AVAHO

In 2013, a prostate-specific antigen (PSA) blood test revealed that Richard LaFrate’s levels had jumped. 

Previously in a normal range, his PSA was now above 6 ng/mL, indicating an elevated likelihood for prostate cancer. The jazz guitarist from Leesburg, Florida, then 70 years old, underwent a biopsy, which found two Gleason 6 lesions. 

Mr. LaFrate had low-risk prostate cancer.

Guidelines now recommend active surveillance for patients like Mr. LaFrate, who have low-risk disease. This strategy would mean monitoring the cancer until LaFrate required treatment, with the upside being he might never need therapy.

Mr. LaFrate’s urologist, however, was pushing whole gland surgery — an invasive and unnecessary procedure given his diagnosis and age. 

Mr. LaFrate decided to look for another doctor. He filled out a form online that pointed him to a new urologist who offered him one option: An investigational procedure known as high-intensity focused ultrasound.

At the time, high-intensity focused ultrasound — a form of focal therapy — was being studied in the United States to treat men with low or intermediate-risk prostate cancer, but it was still relatively early days.

Mr. LaFrate’s urologist asked him to pay $25,000 out of pocket to undergo the focal procedure at a clinic in the Bahamas. He refused and, ultimately, landed on active surveillance as the best strategy to manage for his low-risk disease.

That urologist was “a shyster in my opinion,” Mr. LaFrate said. 

Over the past 10 years, the popularity of focal therapy has grown among men with intermediate-risk prostate cancer — Gleason 3+4 (grade group 2) tumors — as an alternative to invasive surgery and active surveillance. Prestigious medical centers, such as Cleveland Clinic, Mayo Clinic, Memorial Sloan Kettering, UCLA, and the University of Chicago, routinely offer focal therapy. 

But use of the techniques remains controversial and costly.

As the Cleveland Clinic’s website acknowledges, although “the use of focal therapy for localized prostate cancer appears to be a promising development in a number of ways, it is still considered investigational and not yet part of standard therapy.” Major caveats to focal therapy include unknown long-term effectiveness, the possibility of leaving behind untreated cancer, and higher overall costs. 

No major national guidelines endorse the use of focal therapy, unless offered in a research or clinical trial setting. Insurance companies, such as Aetna, Blue Cross Blue Shield, and United, also consider focal therapy for prostate cancer investigational and don’t cover it.

Without a stamp of approval from guideline bodies and insurance companies, patients, like Mr. LaFrate, remain vulnerable to the high out-of-pocket costs for these focal techniques. 

“Almost every place charges $15,000-$30,000 in cash,” said Daniel Spratt, MD, radiation oncology chair at University Hospitals Seidman Cancer Center and Case Western Reserve University in Cleveland. 

Dr. Spratt has seen hundreds of patients after focal therapy, some from prominent centers, who have emptied their bank accounts to undergo treatment with the promise of great results and ultimately felt misled when the cancer has recurred.

“It pains me that there are doctors willing to ignore the Hippocratic oath of ‘Do No Harm’ simply to jump on this fad to bring in revenue,” Dr. Spratt said. 
 

Evidence-Based or Oversold?

Focal therapy gained a foothold in the United Kingdom well before the United States.

Hashim Ahmed, FRCS, urology chair at Imperial College London, has used focal therapy for 15 years, treated over 1000 patients, and taught dozens of surgeons how to use the leading focal therapies — focal cryoablation, in which surgeons use a needle-thin probe to target, freeze, and kill prostate tumors, as well as high-intensity focused ultrasound, which uses sound wave energy to superheat and kill tumors.

“Certainly, in the United Kingdom, focal therapy has been prime time in a number of centers for a number of years,” Dr. Ahmed said. 

In the United States, focal therapy has become an attractive option for men with prostate cancer who want to avoid radiation or radical prostatectomy but don’t feel comfortable simply monitoring their disease with active surveillance. Experts from specialized focal therapy centers touting the promise of this “innovative technique” predict its routine use in the next few years.

But the excitement surrounding the use of focal therapy in prostate cancer has outpaced broader acceptance.

In 2015, the FDA approved high-intensity focused ultrasound to treat prostatic disease, but not prostate cancer specifically. Although the approval language “means that companies cannot advertise that their devices can be used for prostate cancer,” physicians can still determine how to use the technology, which includes treating prostate cancer, Dr. Ahmed said. 

The evidence is starting to catch up to the demand. The latest research suggests that the partial-gland techniques may stand up well to radical prostatectomy.

A 2022 prospective database study comparing radical prostatectomies to focal therapy — mostly high-intensity focused ultrasound — in more than 800 men found similar rates of failure-free survival in the two groups at the 8-year follow-up. A 2019 registry study found that failure-free survival at 3 years was just over 90% in high and intermediate-risk patients receiving focal cryotherapy, with the rate rising to about 93% for the intermediate-risk group. And a 2018 prospective study of 625 patients with intermediate or high-risk prostate cancer who underwent high-intensity focused ultrasound had 5-year metastasis-free survival of 98% and overall survival rates of 100%.

One of the biggest draws of focal therapy vs more aggressive treatments is the “massive differences in side-effect profiles,” said Dr. Ahmed.

In a 2021 meta-analysis, researchers found that 6 months after high-intensity focused ultrasound, 98% of patients remained continent and 80% retained erectile function, while erectile dysfunction can occur in 30% to as many as 85% of patients following prostatectomy or radiotherapy and urinary incontinence can occur in as many as 40% of patients.

Despite these potential advantages of focal therapy, the long-term efficacy of the techniques remains uncertain.

A recent study from a team at MSK, for instance, reported that 40% of men with intermediate (grade 2) or high-risk (grade 3) disease had residual cancer following MRI-guided focused ultrasound. A 2020 prospective registry study found that almost 20% of patients undergoing high-intensity focal ultrasound required a second round following a recurrence. 

Dr. Spratt worries that patients who recur after focal therapy may go on to receive a second round — often offered at half price — and will still ultimately need surgery or radiation therapy later. By that point, however, patients may have spent as much as $45,000 — ie, $30,000 on the initial and another $15,000 on the follow-up procedure.

When patients see Dr. Spratt after a recurrence, he informs them that their side effects will be worse if he gives them radiation or surgery now vs if he had given them curative therapy upfront. “But this is what we’re left with,” he tells them.

Another big concern in the field is “the quality of data for focal therapy is overwhelmingly poor,” said Jonathan Shoag, MD, a urologic oncologist at University Hospitals and an associate professor of urology at Case Western Reserve University School of Medicine in Cleveland. “Essentially, the bulk of the data is from single-institution retrospective series without defined follow-up protocols or endpoints.”

The American Urological Association (AUA) has even cautioned experts and patients about the lack of high-quality data comparing focal therapy techniques to radiation therapy, surgery, and active surveillance. According to the AUA, focal options should only be considered in intermediate-risk prostate cancer in a clinical trial setting.

“The lack of randomized clinical trials poses a major stumbling block for the field,” said Dr. Ahmed.

Although randomized trials would be ideal, the results would take many years to mature, and growing patient demand for these less invasive focal procedures has made randomized trials difficult to complete, explained Arvin George, MD, associate professor at Johns Hopkins School of Medicine in Baltimore. Several randomized trials attempted in Norway and the United Kingdom, for instance, fell apart when patients refused to be randomized between focal and radical therapy, Dr. George said.

Focal therapy is now in the same position that active surveillance was a few years ago, according to Dr. George.

“We are hearing the same concerns about focal therapy now as we did about active surveillance,” he said. The initial evidence supporting active surveillance largely came from real-world experience and retrospective studies. The randomized data came later, and skeptics of active surveillance “were proven wrong,” he added.

But Dr. Shoag has a different take on the trajectory of focal therapy research and care in the United States. 

“I think there’s this emerging kind of tragedy happening in our field now, where you have even academic institutions offering focal therapy to patients off-trial with essentially no data to suggest it is oncologically effective,” Dr. Shoag said.

William Catalona, MD, Northwestern University Feinberg School of Medicine, Chicago, agreed, noting that too many low-risk patients are undergoing focal treatment who should be on active surveillance. “Many men are attracted to focal because they just are uncomfortable having a cancer in their body that’s not treated,” Dr. Catalona said. But “giving these patients focal therapy is really overtreatment.”

Patients with higher-risk disease who want to avoid aggressive treatment are also being lured into focal without guidelines or clear evidence to back up that option, Dr. Catalona explained.

Although it’s not clear how many men in the United States are receiving focal therapy who shouldn’t, even proponents of focal therapy, like George, have expressed concern.

Dr. George agreed that focal therapy marketing geared towards patients is drawing in some men who are not good candidates for these techniques, and feels there’s not enough objective material from medical societies or academic centers giving patients a realistic picture of focal therapy. 

“There is concern that patients may be receiving biased information,” Dr. George said, adding that it’s ultimately up to the physician to reconcile the best available evidence, understand the outcomes, and discuss these options with the patient to guide them to what’s best.

At the end of the day, Dr. Spratt said, physicians giving focal therapy off a clinical trial need to pause and ask themselves “why are they giving a treatment that remains investigational by payers, not recommended by any major guideline, and that lacks any randomized evidence?” 

Mr. LaFrate does not regret his decision to forgo focal therapy in 2013. He has been on active surveillance for about a decade now.

Following an MRI in 2022, Mr. LaFrate’s radiology report found that “clinically significant cancer is very unlikely to be present.”

Still, his PSA has risen two points in the past year to 14. His current urologist feels that the PSA is going up because there’s cancer present and is suggesting focal therapy for Mr. LaFrate.

Mr. LaFrate, who has prostate enlargement issues, remains skeptical of focal therapy and is still resisting the sales pitch.

“My doctor is not aggressively pushing it. He’s just giving me that as one of my options,” he said. “I just have a hunch I don’t need it at this point.”

A version of this article appeared on Medscape.com.

In 2013, a prostate-specific antigen (PSA) blood test revealed that Richard LaFrate’s levels had jumped. 

Previously in a normal range, his PSA was now above 6 ng/mL, indicating an elevated likelihood for prostate cancer. The jazz guitarist from Leesburg, Florida, then 70 years old, underwent a biopsy, which found two Gleason 6 lesions. 

Mr. LaFrate had low-risk prostate cancer.

Guidelines now recommend active surveillance for patients like Mr. LaFrate, who have low-risk disease. This strategy would mean monitoring the cancer until LaFrate required treatment, with the upside being he might never need therapy.

Mr. LaFrate’s urologist, however, was pushing whole gland surgery — an invasive and unnecessary procedure given his diagnosis and age. 

Mr. LaFrate decided to look for another doctor. He filled out a form online that pointed him to a new urologist who offered him one option: An investigational procedure known as high-intensity focused ultrasound.

At the time, high-intensity focused ultrasound — a form of focal therapy — was being studied in the United States to treat men with low or intermediate-risk prostate cancer, but it was still relatively early days.

Mr. LaFrate’s urologist asked him to pay $25,000 out of pocket to undergo the focal procedure at a clinic in the Bahamas. He refused and, ultimately, landed on active surveillance as the best strategy to manage for his low-risk disease.

That urologist was “a shyster in my opinion,” Mr. LaFrate said. 

Over the past 10 years, the popularity of focal therapy has grown among men with intermediate-risk prostate cancer — Gleason 3+4 (grade group 2) tumors — as an alternative to invasive surgery and active surveillance. Prestigious medical centers, such as Cleveland Clinic, Mayo Clinic, Memorial Sloan Kettering, UCLA, and the University of Chicago, routinely offer focal therapy. 

But use of the techniques remains controversial and costly.

As the Cleveland Clinic’s website acknowledges, although “the use of focal therapy for localized prostate cancer appears to be a promising development in a number of ways, it is still considered investigational and not yet part of standard therapy.” Major caveats to focal therapy include unknown long-term effectiveness, the possibility of leaving behind untreated cancer, and higher overall costs. 

No major national guidelines endorse the use of focal therapy, unless offered in a research or clinical trial setting. Insurance companies, such as Aetna, Blue Cross Blue Shield, and United, also consider focal therapy for prostate cancer investigational and don’t cover it.

Without a stamp of approval from guideline bodies and insurance companies, patients, like Mr. LaFrate, remain vulnerable to the high out-of-pocket costs for these focal techniques. 

“Almost every place charges $15,000-$30,000 in cash,” said Daniel Spratt, MD, radiation oncology chair at University Hospitals Seidman Cancer Center and Case Western Reserve University in Cleveland. 

Dr. Spratt has seen hundreds of patients after focal therapy, some from prominent centers, who have emptied their bank accounts to undergo treatment with the promise of great results and ultimately felt misled when the cancer has recurred.

“It pains me that there are doctors willing to ignore the Hippocratic oath of ‘Do No Harm’ simply to jump on this fad to bring in revenue,” Dr. Spratt said. 
 

Evidence-Based or Oversold?

Focal therapy gained a foothold in the United Kingdom well before the United States.

Hashim Ahmed, FRCS, urology chair at Imperial College London, has used focal therapy for 15 years, treated over 1000 patients, and taught dozens of surgeons how to use the leading focal therapies — focal cryoablation, in which surgeons use a needle-thin probe to target, freeze, and kill prostate tumors, as well as high-intensity focused ultrasound, which uses sound wave energy to superheat and kill tumors.

“Certainly, in the United Kingdom, focal therapy has been prime time in a number of centers for a number of years,” Dr. Ahmed said. 

In the United States, focal therapy has become an attractive option for men with prostate cancer who want to avoid radiation or radical prostatectomy but don’t feel comfortable simply monitoring their disease with active surveillance. Experts from specialized focal therapy centers touting the promise of this “innovative technique” predict its routine use in the next few years.

But the excitement surrounding the use of focal therapy in prostate cancer has outpaced broader acceptance.

In 2015, the FDA approved high-intensity focused ultrasound to treat prostatic disease, but not prostate cancer specifically. Although the approval language “means that companies cannot advertise that their devices can be used for prostate cancer,” physicians can still determine how to use the technology, which includes treating prostate cancer, Dr. Ahmed said. 

The evidence is starting to catch up to the demand. The latest research suggests that the partial-gland techniques may stand up well to radical prostatectomy.

A 2022 prospective database study comparing radical prostatectomies to focal therapy — mostly high-intensity focused ultrasound — in more than 800 men found similar rates of failure-free survival in the two groups at the 8-year follow-up. A 2019 registry study found that failure-free survival at 3 years was just over 90% in high and intermediate-risk patients receiving focal cryotherapy, with the rate rising to about 93% for the intermediate-risk group. And a 2018 prospective study of 625 patients with intermediate or high-risk prostate cancer who underwent high-intensity focused ultrasound had 5-year metastasis-free survival of 98% and overall survival rates of 100%.

One of the biggest draws of focal therapy vs more aggressive treatments is the “massive differences in side-effect profiles,” said Dr. Ahmed.

In a 2021 meta-analysis, researchers found that 6 months after high-intensity focused ultrasound, 98% of patients remained continent and 80% retained erectile function, while erectile dysfunction can occur in 30% to as many as 85% of patients following prostatectomy or radiotherapy and urinary incontinence can occur in as many as 40% of patients.

Despite these potential advantages of focal therapy, the long-term efficacy of the techniques remains uncertain.

A recent study from a team at MSK, for instance, reported that 40% of men with intermediate (grade 2) or high-risk (grade 3) disease had residual cancer following MRI-guided focused ultrasound. A 2020 prospective registry study found that almost 20% of patients undergoing high-intensity focal ultrasound required a second round following a recurrence. 

Dr. Spratt worries that patients who recur after focal therapy may go on to receive a second round — often offered at half price — and will still ultimately need surgery or radiation therapy later. By that point, however, patients may have spent as much as $45,000 — ie, $30,000 on the initial and another $15,000 on the follow-up procedure.

When patients see Dr. Spratt after a recurrence, he informs them that their side effects will be worse if he gives them radiation or surgery now vs if he had given them curative therapy upfront. “But this is what we’re left with,” he tells them.

Another big concern in the field is “the quality of data for focal therapy is overwhelmingly poor,” said Jonathan Shoag, MD, a urologic oncologist at University Hospitals and an associate professor of urology at Case Western Reserve University School of Medicine in Cleveland. “Essentially, the bulk of the data is from single-institution retrospective series without defined follow-up protocols or endpoints.”

The American Urological Association (AUA) has even cautioned experts and patients about the lack of high-quality data comparing focal therapy techniques to radiation therapy, surgery, and active surveillance. According to the AUA, focal options should only be considered in intermediate-risk prostate cancer in a clinical trial setting.

“The lack of randomized clinical trials poses a major stumbling block for the field,” said Dr. Ahmed.

Although randomized trials would be ideal, the results would take many years to mature, and growing patient demand for these less invasive focal procedures has made randomized trials difficult to complete, explained Arvin George, MD, associate professor at Johns Hopkins School of Medicine in Baltimore. Several randomized trials attempted in Norway and the United Kingdom, for instance, fell apart when patients refused to be randomized between focal and radical therapy, Dr. George said.

Focal therapy is now in the same position that active surveillance was a few years ago, according to Dr. George.

“We are hearing the same concerns about focal therapy now as we did about active surveillance,” he said. The initial evidence supporting active surveillance largely came from real-world experience and retrospective studies. The randomized data came later, and skeptics of active surveillance “were proven wrong,” he added.

But Dr. Shoag has a different take on the trajectory of focal therapy research and care in the United States. 

“I think there’s this emerging kind of tragedy happening in our field now, where you have even academic institutions offering focal therapy to patients off-trial with essentially no data to suggest it is oncologically effective,” Dr. Shoag said.

William Catalona, MD, Northwestern University Feinberg School of Medicine, Chicago, agreed, noting that too many low-risk patients are undergoing focal treatment who should be on active surveillance. “Many men are attracted to focal because they just are uncomfortable having a cancer in their body that’s not treated,” Dr. Catalona said. But “giving these patients focal therapy is really overtreatment.”

Patients with higher-risk disease who want to avoid aggressive treatment are also being lured into focal without guidelines or clear evidence to back up that option, Dr. Catalona explained.

Although it’s not clear how many men in the United States are receiving focal therapy who shouldn’t, even proponents of focal therapy, like George, have expressed concern.

Dr. George agreed that focal therapy marketing geared towards patients is drawing in some men who are not good candidates for these techniques, and feels there’s not enough objective material from medical societies or academic centers giving patients a realistic picture of focal therapy. 

“There is concern that patients may be receiving biased information,” Dr. George said, adding that it’s ultimately up to the physician to reconcile the best available evidence, understand the outcomes, and discuss these options with the patient to guide them to what’s best.

At the end of the day, Dr. Spratt said, physicians giving focal therapy off a clinical trial need to pause and ask themselves “why are they giving a treatment that remains investigational by payers, not recommended by any major guideline, and that lacks any randomized evidence?” 

Mr. LaFrate does not regret his decision to forgo focal therapy in 2013. He has been on active surveillance for about a decade now.

Following an MRI in 2022, Mr. LaFrate’s radiology report found that “clinically significant cancer is very unlikely to be present.”

Still, his PSA has risen two points in the past year to 14. His current urologist feels that the PSA is going up because there’s cancer present and is suggesting focal therapy for Mr. LaFrate.

Mr. LaFrate, who has prostate enlargement issues, remains skeptical of focal therapy and is still resisting the sales pitch.

“My doctor is not aggressively pushing it. He’s just giving me that as one of my options,” he said. “I just have a hunch I don’t need it at this point.”

A version of this article appeared on Medscape.com.

In 2013, a prostate-specific antigen (PSA) blood test revealed that Richard LaFrate’s levels had jumped. 

Previously in a normal range, his PSA was now above 6 ng/mL, indicating an elevated likelihood for prostate cancer. The jazz guitarist from Leesburg, Florida, then 70 years old, underwent a biopsy, which found two Gleason 6 lesions. 

Mr. LaFrate had low-risk prostate cancer.

Guidelines now recommend active surveillance for patients like Mr. LaFrate, who have low-risk disease. This strategy would mean monitoring the cancer until LaFrate required treatment, with the upside being he might never need therapy.

Mr. LaFrate’s urologist, however, was pushing whole gland surgery — an invasive and unnecessary procedure given his diagnosis and age. 

Mr. LaFrate decided to look for another doctor. He filled out a form online that pointed him to a new urologist who offered him one option: An investigational procedure known as high-intensity focused ultrasound.

At the time, high-intensity focused ultrasound — a form of focal therapy — was being studied in the United States to treat men with low or intermediate-risk prostate cancer, but it was still relatively early days.

Mr. LaFrate’s urologist asked him to pay $25,000 out of pocket to undergo the focal procedure at a clinic in the Bahamas. He refused and, ultimately, landed on active surveillance as the best strategy to manage for his low-risk disease.

That urologist was “a shyster in my opinion,” Mr. LaFrate said. 

Over the past 10 years, the popularity of focal therapy has grown among men with intermediate-risk prostate cancer — Gleason 3+4 (grade group 2) tumors — as an alternative to invasive surgery and active surveillance. Prestigious medical centers, such as Cleveland Clinic, Mayo Clinic, Memorial Sloan Kettering, UCLA, and the University of Chicago, routinely offer focal therapy. 

But use of the techniques remains controversial and costly.

As the Cleveland Clinic’s website acknowledges, although “the use of focal therapy for localized prostate cancer appears to be a promising development in a number of ways, it is still considered investigational and not yet part of standard therapy.” Major caveats to focal therapy include unknown long-term effectiveness, the possibility of leaving behind untreated cancer, and higher overall costs. 

No major national guidelines endorse the use of focal therapy, unless offered in a research or clinical trial setting. Insurance companies, such as Aetna, Blue Cross Blue Shield, and United, also consider focal therapy for prostate cancer investigational and don’t cover it.

Without a stamp of approval from guideline bodies and insurance companies, patients, like Mr. LaFrate, remain vulnerable to the high out-of-pocket costs for these focal techniques. 

“Almost every place charges $15,000-$30,000 in cash,” said Daniel Spratt, MD, radiation oncology chair at University Hospitals Seidman Cancer Center and Case Western Reserve University in Cleveland. 

Dr. Spratt has seen hundreds of patients after focal therapy, some from prominent centers, who have emptied their bank accounts to undergo treatment with the promise of great results and ultimately felt misled when the cancer has recurred.

“It pains me that there are doctors willing to ignore the Hippocratic oath of ‘Do No Harm’ simply to jump on this fad to bring in revenue,” Dr. Spratt said. 
 

Evidence-Based or Oversold?

Focal therapy gained a foothold in the United Kingdom well before the United States.

Hashim Ahmed, FRCS, urology chair at Imperial College London, has used focal therapy for 15 years, treated over 1000 patients, and taught dozens of surgeons how to use the leading focal therapies — focal cryoablation, in which surgeons use a needle-thin probe to target, freeze, and kill prostate tumors, as well as high-intensity focused ultrasound, which uses sound wave energy to superheat and kill tumors.

“Certainly, in the United Kingdom, focal therapy has been prime time in a number of centers for a number of years,” Dr. Ahmed said. 

In the United States, focal therapy has become an attractive option for men with prostate cancer who want to avoid radiation or radical prostatectomy but don’t feel comfortable simply monitoring their disease with active surveillance. Experts from specialized focal therapy centers touting the promise of this “innovative technique” predict its routine use in the next few years.

But the excitement surrounding the use of focal therapy in prostate cancer has outpaced broader acceptance.

In 2015, the FDA approved high-intensity focused ultrasound to treat prostatic disease, but not prostate cancer specifically. Although the approval language “means that companies cannot advertise that their devices can be used for prostate cancer,” physicians can still determine how to use the technology, which includes treating prostate cancer, Dr. Ahmed said. 

The evidence is starting to catch up to the demand. The latest research suggests that the partial-gland techniques may stand up well to radical prostatectomy.

A 2022 prospective database study comparing radical prostatectomies to focal therapy — mostly high-intensity focused ultrasound — in more than 800 men found similar rates of failure-free survival in the two groups at the 8-year follow-up. A 2019 registry study found that failure-free survival at 3 years was just over 90% in high and intermediate-risk patients receiving focal cryotherapy, with the rate rising to about 93% for the intermediate-risk group. And a 2018 prospective study of 625 patients with intermediate or high-risk prostate cancer who underwent high-intensity focused ultrasound had 5-year metastasis-free survival of 98% and overall survival rates of 100%.

One of the biggest draws of focal therapy vs more aggressive treatments is the “massive differences in side-effect profiles,” said Dr. Ahmed.

In a 2021 meta-analysis, researchers found that 6 months after high-intensity focused ultrasound, 98% of patients remained continent and 80% retained erectile function, while erectile dysfunction can occur in 30% to as many as 85% of patients following prostatectomy or radiotherapy and urinary incontinence can occur in as many as 40% of patients.

Despite these potential advantages of focal therapy, the long-term efficacy of the techniques remains uncertain.

A recent study from a team at MSK, for instance, reported that 40% of men with intermediate (grade 2) or high-risk (grade 3) disease had residual cancer following MRI-guided focused ultrasound. A 2020 prospective registry study found that almost 20% of patients undergoing high-intensity focal ultrasound required a second round following a recurrence. 

Dr. Spratt worries that patients who recur after focal therapy may go on to receive a second round — often offered at half price — and will still ultimately need surgery or radiation therapy later. By that point, however, patients may have spent as much as $45,000 — ie, $30,000 on the initial and another $15,000 on the follow-up procedure.

When patients see Dr. Spratt after a recurrence, he informs them that their side effects will be worse if he gives them radiation or surgery now vs if he had given them curative therapy upfront. “But this is what we’re left with,” he tells them.

Another big concern in the field is “the quality of data for focal therapy is overwhelmingly poor,” said Jonathan Shoag, MD, a urologic oncologist at University Hospitals and an associate professor of urology at Case Western Reserve University School of Medicine in Cleveland. “Essentially, the bulk of the data is from single-institution retrospective series without defined follow-up protocols or endpoints.”

The American Urological Association (AUA) has even cautioned experts and patients about the lack of high-quality data comparing focal therapy techniques to radiation therapy, surgery, and active surveillance. According to the AUA, focal options should only be considered in intermediate-risk prostate cancer in a clinical trial setting.

“The lack of randomized clinical trials poses a major stumbling block for the field,” said Dr. Ahmed.

Although randomized trials would be ideal, the results would take many years to mature, and growing patient demand for these less invasive focal procedures has made randomized trials difficult to complete, explained Arvin George, MD, associate professor at Johns Hopkins School of Medicine in Baltimore. Several randomized trials attempted in Norway and the United Kingdom, for instance, fell apart when patients refused to be randomized between focal and radical therapy, Dr. George said.

Focal therapy is now in the same position that active surveillance was a few years ago, according to Dr. George.

“We are hearing the same concerns about focal therapy now as we did about active surveillance,” he said. The initial evidence supporting active surveillance largely came from real-world experience and retrospective studies. The randomized data came later, and skeptics of active surveillance “were proven wrong,” he added.

But Dr. Shoag has a different take on the trajectory of focal therapy research and care in the United States. 

“I think there’s this emerging kind of tragedy happening in our field now, where you have even academic institutions offering focal therapy to patients off-trial with essentially no data to suggest it is oncologically effective,” Dr. Shoag said.

William Catalona, MD, Northwestern University Feinberg School of Medicine, Chicago, agreed, noting that too many low-risk patients are undergoing focal treatment who should be on active surveillance. “Many men are attracted to focal because they just are uncomfortable having a cancer in their body that’s not treated,” Dr. Catalona said. But “giving these patients focal therapy is really overtreatment.”

Patients with higher-risk disease who want to avoid aggressive treatment are also being lured into focal without guidelines or clear evidence to back up that option, Dr. Catalona explained.

Although it’s not clear how many men in the United States are receiving focal therapy who shouldn’t, even proponents of focal therapy, like George, have expressed concern.

Dr. George agreed that focal therapy marketing geared towards patients is drawing in some men who are not good candidates for these techniques, and feels there’s not enough objective material from medical societies or academic centers giving patients a realistic picture of focal therapy. 

“There is concern that patients may be receiving biased information,” Dr. George said, adding that it’s ultimately up to the physician to reconcile the best available evidence, understand the outcomes, and discuss these options with the patient to guide them to what’s best.

At the end of the day, Dr. Spratt said, physicians giving focal therapy off a clinical trial need to pause and ask themselves “why are they giving a treatment that remains investigational by payers, not recommended by any major guideline, and that lacks any randomized evidence?” 

Mr. LaFrate does not regret his decision to forgo focal therapy in 2013. He has been on active surveillance for about a decade now.

Following an MRI in 2022, Mr. LaFrate’s radiology report found that “clinically significant cancer is very unlikely to be present.”

Still, his PSA has risen two points in the past year to 14. His current urologist feels that the PSA is going up because there’s cancer present and is suggesting focal therapy for Mr. LaFrate.

Mr. LaFrate, who has prostate enlargement issues, remains skeptical of focal therapy and is still resisting the sales pitch.

“My doctor is not aggressively pushing it. He’s just giving me that as one of my options,” he said. “I just have a hunch I don’t need it at this point.”

A version of this article appeared on Medscape.com.

TOPLINE:

Transcatheter arterial chemoembolization (TACE), a standard treatment for liver metastases from colorectal cancer, shows promise for treating locally advanced rectal tumors.

METHODOLOGY:

• The combination of neoadjuvant chemoradiotherapy, total mesorectal excision, and postoperative adjuvant chemotherapy is the current standard of care for locally advanced rectal cancer. But with pathological complete response rates of only 10%-15% and more than 30% of patients developing distant metastases within 3 years, outcomes remain suboptimal.
• Chinese investigators took a step to improve the situation, applying TACE — a standard treatment for colorectal liver metastases — to rectal tumors, dubbing the approach transcatheter rectal arterial chemoembolization (TRACE).
• As in TACE, TRACE uses precisely injected chemotherapeutic and vaso-occlusive agents to shut down blood flow to tumors, starving them of oxygen and nutrients.
• The research team tried the approach in 111 patients with stage II or III rectal tumors and performance status scores of 0-1.
• TRACE was delivered with oxaliplatin and followed by radiotherapy and S1 chemotherapy (tegafur, gimeracil, and potassium oteracil). Total mesorectal excisions were performed 4-8 weeks later, followed by mFOLFOX6 (5-fluorouracil, leucovorin, and oxaliplatin) or CAPOX (oxaliplatin and capecitabine) chemotherapy for 4-6 months.

TAKEAWAY:

• Overall, 20.7% of patients undergoing TRACE had a pathological complete response, and almost half (48.65%) had a major pathological response.
• Nearly 62% of patients were disease-free at 5 years, and almost 75% were alive at 5 years.
• No serious surgical complications occurred, but 21.6% of patients had postoperative complications. Overall, about 26% of patients (29 of 111) had grade 3/4 toxicities.

IN PRACTICE:

“The addition of transcatheter rectal arterial chemoembolisation to the neoadjuvant therapy can improve the pathological remission rate and prognosis in patients with locally advanced rectal cancer, without increasing the incidence of preoperative adverse events and postoperative complications,” the researchers concluded. “Given its promising effectiveness and safe profile, incorporating TRACE into the standard treatment strategy for patients with [locally advanced rectal cancer] should be considered.”

SOURCE:

The work, led by W. Yang of the Army Medical University in Chongqing, China, was published in Clinical Oncology.

LIMITATIONS:

The study was performed at a single center with no control arm in a Chinese population.

DISCLOSURES:

The work was funded by the Third Military Medical University in China. The investigators had no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Transcatheter arterial chemoembolization (TACE), a standard treatment for liver metastases from colorectal cancer, shows promise for treating locally advanced rectal tumors.

METHODOLOGY:

• The combination of neoadjuvant chemoradiotherapy, total mesorectal excision, and postoperative adjuvant chemotherapy is the current standard of care for locally advanced rectal cancer. But with pathological complete response rates of only 10%-15% and more than 30% of patients developing distant metastases within 3 years, outcomes remain suboptimal.
• Chinese investigators took a step to improve the situation, applying TACE — a standard treatment for colorectal liver metastases — to rectal tumors, dubbing the approach transcatheter rectal arterial chemoembolization (TRACE).
• As in TACE, TRACE uses precisely injected chemotherapeutic and vaso-occlusive agents to shut down blood flow to tumors, starving them of oxygen and nutrients.
• The research team tried the approach in 111 patients with stage II or III rectal tumors and performance status scores of 0-1.
• TRACE was delivered with oxaliplatin and followed by radiotherapy and S1 chemotherapy (tegafur, gimeracil, and potassium oteracil). Total mesorectal excisions were performed 4-8 weeks later, followed by mFOLFOX6 (5-fluorouracil, leucovorin, and oxaliplatin) or CAPOX (oxaliplatin and capecitabine) chemotherapy for 4-6 months.

TAKEAWAY:

• Overall, 20.7% of patients undergoing TRACE had a pathological complete response, and almost half (48.65%) had a major pathological response.
• Nearly 62% of patients were disease-free at 5 years, and almost 75% were alive at 5 years.
• No serious surgical complications occurred, but 21.6% of patients had postoperative complications. Overall, about 26% of patients (29 of 111) had grade 3/4 toxicities.

IN PRACTICE:

“The addition of transcatheter rectal arterial chemoembolisation to the neoadjuvant therapy can improve the pathological remission rate and prognosis in patients with locally advanced rectal cancer, without increasing the incidence of preoperative adverse events and postoperative complications,” the researchers concluded. “Given its promising effectiveness and safe profile, incorporating TRACE into the standard treatment strategy for patients with [locally advanced rectal cancer] should be considered.”

SOURCE:

The work, led by W. Yang of the Army Medical University in Chongqing, China, was published in Clinical Oncology.

LIMITATIONS:

The study was performed at a single center with no control arm in a Chinese population.

DISCLOSURES:

The work was funded by the Third Military Medical University in China. The investigators had no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Transcatheter arterial chemoembolization (TACE), a standard treatment for liver metastases from colorectal cancer, shows promise for treating locally advanced rectal tumors.

METHODOLOGY:

• The combination of neoadjuvant chemoradiotherapy, total mesorectal excision, and postoperative adjuvant chemotherapy is the current standard of care for locally advanced rectal cancer. But with pathological complete response rates of only 10%-15% and more than 30% of patients developing distant metastases within 3 years, outcomes remain suboptimal.
• Chinese investigators took a step to improve the situation, applying TACE — a standard treatment for colorectal liver metastases — to rectal tumors, dubbing the approach transcatheter rectal arterial chemoembolization (TRACE).
• As in TACE, TRACE uses precisely injected chemotherapeutic and vaso-occlusive agents to shut down blood flow to tumors, starving them of oxygen and nutrients.
• The research team tried the approach in 111 patients with stage II or III rectal tumors and performance status scores of 0-1.
• TRACE was delivered with oxaliplatin and followed by radiotherapy and S1 chemotherapy (tegafur, gimeracil, and potassium oteracil). Total mesorectal excisions were performed 4-8 weeks later, followed by mFOLFOX6 (5-fluorouracil, leucovorin, and oxaliplatin) or CAPOX (oxaliplatin and capecitabine) chemotherapy for 4-6 months.

TAKEAWAY:

• Overall, 20.7% of patients undergoing TRACE had a pathological complete response, and almost half (48.65%) had a major pathological response.
• Nearly 62% of patients were disease-free at 5 years, and almost 75% were alive at 5 years.
• No serious surgical complications occurred, but 21.6% of patients had postoperative complications. Overall, about 26% of patients (29 of 111) had grade 3/4 toxicities.

IN PRACTICE:

“The addition of transcatheter rectal arterial chemoembolisation to the neoadjuvant therapy can improve the pathological remission rate and prognosis in patients with locally advanced rectal cancer, without increasing the incidence of preoperative adverse events and postoperative complications,” the researchers concluded. “Given its promising effectiveness and safe profile, incorporating TRACE into the standard treatment strategy for patients with [locally advanced rectal cancer] should be considered.”

SOURCE:

The work, led by W. Yang of the Army Medical University in Chongqing, China, was published in Clinical Oncology.

LIMITATIONS:

The study was performed at a single center with no control arm in a Chinese population.

DISCLOSURES:

The work was funded by the Third Military Medical University in China. The investigators had no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

ChatGPT (version 3.5) provides relatively poor and inconsistent responses when asked about appropriate colorectal cancer (CRC) screening and surveillance, a new study showed.

METHODOLOGY:

• Three board-certified gastroenterologists with 10+ years of clinical experience developed five CRC screening and five CRC surveillance clinical vignettes (with multiple choice answers), which were fed to ChatGPT version 3.5.
• ChatGPT’s responses were recorded over four separate sessions and screened for accuracy to determine reliability of the tool.
• The average number of correct answers was compared to that of 238 gastroenterologists and colorectal surgeons answering the same questions with and without the help of a previously validated CRC screening mobile app.

TAKEAWAY:

• ChatGPT’s average overall performance was 45%; the average number of correct answers was 2.75 for screening and 1.75 for surveillance.
• ChatGPT’s responses were inconsistent in a large proportion of questions; the tool gave a different answer in four questions among the different sessions.
• The average number of total correct answers of ChatGPT was significantly lower (P < .001) than that of physicians with and without the mobile app (7.71 and 5.62 correct answers, respectively).

IN PRACTICE:

“The use of validated mobile apps with decision-making algorithms could serve as more reliable assistants until large language models developed with AI are further refined,” the authors concluded.

SOURCE:

The study, with first author Lisandro Pereyra, MD, Department of Gastroenterology, Hospital Alemán of Buenos Aires, Argentina, was published online on February 7, 2024, in the Journal of Clinical Gastroenterology.

LIMITATIONS:

The 10 clinical vignettes represented a relatively small sample size to assess accuracy. The study did not use the latest version of ChatGPT. No “fine-tuning” attempts with inputs of diverse prompts, instructions, or relevant data were performed, which could potentially improve the performance of the chatbot.

DISCLOSURES:

The study had no specific funding. The authors declared no conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

ChatGPT (version 3.5) provides relatively poor and inconsistent responses when asked about appropriate colorectal cancer (CRC) screening and surveillance, a new study showed.

METHODOLOGY:

• Three board-certified gastroenterologists with 10+ years of clinical experience developed five CRC screening and five CRC surveillance clinical vignettes (with multiple choice answers), which were fed to ChatGPT version 3.5.
• ChatGPT’s responses were recorded over four separate sessions and screened for accuracy to determine reliability of the tool.
• The average number of correct answers was compared to that of 238 gastroenterologists and colorectal surgeons answering the same questions with and without the help of a previously validated CRC screening mobile app.

TAKEAWAY:

• ChatGPT’s average overall performance was 45%; the average number of correct answers was 2.75 for screening and 1.75 for surveillance.
• ChatGPT’s responses were inconsistent in a large proportion of questions; the tool gave a different answer in four questions among the different sessions.
• The average number of total correct answers of ChatGPT was significantly lower (P < .001) than that of physicians with and without the mobile app (7.71 and 5.62 correct answers, respectively).

IN PRACTICE:

“The use of validated mobile apps with decision-making algorithms could serve as more reliable assistants until large language models developed with AI are further refined,” the authors concluded.

SOURCE:

The study, with first author Lisandro Pereyra, MD, Department of Gastroenterology, Hospital Alemán of Buenos Aires, Argentina, was published online on February 7, 2024, in the Journal of Clinical Gastroenterology.

LIMITATIONS:

The 10 clinical vignettes represented a relatively small sample size to assess accuracy. The study did not use the latest version of ChatGPT. No “fine-tuning” attempts with inputs of diverse prompts, instructions, or relevant data were performed, which could potentially improve the performance of the chatbot.

DISCLOSURES:

The study had no specific funding. The authors declared no conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

ChatGPT (version 3.5) provides relatively poor and inconsistent responses when asked about appropriate colorectal cancer (CRC) screening and surveillance, a new study showed.

METHODOLOGY:

• Three board-certified gastroenterologists with 10+ years of clinical experience developed five CRC screening and five CRC surveillance clinical vignettes (with multiple choice answers), which were fed to ChatGPT version 3.5.
• ChatGPT’s responses were recorded over four separate sessions and screened for accuracy to determine reliability of the tool.
• The average number of correct answers was compared to that of 238 gastroenterologists and colorectal surgeons answering the same questions with and without the help of a previously validated CRC screening mobile app.

TAKEAWAY:

• ChatGPT’s average overall performance was 45%; the average number of correct answers was 2.75 for screening and 1.75 for surveillance.
• ChatGPT’s responses were inconsistent in a large proportion of questions; the tool gave a different answer in four questions among the different sessions.
• The average number of total correct answers of ChatGPT was significantly lower (P < .001) than that of physicians with and without the mobile app (7.71 and 5.62 correct answers, respectively).

IN PRACTICE:

“The use of validated mobile apps with decision-making algorithms could serve as more reliable assistants until large language models developed with AI are further refined,” the authors concluded.

SOURCE:

The study, with first author Lisandro Pereyra, MD, Department of Gastroenterology, Hospital Alemán of Buenos Aires, Argentina, was published online on February 7, 2024, in the Journal of Clinical Gastroenterology.

LIMITATIONS:

The 10 clinical vignettes represented a relatively small sample size to assess accuracy. The study did not use the latest version of ChatGPT. No “fine-tuning” attempts with inputs of diverse prompts, instructions, or relevant data were performed, which could potentially improve the performance of the chatbot.

DISCLOSURES:

The study had no specific funding. The authors declared no conflicts of interest.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved lifileucel (Amtagvi, Iovance Biotherapeutics) for the treatment of certain adults with unresectable or metastatic melanoma, marking the first approval of a cellular therapy in the solid tumor setting.

Specifically, the tumor-derived autologous T-cell immunotherapy is indicated for adult patients previously treated with a programmed cell death protein 1 (PD-1)–blocking antibody, and if BRAF V600–positive, a BRAF inhibitor with or without an MEK inhibitor. 

The approval “offers hope to those with advanced melanoma who have progressed following initial standard of care therapies, as the current treatment options are not effective for many patients,” Samantha R. Guild, JD, president, AIM at Melanoma Foundation, stated in a press release. “This one-time cell therapy represents a promising innovation for the melanoma community, and we are excited by its potential to transform care for patients who are in dire need of additional therapeutic options.”

The approval was based on findings from the open-label single-arm global C-144-01 clinical trial, which showed an objective response rate of 31.5% in 73 patients treated within the recommended dosing rage of 7.5 x 109 to 72 x 109 viable cells. Complete responses occurred in three patients (4.1%) and partial responses occurred in 20 patients (27.4%)

Median duration of response was not reached at 18.6 months of follow-up. The median time to initial response to the therapy was 1.5 months, according to an FDA press release.

“Unresectable or metastatic melanoma is an aggressive form of cancer that can be fatal,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research stated in the FDA release. “The approval of Amtagvi represents the culmination of scientific and clinical research efforts leading to a novel T cell immunotherapy for patients with limited treatment options.”

“The melanoma community is so grateful to the patients, caregivers, and clinicians who have made the clinical trials of this therapy possible and got lifileucel to approval,” Allison Betof Warner, MD, PhD, director of Melanoma Medical Oncology at Stanford Medicine, wrote on X. “We are very excited to bring this life-saving therapy to patients ASAP! Available immediately at @StanfordCancer!!!”

For the C-144-01 trial, lifileucel was administered after a lymphodepletion regimen of 60 mg/kg/d of cyclophosphamide for 2 days followed by 25 mg/m2/d of fludarabine for 5 days. Between 3 and 34 hours after infusion, patients received 600,000 IU/Kg of the interleukin 2 aldesleukin every 8-12 hours for up to six doses to support cell expansion in vivo. 

The full prescribing information for lifileucel contains a boxed warning for treatment-related mortality, prolonged severe cytopenia, severe infection, cardiopulmonary, and renal impairment. The most common adverse reactions, which occurred in at least 20% of patients, were chills, pyrexia, fatigue, tachycardia, diarrhea, febrile neutropenia, edema, rash hypotension, alopecia, infection, hypoxia, and dyspnea.

“Patients receiving this product should be closely monitored before and after infusion for signs and symptoms of adverse reactions. Treatment should be withheld or discontinued in the presence of these symptoms, as indicated,” according to the FDA statement.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved lifileucel (Amtagvi, Iovance Biotherapeutics) for the treatment of certain adults with unresectable or metastatic melanoma, marking the first approval of a cellular therapy in the solid tumor setting.

Specifically, the tumor-derived autologous T-cell immunotherapy is indicated for adult patients previously treated with a programmed cell death protein 1 (PD-1)–blocking antibody, and if BRAF V600–positive, a BRAF inhibitor with or without an MEK inhibitor. 

The approval “offers hope to those with advanced melanoma who have progressed following initial standard of care therapies, as the current treatment options are not effective for many patients,” Samantha R. Guild, JD, president, AIM at Melanoma Foundation, stated in a press release. “This one-time cell therapy represents a promising innovation for the melanoma community, and we are excited by its potential to transform care for patients who are in dire need of additional therapeutic options.”

The approval was based on findings from the open-label single-arm global C-144-01 clinical trial, which showed an objective response rate of 31.5% in 73 patients treated within the recommended dosing rage of 7.5 x 109 to 72 x 109 viable cells. Complete responses occurred in three patients (4.1%) and partial responses occurred in 20 patients (27.4%)

Median duration of response was not reached at 18.6 months of follow-up. The median time to initial response to the therapy was 1.5 months, according to an FDA press release.

“Unresectable or metastatic melanoma is an aggressive form of cancer that can be fatal,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research stated in the FDA release. “The approval of Amtagvi represents the culmination of scientific and clinical research efforts leading to a novel T cell immunotherapy for patients with limited treatment options.”

“The melanoma community is so grateful to the patients, caregivers, and clinicians who have made the clinical trials of this therapy possible and got lifileucel to approval,” Allison Betof Warner, MD, PhD, director of Melanoma Medical Oncology at Stanford Medicine, wrote on X. “We are very excited to bring this life-saving therapy to patients ASAP! Available immediately at @StanfordCancer!!!”

For the C-144-01 trial, lifileucel was administered after a lymphodepletion regimen of 60 mg/kg/d of cyclophosphamide for 2 days followed by 25 mg/m2/d of fludarabine for 5 days. Between 3 and 34 hours after infusion, patients received 600,000 IU/Kg of the interleukin 2 aldesleukin every 8-12 hours for up to six doses to support cell expansion in vivo. 

The full prescribing information for lifileucel contains a boxed warning for treatment-related mortality, prolonged severe cytopenia, severe infection, cardiopulmonary, and renal impairment. The most common adverse reactions, which occurred in at least 20% of patients, were chills, pyrexia, fatigue, tachycardia, diarrhea, febrile neutropenia, edema, rash hypotension, alopecia, infection, hypoxia, and dyspnea.

“Patients receiving this product should be closely monitored before and after infusion for signs and symptoms of adverse reactions. Treatment should be withheld or discontinued in the presence of these symptoms, as indicated,” according to the FDA statement.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved lifileucel (Amtagvi, Iovance Biotherapeutics) for the treatment of certain adults with unresectable or metastatic melanoma, marking the first approval of a cellular therapy in the solid tumor setting.

Specifically, the tumor-derived autologous T-cell immunotherapy is indicated for adult patients previously treated with a programmed cell death protein 1 (PD-1)–blocking antibody, and if BRAF V600–positive, a BRAF inhibitor with or without an MEK inhibitor. 

The approval “offers hope to those with advanced melanoma who have progressed following initial standard of care therapies, as the current treatment options are not effective for many patients,” Samantha R. Guild, JD, president, AIM at Melanoma Foundation, stated in a press release. “This one-time cell therapy represents a promising innovation for the melanoma community, and we are excited by its potential to transform care for patients who are in dire need of additional therapeutic options.”

The approval was based on findings from the open-label single-arm global C-144-01 clinical trial, which showed an objective response rate of 31.5% in 73 patients treated within the recommended dosing rage of 7.5 x 109 to 72 x 109 viable cells. Complete responses occurred in three patients (4.1%) and partial responses occurred in 20 patients (27.4%)

Median duration of response was not reached at 18.6 months of follow-up. The median time to initial response to the therapy was 1.5 months, according to an FDA press release.

“Unresectable or metastatic melanoma is an aggressive form of cancer that can be fatal,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research stated in the FDA release. “The approval of Amtagvi represents the culmination of scientific and clinical research efforts leading to a novel T cell immunotherapy for patients with limited treatment options.”

“The melanoma community is so grateful to the patients, caregivers, and clinicians who have made the clinical trials of this therapy possible and got lifileucel to approval,” Allison Betof Warner, MD, PhD, director of Melanoma Medical Oncology at Stanford Medicine, wrote on X. “We are very excited to bring this life-saving therapy to patients ASAP! Available immediately at @StanfordCancer!!!”

For the C-144-01 trial, lifileucel was administered after a lymphodepletion regimen of 60 mg/kg/d of cyclophosphamide for 2 days followed by 25 mg/m2/d of fludarabine for 5 days. Between 3 and 34 hours after infusion, patients received 600,000 IU/Kg of the interleukin 2 aldesleukin every 8-12 hours for up to six doses to support cell expansion in vivo. 

The full prescribing information for lifileucel contains a boxed warning for treatment-related mortality, prolonged severe cytopenia, severe infection, cardiopulmonary, and renal impairment. The most common adverse reactions, which occurred in at least 20% of patients, were chills, pyrexia, fatigue, tachycardia, diarrhea, febrile neutropenia, edema, rash hypotension, alopecia, infection, hypoxia, and dyspnea.

“Patients receiving this product should be closely monitored before and after infusion for signs and symptoms of adverse reactions. Treatment should be withheld or discontinued in the presence of these symptoms, as indicated,” according to the FDA statement.

A version of this article appeared on Medscape.com.

TOPLINE: 

In patients with stages I-III colorectal cancer (CRC) who are cancer-free 5 years after surgery, the incidence of late recurrence or metachronous disease after 5 years is low and has decreased over time, new data showed.

METHODOLOGY:

• Recent treatment advances in CRC have reduced the likelihood that patients with nonmetastatic disease will recur or develop a second primary cancer more than 6 months after the first. Although late recurrences and metachronous CRC remain infrequent, it’s not clear if patients might benefit from longer term surveillance.
• To investigate whether extending surveillance beyond the recommended 5 years is beneficial, researchers assessed the incidence of late recurrence, metachronous CRC, and second primary cancers 5 years after surgical resection with curative intent.
• The researchers identified patients with stages I-III CRC, under age 80 years, from Danish healthcare registries who underwent surgical resection between January 2004 and December 2013.
• A total of 8883 patients were followed from 5 years after primary surgery until the date of recurrence, metachronous CRC, or second non-CRC primary cancer.

TAKEAWAY:

• Between 5 and 10 years after surgery, 370 survivors developed late recurrence (4.16%), 270 developed metachronous disease (3.0%), and 635 were diagnosed with a second primary cancer (7.15%).
• During 2009-2013 and 2004-2008, the risk for late recurrence decreased by 48% (5.6% vs 2.9%; subdistribution hazard ratio [sHR], 0.52) and the risk for metachronous disease decreased by 50% (4.1% vs 2.1%; sHR, 0.50).
• During the same timeframe, the risk for second non-CRC primary cancer remained unchanged (7.1% vs 7.1%; sHR, 0.98).
• Compared with patients diagnosed with late recurrences (46%), 5-year overall survival was higher for patients with metachronous CRC (72%; adjusted HR, 0.37) and slightly higher for those with second primary cancers (48%; adjusted HR, 0.78).

IN PRACTICE:

Because the incidences of late recurrence and metachronous CRC are low and decreased between 2004 and 2013, the data do not support extending CRC-specific surveillance beyond 5 years, the authors concluded. “Symptoms or suspicion of a cancer occurring 5-10 years from primary CRC treatment, is more likely to represent a non-CRC cancer (7.1%).”

SOURCE:

This study, led by Jesper Nors from Aarhus University Hospital, Aarhus, Denmark, was published on February 7, 2024, in the International Journal of Cancer.

LIMITATIONS:

Misclassification of a late recurrence or metachronous CRC could have affected the findings.

DISCLOSURES:

This work was funded by Institute of Clinical Medicine, Aarhus University, Denmark, Novo Nordisk Foundation, Innovation Fund Denmark, and the Danish Cancer Society. The authors reported no conflict of interests.

A version of this article appeared on Medscape.com.

TOPLINE: 

In patients with stages I-III colorectal cancer (CRC) who are cancer-free 5 years after surgery, the incidence of late recurrence or metachronous disease after 5 years is low and has decreased over time, new data showed.

METHODOLOGY:

• Recent treatment advances in CRC have reduced the likelihood that patients with nonmetastatic disease will recur or develop a second primary cancer more than 6 months after the first. Although late recurrences and metachronous CRC remain infrequent, it’s not clear if patients might benefit from longer term surveillance.
• To investigate whether extending surveillance beyond the recommended 5 years is beneficial, researchers assessed the incidence of late recurrence, metachronous CRC, and second primary cancers 5 years after surgical resection with curative intent.
• The researchers identified patients with stages I-III CRC, under age 80 years, from Danish healthcare registries who underwent surgical resection between January 2004 and December 2013.
• A total of 8883 patients were followed from 5 years after primary surgery until the date of recurrence, metachronous CRC, or second non-CRC primary cancer.

TAKEAWAY:

• Between 5 and 10 years after surgery, 370 survivors developed late recurrence (4.16%), 270 developed metachronous disease (3.0%), and 635 were diagnosed with a second primary cancer (7.15%).
• During 2009-2013 and 2004-2008, the risk for late recurrence decreased by 48% (5.6% vs 2.9%; subdistribution hazard ratio [sHR], 0.52) and the risk for metachronous disease decreased by 50% (4.1% vs 2.1%; sHR, 0.50).
• During the same timeframe, the risk for second non-CRC primary cancer remained unchanged (7.1% vs 7.1%; sHR, 0.98).
• Compared with patients diagnosed with late recurrences (46%), 5-year overall survival was higher for patients with metachronous CRC (72%; adjusted HR, 0.37) and slightly higher for those with second primary cancers (48%; adjusted HR, 0.78).

IN PRACTICE:

Because the incidences of late recurrence and metachronous CRC are low and decreased between 2004 and 2013, the data do not support extending CRC-specific surveillance beyond 5 years, the authors concluded. “Symptoms or suspicion of a cancer occurring 5-10 years from primary CRC treatment, is more likely to represent a non-CRC cancer (7.1%).”

SOURCE:

This study, led by Jesper Nors from Aarhus University Hospital, Aarhus, Denmark, was published on February 7, 2024, in the International Journal of Cancer.

LIMITATIONS:

Misclassification of a late recurrence or metachronous CRC could have affected the findings.

DISCLOSURES:

This work was funded by Institute of Clinical Medicine, Aarhus University, Denmark, Novo Nordisk Foundation, Innovation Fund Denmark, and the Danish Cancer Society. The authors reported no conflict of interests.

A version of this article appeared on Medscape.com.

TOPLINE: 

In patients with stages I-III colorectal cancer (CRC) who are cancer-free 5 years after surgery, the incidence of late recurrence or metachronous disease after 5 years is low and has decreased over time, new data showed.

METHODOLOGY:

• Recent treatment advances in CRC have reduced the likelihood that patients with nonmetastatic disease will recur or develop a second primary cancer more than 6 months after the first. Although late recurrences and metachronous CRC remain infrequent, it’s not clear if patients might benefit from longer term surveillance.
• To investigate whether extending surveillance beyond the recommended 5 years is beneficial, researchers assessed the incidence of late recurrence, metachronous CRC, and second primary cancers 5 years after surgical resection with curative intent.
• The researchers identified patients with stages I-III CRC, under age 80 years, from Danish healthcare registries who underwent surgical resection between January 2004 and December 2013.
• A total of 8883 patients were followed from 5 years after primary surgery until the date of recurrence, metachronous CRC, or second non-CRC primary cancer.

TAKEAWAY:

• Between 5 and 10 years after surgery, 370 survivors developed late recurrence (4.16%), 270 developed metachronous disease (3.0%), and 635 were diagnosed with a second primary cancer (7.15%).
• During 2009-2013 and 2004-2008, the risk for late recurrence decreased by 48% (5.6% vs 2.9%; subdistribution hazard ratio [sHR], 0.52) and the risk for metachronous disease decreased by 50% (4.1% vs 2.1%; sHR, 0.50).
• During the same timeframe, the risk for second non-CRC primary cancer remained unchanged (7.1% vs 7.1%; sHR, 0.98).
• Compared with patients diagnosed with late recurrences (46%), 5-year overall survival was higher for patients with metachronous CRC (72%; adjusted HR, 0.37) and slightly higher for those with second primary cancers (48%; adjusted HR, 0.78).

IN PRACTICE:

Because the incidences of late recurrence and metachronous CRC are low and decreased between 2004 and 2013, the data do not support extending CRC-specific surveillance beyond 5 years, the authors concluded. “Symptoms or suspicion of a cancer occurring 5-10 years from primary CRC treatment, is more likely to represent a non-CRC cancer (7.1%).”

SOURCE:

This study, led by Jesper Nors from Aarhus University Hospital, Aarhus, Denmark, was published on February 7, 2024, in the International Journal of Cancer.

LIMITATIONS:

Misclassification of a late recurrence or metachronous CRC could have affected the findings.

DISCLOSURES:

This work was funded by Institute of Clinical Medicine, Aarhus University, Denmark, Novo Nordisk Foundation, Innovation Fund Denmark, and the Danish Cancer Society. The authors reported no conflict of interests.

A version of this article appeared on Medscape.com.

Although a new study of hyperbaric oxygen therapy in JAMA Oncology has been “ anxiously awaited” by breast radiation oncologists, the trial does not provide the smoking gun evidence that would justify its routine use, according to experts.

Here’s a snapshot of the current state of affairs regarding hyperbaric oxygen therapy in breast radiation oncology.

What Is Hyperbaric Oxygen Therapy?

Hyperbaric oxygen therapy is a medical procedure aimed at reducing the late toxic effects of breast irradiation, including pain, fibrosis, and edema. Patients breathe pure oxygen at greater than atmospheric pressure in a specialized chamber or room. The process leads to increased partial pressures of oxygen in blood and tissues, which can help form new blood vessels and repair damaged irradiated tissue.
 

What Is the Current State of Play?

In 2021, the US Food and Drug Administration (FDA) cleared the therapy for a variety of disorders, including radiation injuries. Some health insurers may cover the procedure as well.

Still, the FDA has cautioned clinicians “to be wary of unproven claims of effect,” University of Toronto radiation oncologist Ezra Hahn, MD, and colleagues Aron Popovtzer, MD, and Benjamin W. Corn, MD, said in a JAMA Oncology editorial.

Despite the FDA clearance, there is limited evidence to suggest hyperbaric oxygen therapy reduces the late toxic effects of breast irradiation, and the research to date has largely come from small and non-randomized studies.

While the procedure is “seldom used by many in practice,” there is growing industry for the procedure. More than 1000 facilities in the United States offer hyperbaric oxygen therapy, but only about 15% are accredited by the Undersea and Hyperbaric Medical Society, which may signal misuse of the procedure.
 

Does the Latest Study Clarify Whether This Therapy Works?

The most recent evidence on hyperbaric oxygen therapy comes from a single-institution, randomized trial from the Netherlands, dubbed HONEY. In the trial, 189 women who experienced late toxic effects following adjuvant breast radiation were randomized 2:1 to hyperbaric oxygen therapy or a control arm. Of the 125 women offered hyperbaric oxygen therapy, only 25% (31 patients) accepted and completed treatment; those who declined received usual follow-up care.

Among women who completed hyperbaric oxygen therapy, 32% (10 of 31) reported moderate or severe pain at follow-up vs 75% of controls — a 66% reduction. Similarly, 17% of women who completed hyperbaric oxygen therapy reported moderate or severe fibrosis at follow-up vs 86% among the hypothetical treatment-completing controls — an 86% reduction. However, the authors did not observe a significant effect of hyperbaric oxygen therapy on breast edema, movement restriction, or overall quality of life.

The authors also included an intention-to-treat analysis, which included patients who declined hyperbaric oxygen therapy as part of the intervention group. This analysis estimated clinical outcomes among patients who had the intervention available to them, with some taking advantage and others not.

Overall, hyperbaric oxygen therapy “seems effective for reducing pain and fibrosis in women with late local toxic effects after breast irradiation,” concluded investigators led by Dieuwke R. Mink van der Molen, PhD, a researcher at the University Medical Centre Utrecht, the Netherlands. However, most patients offered the therapy declined the invitation, largely because of the “high treatment intensity” burden.
 

What Are the Limitations of the Current Study?

The investigators and editorialists highlighted a handful of limitations.

For one, the trial had no sham hyperbaric oxygen therapy procedure in the control group. In fact, control patients were selected from a larger cohort of ongoing studies in the Netherlands who were not aware the trial was being conducted.

Because radiation toxicity fluctuates over time and can improve on its own, “a high-quality control arm” would be needed in such a trial, especially to account for subjective and patient-reported outcomes, the editorialists said.

Another key issue: Only a quarter of women offered hyperbaric oxygen therapy agreed to and completed treatment. The treatment burden was the most common reason for declining the procedure. Study participants underwent 30-40 2-hour sessions over 6-8 weeks.
 

Will the Latest Evidence Usher This Therapy Into More Standard Use?

Probably not, the editorialists concluded.

The HONEY trial “reminds us that convenience has become a factor weighted heavily by patients during the process of decision-making,” Dr. Hahn and colleagues wrote. “Despite experiencing relatively severe symptoms, many declined hyperbaric therapy after being counseled by HONEY investigators about the time commitment.”

Despite its limitations, the trial does offer “modest evidence to justify the use of [hyperbaric oxygen therapy] in treating the chronic morbidities associated with breast irradiation,” the editorialists said. But an “adequately powered randomized, sham-controlled, double-blind trials will be necessary to truly determine the benefit.”

HONEY was partially funded by The Da Vinci Clinic, the Netherlands. The investigators didn’t have any disclosures. One of Dr. Hahn’s coauthors reported personal fees from Lutris Pharma as Chief Medical Officer.
 

A version of this article appeared on Medscape.com.

Although a new study of hyperbaric oxygen therapy in JAMA Oncology has been “ anxiously awaited” by breast radiation oncologists, the trial does not provide the smoking gun evidence that would justify its routine use, according to experts.

Here’s a snapshot of the current state of affairs regarding hyperbaric oxygen therapy in breast radiation oncology.

What Is Hyperbaric Oxygen Therapy?

Hyperbaric oxygen therapy is a medical procedure aimed at reducing the late toxic effects of breast irradiation, including pain, fibrosis, and edema. Patients breathe pure oxygen at greater than atmospheric pressure in a specialized chamber or room. The process leads to increased partial pressures of oxygen in blood and tissues, which can help form new blood vessels and repair damaged irradiated tissue.
 

What Is the Current State of Play?

In 2021, the US Food and Drug Administration (FDA) cleared the therapy for a variety of disorders, including radiation injuries. Some health insurers may cover the procedure as well.

Still, the FDA has cautioned clinicians “to be wary of unproven claims of effect,” University of Toronto radiation oncologist Ezra Hahn, MD, and colleagues Aron Popovtzer, MD, and Benjamin W. Corn, MD, said in a JAMA Oncology editorial.

Despite the FDA clearance, there is limited evidence to suggest hyperbaric oxygen therapy reduces the late toxic effects of breast irradiation, and the research to date has largely come from small and non-randomized studies.

While the procedure is “seldom used by many in practice,” there is growing industry for the procedure. More than 1000 facilities in the United States offer hyperbaric oxygen therapy, but only about 15% are accredited by the Undersea and Hyperbaric Medical Society, which may signal misuse of the procedure.
 

Does the Latest Study Clarify Whether This Therapy Works?

The most recent evidence on hyperbaric oxygen therapy comes from a single-institution, randomized trial from the Netherlands, dubbed HONEY. In the trial, 189 women who experienced late toxic effects following adjuvant breast radiation were randomized 2:1 to hyperbaric oxygen therapy or a control arm. Of the 125 women offered hyperbaric oxygen therapy, only 25% (31 patients) accepted and completed treatment; those who declined received usual follow-up care.

Among women who completed hyperbaric oxygen therapy, 32% (10 of 31) reported moderate or severe pain at follow-up vs 75% of controls — a 66% reduction. Similarly, 17% of women who completed hyperbaric oxygen therapy reported moderate or severe fibrosis at follow-up vs 86% among the hypothetical treatment-completing controls — an 86% reduction. However, the authors did not observe a significant effect of hyperbaric oxygen therapy on breast edema, movement restriction, or overall quality of life.

The authors also included an intention-to-treat analysis, which included patients who declined hyperbaric oxygen therapy as part of the intervention group. This analysis estimated clinical outcomes among patients who had the intervention available to them, with some taking advantage and others not.

Overall, hyperbaric oxygen therapy “seems effective for reducing pain and fibrosis in women with late local toxic effects after breast irradiation,” concluded investigators led by Dieuwke R. Mink van der Molen, PhD, a researcher at the University Medical Centre Utrecht, the Netherlands. However, most patients offered the therapy declined the invitation, largely because of the “high treatment intensity” burden.
 

What Are the Limitations of the Current Study?

The investigators and editorialists highlighted a handful of limitations.

For one, the trial had no sham hyperbaric oxygen therapy procedure in the control group. In fact, control patients were selected from a larger cohort of ongoing studies in the Netherlands who were not aware the trial was being conducted.

Because radiation toxicity fluctuates over time and can improve on its own, “a high-quality control arm” would be needed in such a trial, especially to account for subjective and patient-reported outcomes, the editorialists said.

Another key issue: Only a quarter of women offered hyperbaric oxygen therapy agreed to and completed treatment. The treatment burden was the most common reason for declining the procedure. Study participants underwent 30-40 2-hour sessions over 6-8 weeks.
 

Will the Latest Evidence Usher This Therapy Into More Standard Use?

Probably not, the editorialists concluded.

The HONEY trial “reminds us that convenience has become a factor weighted heavily by patients during the process of decision-making,” Dr. Hahn and colleagues wrote. “Despite experiencing relatively severe symptoms, many declined hyperbaric therapy after being counseled by HONEY investigators about the time commitment.”

Despite its limitations, the trial does offer “modest evidence to justify the use of [hyperbaric oxygen therapy] in treating the chronic morbidities associated with breast irradiation,” the editorialists said. But an “adequately powered randomized, sham-controlled, double-blind trials will be necessary to truly determine the benefit.”

HONEY was partially funded by The Da Vinci Clinic, the Netherlands. The investigators didn’t have any disclosures. One of Dr. Hahn’s coauthors reported personal fees from Lutris Pharma as Chief Medical Officer.
 

A version of this article appeared on Medscape.com.

Although a new study of hyperbaric oxygen therapy in JAMA Oncology has been “ anxiously awaited” by breast radiation oncologists, the trial does not provide the smoking gun evidence that would justify its routine use, according to experts.

Here’s a snapshot of the current state of affairs regarding hyperbaric oxygen therapy in breast radiation oncology.

What Is Hyperbaric Oxygen Therapy?

Hyperbaric oxygen therapy is a medical procedure aimed at reducing the late toxic effects of breast irradiation, including pain, fibrosis, and edema. Patients breathe pure oxygen at greater than atmospheric pressure in a specialized chamber or room. The process leads to increased partial pressures of oxygen in blood and tissues, which can help form new blood vessels and repair damaged irradiated tissue.
 

What Is the Current State of Play?

In 2021, the US Food and Drug Administration (FDA) cleared the therapy for a variety of disorders, including radiation injuries. Some health insurers may cover the procedure as well.

Still, the FDA has cautioned clinicians “to be wary of unproven claims of effect,” University of Toronto radiation oncologist Ezra Hahn, MD, and colleagues Aron Popovtzer, MD, and Benjamin W. Corn, MD, said in a JAMA Oncology editorial.

Despite the FDA clearance, there is limited evidence to suggest hyperbaric oxygen therapy reduces the late toxic effects of breast irradiation, and the research to date has largely come from small and non-randomized studies.

While the procedure is “seldom used by many in practice,” there is growing industry for the procedure. More than 1000 facilities in the United States offer hyperbaric oxygen therapy, but only about 15% are accredited by the Undersea and Hyperbaric Medical Society, which may signal misuse of the procedure.
 

Does the Latest Study Clarify Whether This Therapy Works?

The most recent evidence on hyperbaric oxygen therapy comes from a single-institution, randomized trial from the Netherlands, dubbed HONEY. In the trial, 189 women who experienced late toxic effects following adjuvant breast radiation were randomized 2:1 to hyperbaric oxygen therapy or a control arm. Of the 125 women offered hyperbaric oxygen therapy, only 25% (31 patients) accepted and completed treatment; those who declined received usual follow-up care.

Among women who completed hyperbaric oxygen therapy, 32% (10 of 31) reported moderate or severe pain at follow-up vs 75% of controls — a 66% reduction. Similarly, 17% of women who completed hyperbaric oxygen therapy reported moderate or severe fibrosis at follow-up vs 86% among the hypothetical treatment-completing controls — an 86% reduction. However, the authors did not observe a significant effect of hyperbaric oxygen therapy on breast edema, movement restriction, or overall quality of life.

The authors also included an intention-to-treat analysis, which included patients who declined hyperbaric oxygen therapy as part of the intervention group. This analysis estimated clinical outcomes among patients who had the intervention available to them, with some taking advantage and others not.

Overall, hyperbaric oxygen therapy “seems effective for reducing pain and fibrosis in women with late local toxic effects after breast irradiation,” concluded investigators led by Dieuwke R. Mink van der Molen, PhD, a researcher at the University Medical Centre Utrecht, the Netherlands. However, most patients offered the therapy declined the invitation, largely because of the “high treatment intensity” burden.
 

What Are the Limitations of the Current Study?

The investigators and editorialists highlighted a handful of limitations.

For one, the trial had no sham hyperbaric oxygen therapy procedure in the control group. In fact, control patients were selected from a larger cohort of ongoing studies in the Netherlands who were not aware the trial was being conducted.

Because radiation toxicity fluctuates over time and can improve on its own, “a high-quality control arm” would be needed in such a trial, especially to account for subjective and patient-reported outcomes, the editorialists said.

Another key issue: Only a quarter of women offered hyperbaric oxygen therapy agreed to and completed treatment. The treatment burden was the most common reason for declining the procedure. Study participants underwent 30-40 2-hour sessions over 6-8 weeks.
 

Will the Latest Evidence Usher This Therapy Into More Standard Use?

Probably not, the editorialists concluded.

The HONEY trial “reminds us that convenience has become a factor weighted heavily by patients during the process of decision-making,” Dr. Hahn and colleagues wrote. “Despite experiencing relatively severe symptoms, many declined hyperbaric therapy after being counseled by HONEY investigators about the time commitment.”

Despite its limitations, the trial does offer “modest evidence to justify the use of [hyperbaric oxygen therapy] in treating the chronic morbidities associated with breast irradiation,” the editorialists said. But an “adequately powered randomized, sham-controlled, double-blind trials will be necessary to truly determine the benefit.”

HONEY was partially funded by The Da Vinci Clinic, the Netherlands. The investigators didn’t have any disclosures. One of Dr. Hahn’s coauthors reported personal fees from Lutris Pharma as Chief Medical Officer.
 

A version of this article appeared on Medscape.com.

Several new clinical trials in gynecologic cancers have started enrolling recently. Perhaps one of your patients is eligible to take part?

Persistent or recurrent endometrial cancer or any advanced solid gynecologic tumor with appropriate ATR mutations. Patients with one of these diagnoses may be eligible to join a phase 2, randomized, open-label study of an experimental drug called ART0380. ART0380 inhibits the ability of cancer cells to repair DNA damage by targeting a DNA repair kinase called ATR (ataxia telangiectasia–mutated and Rad3-related) protein, which is faulty in some tumors. The hope is that ART0380 will overwhelm the inadequate DNA repair processes of these cancer cells while sparing the more robust DNA repair in healthy cells. 

All participants in the trial will take daily oral ART0380 until disease progression, withdrawal of consent, or unacceptable toxicity, whichever happens first. Some individuals will receive the treatment for 3 weeks out of every 4. Sites in California, Illinois, Massachusetts, New York, Oklahoma, Pennsylvania, Rhode Island, and France started recruiting 60 participants with endometrial cancer or any solid tumor in September 2023. The primary outcome is objective response rate. Overall survival is a secondary measure and quality of life (QOL) is not assessed. More details at ClinicalTrials.gov

Maurie Markman, MD, president of medicine and science at City of Hope, Atlanta, who is not involved in this trial, explained that because “ a meaningful proportion of this population may have a defect in this DNA repair mechanism,” this hypothesis seems “worthy of clinical exploration.” 

Cancer of the endometrium, cervix, vagina, or vulva. Women with one of these types of cancer who can read and understand English or Spanish can join a randomized, open-label phase 2 trial to determine whether Reiki therapy can reduce pain and distress associated with brachytherapy. 

Reiki is a complementary therapy that involves a Reiki practitioner holding their hands lightly on or above the patient’s body for several minutes. Some hospitals in the US and the UK offer Reiki as a relaxation aid, although high-quality science is lacking.

In this study, one group of participants will each undergo Reiki in a quiet clinic room during the lengthy waiting period between placement of the vaginal cylinder and infusion of the radiation source, which is a time of anxiety and discomfort for many women. A second group of women will simply lie and wait in a clinic room, if desired accompanied by a friend or family member. 

The Huntsman Cancer Institute, Salt Lake City, Utah, started recruiting its 68 participants in October 2023. The primary outcome is self-reported anxiety. The secondary outcomes are other validated measures of anxiety, pain, and depression. Overall survival and broader measures of QOL will not be assessed. More details at ClinicalTrials.gov

Dr. Markman said that the benefits of Reiki may be “nothing more than a placebo effect.” But he highlighted the novelty of conducting a randomized trial to scientifically test Reiki’s “widely applied (without any real evidence) ‘integrative medicine’ approach to symptom management.”

Unresectable or metastatic endometrial cancer with deficient mismatch repair /high microsatellite instability. People in this clinical situation whose disease has progressed after one or two lines of prior chemotherapy, including platinum-based treatment, may be interested in an open-label nonrandomized, phase 2 investigation of bispecific antibody acasunlimab in combination with pembrolizumab (Keytruda). 

Acasunlimab stimulates T-cell antitumor activity as well as blocking programmed death ligand 1 (PD-L1) and is being tested in several types of solid-tumor cancer. For up to 2 years, all participants will receive intravenous (IV) infusions of the drug combination. Study sites in Florida and Europe opened in January 2024, ready for 80 participants. The primary outcome is objective response rate. Overall survival will not be assessed. More details at ClinicalTrials.gov

“In the absence of a randomized population to compare treatment outcomes, the results of this trial will likely provide limited data upon which to determine the clinical benefits of this novel drug combination strategy,” said Dr. Markman. However, he added, “the results will be helpful in assessing the potential toxicity of this approach.”

Recurrent or metastatic endometrial cancer with proficient mismatch repair. Women with this diagnosis who have progressed after one prior platinum chemotherapy regimen in any setting may wish to consider a randomized, triple-blind, phase 2 trial of pembrolizumab plus favezelimab. Favezelimab, which blocks the lymphocyte activation gene 3 (LAG3), appears to boost the antitumor activity of programmed cell death protein 1 (PD-1) inhibition in other cancers such as classic Hodgkin lymphoma. 

In the trial, participants will be assigned to one of four groups. One group will receive 17 doses of the combination treatment IV every 3 weeks — three doses in the neoadjuvant period and 14 as adjuvant therapy. A second group of individuals will receive IV pembrolizumab monotherapy on the same schedule. A third will be given up to 35 doses of the combo therapy every 3 weeks plus a daily capsule of lenvatinib (Lenvima). The fourth group will receive 35 doses of pembrolizumab plus daily lenvatinib. 

Sites in North Carolina, New Jersey, Pennsylvania, and four countries other than the US started recruiting 60 participants with a solid tumor in September 2023. Pathologic complete response and objective response rate are the primary endpoints. Overall survival over approximately 3.5 years is a secondary endpoint, and QOL will not be measured. More details at ClinicalTrials.gov

Unresectable advanced or metastatic HER2-positive endometrial or ovarian cancer. Adults with one of these diagnoses in whom failed platinum-based therapy has failed may enroll in an open-label, phase 2 study to see whether their disease will respond to the antibody-drug conjugate disitamab vedotin. Everyone in the trial will receive IV disitamab vedotin every 2 weeks for up to approximately 5 years. 

Study sites in California, Connecticut, Michigan, Minnesota, Montana, New York, Ohio, Texas, and Canada began welcoming their 190 participants with one of a range of solid cancers in November 2023. The primary outcome is objective response rate. Overall survival is a secondary measure and QOL will not be tracked. More details at ClinicalTrials.gov

High-risk locally advanced cervical cancer. Girls and women older than 14 years with this cancer that has not progressed after platinum-based chemoradiation are sought for a randomized, quadruple-blind, phase 3 trial to determine whether the investigational immunotherapy volrustomig can slow disease progression. Volrustomig targets PD-1 and cytotoxic T lymphocyte protein 4 (CTLA4) and is being tested in a wide range of solid cancers. 

For approximately 3 years or until disease progression or death, whichever happens first, half of participants will receive IV infusions of volrustomig while the others will receive saline. Asian research sites started seeking the study’s 1000 participants in September 2023, while centers in 12 US states and eight other countries are gearing up for patient enrollment. Progression-free survival in participants with PD-L1 expression is the primary endpoint; overall survival and QOL are secondary endpoints. More details at ClinicalTrials.gov

All trial information is from the National Institutes of Health US National Library of Medicine (online at ClinicalTrials.gov). Dr. Markman declared he is not involved with these trials.

A version of this article appeared on Medscape.com .

Several new clinical trials in gynecologic cancers have started enrolling recently. Perhaps one of your patients is eligible to take part?

Persistent or recurrent endometrial cancer or any advanced solid gynecologic tumor with appropriate ATR mutations. Patients with one of these diagnoses may be eligible to join a phase 2, randomized, open-label study of an experimental drug called ART0380. ART0380 inhibits the ability of cancer cells to repair DNA damage by targeting a DNA repair kinase called ATR (ataxia telangiectasia–mutated and Rad3-related) protein, which is faulty in some tumors. The hope is that ART0380 will overwhelm the inadequate DNA repair processes of these cancer cells while sparing the more robust DNA repair in healthy cells. 

All participants in the trial will take daily oral ART0380 until disease progression, withdrawal of consent, or unacceptable toxicity, whichever happens first. Some individuals will receive the treatment for 3 weeks out of every 4. Sites in California, Illinois, Massachusetts, New York, Oklahoma, Pennsylvania, Rhode Island, and France started recruiting 60 participants with endometrial cancer or any solid tumor in September 2023. The primary outcome is objective response rate. Overall survival is a secondary measure and quality of life (QOL) is not assessed. More details at ClinicalTrials.gov

Maurie Markman, MD, president of medicine and science at City of Hope, Atlanta, who is not involved in this trial, explained that because “ a meaningful proportion of this population may have a defect in this DNA repair mechanism,” this hypothesis seems “worthy of clinical exploration.” 

Cancer of the endometrium, cervix, vagina, or vulva. Women with one of these types of cancer who can read and understand English or Spanish can join a randomized, open-label phase 2 trial to determine whether Reiki therapy can reduce pain and distress associated with brachytherapy. 

Reiki is a complementary therapy that involves a Reiki practitioner holding their hands lightly on or above the patient’s body for several minutes. Some hospitals in the US and the UK offer Reiki as a relaxation aid, although high-quality science is lacking.

In this study, one group of participants will each undergo Reiki in a quiet clinic room during the lengthy waiting period between placement of the vaginal cylinder and infusion of the radiation source, which is a time of anxiety and discomfort for many women. A second group of women will simply lie and wait in a clinic room, if desired accompanied by a friend or family member. 

The Huntsman Cancer Institute, Salt Lake City, Utah, started recruiting its 68 participants in October 2023. The primary outcome is self-reported anxiety. The secondary outcomes are other validated measures of anxiety, pain, and depression. Overall survival and broader measures of QOL will not be assessed. More details at ClinicalTrials.gov

Dr. Markman said that the benefits of Reiki may be “nothing more than a placebo effect.” But he highlighted the novelty of conducting a randomized trial to scientifically test Reiki’s “widely applied (without any real evidence) ‘integrative medicine’ approach to symptom management.”

Unresectable or metastatic endometrial cancer with deficient mismatch repair /high microsatellite instability. People in this clinical situation whose disease has progressed after one or two lines of prior chemotherapy, including platinum-based treatment, may be interested in an open-label nonrandomized, phase 2 investigation of bispecific antibody acasunlimab in combination with pembrolizumab (Keytruda). 

Acasunlimab stimulates T-cell antitumor activity as well as blocking programmed death ligand 1 (PD-L1) and is being tested in several types of solid-tumor cancer. For up to 2 years, all participants will receive intravenous (IV) infusions of the drug combination. Study sites in Florida and Europe opened in January 2024, ready for 80 participants. The primary outcome is objective response rate. Overall survival will not be assessed. More details at ClinicalTrials.gov

“In the absence of a randomized population to compare treatment outcomes, the results of this trial will likely provide limited data upon which to determine the clinical benefits of this novel drug combination strategy,” said Dr. Markman. However, he added, “the results will be helpful in assessing the potential toxicity of this approach.”

Recurrent or metastatic endometrial cancer with proficient mismatch repair. Women with this diagnosis who have progressed after one prior platinum chemotherapy regimen in any setting may wish to consider a randomized, triple-blind, phase 2 trial of pembrolizumab plus favezelimab. Favezelimab, which blocks the lymphocyte activation gene 3 (LAG3), appears to boost the antitumor activity of programmed cell death protein 1 (PD-1) inhibition in other cancers such as classic Hodgkin lymphoma. 

In the trial, participants will be assigned to one of four groups. One group will receive 17 doses of the combination treatment IV every 3 weeks — three doses in the neoadjuvant period and 14 as adjuvant therapy. A second group of individuals will receive IV pembrolizumab monotherapy on the same schedule. A third will be given up to 35 doses of the combo therapy every 3 weeks plus a daily capsule of lenvatinib (Lenvima). The fourth group will receive 35 doses of pembrolizumab plus daily lenvatinib. 

Sites in North Carolina, New Jersey, Pennsylvania, and four countries other than the US started recruiting 60 participants with a solid tumor in September 2023. Pathologic complete response and objective response rate are the primary endpoints. Overall survival over approximately 3.5 years is a secondary endpoint, and QOL will not be measured. More details at ClinicalTrials.gov

Unresectable advanced or metastatic HER2-positive endometrial or ovarian cancer. Adults with one of these diagnoses in whom failed platinum-based therapy has failed may enroll in an open-label, phase 2 study to see whether their disease will respond to the antibody-drug conjugate disitamab vedotin. Everyone in the trial will receive IV disitamab vedotin every 2 weeks for up to approximately 5 years. 

Study sites in California, Connecticut, Michigan, Minnesota, Montana, New York, Ohio, Texas, and Canada began welcoming their 190 participants with one of a range of solid cancers in November 2023. The primary outcome is objective response rate. Overall survival is a secondary measure and QOL will not be tracked. More details at ClinicalTrials.gov

High-risk locally advanced cervical cancer. Girls and women older than 14 years with this cancer that has not progressed after platinum-based chemoradiation are sought for a randomized, quadruple-blind, phase 3 trial to determine whether the investigational immunotherapy volrustomig can slow disease progression. Volrustomig targets PD-1 and cytotoxic T lymphocyte protein 4 (CTLA4) and is being tested in a wide range of solid cancers. 

For approximately 3 years or until disease progression or death, whichever happens first, half of participants will receive IV infusions of volrustomig while the others will receive saline. Asian research sites started seeking the study’s 1000 participants in September 2023, while centers in 12 US states and eight other countries are gearing up for patient enrollment. Progression-free survival in participants with PD-L1 expression is the primary endpoint; overall survival and QOL are secondary endpoints. More details at ClinicalTrials.gov

All trial information is from the National Institutes of Health US National Library of Medicine (online at ClinicalTrials.gov). Dr. Markman declared he is not involved with these trials.

A version of this article appeared on Medscape.com .

Several new clinical trials in gynecologic cancers have started enrolling recently. Perhaps one of your patients is eligible to take part?

Persistent or recurrent endometrial cancer or any advanced solid gynecologic tumor with appropriate ATR mutations. Patients with one of these diagnoses may be eligible to join a phase 2, randomized, open-label study of an experimental drug called ART0380. ART0380 inhibits the ability of cancer cells to repair DNA damage by targeting a DNA repair kinase called ATR (ataxia telangiectasia–mutated and Rad3-related) protein, which is faulty in some tumors. The hope is that ART0380 will overwhelm the inadequate DNA repair processes of these cancer cells while sparing the more robust DNA repair in healthy cells. 

All participants in the trial will take daily oral ART0380 until disease progression, withdrawal of consent, or unacceptable toxicity, whichever happens first. Some individuals will receive the treatment for 3 weeks out of every 4. Sites in California, Illinois, Massachusetts, New York, Oklahoma, Pennsylvania, Rhode Island, and France started recruiting 60 participants with endometrial cancer or any solid tumor in September 2023. The primary outcome is objective response rate. Overall survival is a secondary measure and quality of life (QOL) is not assessed. More details at ClinicalTrials.gov

Maurie Markman, MD, president of medicine and science at City of Hope, Atlanta, who is not involved in this trial, explained that because “ a meaningful proportion of this population may have a defect in this DNA repair mechanism,” this hypothesis seems “worthy of clinical exploration.” 

Cancer of the endometrium, cervix, vagina, or vulva. Women with one of these types of cancer who can read and understand English or Spanish can join a randomized, open-label phase 2 trial to determine whether Reiki therapy can reduce pain and distress associated with brachytherapy. 

Reiki is a complementary therapy that involves a Reiki practitioner holding their hands lightly on or above the patient’s body for several minutes. Some hospitals in the US and the UK offer Reiki as a relaxation aid, although high-quality science is lacking.

In this study, one group of participants will each undergo Reiki in a quiet clinic room during the lengthy waiting period between placement of the vaginal cylinder and infusion of the radiation source, which is a time of anxiety and discomfort for many women. A second group of women will simply lie and wait in a clinic room, if desired accompanied by a friend or family member. 

The Huntsman Cancer Institute, Salt Lake City, Utah, started recruiting its 68 participants in October 2023. The primary outcome is self-reported anxiety. The secondary outcomes are other validated measures of anxiety, pain, and depression. Overall survival and broader measures of QOL will not be assessed. More details at ClinicalTrials.gov

Dr. Markman said that the benefits of Reiki may be “nothing more than a placebo effect.” But he highlighted the novelty of conducting a randomized trial to scientifically test Reiki’s “widely applied (without any real evidence) ‘integrative medicine’ approach to symptom management.”

Unresectable or metastatic endometrial cancer with deficient mismatch repair /high microsatellite instability. People in this clinical situation whose disease has progressed after one or two lines of prior chemotherapy, including platinum-based treatment, may be interested in an open-label nonrandomized, phase 2 investigation of bispecific antibody acasunlimab in combination with pembrolizumab (Keytruda). 

Acasunlimab stimulates T-cell antitumor activity as well as blocking programmed death ligand 1 (PD-L1) and is being tested in several types of solid-tumor cancer. For up to 2 years, all participants will receive intravenous (IV) infusions of the drug combination. Study sites in Florida and Europe opened in January 2024, ready for 80 participants. The primary outcome is objective response rate. Overall survival will not be assessed. More details at ClinicalTrials.gov

“In the absence of a randomized population to compare treatment outcomes, the results of this trial will likely provide limited data upon which to determine the clinical benefits of this novel drug combination strategy,” said Dr. Markman. However, he added, “the results will be helpful in assessing the potential toxicity of this approach.”

Recurrent or metastatic endometrial cancer with proficient mismatch repair. Women with this diagnosis who have progressed after one prior platinum chemotherapy regimen in any setting may wish to consider a randomized, triple-blind, phase 2 trial of pembrolizumab plus favezelimab. Favezelimab, which blocks the lymphocyte activation gene 3 (LAG3), appears to boost the antitumor activity of programmed cell death protein 1 (PD-1) inhibition in other cancers such as classic Hodgkin lymphoma. 

In the trial, participants will be assigned to one of four groups. One group will receive 17 doses of the combination treatment IV every 3 weeks — three doses in the neoadjuvant period and 14 as adjuvant therapy. A second group of individuals will receive IV pembrolizumab monotherapy on the same schedule. A third will be given up to 35 doses of the combo therapy every 3 weeks plus a daily capsule of lenvatinib (Lenvima). The fourth group will receive 35 doses of pembrolizumab plus daily lenvatinib. 

Sites in North Carolina, New Jersey, Pennsylvania, and four countries other than the US started recruiting 60 participants with a solid tumor in September 2023. Pathologic complete response and objective response rate are the primary endpoints. Overall survival over approximately 3.5 years is a secondary endpoint, and QOL will not be measured. More details at ClinicalTrials.gov

Unresectable advanced or metastatic HER2-positive endometrial or ovarian cancer. Adults with one of these diagnoses in whom failed platinum-based therapy has failed may enroll in an open-label, phase 2 study to see whether their disease will respond to the antibody-drug conjugate disitamab vedotin. Everyone in the trial will receive IV disitamab vedotin every 2 weeks for up to approximately 5 years. 

Study sites in California, Connecticut, Michigan, Minnesota, Montana, New York, Ohio, Texas, and Canada began welcoming their 190 participants with one of a range of solid cancers in November 2023. The primary outcome is objective response rate. Overall survival is a secondary measure and QOL will not be tracked. More details at ClinicalTrials.gov

High-risk locally advanced cervical cancer. Girls and women older than 14 years with this cancer that has not progressed after platinum-based chemoradiation are sought for a randomized, quadruple-blind, phase 3 trial to determine whether the investigational immunotherapy volrustomig can slow disease progression. Volrustomig targets PD-1 and cytotoxic T lymphocyte protein 4 (CTLA4) and is being tested in a wide range of solid cancers. 

For approximately 3 years or until disease progression or death, whichever happens first, half of participants will receive IV infusions of volrustomig while the others will receive saline. Asian research sites started seeking the study’s 1000 participants in September 2023, while centers in 12 US states and eight other countries are gearing up for patient enrollment. Progression-free survival in participants with PD-L1 expression is the primary endpoint; overall survival and QOL are secondary endpoints. More details at ClinicalTrials.gov

All trial information is from the National Institutes of Health US National Library of Medicine (online at ClinicalTrials.gov). Dr. Markman declared he is not involved with these trials.

A version of this article appeared on Medscape.com .

A plant-based diet, low in dairy and meat but rich in fruits, vegetables, grains, and nuts, can improve sexual and urinary health in patients treated for local prostate cancer, new research showed.

The findings, published on February 13, 2024, in the journal Cancer, bolster previous research showing plant-based diets can reduce the risk for recurrence and improve survivorship in men with prostate cancer.

“The current study shows for the first time an association between eating more plant-based food with better scores for quality of life among patients diagnosed with prostate cancer,” Stacy Loeb, MD, a urologist in the departments of Urology and Population Health at NYU Langone Health, in New York City, who led the research.

For the new study, Dr. Loeb and her colleagues looked at data from more than 3500 men with prostate cancer in the Health Professionals Follow-Up Study, an ongoing investigation begun in 1986 and sponsored by Harvard T.H. Chan School of Public Health. The dataset included more than 50,000 male dentists, pharmacists, optometrists, osteopaths, podiatrists, and veterinarians.

The median age of prostate cancer diagnosis was 68 years; 48% of patients underwent radical prostatectomy and 35% had radiation as primary therapy. None of the patients were known to have had metastatic disease.

Men in the study answered a questionnaire every 4 years about the kinds of foods they ate and in what proportions. Another survey, administered every 2 years, assessed the frequency of incontinence, difficulties maintaining an erection, and problems with bowels, energy, and mood, among many other health concerns.

Dr. Loeb and her colleagues sorted patients into quintiles based on the proportion of plant vs animal foods the men said they eat. The authors found those who consumed the most plant-based foods scored 8%-11% better in measures of sexual function than the group that consumed the least of these products.

These men also reported up to 14% better scores for urinary health, with fewer instances of incontinence, obstruction, and irritation, and up to 13% better scores in hormonal health, marked by symptoms like low energy, depression, and hot flashes.

Justin Gregg, MD, a urology researcher at the University of Texas MD Anderson Cancer Center, in Houston, Texas, whose research has found the Mediterranean diet can slow tumor progression among men with localized prostate cancer on active surveillance, called the results “not entirely surprising, as prior studies have shown associations between plant-based diet and outcomes like erectile function among men who do not have prostate cancer.”

But Kenneth Jacobsohn, MD, professor of urology and director of lifestyle medicine at the Medical College of Wisconsin, in Milwaukee, said the new findings help establish “the positive role of diet quality and plant-based diets, specifically on quality of life after prostate cancer diagnosis and treatment for men with nonmetastatic prostate cancer.”

Dr. Jacobsohn said the study was limited by its retrospective nature and the manner of the dietary assessment.

“As the authors point out, a plant-based diet may be helpful, though it’s important to keep in mind the strong data for its protective effect in terms of cardiovascular disease risk, which is very important for men who have a history of prostate cancer as many will die of cardiovascular disease,” Dr. Gregg added.

Dr. Loeb, Dr. Gregg, and Dr. Jacobsohn reported no conflicts of interest. Some of the study authors reported a variety of potential conflicts.
 

A version of this article appeared on Medscape.com .

A plant-based diet, low in dairy and meat but rich in fruits, vegetables, grains, and nuts, can improve sexual and urinary health in patients treated for local prostate cancer, new research showed.

The findings, published on February 13, 2024, in the journal Cancer, bolster previous research showing plant-based diets can reduce the risk for recurrence and improve survivorship in men with prostate cancer.

“The current study shows for the first time an association between eating more plant-based food with better scores for quality of life among patients diagnosed with prostate cancer,” Stacy Loeb, MD, a urologist in the departments of Urology and Population Health at NYU Langone Health, in New York City, who led the research.

For the new study, Dr. Loeb and her colleagues looked at data from more than 3500 men with prostate cancer in the Health Professionals Follow-Up Study, an ongoing investigation begun in 1986 and sponsored by Harvard T.H. Chan School of Public Health. The dataset included more than 50,000 male dentists, pharmacists, optometrists, osteopaths, podiatrists, and veterinarians.

The median age of prostate cancer diagnosis was 68 years; 48% of patients underwent radical prostatectomy and 35% had radiation as primary therapy. None of the patients were known to have had metastatic disease.

Men in the study answered a questionnaire every 4 years about the kinds of foods they ate and in what proportions. Another survey, administered every 2 years, assessed the frequency of incontinence, difficulties maintaining an erection, and problems with bowels, energy, and mood, among many other health concerns.

Dr. Loeb and her colleagues sorted patients into quintiles based on the proportion of plant vs animal foods the men said they eat. The authors found those who consumed the most plant-based foods scored 8%-11% better in measures of sexual function than the group that consumed the least of these products.

These men also reported up to 14% better scores for urinary health, with fewer instances of incontinence, obstruction, and irritation, and up to 13% better scores in hormonal health, marked by symptoms like low energy, depression, and hot flashes.

Justin Gregg, MD, a urology researcher at the University of Texas MD Anderson Cancer Center, in Houston, Texas, whose research has found the Mediterranean diet can slow tumor progression among men with localized prostate cancer on active surveillance, called the results “not entirely surprising, as prior studies have shown associations between plant-based diet and outcomes like erectile function among men who do not have prostate cancer.”

But Kenneth Jacobsohn, MD, professor of urology and director of lifestyle medicine at the Medical College of Wisconsin, in Milwaukee, said the new findings help establish “the positive role of diet quality and plant-based diets, specifically on quality of life after prostate cancer diagnosis and treatment for men with nonmetastatic prostate cancer.”

Dr. Jacobsohn said the study was limited by its retrospective nature and the manner of the dietary assessment.

“As the authors point out, a plant-based diet may be helpful, though it’s important to keep in mind the strong data for its protective effect in terms of cardiovascular disease risk, which is very important for men who have a history of prostate cancer as many will die of cardiovascular disease,” Dr. Gregg added.

Dr. Loeb, Dr. Gregg, and Dr. Jacobsohn reported no conflicts of interest. Some of the study authors reported a variety of potential conflicts.
 

A version of this article appeared on Medscape.com .

A plant-based diet, low in dairy and meat but rich in fruits, vegetables, grains, and nuts, can improve sexual and urinary health in patients treated for local prostate cancer, new research showed.

The findings, published on February 13, 2024, in the journal Cancer, bolster previous research showing plant-based diets can reduce the risk for recurrence and improve survivorship in men with prostate cancer.

“The current study shows for the first time an association between eating more plant-based food with better scores for quality of life among patients diagnosed with prostate cancer,” Stacy Loeb, MD, a urologist in the departments of Urology and Population Health at NYU Langone Health, in New York City, who led the research.

For the new study, Dr. Loeb and her colleagues looked at data from more than 3500 men with prostate cancer in the Health Professionals Follow-Up Study, an ongoing investigation begun in 1986 and sponsored by Harvard T.H. Chan School of Public Health. The dataset included more than 50,000 male dentists, pharmacists, optometrists, osteopaths, podiatrists, and veterinarians.

The median age of prostate cancer diagnosis was 68 years; 48% of patients underwent radical prostatectomy and 35% had radiation as primary therapy. None of the patients were known to have had metastatic disease.

Men in the study answered a questionnaire every 4 years about the kinds of foods they ate and in what proportions. Another survey, administered every 2 years, assessed the frequency of incontinence, difficulties maintaining an erection, and problems with bowels, energy, and mood, among many other health concerns.

Dr. Loeb and her colleagues sorted patients into quintiles based on the proportion of plant vs animal foods the men said they eat. The authors found those who consumed the most plant-based foods scored 8%-11% better in measures of sexual function than the group that consumed the least of these products.

These men also reported up to 14% better scores for urinary health, with fewer instances of incontinence, obstruction, and irritation, and up to 13% better scores in hormonal health, marked by symptoms like low energy, depression, and hot flashes.

Justin Gregg, MD, a urology researcher at the University of Texas MD Anderson Cancer Center, in Houston, Texas, whose research has found the Mediterranean diet can slow tumor progression among men with localized prostate cancer on active surveillance, called the results “not entirely surprising, as prior studies have shown associations between plant-based diet and outcomes like erectile function among men who do not have prostate cancer.”

But Kenneth Jacobsohn, MD, professor of urology and director of lifestyle medicine at the Medical College of Wisconsin, in Milwaukee, said the new findings help establish “the positive role of diet quality and plant-based diets, specifically on quality of life after prostate cancer diagnosis and treatment for men with nonmetastatic prostate cancer.”

Dr. Jacobsohn said the study was limited by its retrospective nature and the manner of the dietary assessment.

“As the authors point out, a plant-based diet may be helpful, though it’s important to keep in mind the strong data for its protective effect in terms of cardiovascular disease risk, which is very important for men who have a history of prostate cancer as many will die of cardiovascular disease,” Dr. Gregg added.

Dr. Loeb, Dr. Gregg, and Dr. Jacobsohn reported no conflicts of interest. Some of the study authors reported a variety of potential conflicts.
 

A version of this article appeared on Medscape.com .

Reports of a small number of patients developing secondary T-cell malignancies following treatment with chimeric antigen receptor (CAR) T-cell immunotherapy have raised concerns and prompted a class-wide boxed warning to the labeling of the therapies by the US Food and Drug Administration (FDA), but for now experts underscore that the benefits of the groundbreaking therapies still appear to well outweigh the risks.

Importantly, most specialists agree, so far the risk appears no greater than the known risk of secondary primary malignancies that is well established with other cancer therapies.

“The data that we have so far suggest that the risk of secondary T-cell lymphoma in patients treated with CAR T-cells is similar to [that] of patients treated with other cancer therapies, [including] chemotherapy, radiation, transplantation,” Marco Ruella, MD, said in an interview. He reported on a case of a T-cell lymphoma occurring following CAR-T therapy at the University of Pennsylvania.

While his team is still investigating the development of such malignancies, “the FDA notice does not change our clinical practice and patients should be reassured that the benefit of CAR-T therapy significantly outweighs the potential risk of secondary malignancies including T-cell lymphoma,” said Dr. Ruella, scientific director of the Lymphoma Program, Division of Hematology and Oncology and Center for Cellular Immunotherapies, at the University of Pennsylvania, Philadelphia.
 

FDA: 28 Reports of Malignancies; 3 with Evidence of ‘Likely’ CAR T Involvement

Concerns were raised last November when the FDA announced in a safety communication that it was investigating the “serious risk of T-cell malignancy” following B-cell maturation antigen (BCMA)-directed or CD19-directed CAR T-cell immunotherapies, citing reports from clinical trials and/or postmarketing adverse event data sources. Subsequently, in January, the FDA called for the boxed warning on all approved BCMA- and CD19-targeted genetically modified autologous T-cell immunotherapies, which include: Abecma (idecabtagene vicleucel); Breyanzi (lisocabtagene maraleucel); Carvykti (ciltacabtagene autoleucel); Kymriah (tisagenlecleucel); Tecartus (brexucabtagene autoleucel); and Yescarta (axicabtagene ciloleucel).

“Although the overall benefits of these products continue to outweigh their potential risks for their approved uses, the FDA continues to investigate the identified risk of T-cell malignancy with serious outcomes, including hospitalization and death,” the FDA reported in discussing the safety warnings.

The cases were detailed in a report from FDA researchers published in the New England Journal of Medicine, noting that as of December 31, 2023, the FDA had become aware of 22 cases of T-cell cancers occurring following CAR T-cell treatment, including T-cell lymphoma, T-cell large granular lymphocytosis, peripheral T-cell lymphoma, and cutaneous T-cell lymphoma.

Report coauthor Peter Marks, MD, PhD, of the FDA’s Center for Biologics Evaluation and Research in Silver Spring, Maryland, said in an interview that since the publication of their report, six new cases have emerged.

“As reported in the NEJM Perspective, there were 22 cases of T-cell malignancy after treatment with CAR T-cell immunotherapies as of December 31, 2023, but we have received additional reports and, as of February 9, 2024, FDA has now received 28 reports,” he said. “Note that as new cases are being reported, there will be updates to the total number of cases under ongoing review by FDA.”

The initial 22 cases all occurred relatively soon after treatment. Of 14 cases with sufficient data, all developed within 2 years of the CAR-T therapy, ranging from 1 to 19 months, with about half occurring in the first year after administration.

The cases involved five of the six FDA-approved CAR-T products, with the numbers too low to suggest an association with any particular product.

In three of the cases, the lymphoma was found in genetic testing to contain the CAR construction, “indicating that the CAR-T product was most likely involved in the development of the T-cell cancer,” according to the FDA researchers.

With inadequate genetic sampling in most of the remaining 19 cases, the association is less clear, however “the timing of several of the cases makes association a possibility,” Dr. Marks said. In their report, Dr. Marks and colleagues added that “determination of whether the T-cell cancer is associated with the CAR construct ... most likely won’t be possible for every case reported to date.”

Even if all the reported cases are assumed to be related to CAR-T treatment, the numbers still represent a very small proportion of the more than 27,000 doses of the six CAR-T therapies approved in the United States, the authors noted, but they cautioned that the numbers could indeed be higher than reported.

“Relying on postmarketing reporting may lead to underestimates of such cases,” they said.
 

Life-Long Monitoring Recommended

In response to the reports, the FDA is urging that clinicians’ monitoring of patients treated with CAR-T therapy should be lifelong.

“Patients and clinical trial participants receiving treatment with these products should be monitored lifelong for new malignancies,” Dr. Marks said.

“In the event that a new malignancy occurs following treatment with these products, contact the manufacturer to report the event and obtain instructions on collection of patient samples for testing for the presence of the CAR transgene.”

In addition, cases should be reported to the FDA, either by calling or through the FDA’s medical product safety reporting program.
 

T-Cell Malignancy Case Report

In describing the case at their medical center in the report in Nature Medicine, Dr. Ruella and colleagues said a T-cell lymphoma occurred in a patient with non-Hodgkin B-cell lymphoma 3 months after an anti-CD19 CAR T-cell treatment.

As a result, the team conducted a subsequent analysis of 449 patients treated with CAR-T therapy at the University of Pennsylvania center, and with a median follow-up of 10.3 months, 16 patients (3.6%) had developed a secondary primary malignancy, with a median onset time of 26.4 months for solid and 9.7 months for hematological malignancies.

The patient who had developed a T-cell lymphoma tested negative for CAR integration upon diagnosis, and regarding the other cancers, Dr. Ruella noted that “we have no indication that the secondary malignancies are directly caused by the CAR-T therapy.

“We have many patients with a very long follow-up beyond 5 and even 10 years,” he said. “In these patients, we don’t see an increased risk of T-cell lymphoma.”
 

‘Cautious Reassurance’ Urged in Discussion with Patients

With alarming headlines on the findings suggesting that CAR-T therapy may cause cancer, Rahul Banerjee, MD, and colleagues at the University of Washington, Seattle, recommend the use of “cautious reassurance” in discussing the issue with patients. In a paper published in January in Blood Advances, they suggest a three-part response: underscoring that the benefits of CAR T “far outweigh” the risks in relapsed/refractory malignancies, that the ‘one-and-done’ nature of CAR-T infusions provide meaningful improvements in quality of life, and that the active cancer at hand is “a much larger threat than a hypothetical cancer years later.”

In many cases, patients may only have months to live without CAR-T therapy and will have already had multiple prior lines of therapy, therefore the CAR-T treatment itself may provide time for the secondary primary cancers from any of the treatments to emerge, as experts have noted.

“One has to be alive to be diagnosed with a secondary primary malignancy, and it’s thus very possible that CAR-T may be creating a type of ‘immortal time bias’ wherein patients live long enough to experience the unfortunate sequelae of their previous therapies,” Dr. Banerjee explained in an interview.

Nevertheless, the potential for substantial improvements in quality of life with CAR-T therapy compared with traditional treatments addresses a top priority for patients, he added.

“For most patients with [for instance], myeloma, the ability of CAR-T to put them rapidly into a deep remission without the need for maintenance is an unheard-of potential for them,” Dr. Banerjee said.

“In multiple myeloma, no CAR-T therapy has (yet) demonstrated an overall survival benefit — but I think the substantial quality-of-life benefit stands by itself as a big reason why patients continue to prefer CAR-T.”
 

Keep Patients In Touch with CAR T Centers

In light of the concerns regarding the secondary malignancies, Dr. Banerjee underscored that CAR-T patients should be kept in close touch with centers that have CAR-T treatment expertise.

With most patients followed primarily at community practices where CAR-T therapy is not administered, “I’d strongly encourage my colleagues in community practices to refer all eligible patients to a CAR-T-capable center for evaluation regardless of what their risk of post-CAR-T secondary primary malignancies may be,” Dr. Banerjee urged.

“Based on the evidence we have currently, which includes the FDA’s updated information, there are many more unknowns about this potential secondary primary malignancy risk than knowns,” he said. “This is of course a much more nuanced issue than any one package insert can convey, and CAR-T experts at treating centers can have these conversations at length with eligible patients who are nervous about these recent updates.”

Dr. Ruella disclosed that he holds patents related to CD19 CAR T cells, as well as relationships with NanoString, Bristol Myers Squibb, GlaxoSmithKline, Scailyte, Bayer, AbClon, Oxford NanoImaging, CURIOX, and Beckman Coulter, and he was the scientific founder of viTToria Biotherapeutics. Dr. Banerjee reported ties with BMS, Caribou Biosciences, Genentech, Janssen, Karyopharm, Pfizer, Sanofi, SparkCures, Novartis, and Pack Health.

Reports of a small number of patients developing secondary T-cell malignancies following treatment with chimeric antigen receptor (CAR) T-cell immunotherapy have raised concerns and prompted a class-wide boxed warning to the labeling of the therapies by the US Food and Drug Administration (FDA), but for now experts underscore that the benefits of the groundbreaking therapies still appear to well outweigh the risks.

Importantly, most specialists agree, so far the risk appears no greater than the known risk of secondary primary malignancies that is well established with other cancer therapies.

“The data that we have so far suggest that the risk of secondary T-cell lymphoma in patients treated with CAR T-cells is similar to [that] of patients treated with other cancer therapies, [including] chemotherapy, radiation, transplantation,” Marco Ruella, MD, said in an interview. He reported on a case of a T-cell lymphoma occurring following CAR-T therapy at the University of Pennsylvania.

While his team is still investigating the development of such malignancies, “the FDA notice does not change our clinical practice and patients should be reassured that the benefit of CAR-T therapy significantly outweighs the potential risk of secondary malignancies including T-cell lymphoma,” said Dr. Ruella, scientific director of the Lymphoma Program, Division of Hematology and Oncology and Center for Cellular Immunotherapies, at the University of Pennsylvania, Philadelphia.
 

FDA: 28 Reports of Malignancies; 3 with Evidence of ‘Likely’ CAR T Involvement

Concerns were raised last November when the FDA announced in a safety communication that it was investigating the “serious risk of T-cell malignancy” following B-cell maturation antigen (BCMA)-directed or CD19-directed CAR T-cell immunotherapies, citing reports from clinical trials and/or postmarketing adverse event data sources. Subsequently, in January, the FDA called for the boxed warning on all approved BCMA- and CD19-targeted genetically modified autologous T-cell immunotherapies, which include: Abecma (idecabtagene vicleucel); Breyanzi (lisocabtagene maraleucel); Carvykti (ciltacabtagene autoleucel); Kymriah (tisagenlecleucel); Tecartus (brexucabtagene autoleucel); and Yescarta (axicabtagene ciloleucel).

“Although the overall benefits of these products continue to outweigh their potential risks for their approved uses, the FDA continues to investigate the identified risk of T-cell malignancy with serious outcomes, including hospitalization and death,” the FDA reported in discussing the safety warnings.

The cases were detailed in a report from FDA researchers published in the New England Journal of Medicine, noting that as of December 31, 2023, the FDA had become aware of 22 cases of T-cell cancers occurring following CAR T-cell treatment, including T-cell lymphoma, T-cell large granular lymphocytosis, peripheral T-cell lymphoma, and cutaneous T-cell lymphoma.

Report coauthor Peter Marks, MD, PhD, of the FDA’s Center for Biologics Evaluation and Research in Silver Spring, Maryland, said in an interview that since the publication of their report, six new cases have emerged.

“As reported in the NEJM Perspective, there were 22 cases of T-cell malignancy after treatment with CAR T-cell immunotherapies as of December 31, 2023, but we have received additional reports and, as of February 9, 2024, FDA has now received 28 reports,” he said. “Note that as new cases are being reported, there will be updates to the total number of cases under ongoing review by FDA.”

The initial 22 cases all occurred relatively soon after treatment. Of 14 cases with sufficient data, all developed within 2 years of the CAR-T therapy, ranging from 1 to 19 months, with about half occurring in the first year after administration.

The cases involved five of the six FDA-approved CAR-T products, with the numbers too low to suggest an association with any particular product.

In three of the cases, the lymphoma was found in genetic testing to contain the CAR construction, “indicating that the CAR-T product was most likely involved in the development of the T-cell cancer,” according to the FDA researchers.

With inadequate genetic sampling in most of the remaining 19 cases, the association is less clear, however “the timing of several of the cases makes association a possibility,” Dr. Marks said. In their report, Dr. Marks and colleagues added that “determination of whether the T-cell cancer is associated with the CAR construct ... most likely won’t be possible for every case reported to date.”

Even if all the reported cases are assumed to be related to CAR-T treatment, the numbers still represent a very small proportion of the more than 27,000 doses of the six CAR-T therapies approved in the United States, the authors noted, but they cautioned that the numbers could indeed be higher than reported.

“Relying on postmarketing reporting may lead to underestimates of such cases,” they said.
 

Life-Long Monitoring Recommended

In response to the reports, the FDA is urging that clinicians’ monitoring of patients treated with CAR-T therapy should be lifelong.

“Patients and clinical trial participants receiving treatment with these products should be monitored lifelong for new malignancies,” Dr. Marks said.

“In the event that a new malignancy occurs following treatment with these products, contact the manufacturer to report the event and obtain instructions on collection of patient samples for testing for the presence of the CAR transgene.”

In addition, cases should be reported to the FDA, either by calling or through the FDA’s medical product safety reporting program.
 

T-Cell Malignancy Case Report

In describing the case at their medical center in the report in Nature Medicine, Dr. Ruella and colleagues said a T-cell lymphoma occurred in a patient with non-Hodgkin B-cell lymphoma 3 months after an anti-CD19 CAR T-cell treatment.

As a result, the team conducted a subsequent analysis of 449 patients treated with CAR-T therapy at the University of Pennsylvania center, and with a median follow-up of 10.3 months, 16 patients (3.6%) had developed a secondary primary malignancy, with a median onset time of 26.4 months for solid and 9.7 months for hematological malignancies.

The patient who had developed a T-cell lymphoma tested negative for CAR integration upon diagnosis, and regarding the other cancers, Dr. Ruella noted that “we have no indication that the secondary malignancies are directly caused by the CAR-T therapy.

“We have many patients with a very long follow-up beyond 5 and even 10 years,” he said. “In these patients, we don’t see an increased risk of T-cell lymphoma.”
 

‘Cautious Reassurance’ Urged in Discussion with Patients

With alarming headlines on the findings suggesting that CAR-T therapy may cause cancer, Rahul Banerjee, MD, and colleagues at the University of Washington, Seattle, recommend the use of “cautious reassurance” in discussing the issue with patients. In a paper published in January in Blood Advances, they suggest a three-part response: underscoring that the benefits of CAR T “far outweigh” the risks in relapsed/refractory malignancies, that the ‘one-and-done’ nature of CAR-T infusions provide meaningful improvements in quality of life, and that the active cancer at hand is “a much larger threat than a hypothetical cancer years later.”

In many cases, patients may only have months to live without CAR-T therapy and will have already had multiple prior lines of therapy, therefore the CAR-T treatment itself may provide time for the secondary primary cancers from any of the treatments to emerge, as experts have noted.

“One has to be alive to be diagnosed with a secondary primary malignancy, and it’s thus very possible that CAR-T may be creating a type of ‘immortal time bias’ wherein patients live long enough to experience the unfortunate sequelae of their previous therapies,” Dr. Banerjee explained in an interview.

Nevertheless, the potential for substantial improvements in quality of life with CAR-T therapy compared with traditional treatments addresses a top priority for patients, he added.

“For most patients with [for instance], myeloma, the ability of CAR-T to put them rapidly into a deep remission without the need for maintenance is an unheard-of potential for them,” Dr. Banerjee said.

“In multiple myeloma, no CAR-T therapy has (yet) demonstrated an overall survival benefit — but I think the substantial quality-of-life benefit stands by itself as a big reason why patients continue to prefer CAR-T.”
 

Keep Patients In Touch with CAR T Centers

In light of the concerns regarding the secondary malignancies, Dr. Banerjee underscored that CAR-T patients should be kept in close touch with centers that have CAR-T treatment expertise.

With most patients followed primarily at community practices where CAR-T therapy is not administered, “I’d strongly encourage my colleagues in community practices to refer all eligible patients to a CAR-T-capable center for evaluation regardless of what their risk of post-CAR-T secondary primary malignancies may be,” Dr. Banerjee urged.

“Based on the evidence we have currently, which includes the FDA’s updated information, there are many more unknowns about this potential secondary primary malignancy risk than knowns,” he said. “This is of course a much more nuanced issue than any one package insert can convey, and CAR-T experts at treating centers can have these conversations at length with eligible patients who are nervous about these recent updates.”

Dr. Ruella disclosed that he holds patents related to CD19 CAR T cells, as well as relationships with NanoString, Bristol Myers Squibb, GlaxoSmithKline, Scailyte, Bayer, AbClon, Oxford NanoImaging, CURIOX, and Beckman Coulter, and he was the scientific founder of viTToria Biotherapeutics. Dr. Banerjee reported ties with BMS, Caribou Biosciences, Genentech, Janssen, Karyopharm, Pfizer, Sanofi, SparkCures, Novartis, and Pack Health.

Reports of a small number of patients developing secondary T-cell malignancies following treatment with chimeric antigen receptor (CAR) T-cell immunotherapy have raised concerns and prompted a class-wide boxed warning to the labeling of the therapies by the US Food and Drug Administration (FDA), but for now experts underscore that the benefits of the groundbreaking therapies still appear to well outweigh the risks.

Importantly, most specialists agree, so far the risk appears no greater than the known risk of secondary primary malignancies that is well established with other cancer therapies.

“The data that we have so far suggest that the risk of secondary T-cell lymphoma in patients treated with CAR T-cells is similar to [that] of patients treated with other cancer therapies, [including] chemotherapy, radiation, transplantation,” Marco Ruella, MD, said in an interview. He reported on a case of a T-cell lymphoma occurring following CAR-T therapy at the University of Pennsylvania.

While his team is still investigating the development of such malignancies, “the FDA notice does not change our clinical practice and patients should be reassured that the benefit of CAR-T therapy significantly outweighs the potential risk of secondary malignancies including T-cell lymphoma,” said Dr. Ruella, scientific director of the Lymphoma Program, Division of Hematology and Oncology and Center for Cellular Immunotherapies, at the University of Pennsylvania, Philadelphia.
 

FDA: 28 Reports of Malignancies; 3 with Evidence of ‘Likely’ CAR T Involvement

Concerns were raised last November when the FDA announced in a safety communication that it was investigating the “serious risk of T-cell malignancy” following B-cell maturation antigen (BCMA)-directed or CD19-directed CAR T-cell immunotherapies, citing reports from clinical trials and/or postmarketing adverse event data sources. Subsequently, in January, the FDA called for the boxed warning on all approved BCMA- and CD19-targeted genetically modified autologous T-cell immunotherapies, which include: Abecma (idecabtagene vicleucel); Breyanzi (lisocabtagene maraleucel); Carvykti (ciltacabtagene autoleucel); Kymriah (tisagenlecleucel); Tecartus (brexucabtagene autoleucel); and Yescarta (axicabtagene ciloleucel).

“Although the overall benefits of these products continue to outweigh their potential risks for their approved uses, the FDA continues to investigate the identified risk of T-cell malignancy with serious outcomes, including hospitalization and death,” the FDA reported in discussing the safety warnings.

The cases were detailed in a report from FDA researchers published in the New England Journal of Medicine, noting that as of December 31, 2023, the FDA had become aware of 22 cases of T-cell cancers occurring following CAR T-cell treatment, including T-cell lymphoma, T-cell large granular lymphocytosis, peripheral T-cell lymphoma, and cutaneous T-cell lymphoma.

Report coauthor Peter Marks, MD, PhD, of the FDA’s Center for Biologics Evaluation and Research in Silver Spring, Maryland, said in an interview that since the publication of their report, six new cases have emerged.

“As reported in the NEJM Perspective, there were 22 cases of T-cell malignancy after treatment with CAR T-cell immunotherapies as of December 31, 2023, but we have received additional reports and, as of February 9, 2024, FDA has now received 28 reports,” he said. “Note that as new cases are being reported, there will be updates to the total number of cases under ongoing review by FDA.”

The initial 22 cases all occurred relatively soon after treatment. Of 14 cases with sufficient data, all developed within 2 years of the CAR-T therapy, ranging from 1 to 19 months, with about half occurring in the first year after administration.

The cases involved five of the six FDA-approved CAR-T products, with the numbers too low to suggest an association with any particular product.

In three of the cases, the lymphoma was found in genetic testing to contain the CAR construction, “indicating that the CAR-T product was most likely involved in the development of the T-cell cancer,” according to the FDA researchers.

With inadequate genetic sampling in most of the remaining 19 cases, the association is less clear, however “the timing of several of the cases makes association a possibility,” Dr. Marks said. In their report, Dr. Marks and colleagues added that “determination of whether the T-cell cancer is associated with the CAR construct ... most likely won’t be possible for every case reported to date.”

Even if all the reported cases are assumed to be related to CAR-T treatment, the numbers still represent a very small proportion of the more than 27,000 doses of the six CAR-T therapies approved in the United States, the authors noted, but they cautioned that the numbers could indeed be higher than reported.

“Relying on postmarketing reporting may lead to underestimates of such cases,” they said.
 

Life-Long Monitoring Recommended

In response to the reports, the FDA is urging that clinicians’ monitoring of patients treated with CAR-T therapy should be lifelong.

“Patients and clinical trial participants receiving treatment with these products should be monitored lifelong for new malignancies,” Dr. Marks said.

“In the event that a new malignancy occurs following treatment with these products, contact the manufacturer to report the event and obtain instructions on collection of patient samples for testing for the presence of the CAR transgene.”

In addition, cases should be reported to the FDA, either by calling or through the FDA’s medical product safety reporting program.
 

T-Cell Malignancy Case Report

In describing the case at their medical center in the report in Nature Medicine, Dr. Ruella and colleagues said a T-cell lymphoma occurred in a patient with non-Hodgkin B-cell lymphoma 3 months after an anti-CD19 CAR T-cell treatment.

As a result, the team conducted a subsequent analysis of 449 patients treated with CAR-T therapy at the University of Pennsylvania center, and with a median follow-up of 10.3 months, 16 patients (3.6%) had developed a secondary primary malignancy, with a median onset time of 26.4 months for solid and 9.7 months for hematological malignancies.

The patient who had developed a T-cell lymphoma tested negative for CAR integration upon diagnosis, and regarding the other cancers, Dr. Ruella noted that “we have no indication that the secondary malignancies are directly caused by the CAR-T therapy.

“We have many patients with a very long follow-up beyond 5 and even 10 years,” he said. “In these patients, we don’t see an increased risk of T-cell lymphoma.”
 

‘Cautious Reassurance’ Urged in Discussion with Patients

With alarming headlines on the findings suggesting that CAR-T therapy may cause cancer, Rahul Banerjee, MD, and colleagues at the University of Washington, Seattle, recommend the use of “cautious reassurance” in discussing the issue with patients. In a paper published in January in Blood Advances, they suggest a three-part response: underscoring that the benefits of CAR T “far outweigh” the risks in relapsed/refractory malignancies, that the ‘one-and-done’ nature of CAR-T infusions provide meaningful improvements in quality of life, and that the active cancer at hand is “a much larger threat than a hypothetical cancer years later.”

In many cases, patients may only have months to live without CAR-T therapy and will have already had multiple prior lines of therapy, therefore the CAR-T treatment itself may provide time for the secondary primary cancers from any of the treatments to emerge, as experts have noted.

“One has to be alive to be diagnosed with a secondary primary malignancy, and it’s thus very possible that CAR-T may be creating a type of ‘immortal time bias’ wherein patients live long enough to experience the unfortunate sequelae of their previous therapies,” Dr. Banerjee explained in an interview.

Nevertheless, the potential for substantial improvements in quality of life with CAR-T therapy compared with traditional treatments addresses a top priority for patients, he added.

“For most patients with [for instance], myeloma, the ability of CAR-T to put them rapidly into a deep remission without the need for maintenance is an unheard-of potential for them,” Dr. Banerjee said.

“In multiple myeloma, no CAR-T therapy has (yet) demonstrated an overall survival benefit — but I think the substantial quality-of-life benefit stands by itself as a big reason why patients continue to prefer CAR-T.”
 

Keep Patients In Touch with CAR T Centers

In light of the concerns regarding the secondary malignancies, Dr. Banerjee underscored that CAR-T patients should be kept in close touch with centers that have CAR-T treatment expertise.

With most patients followed primarily at community practices where CAR-T therapy is not administered, “I’d strongly encourage my colleagues in community practices to refer all eligible patients to a CAR-T-capable center for evaluation regardless of what their risk of post-CAR-T secondary primary malignancies may be,” Dr. Banerjee urged.

“Based on the evidence we have currently, which includes the FDA’s updated information, there are many more unknowns about this potential secondary primary malignancy risk than knowns,” he said. “This is of course a much more nuanced issue than any one package insert can convey, and CAR-T experts at treating centers can have these conversations at length with eligible patients who are nervous about these recent updates.”

Dr. Ruella disclosed that he holds patents related to CD19 CAR T cells, as well as relationships with NanoString, Bristol Myers Squibb, GlaxoSmithKline, Scailyte, Bayer, AbClon, Oxford NanoImaging, CURIOX, and Beckman Coulter, and he was the scientific founder of viTToria Biotherapeutics. Dr. Banerjee reported ties with BMS, Caribou Biosciences, Genentech, Janssen, Karyopharm, Pfizer, Sanofi, SparkCures, Novartis, and Pack Health.

TOPLINE:

Multivitamin supplements at a moderate dose appear to lower the risk for both all-cause and cancer-related mortality in patients with colorectal cancer (CRC); however, high doses of multivitamin supplements may increase the risk for CRC-specific mortality.

METHODOLOGY:

• Some studies suggest that multivitamin supplements might increase a person’s risk for CRC, and other research indicates that certain components of multivitamins, such as vitamins C and D, may have anti-CRC properties.
• Because as many as half of CRC survivors take a multivitamin, researchers wanted to assess whether multivitamin use affects overall survival among people with CRC.
• In the current prospective cohort study, researchers evaluated the use and dose of multivitamin supplements in 2424 patients with stages I-III CRC, using detailed information from patients in the Nurses’ Health Study and Health Professionals Follow‐Up Study.
• The participants completed a mailed questionnaire every 2 years, which included questions about the current use of multivitamin supplements as well as doses per week (0, 1-2, 3-5, 6-9, and ≥ 10 tablets).
• The researchers assessed the potential association between multivitamin use and CRC-related as well as all‐cause mortality.

TAKEAWAY:

• Over a median follow-up period of 11 years, 1512 deaths and 343 cancer-specific deaths occurred.
• For patients diagnosed with CRC, a moderate dose of multivitamins (three to five tablets per week) vs no multivitamin use was associated with a 45% lower risk for cancer-related mortality (adjusted hazard ratio [aHR], 0.55; P = .005).
• Moderate multivitamin use was also associated with a lower risk for all-cause mortality (aHR, 0.81; P = .04) as was a higher dose of six to nine tablets per week (aHR, 0.79; P < .001).
• However, high doses of 10 or more tablets per week were associated with a 60% higher risk for cancer-related mortality (aHR, 1.60; P = .02).

IN PRACTICE:

The study findings suggested that moderate multivitamin supplement use may come with a survival benefit in patients with CRC, while high doses may not, but “further studies are needed before making clinical recommendations for multivitamin use in patients with CRC,” the authors said.

SOURCE:

This work, led by Ming‐ming He of Sun Yat‐sen University Cancer Center, Guangzhou, China, was published in Cancer.

LIMITATIONS:

Given the study’s observational design, residual confounding may be possible. Reverse causation and recall bias are also possible limitations.

DISCLOSURES:

This study was funded by the National Institutes of Health, American Institute for Cancer Research, Wellesley College, Dana‐Farber Cancer Institute, and the Entertainment Industry Foundation. Three study authors reported financial relationships outside this work.

A version of this article appeared on Medscape.com.

TOPLINE:

Multivitamin supplements at a moderate dose appear to lower the risk for both all-cause and cancer-related mortality in patients with colorectal cancer (CRC); however, high doses of multivitamin supplements may increase the risk for CRC-specific mortality.

METHODOLOGY:

• Some studies suggest that multivitamin supplements might increase a person’s risk for CRC, and other research indicates that certain components of multivitamins, such as vitamins C and D, may have anti-CRC properties.
• Because as many as half of CRC survivors take a multivitamin, researchers wanted to assess whether multivitamin use affects overall survival among people with CRC.
• In the current prospective cohort study, researchers evaluated the use and dose of multivitamin supplements in 2424 patients with stages I-III CRC, using detailed information from patients in the Nurses’ Health Study and Health Professionals Follow‐Up Study.
• The participants completed a mailed questionnaire every 2 years, which included questions about the current use of multivitamin supplements as well as doses per week (0, 1-2, 3-5, 6-9, and ≥ 10 tablets).
• The researchers assessed the potential association between multivitamin use and CRC-related as well as all‐cause mortality.

TAKEAWAY:

• Over a median follow-up period of 11 years, 1512 deaths and 343 cancer-specific deaths occurred.
• For patients diagnosed with CRC, a moderate dose of multivitamins (three to five tablets per week) vs no multivitamin use was associated with a 45% lower risk for cancer-related mortality (adjusted hazard ratio [aHR], 0.55; P = .005).
• Moderate multivitamin use was also associated with a lower risk for all-cause mortality (aHR, 0.81; P = .04) as was a higher dose of six to nine tablets per week (aHR, 0.79; P < .001).
• However, high doses of 10 or more tablets per week were associated with a 60% higher risk for cancer-related mortality (aHR, 1.60; P = .02).

IN PRACTICE:

The study findings suggested that moderate multivitamin supplement use may come with a survival benefit in patients with CRC, while high doses may not, but “further studies are needed before making clinical recommendations for multivitamin use in patients with CRC,” the authors said.

SOURCE:

This work, led by Ming‐ming He of Sun Yat‐sen University Cancer Center, Guangzhou, China, was published in Cancer.

LIMITATIONS:

Given the study’s observational design, residual confounding may be possible. Reverse causation and recall bias are also possible limitations.

DISCLOSURES:

This study was funded by the National Institutes of Health, American Institute for Cancer Research, Wellesley College, Dana‐Farber Cancer Institute, and the Entertainment Industry Foundation. Three study authors reported financial relationships outside this work.

A version of this article appeared on Medscape.com.

TOPLINE:

Multivitamin supplements at a moderate dose appear to lower the risk for both all-cause and cancer-related mortality in patients with colorectal cancer (CRC); however, high doses of multivitamin supplements may increase the risk for CRC-specific mortality.

METHODOLOGY:

• Some studies suggest that multivitamin supplements might increase a person’s risk for CRC, and other research indicates that certain components of multivitamins, such as vitamins C and D, may have anti-CRC properties.
• Because as many as half of CRC survivors take a multivitamin, researchers wanted to assess whether multivitamin use affects overall survival among people with CRC.
• In the current prospective cohort study, researchers evaluated the use and dose of multivitamin supplements in 2424 patients with stages I-III CRC, using detailed information from patients in the Nurses’ Health Study and Health Professionals Follow‐Up Study.
• The participants completed a mailed questionnaire every 2 years, which included questions about the current use of multivitamin supplements as well as doses per week (0, 1-2, 3-5, 6-9, and ≥ 10 tablets).
• The researchers assessed the potential association between multivitamin use and CRC-related as well as all‐cause mortality.

TAKEAWAY:

• Over a median follow-up period of 11 years, 1512 deaths and 343 cancer-specific deaths occurred.
• For patients diagnosed with CRC, a moderate dose of multivitamins (three to five tablets per week) vs no multivitamin use was associated with a 45% lower risk for cancer-related mortality (adjusted hazard ratio [aHR], 0.55; P = .005).
• Moderate multivitamin use was also associated with a lower risk for all-cause mortality (aHR, 0.81; P = .04) as was a higher dose of six to nine tablets per week (aHR, 0.79; P < .001).
• However, high doses of 10 or more tablets per week were associated with a 60% higher risk for cancer-related mortality (aHR, 1.60; P = .02).

IN PRACTICE:

The study findings suggested that moderate multivitamin supplement use may come with a survival benefit in patients with CRC, while high doses may not, but “further studies are needed before making clinical recommendations for multivitamin use in patients with CRC,” the authors said.

SOURCE:

This work, led by Ming‐ming He of Sun Yat‐sen University Cancer Center, Guangzhou, China, was published in Cancer.

LIMITATIONS:

Given the study’s observational design, residual confounding may be possible. Reverse causation and recall bias are also possible limitations.

DISCLOSURES:

This study was funded by the National Institutes of Health, American Institute for Cancer Research, Wellesley College, Dana‐Farber Cancer Institute, and the Entertainment Industry Foundation. Three study authors reported financial relationships outside this work.

A version of this article appeared on Medscape.com.