum of $300 per day to up to $5,500 per day, based on hospital bed size, which would total over $2 million per year, Dr. Xiao said in an interview.

“We would expect that this significant financial penalty would encourage more consistent reporting,” he said.

The study had no specific funding. Dr. Xiao has disclosed no relevant disclosures.
 

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

NEW ORLEANS – For patients with resectable non–small cell lung cancer (NSCLC), further clinical data continue to show benefit from preoperative treatment with the immune checkpoint inhibitor nivolumab (Opdivo) with chemotherapy.

The combination resulted in significantly longer event-free survival and a 14-fold greater chance of having a pathological complete response compared with chemotherapy alone.

Adding immunotherapy (IO) to chemotherapy in the neoadjuvant setting represents “a quantum leap in lung cancer therapy,” commented David P. Carbone, MD, PhD, director of the James Thoracic Center at Ohio State University, Columbus.

“Combining IO with surgery I think is a new standard of care and will almost certainly improve overall survival [OS] in early-stage disease, for the first time in decades, in my entire career,” he said while discussing the new data at the annual meeting of the American Association for Cancer Research.

The data come from the phase 3 CheckMate 816 study, an open-label trial involving patients with stage IB-IIIA resectable NSCLC. The study was published in the New England Journal of Medicine to coincide with the presentation.

Results from this trial were the basis of the Food and Drug Administration’s recent approval of neoadjuvant therapy with nivolumab (Opdivo) and platinum-based chemotherapy in this population, which one expert described as “a turning point in how we treat resectable NSCLC.”

“Neoadjuvant IO has multiple theoretical advantages of over adjuvant IO,” commented Dr. Carbone. “CheckMate 816 suggests that practice will prove this theory correct.”

Importance of Neoadjuvant Immunotherapy

New details of the results were presented at the meeting by Nicolas Girard, MD, from Institut Curie in Paris.

Among 358 patients in the trial, the median event-free survival (EFS) was 31.6 months for patients randomly assigned to the combination of the immune checkpoint inhibitor nivolumab and platinum-base chemotherapy, compared with 20.8 months for patients assigned to chemotherapy alone. This translated into a hazard ratio for disease recurrence, progression, or death of 0.63 (P = .005).

In addition, 24% of patients assigned to the nivolumab plus chemotherapy arm had a pathological complete response (pCR) to neoadjuvant therapy, compared with only 2.2% of those assigned to chemotherapy alone (P < .001).

Dr. Girard said the study provided important clues to the importance of neoadjuvant therapy for improving objective responses.

“Event-free survival was improved in patients with a pathological complete response, compared with those without, suggesting pCR is a surrogate endpoint for long-term outcomes in resectable non–small cell lung cancer, and this is the first time [this has been shown] in a randomized, phase 3 study,” he said.
 

Neoadjuvant slow to catch on

About one -fourth of all patients who are diagnosed with NSCLC have resectable disease, Dr. Girard and colleagues noted. However, 30%-55% of patients who undergo surgery with curative intent ultimately experience recurrence and die from their disease.

Neoadjuvant therapy may improve chances for complete resection and prevent or delay recurrence after surgery, but the absolute difference in 5-year recurrence-free survival and OS with neoadjuvant chemotherapy alone is only about 6%, they noted.

The new results suggest that adding neoadjuvant immunotherapy to chemotherapy will improve upon this, although so far, the OS data from this trial are immature.

In an interim analysis, the median OS rate was 83% at 2 years for patients treated with nivolumab plus chemotherapy, compared with 71% for patients treated with chemotherapy alone. The published results show a significant improvement in the two primary endpoints – EFS and pCR.

In an editorial accompanying the study, Christine M. Lovly, MD, PhD, from the Vanderbilt-Ingram Cancer Center at Vanderbilt University in Nashville, Tenn., commented that the results of the trial are expected to change practice.

“However, several issues remain to be addressed,” she wrote. “First, is a pathological complete response predictive of event-free survival? Can event-free survival be used as a surrogate endpoint for overall survival? Second, although not mandated for this trial, approximately 20% of the patients received postoperative therapy. Is adjuvant therapy necessary? What criteria should be used to select patients to receive adjuvant therapy?”

Dr. Lovly also pointed out that patients with tumors harboring mutations in the genes EGFR or ALK were excluded from the trial.

“Therefore, implementation of neoadjuvant therapies requires biomarker testing for patients with early-stage disease at the time of diagnosis, a considerable alteration in the routine practice of lung-cancer medicine,” she wrote.
 

Fears of delaying surgery

In an interview, Upal Basu Roy, PhD, MPH, executive director of research at the LUNGevity Foundation, who was not involved in the study, gave a reason why neoadjuvant therapy is not more widely prescribed for patients with resectable NSCLC.

“Clinicians are always scared, and I think patients are as well, that giving a treatment before surgery would delay surgery,” he said. “When patients are diagnosed with lung cancer and they’re told that surgery offers the potential of cure and then hear that you’re giving them a treatment before surgery and that treatment may potentially delay surgery, that is a huge source of anxiety.”

In addition, clinicians until recently were unsure about which patients were most likely to benefit from neoadjuvant therapy when the only option was chemotherapy, “but that’s changing, obviously, with the recent approval of neoadjuvant nivolumab through CheckMate 816,” he said.
 

CheckMate 816 details

In the CheckMate 816 study, investigators enrolled patients with newly diagnosed resectable NSCLC (stage IB-IIIA) who had good performance status and no known sensitizing EGFR mutations or ALK alterations.

After stratification by stage, programmed death–1 status, and sex, the team randomly assigned patients to receive either nivolumab 360 mg plus platinum-based chemotherapy every 3 weeks for a total of three cycles or chemotherapy alone.

At the end of neoadjuvant therapy, patients underwent radiologic restaging and surgery within 6 weeks. Patients could also receive optional adjuvant chemotherapy with or without radiotherapy.

Of the 179 patients in each arm, 176 received the assigned treatment. In all, 149 (83%) of those assigned to the combination had definitive surgery, as did 135 (75%) of those assigned to chemotherapy alone.

In addition, 35 patients (20%) of those assigned to nivolumab-chemo and 56 (32%) assigned to chemotherapy alone received adjuvant therapy.

The coprimary endpoints of EFS and pCR favored the combination, both in the overall population and across most subgroups, including patients younger than 65, men and women, Asian patients, those with stage IIIA disease, nonsquamous histology, current smokers and never-smokers, and patients with higher levels of PD–ligand 1 expression.

The rates of grade 3 or 4 treatment-related adverse events were similar between the groups, at 33.5% with the combination and 36.9% with chemotherapy alone.

Rates of adverse events leading to study discontinuation, treatment-related adverse events, and surgery-related adverse events were similar between the groups. There were two treatment-related deaths, both in the chemotherapy-alone arm.

CheckMate 816 was funded by Bristol-Myers Squibb (manufacturer of nivolumab). Girard has consulted for and has received grant support from Bristol-Myers Squibb and other companies. Dr. Carbone has consulted for Bristol-Myers Squibb and other companies. Dr. Lovly has consulted for various companies. Dr. Roy has received grants from Bristol-Myers Squibb to the LUNGevity Foundation.

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

NEW ORLEANS – For patients with resectable non–small cell lung cancer (NSCLC), further clinical data continue to show benefit from preoperative treatment with the immune checkpoint inhibitor nivolumab (Opdivo) with chemotherapy.

The combination resulted in significantly longer event-free survival and a 14-fold greater chance of having a pathological complete response compared with chemotherapy alone.

Adding immunotherapy (IO) to chemotherapy in the neoadjuvant setting represents “a quantum leap in lung cancer therapy,” commented David P. Carbone, MD, PhD, director of the James Thoracic Center at Ohio State University, Columbus.

“Combining IO with surgery I think is a new standard of care and will almost certainly improve overall survival [OS] in early-stage disease, for the first time in decades, in my entire career,” he said while discussing the new data at the annual meeting of the American Association for Cancer Research.

The data come from the phase 3 CheckMate 816 study, an open-label trial involving patients with stage IB-IIIA resectable NSCLC. The study was published in the New England Journal of Medicine to coincide with the presentation.

Results from this trial were the basis of the Food and Drug Administration’s recent approval of neoadjuvant therapy with nivolumab (Opdivo) and platinum-based chemotherapy in this population, which one expert described as “a turning point in how we treat resectable NSCLC.”

“Neoadjuvant IO has multiple theoretical advantages of over adjuvant IO,” commented Dr. Carbone. “CheckMate 816 suggests that practice will prove this theory correct.”

Importance of Neoadjuvant Immunotherapy

New details of the results were presented at the meeting by Nicolas Girard, MD, from Institut Curie in Paris.

Among 358 patients in the trial, the median event-free survival (EFS) was 31.6 months for patients randomly assigned to the combination of the immune checkpoint inhibitor nivolumab and platinum-base chemotherapy, compared with 20.8 months for patients assigned to chemotherapy alone. This translated into a hazard ratio for disease recurrence, progression, or death of 0.63 (P = .005).

In addition, 24% of patients assigned to the nivolumab plus chemotherapy arm had a pathological complete response (pCR) to neoadjuvant therapy, compared with only 2.2% of those assigned to chemotherapy alone (P < .001).

Dr. Girard said the study provided important clues to the importance of neoadjuvant therapy for improving objective responses.

“Event-free survival was improved in patients with a pathological complete response, compared with those without, suggesting pCR is a surrogate endpoint for long-term outcomes in resectable non–small cell lung cancer, and this is the first time [this has been shown] in a randomized, phase 3 study,” he said.
 

Neoadjuvant slow to catch on

About one -fourth of all patients who are diagnosed with NSCLC have resectable disease, Dr. Girard and colleagues noted. However, 30%-55% of patients who undergo surgery with curative intent ultimately experience recurrence and die from their disease.

Neoadjuvant therapy may improve chances for complete resection and prevent or delay recurrence after surgery, but the absolute difference in 5-year recurrence-free survival and OS with neoadjuvant chemotherapy alone is only about 6%, they noted.

The new results suggest that adding neoadjuvant immunotherapy to chemotherapy will improve upon this, although so far, the OS data from this trial are immature.

In an interim analysis, the median OS rate was 83% at 2 years for patients treated with nivolumab plus chemotherapy, compared with 71% for patients treated with chemotherapy alone. The published results show a significant improvement in the two primary endpoints – EFS and pCR.

In an editorial accompanying the study, Christine M. Lovly, MD, PhD, from the Vanderbilt-Ingram Cancer Center at Vanderbilt University in Nashville, Tenn., commented that the results of the trial are expected to change practice.

“However, several issues remain to be addressed,” she wrote. “First, is a pathological complete response predictive of event-free survival? Can event-free survival be used as a surrogate endpoint for overall survival? Second, although not mandated for this trial, approximately 20% of the patients received postoperative therapy. Is adjuvant therapy necessary? What criteria should be used to select patients to receive adjuvant therapy?”

Dr. Lovly also pointed out that patients with tumors harboring mutations in the genes EGFR or ALK were excluded from the trial.

“Therefore, implementation of neoadjuvant therapies requires biomarker testing for patients with early-stage disease at the time of diagnosis, a considerable alteration in the routine practice of lung-cancer medicine,” she wrote.
 

Fears of delaying surgery

In an interview, Upal Basu Roy, PhD, MPH, executive director of research at the LUNGevity Foundation, who was not involved in the study, gave a reason why neoadjuvant therapy is not more widely prescribed for patients with resectable NSCLC.

“Clinicians are always scared, and I think patients are as well, that giving a treatment before surgery would delay surgery,” he said. “When patients are diagnosed with lung cancer and they’re told that surgery offers the potential of cure and then hear that you’re giving them a treatment before surgery and that treatment may potentially delay surgery, that is a huge source of anxiety.”

In addition, clinicians until recently were unsure about which patients were most likely to benefit from neoadjuvant therapy when the only option was chemotherapy, “but that’s changing, obviously, with the recent approval of neoadjuvant nivolumab through CheckMate 816,” he said.
 

CheckMate 816 details

In the CheckMate 816 study, investigators enrolled patients with newly diagnosed resectable NSCLC (stage IB-IIIA) who had good performance status and no known sensitizing EGFR mutations or ALK alterations.

After stratification by stage, programmed death–1 status, and sex, the team randomly assigned patients to receive either nivolumab 360 mg plus platinum-based chemotherapy every 3 weeks for a total of three cycles or chemotherapy alone.

At the end of neoadjuvant therapy, patients underwent radiologic restaging and surgery within 6 weeks. Patients could also receive optional adjuvant chemotherapy with or without radiotherapy.

Of the 179 patients in each arm, 176 received the assigned treatment. In all, 149 (83%) of those assigned to the combination had definitive surgery, as did 135 (75%) of those assigned to chemotherapy alone.

In addition, 35 patients (20%) of those assigned to nivolumab-chemo and 56 (32%) assigned to chemotherapy alone received adjuvant therapy.

The coprimary endpoints of EFS and pCR favored the combination, both in the overall population and across most subgroups, including patients younger than 65, men and women, Asian patients, those with stage IIIA disease, nonsquamous histology, current smokers and never-smokers, and patients with higher levels of PD–ligand 1 expression.

The rates of grade 3 or 4 treatment-related adverse events were similar between the groups, at 33.5% with the combination and 36.9% with chemotherapy alone.

Rates of adverse events leading to study discontinuation, treatment-related adverse events, and surgery-related adverse events were similar between the groups. There were two treatment-related deaths, both in the chemotherapy-alone arm.

CheckMate 816 was funded by Bristol-Myers Squibb (manufacturer of nivolumab). Girard has consulted for and has received grant support from Bristol-Myers Squibb and other companies. Dr. Carbone has consulted for Bristol-Myers Squibb and other companies. Dr. Lovly has consulted for various companies. Dr. Roy has received grants from Bristol-Myers Squibb to the LUNGevity Foundation.

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

NEW ORLEANS – For patients with resectable non–small cell lung cancer (NSCLC), further clinical data continue to show benefit from preoperative treatment with the immune checkpoint inhibitor nivolumab (Opdivo) with chemotherapy.

The combination resulted in significantly longer event-free survival and a 14-fold greater chance of having a pathological complete response compared with chemotherapy alone.

Adding immunotherapy (IO) to chemotherapy in the neoadjuvant setting represents “a quantum leap in lung cancer therapy,” commented David P. Carbone, MD, PhD, director of the James Thoracic Center at Ohio State University, Columbus.

“Combining IO with surgery I think is a new standard of care and will almost certainly improve overall survival [OS] in early-stage disease, for the first time in decades, in my entire career,” he said while discussing the new data at the annual meeting of the American Association for Cancer Research.

The data come from the phase 3 CheckMate 816 study, an open-label trial involving patients with stage IB-IIIA resectable NSCLC. The study was published in the New England Journal of Medicine to coincide with the presentation.

Results from this trial were the basis of the Food and Drug Administration’s recent approval of neoadjuvant therapy with nivolumab (Opdivo) and platinum-based chemotherapy in this population, which one expert described as “a turning point in how we treat resectable NSCLC.”

“Neoadjuvant IO has multiple theoretical advantages of over adjuvant IO,” commented Dr. Carbone. “CheckMate 816 suggests that practice will prove this theory correct.”

Importance of Neoadjuvant Immunotherapy

New details of the results were presented at the meeting by Nicolas Girard, MD, from Institut Curie in Paris.

Among 358 patients in the trial, the median event-free survival (EFS) was 31.6 months for patients randomly assigned to the combination of the immune checkpoint inhibitor nivolumab and platinum-base chemotherapy, compared with 20.8 months for patients assigned to chemotherapy alone. This translated into a hazard ratio for disease recurrence, progression, or death of 0.63 (P = .005).

In addition, 24% of patients assigned to the nivolumab plus chemotherapy arm had a pathological complete response (pCR) to neoadjuvant therapy, compared with only 2.2% of those assigned to chemotherapy alone (P < .001).

Dr. Girard said the study provided important clues to the importance of neoadjuvant therapy for improving objective responses.

“Event-free survival was improved in patients with a pathological complete response, compared with those without, suggesting pCR is a surrogate endpoint for long-term outcomes in resectable non–small cell lung cancer, and this is the first time [this has been shown] in a randomized, phase 3 study,” he said.
 

Neoadjuvant slow to catch on

About one -fourth of all patients who are diagnosed with NSCLC have resectable disease, Dr. Girard and colleagues noted. However, 30%-55% of patients who undergo surgery with curative intent ultimately experience recurrence and die from their disease.

Neoadjuvant therapy may improve chances for complete resection and prevent or delay recurrence after surgery, but the absolute difference in 5-year recurrence-free survival and OS with neoadjuvant chemotherapy alone is only about 6%, they noted.

The new results suggest that adding neoadjuvant immunotherapy to chemotherapy will improve upon this, although so far, the OS data from this trial are immature.

In an interim analysis, the median OS rate was 83% at 2 years for patients treated with nivolumab plus chemotherapy, compared with 71% for patients treated with chemotherapy alone. The published results show a significant improvement in the two primary endpoints – EFS and pCR.

In an editorial accompanying the study, Christine M. Lovly, MD, PhD, from the Vanderbilt-Ingram Cancer Center at Vanderbilt University in Nashville, Tenn., commented that the results of the trial are expected to change practice.

“However, several issues remain to be addressed,” she wrote. “First, is a pathological complete response predictive of event-free survival? Can event-free survival be used as a surrogate endpoint for overall survival? Second, although not mandated for this trial, approximately 20% of the patients received postoperative therapy. Is adjuvant therapy necessary? What criteria should be used to select patients to receive adjuvant therapy?”

Dr. Lovly also pointed out that patients with tumors harboring mutations in the genes EGFR or ALK were excluded from the trial.

“Therefore, implementation of neoadjuvant therapies requires biomarker testing for patients with early-stage disease at the time of diagnosis, a considerable alteration in the routine practice of lung-cancer medicine,” she wrote.
 

Fears of delaying surgery

In an interview, Upal Basu Roy, PhD, MPH, executive director of research at the LUNGevity Foundation, who was not involved in the study, gave a reason why neoadjuvant therapy is not more widely prescribed for patients with resectable NSCLC.

“Clinicians are always scared, and I think patients are as well, that giving a treatment before surgery would delay surgery,” he said. “When patients are diagnosed with lung cancer and they’re told that surgery offers the potential of cure and then hear that you’re giving them a treatment before surgery and that treatment may potentially delay surgery, that is a huge source of anxiety.”

In addition, clinicians until recently were unsure about which patients were most likely to benefit from neoadjuvant therapy when the only option was chemotherapy, “but that’s changing, obviously, with the recent approval of neoadjuvant nivolumab through CheckMate 816,” he said.
 

CheckMate 816 details

In the CheckMate 816 study, investigators enrolled patients with newly diagnosed resectable NSCLC (stage IB-IIIA) who had good performance status and no known sensitizing EGFR mutations or ALK alterations.

After stratification by stage, programmed death–1 status, and sex, the team randomly assigned patients to receive either nivolumab 360 mg plus platinum-based chemotherapy every 3 weeks for a total of three cycles or chemotherapy alone.

At the end of neoadjuvant therapy, patients underwent radiologic restaging and surgery within 6 weeks. Patients could also receive optional adjuvant chemotherapy with or without radiotherapy.

Of the 179 patients in each arm, 176 received the assigned treatment. In all, 149 (83%) of those assigned to the combination had definitive surgery, as did 135 (75%) of those assigned to chemotherapy alone.

In addition, 35 patients (20%) of those assigned to nivolumab-chemo and 56 (32%) assigned to chemotherapy alone received adjuvant therapy.

The coprimary endpoints of EFS and pCR favored the combination, both in the overall population and across most subgroups, including patients younger than 65, men and women, Asian patients, those with stage IIIA disease, nonsquamous histology, current smokers and never-smokers, and patients with higher levels of PD–ligand 1 expression.

The rates of grade 3 or 4 treatment-related adverse events were similar between the groups, at 33.5% with the combination and 36.9% with chemotherapy alone.

Rates of adverse events leading to study discontinuation, treatment-related adverse events, and surgery-related adverse events were similar between the groups. There were two treatment-related deaths, both in the chemotherapy-alone arm.

CheckMate 816 was funded by Bristol-Myers Squibb (manufacturer of nivolumab). Girard has consulted for and has received grant support from Bristol-Myers Squibb and other companies. Dr. Carbone has consulted for Bristol-Myers Squibb and other companies. Dr. Lovly has consulted for various companies. Dr. Roy has received grants from Bristol-Myers Squibb to the LUNGevity Foundation.

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

Higher consumption of ultraprocessed foods was linked with a significantly higher risk of Crohn’s disease (CD), but not ulcerative colitis, in a large prospective cohort study published online in Clinical Gastroenterology and Hepatology.

Researchers, led by Chun-Han Lo, MD, of Massachusetts General Hospital, Boston, defined ultraprocessed foods “as ready-to-consume formulations of ingredients, typically created by [a] series industrial techniques and processes. They frequently involve the incorporation of additives, such as sweeteners, preservatives, emulsifiers, thickeners, and flavors, which aid in food preservation and produce hyperpalatable products.”

The rising global incidence of inflammatory bowel disease (IBD) in regions undergoing Westernization has overlapped with rising increase in consumption of ultraprocessed food (UPF) over the past few decades, according to the authors. Previous studies have focused on links with individual nutrients and IBD, but this study focuses on the processing role itself. This study comprised 245,112 participants (203,516 women and 41,596 men) and more than 5,468,444 person-years of follow-up, taken from three cohorts: Nurses’ Health Study, Nurses’ Health Study II, and Health Professionals Follow-up Study.

In the highest quartile, UPFs made up on average nearly half (46.4%) of participants’ total energy consumption, compared with 21% in the lowest quartile.

The researchers found that compared with participants in the lowest quartile of simple updated UPF consumption, those in the highest quartile had a significantly increased risk of CD (adjusted hazard ratio, 1.70; 95% confidence interval, 1.23-2.35).

In addition, “a secondary analysis across different CD locations demonstrated that participants in the highest quartile of simple updated UPF intake had the highest risk of ileal, colonic, and ileocolonic CD,” the authors wrote.
 

Three groups of processed foods driving risk increase

Three groups of UPFs appeared to drive the increased risk of CD: ultraprocessed breads and breakfast foods; frozen or shelf-stable ready-to-eat/heat meals; and sauces, cheeses, spreads, and gravies.

Just as with overall consumption, researchers did not find an association between any of those three subgroups and UC risk.

The authors suggested several reasons for the link with Crohn’s disease. Among them were that higher UPF consumption may mean those foods are taking the place of unprocessed or minimally processed foods, such as those rich in fiber. Second, UPFs contain additives, such as salt, that may promote intestinal inflammation. Third, artificial sweeteners in UPFs may predispose the gut to inflammation, as supported by supplementing sucralose/maltodextrins in mice models of spontaneous ileitis.

As for why CD, but not UC, the authors said diet may be more relevant and have a stronger effect biologically in CD compared with UC. Another potential reason, they said, is that results “may reflect the greater specificity of dietary ligands and metabolites on the small intestine compared with the colon.”
 

Data from three large, prospective cohorts

Researchers used data from three ongoing, prospective nationwide cohorts of health professionals in the United States – the Nurses’ Health Study (1986-2014); the Nurses’ Health Study II (1991-2017); and the Health Professionals Follow-up Study (1986-2012).

In all three cohorts, participants filled in questionnaires at enrollment and every 2 years thereafter with information such as medical history and lifestyle factors. Diet was assessed via validated semi-quantitative food frequency questionnaires.

They used Cox proportional hazards models, adjusting for confounders to estimate the hazard ratios (HRs) and 95% confidence intervals for Crohn’s disease and ulcerative colitis, according to participants’ self-reports of their consumption of ultraprocessed foods.

Further studies could help determine which UPF components are driving the higher risk for Crohn’s disease and whether risk differs by length of exposure to UPFs.

“By avoiding UPF consumption, individuals might substantially lower their risk of developing CD in addition to gaining other health benefits,” the authors wrote.

A coauthor, James M. Richter, MD, is a consultant for Policy Analysis Inc and Takeda Pharmaceuticals. Andrew T. Chan, MD, serves as a consultant for Janssen Pharmaceuticals, Pfizer Inc, and Bayer Pharma AG. Ashwin N. Ananthakrishnan, MD, has served as a scientific advisory board member for Abbvie, Gilead, and Kyn Therapeutics, and received research grants from Pfizer and Merck. The remaining authors disclosed no conflicts. This work was supported by the National Institutes of Health; the Beker Foundation, the Chleck Family Foundation, and the Crohn’s and Colitis Foundation.

Higher consumption of ultraprocessed foods was linked with a significantly higher risk of Crohn’s disease (CD), but not ulcerative colitis, in a large prospective cohort study published online in Clinical Gastroenterology and Hepatology.

Researchers, led by Chun-Han Lo, MD, of Massachusetts General Hospital, Boston, defined ultraprocessed foods “as ready-to-consume formulations of ingredients, typically created by [a] series industrial techniques and processes. They frequently involve the incorporation of additives, such as sweeteners, preservatives, emulsifiers, thickeners, and flavors, which aid in food preservation and produce hyperpalatable products.”

The rising global incidence of inflammatory bowel disease (IBD) in regions undergoing Westernization has overlapped with rising increase in consumption of ultraprocessed food (UPF) over the past few decades, according to the authors. Previous studies have focused on links with individual nutrients and IBD, but this study focuses on the processing role itself. This study comprised 245,112 participants (203,516 women and 41,596 men) and more than 5,468,444 person-years of follow-up, taken from three cohorts: Nurses’ Health Study, Nurses’ Health Study II, and Health Professionals Follow-up Study.

In the highest quartile, UPFs made up on average nearly half (46.4%) of participants’ total energy consumption, compared with 21% in the lowest quartile.

The researchers found that compared with participants in the lowest quartile of simple updated UPF consumption, those in the highest quartile had a significantly increased risk of CD (adjusted hazard ratio, 1.70; 95% confidence interval, 1.23-2.35).

In addition, “a secondary analysis across different CD locations demonstrated that participants in the highest quartile of simple updated UPF intake had the highest risk of ileal, colonic, and ileocolonic CD,” the authors wrote.
 

Three groups of processed foods driving risk increase

Three groups of UPFs appeared to drive the increased risk of CD: ultraprocessed breads and breakfast foods; frozen or shelf-stable ready-to-eat/heat meals; and sauces, cheeses, spreads, and gravies.

Just as with overall consumption, researchers did not find an association between any of those three subgroups and UC risk.

The authors suggested several reasons for the link with Crohn’s disease. Among them were that higher UPF consumption may mean those foods are taking the place of unprocessed or minimally processed foods, such as those rich in fiber. Second, UPFs contain additives, such as salt, that may promote intestinal inflammation. Third, artificial sweeteners in UPFs may predispose the gut to inflammation, as supported by supplementing sucralose/maltodextrins in mice models of spontaneous ileitis.

As for why CD, but not UC, the authors said diet may be more relevant and have a stronger effect biologically in CD compared with UC. Another potential reason, they said, is that results “may reflect the greater specificity of dietary ligands and metabolites on the small intestine compared with the colon.”
 

Data from three large, prospective cohorts

Researchers used data from three ongoing, prospective nationwide cohorts of health professionals in the United States – the Nurses’ Health Study (1986-2014); the Nurses’ Health Study II (1991-2017); and the Health Professionals Follow-up Study (1986-2012).

In all three cohorts, participants filled in questionnaires at enrollment and every 2 years thereafter with information such as medical history and lifestyle factors. Diet was assessed via validated semi-quantitative food frequency questionnaires.

They used Cox proportional hazards models, adjusting for confounders to estimate the hazard ratios (HRs) and 95% confidence intervals for Crohn’s disease and ulcerative colitis, according to participants’ self-reports of their consumption of ultraprocessed foods.

Further studies could help determine which UPF components are driving the higher risk for Crohn’s disease and whether risk differs by length of exposure to UPFs.

“By avoiding UPF consumption, individuals might substantially lower their risk of developing CD in addition to gaining other health benefits,” the authors wrote.

A coauthor, James M. Richter, MD, is a consultant for Policy Analysis Inc and Takeda Pharmaceuticals. Andrew T. Chan, MD, serves as a consultant for Janssen Pharmaceuticals, Pfizer Inc, and Bayer Pharma AG. Ashwin N. Ananthakrishnan, MD, has served as a scientific advisory board member for Abbvie, Gilead, and Kyn Therapeutics, and received research grants from Pfizer and Merck. The remaining authors disclosed no conflicts. This work was supported by the National Institutes of Health; the Beker Foundation, the Chleck Family Foundation, and the Crohn’s and Colitis Foundation.

Higher consumption of ultraprocessed foods was linked with a significantly higher risk of Crohn’s disease (CD), but not ulcerative colitis, in a large prospective cohort study published online in Clinical Gastroenterology and Hepatology.

Researchers, led by Chun-Han Lo, MD, of Massachusetts General Hospital, Boston, defined ultraprocessed foods “as ready-to-consume formulations of ingredients, typically created by [a] series industrial techniques and processes. They frequently involve the incorporation of additives, such as sweeteners, preservatives, emulsifiers, thickeners, and flavors, which aid in food preservation and produce hyperpalatable products.”

The rising global incidence of inflammatory bowel disease (IBD) in regions undergoing Westernization has overlapped with rising increase in consumption of ultraprocessed food (UPF) over the past few decades, according to the authors. Previous studies have focused on links with individual nutrients and IBD, but this study focuses on the processing role itself. This study comprised 245,112 participants (203,516 women and 41,596 men) and more than 5,468,444 person-years of follow-up, taken from three cohorts: Nurses’ Health Study, Nurses’ Health Study II, and Health Professionals Follow-up Study.

In the highest quartile, UPFs made up on average nearly half (46.4%) of participants’ total energy consumption, compared with 21% in the lowest quartile.

The researchers found that compared with participants in the lowest quartile of simple updated UPF consumption, those in the highest quartile had a significantly increased risk of CD (adjusted hazard ratio, 1.70; 95% confidence interval, 1.23-2.35).

In addition, “a secondary analysis across different CD locations demonstrated that participants in the highest quartile of simple updated UPF intake had the highest risk of ileal, colonic, and ileocolonic CD,” the authors wrote.
 

Three groups of processed foods driving risk increase

Three groups of UPFs appeared to drive the increased risk of CD: ultraprocessed breads and breakfast foods; frozen or shelf-stable ready-to-eat/heat meals; and sauces, cheeses, spreads, and gravies.

Just as with overall consumption, researchers did not find an association between any of those three subgroups and UC risk.

The authors suggested several reasons for the link with Crohn’s disease. Among them were that higher UPF consumption may mean those foods are taking the place of unprocessed or minimally processed foods, such as those rich in fiber. Second, UPFs contain additives, such as salt, that may promote intestinal inflammation. Third, artificial sweeteners in UPFs may predispose the gut to inflammation, as supported by supplementing sucralose/maltodextrins in mice models of spontaneous ileitis.

As for why CD, but not UC, the authors said diet may be more relevant and have a stronger effect biologically in CD compared with UC. Another potential reason, they said, is that results “may reflect the greater specificity of dietary ligands and metabolites on the small intestine compared with the colon.”
 

Data from three large, prospective cohorts

Researchers used data from three ongoing, prospective nationwide cohorts of health professionals in the United States – the Nurses’ Health Study (1986-2014); the Nurses’ Health Study II (1991-2017); and the Health Professionals Follow-up Study (1986-2012).

In all three cohorts, participants filled in questionnaires at enrollment and every 2 years thereafter with information such as medical history and lifestyle factors. Diet was assessed via validated semi-quantitative food frequency questionnaires.

They used Cox proportional hazards models, adjusting for confounders to estimate the hazard ratios (HRs) and 95% confidence intervals for Crohn’s disease and ulcerative colitis, according to participants’ self-reports of their consumption of ultraprocessed foods.

Further studies could help determine which UPF components are driving the higher risk for Crohn’s disease and whether risk differs by length of exposure to UPFs.

“By avoiding UPF consumption, individuals might substantially lower their risk of developing CD in addition to gaining other health benefits,” the authors wrote.

A coauthor, James M. Richter, MD, is a consultant for Policy Analysis Inc and Takeda Pharmaceuticals. Andrew T. Chan, MD, serves as a consultant for Janssen Pharmaceuticals, Pfizer Inc, and Bayer Pharma AG. Ashwin N. Ananthakrishnan, MD, has served as a scientific advisory board member for Abbvie, Gilead, and Kyn Therapeutics, and received research grants from Pfizer and Merck. The remaining authors disclosed no conflicts. This work was supported by the National Institutes of Health; the Beker Foundation, the Chleck Family Foundation, and the Crohn’s and Colitis Foundation.

NEW ORLEANS – In just over one-third of patients with metastatic melanoma who had experienced disease progression while receiving multiple prior lines of therapy, including immunotherapy and targeted agents, objective clinical responses occurred with a customized cell therapy based on T cells extracted directly from tumor tissue.

The product, called lifileucel, is custom made for each patient and utilizes tumor-infiltrating lymphocytes (TILs) extracted from tumor lesions. This approach differs from other cell-based therapies, such as chimeric antigen receptor (CAR) T cell therapy, which utilizes T cells collected from the patient’s blood.

The new results come from a phase 2 trial conducted in 66 patients with previously treated unresectable or metastatic melanoma who received a single dose of the product. The objective response rate was 36.4%.

“Lifileucel has demonstrated efficacy and durability of response for patients with metastatic melanoma and represents a viable therapeutic option warranting further investigation,” commented Jason Alan Chesney, MD, PhD, from the James Graham Brown Cancer Center, the University of Louisville (Ky.).

He presented the new data at the virtual American Association for Cancer Research (AACR) Annual Meeting 2021.

Customized cell therapy with TILs has been explored for the treatment of melanoma for more than a decade. Some researchers have reported durable response in 25% of patients.

However, “generalizing TIL therapy has been hampered by the complex and really not absolutely defined process for generating cells,” commented Philip Greenberg, MD, professor and head of the program in immunology in the Clinical Research Division of the Fred Hutchinson Cancer Center, Seattle, who was the invited discussant.

The current study demonstrates that cell generation can be performed at a centralized facility that has the required technical expertise. The patient-specific products are then disseminated to multiple centers, he said. The study also demonstrates that TILs can be successfully generated from tumor sites other than skin or lymph nodes.

“Toxicity was, however, significant, although it was generally manageable, and it did occur early, generally within the first 2 weeks,” he noted.
 

Patient-derived product

Lifileucel is a tailor-made immunotherapy product created from melanoma tumor tissues resected from lesions in skin, lymph nodes, liver, lung, peritoneum, musculoskeletal system, breast, or other visceral organs. The cells are shipped to a central manufacturing facility, whre the TILs are isolated, cultured, expanded, and reinvigorated. The cells are then harvested and cryopreserved. The process takes about 22 days. The cryopreserved product is then shipped back to the treating facility.

Prior to receiving the expanded and rejuvenated TILs, patients undergo myeloablative conditioning with cyclophosphamide followed by fludarabine. The TILs are then delivered in a single infusion, followed by administration of up to six doses of interleukin-2 (IL-2).
 

Details from clinical trial

At the meeting, Dr. Chesney reported details on the 66 patients in the trial. They had metastatic melanoma that was progressing on treatment. The mean number of prior lines of therapy was 3.3. All of the patients had received prior anti–programmed cell death protein–1 (PD-1) or programmed cell death–ligand-1 (PD-L1) agents; 53 had received a cytotoxic T lymphocyte protein 4 (CTLA-4) inhibitor; and 15 had received a BRAF/MEK inhibitor.

These patients had a mean of six baseline target and nontarget lesions, and 28 patients had liver and/or brain metastases.

Just over a third of patients (24 of 66, 36.4%) had an objective response; three patients had a complete response; and 21 had a partial response. In addition, 29 patients had stable disease, and nine experienced disease progression. Four patients had not undergone the first assessment at the time of data cutoff.

After a median follow-up of 28.1 months, the median duration of response was not reached. It ranged from 2.2 to > 35.2 months.

Since the data cutoff in April 2020, reduction of tumor burden has occurred in 50 of 62 evaluable patients. Reductions in the target lesion sum of diameters has occurred in 11 patients. In one patient, a partial response converted to a complete response 24 months after infusion, Dr. Chesney noted.

The mean number of TILs infused was 27.3 billion (27.3 x 109). Appropriate amounts of TILs were manufactured from tumor samples acquired across all sites, and reductions in target lesion sum of diameter were seen across the range of TIL total cell doses.

All patients experienced at least one adverse event of any grade; all but two experienced grade 3 or 4 adverse events. Two patients died, one as a result of intra-abdominal hemorrhage considered possibly related to TIL therapy, and one from acute respiratory failure deemed not related to TILs.

The most common grade 3 or 4 adverse events were thrombocytopenia, anemia, febrile neutropenia, neutropenia, hypophosphatemia, and lymphopenia.

“The adverse event profile was manageable and was consistent with the underlying and the known profiles of the nonmyeloblative depletion regimen and IL-2,” Dr. Chesney said.

The decreasing frequency of adverse events over time reflects the potential benefit of the one-time infusion, and no new safety risks have been identified during more than 2 years of follow-up, he added.
 

Remaining questions, next steps

Dr. Greenberg commented that the one of the limitations of the study is that the investigators did not characterize the TIL product.

“Studies have predicted that there’s a particular type of cell, a stemlike T cell, that’s responsible for mediating the efficacy,” he commented. He referred to research from Steven Rosenberg, MD, PhD, and colleagues at the National Cancer Institute, where TILs were first used in 2002.

Dr. Greenberg also raised the question of whether high-dose IL-2 was required post infusion, given that the patients were lymphodepleted before receiving lifileucel.

Future steps for TIL therapy, he said, should include identification of biomarkers for success or failure; strategies to enhance generation and expansion of tumor-reactive T cells; postinfusion strategies, such as using vaccines and/or checkpoint inhibitors to increase therapeutic activity; genetic modifications to enhance the function of TILs in the tumor microenvironment; and research into other tumor types that may be effectively treated with TILs.

The study was supported by Iovance Biotherapeutics. Dr. Chesney has received research funding from Iovance and other companies and has consulted for Amgen and Replimune. Dr. Greenberg has served on scientific advisory boards, has received grant/research support, and owns stock in several companies that do not include Iovance.

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

NEW ORLEANS – In just over one-third of patients with metastatic melanoma who had experienced disease progression while receiving multiple prior lines of therapy, including immunotherapy and targeted agents, objective clinical responses occurred with a customized cell therapy based on T cells extracted directly from tumor tissue.

The product, called lifileucel, is custom made for each patient and utilizes tumor-infiltrating lymphocytes (TILs) extracted from tumor lesions. This approach differs from other cell-based therapies, such as chimeric antigen receptor (CAR) T cell therapy, which utilizes T cells collected from the patient’s blood.

The new results come from a phase 2 trial conducted in 66 patients with previously treated unresectable or metastatic melanoma who received a single dose of the product. The objective response rate was 36.4%.

“Lifileucel has demonstrated efficacy and durability of response for patients with metastatic melanoma and represents a viable therapeutic option warranting further investigation,” commented Jason Alan Chesney, MD, PhD, from the James Graham Brown Cancer Center, the University of Louisville (Ky.).

He presented the new data at the virtual American Association for Cancer Research (AACR) Annual Meeting 2021.

Customized cell therapy with TILs has been explored for the treatment of melanoma for more than a decade. Some researchers have reported durable response in 25% of patients.

However, “generalizing TIL therapy has been hampered by the complex and really not absolutely defined process for generating cells,” commented Philip Greenberg, MD, professor and head of the program in immunology in the Clinical Research Division of the Fred Hutchinson Cancer Center, Seattle, who was the invited discussant.

The current study demonstrates that cell generation can be performed at a centralized facility that has the required technical expertise. The patient-specific products are then disseminated to multiple centers, he said. The study also demonstrates that TILs can be successfully generated from tumor sites other than skin or lymph nodes.

“Toxicity was, however, significant, although it was generally manageable, and it did occur early, generally within the first 2 weeks,” he noted.
 

Patient-derived product

Lifileucel is a tailor-made immunotherapy product created from melanoma tumor tissues resected from lesions in skin, lymph nodes, liver, lung, peritoneum, musculoskeletal system, breast, or other visceral organs. The cells are shipped to a central manufacturing facility, whre the TILs are isolated, cultured, expanded, and reinvigorated. The cells are then harvested and cryopreserved. The process takes about 22 days. The cryopreserved product is then shipped back to the treating facility.

Prior to receiving the expanded and rejuvenated TILs, patients undergo myeloablative conditioning with cyclophosphamide followed by fludarabine. The TILs are then delivered in a single infusion, followed by administration of up to six doses of interleukin-2 (IL-2).
 

Details from clinical trial

At the meeting, Dr. Chesney reported details on the 66 patients in the trial. They had metastatic melanoma that was progressing on treatment. The mean number of prior lines of therapy was 3.3. All of the patients had received prior anti–programmed cell death protein–1 (PD-1) or programmed cell death–ligand-1 (PD-L1) agents; 53 had received a cytotoxic T lymphocyte protein 4 (CTLA-4) inhibitor; and 15 had received a BRAF/MEK inhibitor.

These patients had a mean of six baseline target and nontarget lesions, and 28 patients had liver and/or brain metastases.

Just over a third of patients (24 of 66, 36.4%) had an objective response; three patients had a complete response; and 21 had a partial response. In addition, 29 patients had stable disease, and nine experienced disease progression. Four patients had not undergone the first assessment at the time of data cutoff.

After a median follow-up of 28.1 months, the median duration of response was not reached. It ranged from 2.2 to > 35.2 months.

Since the data cutoff in April 2020, reduction of tumor burden has occurred in 50 of 62 evaluable patients. Reductions in the target lesion sum of diameters has occurred in 11 patients. In one patient, a partial response converted to a complete response 24 months after infusion, Dr. Chesney noted.

The mean number of TILs infused was 27.3 billion (27.3 x 109). Appropriate amounts of TILs were manufactured from tumor samples acquired across all sites, and reductions in target lesion sum of diameter were seen across the range of TIL total cell doses.

All patients experienced at least one adverse event of any grade; all but two experienced grade 3 or 4 adverse events. Two patients died, one as a result of intra-abdominal hemorrhage considered possibly related to TIL therapy, and one from acute respiratory failure deemed not related to TILs.

The most common grade 3 or 4 adverse events were thrombocytopenia, anemia, febrile neutropenia, neutropenia, hypophosphatemia, and lymphopenia.

“The adverse event profile was manageable and was consistent with the underlying and the known profiles of the nonmyeloblative depletion regimen and IL-2,” Dr. Chesney said.

The decreasing frequency of adverse events over time reflects the potential benefit of the one-time infusion, and no new safety risks have been identified during more than 2 years of follow-up, he added.
 

Remaining questions, next steps

Dr. Greenberg commented that the one of the limitations of the study is that the investigators did not characterize the TIL product.

“Studies have predicted that there’s a particular type of cell, a stemlike T cell, that’s responsible for mediating the efficacy,” he commented. He referred to research from Steven Rosenberg, MD, PhD, and colleagues at the National Cancer Institute, where TILs were first used in 2002.

Dr. Greenberg also raised the question of whether high-dose IL-2 was required post infusion, given that the patients were lymphodepleted before receiving lifileucel.

Future steps for TIL therapy, he said, should include identification of biomarkers for success or failure; strategies to enhance generation and expansion of tumor-reactive T cells; postinfusion strategies, such as using vaccines and/or checkpoint inhibitors to increase therapeutic activity; genetic modifications to enhance the function of TILs in the tumor microenvironment; and research into other tumor types that may be effectively treated with TILs.

The study was supported by Iovance Biotherapeutics. Dr. Chesney has received research funding from Iovance and other companies and has consulted for Amgen and Replimune. Dr. Greenberg has served on scientific advisory boards, has received grant/research support, and owns stock in several companies that do not include Iovance.

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

NEW ORLEANS – In just over one-third of patients with metastatic melanoma who had experienced disease progression while receiving multiple prior lines of therapy, including immunotherapy and targeted agents, objective clinical responses occurred with a customized cell therapy based on T cells extracted directly from tumor tissue.

The product, called lifileucel, is custom made for each patient and utilizes tumor-infiltrating lymphocytes (TILs) extracted from tumor lesions. This approach differs from other cell-based therapies, such as chimeric antigen receptor (CAR) T cell therapy, which utilizes T cells collected from the patient’s blood.

The new results come from a phase 2 trial conducted in 66 patients with previously treated unresectable or metastatic melanoma who received a single dose of the product. The objective response rate was 36.4%.

“Lifileucel has demonstrated efficacy and durability of response for patients with metastatic melanoma and represents a viable therapeutic option warranting further investigation,” commented Jason Alan Chesney, MD, PhD, from the James Graham Brown Cancer Center, the University of Louisville (Ky.).

He presented the new data at the virtual American Association for Cancer Research (AACR) Annual Meeting 2021.

Customized cell therapy with TILs has been explored for the treatment of melanoma for more than a decade. Some researchers have reported durable response in 25% of patients.

However, “generalizing TIL therapy has been hampered by the complex and really not absolutely defined process for generating cells,” commented Philip Greenberg, MD, professor and head of the program in immunology in the Clinical Research Division of the Fred Hutchinson Cancer Center, Seattle, who was the invited discussant.

The current study demonstrates that cell generation can be performed at a centralized facility that has the required technical expertise. The patient-specific products are then disseminated to multiple centers, he said. The study also demonstrates that TILs can be successfully generated from tumor sites other than skin or lymph nodes.

“Toxicity was, however, significant, although it was generally manageable, and it did occur early, generally within the first 2 weeks,” he noted.
 

Patient-derived product

Lifileucel is a tailor-made immunotherapy product created from melanoma tumor tissues resected from lesions in skin, lymph nodes, liver, lung, peritoneum, musculoskeletal system, breast, or other visceral organs. The cells are shipped to a central manufacturing facility, whre the TILs are isolated, cultured, expanded, and reinvigorated. The cells are then harvested and cryopreserved. The process takes about 22 days. The cryopreserved product is then shipped back to the treating facility.

Prior to receiving the expanded and rejuvenated TILs, patients undergo myeloablative conditioning with cyclophosphamide followed by fludarabine. The TILs are then delivered in a single infusion, followed by administration of up to six doses of interleukin-2 (IL-2).
 

Details from clinical trial

At the meeting, Dr. Chesney reported details on the 66 patients in the trial. They had metastatic melanoma that was progressing on treatment. The mean number of prior lines of therapy was 3.3. All of the patients had received prior anti–programmed cell death protein–1 (PD-1) or programmed cell death–ligand-1 (PD-L1) agents; 53 had received a cytotoxic T lymphocyte protein 4 (CTLA-4) inhibitor; and 15 had received a BRAF/MEK inhibitor.

These patients had a mean of six baseline target and nontarget lesions, and 28 patients had liver and/or brain metastases.

Just over a third of patients (24 of 66, 36.4%) had an objective response; three patients had a complete response; and 21 had a partial response. In addition, 29 patients had stable disease, and nine experienced disease progression. Four patients had not undergone the first assessment at the time of data cutoff.

After a median follow-up of 28.1 months, the median duration of response was not reached. It ranged from 2.2 to > 35.2 months.

Since the data cutoff in April 2020, reduction of tumor burden has occurred in 50 of 62 evaluable patients. Reductions in the target lesion sum of diameters has occurred in 11 patients. In one patient, a partial response converted to a complete response 24 months after infusion, Dr. Chesney noted.

The mean number of TILs infused was 27.3 billion (27.3 x 109). Appropriate amounts of TILs were manufactured from tumor samples acquired across all sites, and reductions in target lesion sum of diameter were seen across the range of TIL total cell doses.

All patients experienced at least one adverse event of any grade; all but two experienced grade 3 or 4 adverse events. Two patients died, one as a result of intra-abdominal hemorrhage considered possibly related to TIL therapy, and one from acute respiratory failure deemed not related to TILs.

The most common grade 3 or 4 adverse events were thrombocytopenia, anemia, febrile neutropenia, neutropenia, hypophosphatemia, and lymphopenia.

“The adverse event profile was manageable and was consistent with the underlying and the known profiles of the nonmyeloblative depletion regimen and IL-2,” Dr. Chesney said.

The decreasing frequency of adverse events over time reflects the potential benefit of the one-time infusion, and no new safety risks have been identified during more than 2 years of follow-up, he added.
 

Remaining questions, next steps

Dr. Greenberg commented that the one of the limitations of the study is that the investigators did not characterize the TIL product.

“Studies have predicted that there’s a particular type of cell, a stemlike T cell, that’s responsible for mediating the efficacy,” he commented. He referred to research from Steven Rosenberg, MD, PhD, and colleagues at the National Cancer Institute, where TILs were first used in 2002.

Dr. Greenberg also raised the question of whether high-dose IL-2 was required post infusion, given that the patients were lymphodepleted before receiving lifileucel.

Future steps for TIL therapy, he said, should include identification of biomarkers for success or failure; strategies to enhance generation and expansion of tumor-reactive T cells; postinfusion strategies, such as using vaccines and/or checkpoint inhibitors to increase therapeutic activity; genetic modifications to enhance the function of TILs in the tumor microenvironment; and research into other tumor types that may be effectively treated with TILs.

The study was supported by Iovance Biotherapeutics. Dr. Chesney has received research funding from Iovance and other companies and has consulted for Amgen and Replimune. Dr. Greenberg has served on scientific advisory boards, has received grant/research support, and owns stock in several companies that do not include Iovance.

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

Even within the first year of implementation, the Research to Accelerate Cures and Equity (RACE) for Children Act has made an impact.

“In the year prior to RACE implementation, there were no approvals of therapeutics that required pediatric studies,” said Brittany Avin McKelvey, PhD, science policy analyst with Friends of Cancer Research and a childhood cancer survivor. “Within the first year of implementation, almost half of approved therapeutics required pediatric study.”

The legislation was passed by Congress in 2017 and took effect in August 2020. It requires that therapeutics that are approved for adult cancers be tested in pediatric cancers if those drugs are directed at molecular targets relevant for pediatric cancers.

The RACE Act also requires testing of therapeutics that are given an orphan drug designation. Such drugs were previously exempt from pediatric trials.

Dr. McKelvey presented the new findings at the annual meeting of the American Association for Cancer Research.

To evaluate the impact of the RACE Act during the first year of its implementation, her team assessed all the new cancer drugs approved between August 2019 and August 2021.

Nineteen drugs were identified; 63.2% were approved in the year before the RACE Act took effect, and 36.8% were approved after its implementation. The team suspects that the coronavirus pandemic may have contributed to the lower number of post-RACE approvals.

The researchers found that prior to implementation of the RACE Act, none of the approved adult cancer therapeutics were required to be studied in pediatric populations. But more than 90% of those had molecular targets that would have required that they be studied in pediatric cancers had the RACE Act been in place. The majority of these drugs were exempt because of their designation as orphan drugs.

In the post-RACE group, however, 42.9% of approved drugs are required to be studied in pediatric cancers. One example is infigratinib (Truseltiq), a drug for adult cholangiocarcinoma that targets the protein fibroblast growth factor receptor 2 (FGFR2). Truseltiq is an orphan drug – and thus would have been exempt prior to the RACE Act – but it will now be studied in pediatric patients with advanced or metastatic tumors harboring alterations in FGFR2.

“I find these results encouraging, but it is still very early,” said John Maris, MD, an attending physician and professor of pediatrics at the Children’s Hospital of Philadelphia, who was not involved in the study. “This is only 1 year into implementation, and this legislation will be around for a long time.”

In an interview, Dr. McKelvey noted that although a handful of clinical trials for pediatric cancers have been launched since implementation of RACE, many drugs are still being waived for pediatric study even when a relevant mechanism of action is present – largely because the extremely low incidence of many childhood cancers makes it impractical or, in some cases, impossible to conduct such studies. “This highlights the need for additional opportunities to help facilitate and encourage robust pediatric studies,” she said.

The main limitation of the study is that it examined data 1 year after the implementation of the RACE Act; further analysis is needed to determine the full extent of its impact, Dr. McKelvey said. “The true measure of success will be determined by whether increased pediatric studies actually translate to label expansions for pediatric patient populations and access to these therapies.”

The study was supported by funding from Friends of Cancer Research.

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

Even within the first year of implementation, the Research to Accelerate Cures and Equity (RACE) for Children Act has made an impact.

“In the year prior to RACE implementation, there were no approvals of therapeutics that required pediatric studies,” said Brittany Avin McKelvey, PhD, science policy analyst with Friends of Cancer Research and a childhood cancer survivor. “Within the first year of implementation, almost half of approved therapeutics required pediatric study.”

The legislation was passed by Congress in 2017 and took effect in August 2020. It requires that therapeutics that are approved for adult cancers be tested in pediatric cancers if those drugs are directed at molecular targets relevant for pediatric cancers.

The RACE Act also requires testing of therapeutics that are given an orphan drug designation. Such drugs were previously exempt from pediatric trials.

Dr. McKelvey presented the new findings at the annual meeting of the American Association for Cancer Research.

To evaluate the impact of the RACE Act during the first year of its implementation, her team assessed all the new cancer drugs approved between August 2019 and August 2021.

Nineteen drugs were identified; 63.2% were approved in the year before the RACE Act took effect, and 36.8% were approved after its implementation. The team suspects that the coronavirus pandemic may have contributed to the lower number of post-RACE approvals.

The researchers found that prior to implementation of the RACE Act, none of the approved adult cancer therapeutics were required to be studied in pediatric populations. But more than 90% of those had molecular targets that would have required that they be studied in pediatric cancers had the RACE Act been in place. The majority of these drugs were exempt because of their designation as orphan drugs.

In the post-RACE group, however, 42.9% of approved drugs are required to be studied in pediatric cancers. One example is infigratinib (Truseltiq), a drug for adult cholangiocarcinoma that targets the protein fibroblast growth factor receptor 2 (FGFR2). Truseltiq is an orphan drug – and thus would have been exempt prior to the RACE Act – but it will now be studied in pediatric patients with advanced or metastatic tumors harboring alterations in FGFR2.

“I find these results encouraging, but it is still very early,” said John Maris, MD, an attending physician and professor of pediatrics at the Children’s Hospital of Philadelphia, who was not involved in the study. “This is only 1 year into implementation, and this legislation will be around for a long time.”

In an interview, Dr. McKelvey noted that although a handful of clinical trials for pediatric cancers have been launched since implementation of RACE, many drugs are still being waived for pediatric study even when a relevant mechanism of action is present – largely because the extremely low incidence of many childhood cancers makes it impractical or, in some cases, impossible to conduct such studies. “This highlights the need for additional opportunities to help facilitate and encourage robust pediatric studies,” she said.

The main limitation of the study is that it examined data 1 year after the implementation of the RACE Act; further analysis is needed to determine the full extent of its impact, Dr. McKelvey said. “The true measure of success will be determined by whether increased pediatric studies actually translate to label expansions for pediatric patient populations and access to these therapies.”

The study was supported by funding from Friends of Cancer Research.

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

Even within the first year of implementation, the Research to Accelerate Cures and Equity (RACE) for Children Act has made an impact.

“In the year prior to RACE implementation, there were no approvals of therapeutics that required pediatric studies,” said Brittany Avin McKelvey, PhD, science policy analyst with Friends of Cancer Research and a childhood cancer survivor. “Within the first year of implementation, almost half of approved therapeutics required pediatric study.”

The legislation was passed by Congress in 2017 and took effect in August 2020. It requires that therapeutics that are approved for adult cancers be tested in pediatric cancers if those drugs are directed at molecular targets relevant for pediatric cancers.

The RACE Act also requires testing of therapeutics that are given an orphan drug designation. Such drugs were previously exempt from pediatric trials.

Dr. McKelvey presented the new findings at the annual meeting of the American Association for Cancer Research.

To evaluate the impact of the RACE Act during the first year of its implementation, her team assessed all the new cancer drugs approved between August 2019 and August 2021.

Nineteen drugs were identified; 63.2% were approved in the year before the RACE Act took effect, and 36.8% were approved after its implementation. The team suspects that the coronavirus pandemic may have contributed to the lower number of post-RACE approvals.

The researchers found that prior to implementation of the RACE Act, none of the approved adult cancer therapeutics were required to be studied in pediatric populations. But more than 90% of those had molecular targets that would have required that they be studied in pediatric cancers had the RACE Act been in place. The majority of these drugs were exempt because of their designation as orphan drugs.

In the post-RACE group, however, 42.9% of approved drugs are required to be studied in pediatric cancers. One example is infigratinib (Truseltiq), a drug for adult cholangiocarcinoma that targets the protein fibroblast growth factor receptor 2 (FGFR2). Truseltiq is an orphan drug – and thus would have been exempt prior to the RACE Act – but it will now be studied in pediatric patients with advanced or metastatic tumors harboring alterations in FGFR2.

“I find these results encouraging, but it is still very early,” said John Maris, MD, an attending physician and professor of pediatrics at the Children’s Hospital of Philadelphia, who was not involved in the study. “This is only 1 year into implementation, and this legislation will be around for a long time.”

In an interview, Dr. McKelvey noted that although a handful of clinical trials for pediatric cancers have been launched since implementation of RACE, many drugs are still being waived for pediatric study even when a relevant mechanism of action is present – largely because the extremely low incidence of many childhood cancers makes it impractical or, in some cases, impossible to conduct such studies. “This highlights the need for additional opportunities to help facilitate and encourage robust pediatric studies,” she said.

The main limitation of the study is that it examined data 1 year after the implementation of the RACE Act; further analysis is needed to determine the full extent of its impact, Dr. McKelvey said. “The true measure of success will be determined by whether increased pediatric studies actually translate to label expansions for pediatric patient populations and access to these therapies.”

The study was supported by funding from Friends of Cancer Research.

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

The goal of this activity is to update primary care practitioners (PCPs) on risk factors and trends in hepatocellular carcinoma (HCC) development, as well as guideline recommendations and best practices for collaborating with specialists in HCC surveillance.

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The goal of this activity is to update primary care practitioners (PCPs) on risk factors and trends in hepatocellular carcinoma (HCC) development, as well as guideline recommendations and best practices for collaborating with specialists in HCC surveillance.

Click here to access this content now 

The goal of this activity is to update primary care practitioners (PCPs) on risk factors and trends in hepatocellular carcinoma (HCC) development, as well as guideline recommendations and best practices for collaborating with specialists in HCC surveillance.

Click here to access this content now 

In more than 10% of cases in which ductal carcinoma in situ (DCIS) recurs in the same breast, the new lesion is genetically distinct from the original lesion, according to a study presented at the annual meeting of the American Association for Cancer Research.

If these findings of de novo tumor recurrences hold true, “it should change how you should treat the patients in the clinic,” commented lead author Tanjina Kader, PhD, a postdoctoral researcher in the department of oncology at the Peter MacCallum Cancer Centre in the University of Melbourne.

Up to a quarter of cases of DCIS recur, and half of those cases emerge in the form of invasive breast cancer. Currently, all recurrent tumor patients are provided the same treatment on the assumption that all recurrences arise from the primary lesion, Dr. Kader commented.

But the new findings could change this practice. If a patient with DCIS returns to the clinic with a tumor independent of the primary lesion, physicians should consider preventive therapies, such as mastectomy or genetic counseling, she said in an interview.

For their study, Dr. Kader and colleagues gathered patient samples and extracted 67 pairs of primary DCIS and their recurrences from the same breast. They also collected 32 samples from nonrecurrent cases of DCIS.

They then used advanced DNA sequencing methods to conduct detailed molecular analyses in order to determine whether the recurrences were genetically distinct from the original lesion.

The team found that 82% of cases appeared to be clonal – derived from the same ancestral cell as the original tumor – and 18% were nonclonal – arose independently of the original DCIS.

The researchers also identified specific genetic changes, including a mutation in the TP53 gene, that were present in recurrences of DCIS but not in nonrecurrent or nonclonal cases.

“It was surprising to see that nonclonal tumors have a similar genetic profile as nonrecurrent tumors,” Dr. Kader said. This means that, if these genetic changes are used as biomarkers to predict the recurrence of DCIS, they could lead to the undertreatment of patients who could develop nonclonal tumors, since these individuals may be categorized as having a low risk of recurrence, she explained.

“For the last 10 years, everyone has been trying their best to find a biomarker without actually taking into account that independent tumors can actually arise on the same breast independently,” Dr. Kader said.

The main limitation of this study was the lack of DNA from matched healthy cells to compare to the patient samples, said Dr. Kader. Because of the lack of these samples, the study focused only on chromosomal changes.

This study is “highly relevant, as it adds to our knowledge to what extent DCIS can be considered a precursor lesion as well as a risk lesion,” said Jelle Wesseling, MD, PhD, a breast pathologist at the Netherlands Cancer Institute. He was not involved in this research, but his team has also found that primary DCIS lesions and their subsequent events can be clonally unrelated.

Dr. Wesseling said there are still many questions, such as whether inherited genetic variants or the tumor microenvironment contribute to DCIS recurrences. “There is a lot more work to be done here to tease this out in more detail.”

The study was funded by grants from the National Breast Cancer Foundation, the Cancer Council Victoria, and the Victorian Cancer Agency.

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

In more than 10% of cases in which ductal carcinoma in situ (DCIS) recurs in the same breast, the new lesion is genetically distinct from the original lesion, according to a study presented at the annual meeting of the American Association for Cancer Research.

If these findings of de novo tumor recurrences hold true, “it should change how you should treat the patients in the clinic,” commented lead author Tanjina Kader, PhD, a postdoctoral researcher in the department of oncology at the Peter MacCallum Cancer Centre in the University of Melbourne.

Up to a quarter of cases of DCIS recur, and half of those cases emerge in the form of invasive breast cancer. Currently, all recurrent tumor patients are provided the same treatment on the assumption that all recurrences arise from the primary lesion, Dr. Kader commented.

But the new findings could change this practice. If a patient with DCIS returns to the clinic with a tumor independent of the primary lesion, physicians should consider preventive therapies, such as mastectomy or genetic counseling, she said in an interview.

For their study, Dr. Kader and colleagues gathered patient samples and extracted 67 pairs of primary DCIS and their recurrences from the same breast. They also collected 32 samples from nonrecurrent cases of DCIS.

They then used advanced DNA sequencing methods to conduct detailed molecular analyses in order to determine whether the recurrences were genetically distinct from the original lesion.

The team found that 82% of cases appeared to be clonal – derived from the same ancestral cell as the original tumor – and 18% were nonclonal – arose independently of the original DCIS.

The researchers also identified specific genetic changes, including a mutation in the TP53 gene, that were present in recurrences of DCIS but not in nonrecurrent or nonclonal cases.

“It was surprising to see that nonclonal tumors have a similar genetic profile as nonrecurrent tumors,” Dr. Kader said. This means that, if these genetic changes are used as biomarkers to predict the recurrence of DCIS, they could lead to the undertreatment of patients who could develop nonclonal tumors, since these individuals may be categorized as having a low risk of recurrence, she explained.

“For the last 10 years, everyone has been trying their best to find a biomarker without actually taking into account that independent tumors can actually arise on the same breast independently,” Dr. Kader said.

The main limitation of this study was the lack of DNA from matched healthy cells to compare to the patient samples, said Dr. Kader. Because of the lack of these samples, the study focused only on chromosomal changes.

This study is “highly relevant, as it adds to our knowledge to what extent DCIS can be considered a precursor lesion as well as a risk lesion,” said Jelle Wesseling, MD, PhD, a breast pathologist at the Netherlands Cancer Institute. He was not involved in this research, but his team has also found that primary DCIS lesions and their subsequent events can be clonally unrelated.

Dr. Wesseling said there are still many questions, such as whether inherited genetic variants or the tumor microenvironment contribute to DCIS recurrences. “There is a lot more work to be done here to tease this out in more detail.”

The study was funded by grants from the National Breast Cancer Foundation, the Cancer Council Victoria, and the Victorian Cancer Agency.

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

In more than 10% of cases in which ductal carcinoma in situ (DCIS) recurs in the same breast, the new lesion is genetically distinct from the original lesion, according to a study presented at the annual meeting of the American Association for Cancer Research.

If these findings of de novo tumor recurrences hold true, “it should change how you should treat the patients in the clinic,” commented lead author Tanjina Kader, PhD, a postdoctoral researcher in the department of oncology at the Peter MacCallum Cancer Centre in the University of Melbourne.

Up to a quarter of cases of DCIS recur, and half of those cases emerge in the form of invasive breast cancer. Currently, all recurrent tumor patients are provided the same treatment on the assumption that all recurrences arise from the primary lesion, Dr. Kader commented.

But the new findings could change this practice. If a patient with DCIS returns to the clinic with a tumor independent of the primary lesion, physicians should consider preventive therapies, such as mastectomy or genetic counseling, she said in an interview.

For their study, Dr. Kader and colleagues gathered patient samples and extracted 67 pairs of primary DCIS and their recurrences from the same breast. They also collected 32 samples from nonrecurrent cases of DCIS.

They then used advanced DNA sequencing methods to conduct detailed molecular analyses in order to determine whether the recurrences were genetically distinct from the original lesion.

The team found that 82% of cases appeared to be clonal – derived from the same ancestral cell as the original tumor – and 18% were nonclonal – arose independently of the original DCIS.

The researchers also identified specific genetic changes, including a mutation in the TP53 gene, that were present in recurrences of DCIS but not in nonrecurrent or nonclonal cases.

“It was surprising to see that nonclonal tumors have a similar genetic profile as nonrecurrent tumors,” Dr. Kader said. This means that, if these genetic changes are used as biomarkers to predict the recurrence of DCIS, they could lead to the undertreatment of patients who could develop nonclonal tumors, since these individuals may be categorized as having a low risk of recurrence, she explained.

“For the last 10 years, everyone has been trying their best to find a biomarker without actually taking into account that independent tumors can actually arise on the same breast independently,” Dr. Kader said.

The main limitation of this study was the lack of DNA from matched healthy cells to compare to the patient samples, said Dr. Kader. Because of the lack of these samples, the study focused only on chromosomal changes.

This study is “highly relevant, as it adds to our knowledge to what extent DCIS can be considered a precursor lesion as well as a risk lesion,” said Jelle Wesseling, MD, PhD, a breast pathologist at the Netherlands Cancer Institute. He was not involved in this research, but his team has also found that primary DCIS lesions and their subsequent events can be clonally unrelated.

Dr. Wesseling said there are still many questions, such as whether inherited genetic variants or the tumor microenvironment contribute to DCIS recurrences. “There is a lot more work to be done here to tease this out in more detail.”

The study was funded by grants from the National Breast Cancer Foundation, the Cancer Council Victoria, and the Victorian Cancer Agency.

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