AVAHO

TOPLINE:

Higher plasma levels of omega-6 and omega-3 fatty acids are associated with a lower incidence of cancer. However, omega-3 fatty acids are linked to an increased risk for prostate cancer, specifically.

METHODOLOGY:

• Researchers looked for associations of plasma omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) with the incidence of cancer overall and 19 site-specific cancers in the large population-based prospective UK Biobank cohort.
• They included 253,138 participants aged 37-73 years who were followed for an average of 12.9 years, with 29,838 diagnosed with cancer.
• Plasma levels of omega-3 and omega-6 fatty acids were measured using nuclear magnetic resonance and expressed as percentages of total fatty acids.
• Participants with cancer diagnoses at baseline, those who withdrew from the study, and those with missing data on plasma PUFAs were excluded.
• The study adjusted for multiple covariates, including age, sex, ethnicity, socioeconomic status, lifestyle behaviors, and family history of diseases.

TAKEAWAY:

• Higher plasma levels of omega-6 and omega-3 fatty acids were associated with a 2% and 1% reduction in overall cancer risk per SD increase, respectively (P = .001 and P = .03).
• Omega-6 fatty acids were inversely associated with 14 site-specific cancers, whereas omega-3 fatty acids were inversely associated with five site-specific cancers.
• Prostate cancer was positively associated with omega-3 fatty acids, with a 3% increased risk per SD increase (P = .049).
• A higher omega-6/omega-3 ratio was associated with an increased risk for overall cancer, and three site-specific cancers showed positive associations with the ratio. “Each standard deviation increase, corresponding to a 13.13 increase in the omega ratio, was associated with a 2% increase in the risk of rectum cancer,” for example, the authors wrote.

IN PRACTICE:

“Overall, our findings provide support for possible small net protective roles of omega-3 and omega-6 PUFAs in the development of new cancer incidence. Our study also suggests that the usage of circulating blood biomarkers captures different aspects of dietary intake, reduces measurement errors, and thus enhances statistical power. The differential effects of omega-6% and omega-3% in age and sex subgroups warrant future investigation,” wrote the authors of the study.

SOURCE:

The study was led by Yuchen Zhang of the University of Georgia in Athens, Georgia. It was published online in the International Journal of Cancer.

LIMITATIONS:

The study’s potential for selective bias persists due to the participant sample skewing heavily toward European ancestry and White ethnicity. The number of events was small for some specific cancer sites, which may have limited the statistical power. The study focused on total omega-3 and omega-6 PUFAs, with only two individual fatty acids measured. Future studies are needed to examine the roles of other individual PUFAs and specific genetic variants. 

DISCLOSURES:

This study was supported by grants from the National Institute of General Medical Sciences of the National Institutes of Health. No relevant conflicts of interest were disclosed by the authors.
 

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

TOPLINE:

Higher plasma levels of omega-6 and omega-3 fatty acids are associated with a lower incidence of cancer. However, omega-3 fatty acids are linked to an increased risk for prostate cancer, specifically.

METHODOLOGY:

• Researchers looked for associations of plasma omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) with the incidence of cancer overall and 19 site-specific cancers in the large population-based prospective UK Biobank cohort.
• They included 253,138 participants aged 37-73 years who were followed for an average of 12.9 years, with 29,838 diagnosed with cancer.
• Plasma levels of omega-3 and omega-6 fatty acids were measured using nuclear magnetic resonance and expressed as percentages of total fatty acids.
• Participants with cancer diagnoses at baseline, those who withdrew from the study, and those with missing data on plasma PUFAs were excluded.
• The study adjusted for multiple covariates, including age, sex, ethnicity, socioeconomic status, lifestyle behaviors, and family history of diseases.

TAKEAWAY:

• Higher plasma levels of omega-6 and omega-3 fatty acids were associated with a 2% and 1% reduction in overall cancer risk per SD increase, respectively (P = .001 and P = .03).
• Omega-6 fatty acids were inversely associated with 14 site-specific cancers, whereas omega-3 fatty acids were inversely associated with five site-specific cancers.
• Prostate cancer was positively associated with omega-3 fatty acids, with a 3% increased risk per SD increase (P = .049).
• A higher omega-6/omega-3 ratio was associated with an increased risk for overall cancer, and three site-specific cancers showed positive associations with the ratio. “Each standard deviation increase, corresponding to a 13.13 increase in the omega ratio, was associated with a 2% increase in the risk of rectum cancer,” for example, the authors wrote.

IN PRACTICE:

“Overall, our findings provide support for possible small net protective roles of omega-3 and omega-6 PUFAs in the development of new cancer incidence. Our study also suggests that the usage of circulating blood biomarkers captures different aspects of dietary intake, reduces measurement errors, and thus enhances statistical power. The differential effects of omega-6% and omega-3% in age and sex subgroups warrant future investigation,” wrote the authors of the study.

SOURCE:

The study was led by Yuchen Zhang of the University of Georgia in Athens, Georgia. It was published online in the International Journal of Cancer.

LIMITATIONS:

The study’s potential for selective bias persists due to the participant sample skewing heavily toward European ancestry and White ethnicity. The number of events was small for some specific cancer sites, which may have limited the statistical power. The study focused on total omega-3 and omega-6 PUFAs, with only two individual fatty acids measured. Future studies are needed to examine the roles of other individual PUFAs and specific genetic variants. 

DISCLOSURES:

This study was supported by grants from the National Institute of General Medical Sciences of the National Institutes of Health. No relevant conflicts of interest were disclosed by the authors.
 

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

TOPLINE:

Higher plasma levels of omega-6 and omega-3 fatty acids are associated with a lower incidence of cancer. However, omega-3 fatty acids are linked to an increased risk for prostate cancer, specifically.

METHODOLOGY:

• Researchers looked for associations of plasma omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) with the incidence of cancer overall and 19 site-specific cancers in the large population-based prospective UK Biobank cohort.
• They included 253,138 participants aged 37-73 years who were followed for an average of 12.9 years, with 29,838 diagnosed with cancer.
• Plasma levels of omega-3 and omega-6 fatty acids were measured using nuclear magnetic resonance and expressed as percentages of total fatty acids.
• Participants with cancer diagnoses at baseline, those who withdrew from the study, and those with missing data on plasma PUFAs were excluded.
• The study adjusted for multiple covariates, including age, sex, ethnicity, socioeconomic status, lifestyle behaviors, and family history of diseases.

TAKEAWAY:

• Higher plasma levels of omega-6 and omega-3 fatty acids were associated with a 2% and 1% reduction in overall cancer risk per SD increase, respectively (P = .001 and P = .03).
• Omega-6 fatty acids were inversely associated with 14 site-specific cancers, whereas omega-3 fatty acids were inversely associated with five site-specific cancers.
• Prostate cancer was positively associated with omega-3 fatty acids, with a 3% increased risk per SD increase (P = .049).
• A higher omega-6/omega-3 ratio was associated with an increased risk for overall cancer, and three site-specific cancers showed positive associations with the ratio. “Each standard deviation increase, corresponding to a 13.13 increase in the omega ratio, was associated with a 2% increase in the risk of rectum cancer,” for example, the authors wrote.

IN PRACTICE:

“Overall, our findings provide support for possible small net protective roles of omega-3 and omega-6 PUFAs in the development of new cancer incidence. Our study also suggests that the usage of circulating blood biomarkers captures different aspects of dietary intake, reduces measurement errors, and thus enhances statistical power. The differential effects of omega-6% and omega-3% in age and sex subgroups warrant future investigation,” wrote the authors of the study.

SOURCE:

The study was led by Yuchen Zhang of the University of Georgia in Athens, Georgia. It was published online in the International Journal of Cancer.

LIMITATIONS:

The study’s potential for selective bias persists due to the participant sample skewing heavily toward European ancestry and White ethnicity. The number of events was small for some specific cancer sites, which may have limited the statistical power. The study focused on total omega-3 and omega-6 PUFAs, with only two individual fatty acids measured. Future studies are needed to examine the roles of other individual PUFAs and specific genetic variants. 

DISCLOSURES:

This study was supported by grants from the National Institute of General Medical Sciences of the National Institutes of Health. No relevant conflicts of interest were disclosed by the authors.
 

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

TOPLINE:

Patients treated for prostate cancer had higher rates of complications, including urinary and sexual issues, than a control group of men. Radiotherapy increases the risk for bladder cancer and radiation-specific complications, according to the new cohort study.
 

METHODOLOGY:

• Researchers conducted a cohort study to try to characterize long-term treatment-related adverse effects and complications in patients treated for prostate cancer, compared with a general population of older males.
• They used data from the Prostate Cancer Prevention Trial and the Selenium and Vitamin E Cancer Prevention Trial, linked with Medicare claims. A total of 29,196 participants were included in the study’s control group. Of 3946 patients diagnosed with prostate cancer, 655 were treated with prostatectomy, and 1056 were treated with radiotherapy.
• Participants were followed for a median of 10.2 years, with specific follow-up durations being 10.5 years and 8.5 years for the prostatectomy and radiotherapy groups, respectively.
• The study analyzed ten potential treatment-related complications using Medicare claims data, including urinary incontinence, erectile dysfunction, and secondary cancers. 
• Multivariable Cox regression was used to adjust for age, race, and year of time-at-risk initiation, with stratification by study and intervention arm. 

TAKEAWAY:

• At 12 years, there was a 7.23 increase in hazard risk for urinary or sexual complications for patients who had prostatectomy, compared with controls (P < .001).
• Radiotherapy-treated patients had a nearly three times greater hazard risk for bladder cancer and a 100-fold increased hazard risk for radiation-specific complications, such as radiation cystitis and radiation proctitis (P < .001).
• The incidence of any treatment-related complication per 1000 person-years was 124.26 for prostatectomy, 62.15 for radiotherapy, and 23.61 for untreated participants.
• The authors stated that these findings highlight the importance of patient counseling before prostate cancer screening and treatment.

IN PRACTICE:

“We found that, after accounting for baseline population rates, most patients with PCA undergoing treatment experience complications associated with worse quality of life and/or new health risks. The magnitude of these risks, compared with the relatively small benefit found by randomized clinical trials of PCA screening and treatment, should be explicitly reflected in national cancer screening and treatment guidelines and be integral to shared decision-making with patients before initiation of PSA screening, biopsy, or PCA treatment,” wrote the authors of the study.
 

SOURCE:

The study was led by Joseph M. Unger, PhD, SWOG Statistics and Data Management Center, Fred Hutchinson Cancer Center in Seattle, Washington. It was published online on November 7, 2024, in JAMA Oncology.
 

LIMITATIONS:

The study did not account for multiple comparisons, which may affect the statistical significance of some findings. Claims data are subject to misclassification and may underreport complications that are not reported to a physician. The study did not differentiate among strategies of prostatectomy or radiotherapy, which may result in different patterns of complications. The cohort comprised men enrolled in large, randomized prevention trials, which may limit the generalizability of the incidence estimates. Confounding by unknown factors cannot be ruled out, affecting the attribution of risks to prostate cancer treatment alone.
 

DISCLOSURES:

Unger disclosed consulting fees from AstraZeneca and Loxo/Lilly outside the submitted work. One coauthor reported grants from the US National Cancer Institute during the conduct of the study. Another coauthor reported employment with Flatiron Health at the time of manuscript submission and review. Additional disclosures are noted in the original article.

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

TOPLINE:

Patients treated for prostate cancer had higher rates of complications, including urinary and sexual issues, than a control group of men. Radiotherapy increases the risk for bladder cancer and radiation-specific complications, according to the new cohort study.
 

METHODOLOGY:

• Researchers conducted a cohort study to try to characterize long-term treatment-related adverse effects and complications in patients treated for prostate cancer, compared with a general population of older males.
• They used data from the Prostate Cancer Prevention Trial and the Selenium and Vitamin E Cancer Prevention Trial, linked with Medicare claims. A total of 29,196 participants were included in the study’s control group. Of 3946 patients diagnosed with prostate cancer, 655 were treated with prostatectomy, and 1056 were treated with radiotherapy.
• Participants were followed for a median of 10.2 years, with specific follow-up durations being 10.5 years and 8.5 years for the prostatectomy and radiotherapy groups, respectively.
• The study analyzed ten potential treatment-related complications using Medicare claims data, including urinary incontinence, erectile dysfunction, and secondary cancers. 
• Multivariable Cox regression was used to adjust for age, race, and year of time-at-risk initiation, with stratification by study and intervention arm. 

TAKEAWAY:

• At 12 years, there was a 7.23 increase in hazard risk for urinary or sexual complications for patients who had prostatectomy, compared with controls (P < .001).
• Radiotherapy-treated patients had a nearly three times greater hazard risk for bladder cancer and a 100-fold increased hazard risk for radiation-specific complications, such as radiation cystitis and radiation proctitis (P < .001).
• The incidence of any treatment-related complication per 1000 person-years was 124.26 for prostatectomy, 62.15 for radiotherapy, and 23.61 for untreated participants.
• The authors stated that these findings highlight the importance of patient counseling before prostate cancer screening and treatment.

IN PRACTICE:

“We found that, after accounting for baseline population rates, most patients with PCA undergoing treatment experience complications associated with worse quality of life and/or new health risks. The magnitude of these risks, compared with the relatively small benefit found by randomized clinical trials of PCA screening and treatment, should be explicitly reflected in national cancer screening and treatment guidelines and be integral to shared decision-making with patients before initiation of PSA screening, biopsy, or PCA treatment,” wrote the authors of the study.
 

SOURCE:

The study was led by Joseph M. Unger, PhD, SWOG Statistics and Data Management Center, Fred Hutchinson Cancer Center in Seattle, Washington. It was published online on November 7, 2024, in JAMA Oncology.
 

LIMITATIONS:

The study did not account for multiple comparisons, which may affect the statistical significance of some findings. Claims data are subject to misclassification and may underreport complications that are not reported to a physician. The study did not differentiate among strategies of prostatectomy or radiotherapy, which may result in different patterns of complications. The cohort comprised men enrolled in large, randomized prevention trials, which may limit the generalizability of the incidence estimates. Confounding by unknown factors cannot be ruled out, affecting the attribution of risks to prostate cancer treatment alone.
 

DISCLOSURES:

Unger disclosed consulting fees from AstraZeneca and Loxo/Lilly outside the submitted work. One coauthor reported grants from the US National Cancer Institute during the conduct of the study. Another coauthor reported employment with Flatiron Health at the time of manuscript submission and review. Additional disclosures are noted in the original article.

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

TOPLINE:

Patients treated for prostate cancer had higher rates of complications, including urinary and sexual issues, than a control group of men. Radiotherapy increases the risk for bladder cancer and radiation-specific complications, according to the new cohort study.
 

METHODOLOGY:

• Researchers conducted a cohort study to try to characterize long-term treatment-related adverse effects and complications in patients treated for prostate cancer, compared with a general population of older males.
• They used data from the Prostate Cancer Prevention Trial and the Selenium and Vitamin E Cancer Prevention Trial, linked with Medicare claims. A total of 29,196 participants were included in the study’s control group. Of 3946 patients diagnosed with prostate cancer, 655 were treated with prostatectomy, and 1056 were treated with radiotherapy.
• Participants were followed for a median of 10.2 years, with specific follow-up durations being 10.5 years and 8.5 years for the prostatectomy and radiotherapy groups, respectively.
• The study analyzed ten potential treatment-related complications using Medicare claims data, including urinary incontinence, erectile dysfunction, and secondary cancers. 
• Multivariable Cox regression was used to adjust for age, race, and year of time-at-risk initiation, with stratification by study and intervention arm. 

TAKEAWAY:

• At 12 years, there was a 7.23 increase in hazard risk for urinary or sexual complications for patients who had prostatectomy, compared with controls (P < .001).
• Radiotherapy-treated patients had a nearly three times greater hazard risk for bladder cancer and a 100-fold increased hazard risk for radiation-specific complications, such as radiation cystitis and radiation proctitis (P < .001).
• The incidence of any treatment-related complication per 1000 person-years was 124.26 for prostatectomy, 62.15 for radiotherapy, and 23.61 for untreated participants.
• The authors stated that these findings highlight the importance of patient counseling before prostate cancer screening and treatment.

IN PRACTICE:

“We found that, after accounting for baseline population rates, most patients with PCA undergoing treatment experience complications associated with worse quality of life and/or new health risks. The magnitude of these risks, compared with the relatively small benefit found by randomized clinical trials of PCA screening and treatment, should be explicitly reflected in national cancer screening and treatment guidelines and be integral to shared decision-making with patients before initiation of PSA screening, biopsy, or PCA treatment,” wrote the authors of the study.
 

SOURCE:

The study was led by Joseph M. Unger, PhD, SWOG Statistics and Data Management Center, Fred Hutchinson Cancer Center in Seattle, Washington. It was published online on November 7, 2024, in JAMA Oncology.
 

LIMITATIONS:

The study did not account for multiple comparisons, which may affect the statistical significance of some findings. Claims data are subject to misclassification and may underreport complications that are not reported to a physician. The study did not differentiate among strategies of prostatectomy or radiotherapy, which may result in different patterns of complications. The cohort comprised men enrolled in large, randomized prevention trials, which may limit the generalizability of the incidence estimates. Confounding by unknown factors cannot be ruled out, affecting the attribution of risks to prostate cancer treatment alone.
 

DISCLOSURES:

Unger disclosed consulting fees from AstraZeneca and Loxo/Lilly outside the submitted work. One coauthor reported grants from the US National Cancer Institute during the conduct of the study. Another coauthor reported employment with Flatiron Health at the time of manuscript submission and review. Additional disclosures are noted in the original article.

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

A growing body of research suggests that clinicians can offer chimeric antigen receptor (CAR) T-cell therapy safely and effectively on an outpatient basis — a positive development as clinicians strive to expand access beyond metropolitan areas.

In one recent study, an industry-funded phase 2 trial, researchers found similar outcomes from outpatient and inpatient CAR T-cell therapy for relapsed/refractory large B-cell lymphoma with lisocabtagene maraleucel (Breyanzi). 

Another recent study reported that outpatient treatment of B cell non-Hodgkin lymphoma with tisagenlecleucel (Kymriah) had similar efficacy to inpatient treatment. Meanwhile, a 2023 review of CAR T-cell therapy in various settings found similar outcomes in outpatient and inpatient treatment. 

“The future of CAR T-cell therapy lies in balancing safety with accessibility,” said Rayne Rouce, MD, a pediatric oncologist at Texas Children’s Cancer Center in Houston, Texas, in an interview. “Expanding CAR T-cell therapy beyond large medical centers is a critical next step.” 
 

Great Outcomes, Low Access

Since 2017, the FDA has approved six CAR T-cell therapies, which target cancer by harnessing the power of a patient’s own T cells. As an Oregon Health & Sciences University/Knight Cancer Center website explains, T cells are removed from the patient’s body, “genetically modified to make the chimeric antigen receptor, or CAR, [which] protein binds to specific proteins on the surface of cancer cells.”

Modified cells are grown and then infused back into the body, where they “multiply and may be able to destroy all the cancer cells.”

As Rouce puts it, “CAR T-cells have revolutionized the treatment of relapsed or refractory blood cancers.” One or more of the therapies have been approved to treat types of lymphoblastic leukemia, B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, and multiple myeloma.

A 2023 review of clinical trial data reported complete response rates of 40%-54% in aggressive B-cell lymphoma, 67% in mantle cell lymphoma, and 69%-74% in indolent B cell lymphoma.

“Commercialization of CAR T-cell therapy brought hope that access would expand beyond the major academic medical centers with the highly specialized infrastructure and advanced laboratories required to manufacture and ultimately treat patients,” Rouce said. “However, it quickly became clear that patients who are underinsured or uninsured — or who live outside the network of the well-resourced institutions that house these therapies — are still unable to access these potentially life-saving therapies.”

A 2024 report estimated the cost of CAR T-cell therapy as $700,000-$1 million and said only a small percentage of those who could benefit from the treatment actually get it. For example, an estimated 10,000 patients with diffuse large B-cell lymphoma alone could benefit from CAR T therapy annually, but a survey of 200 US healthcare centers in 2021 found that 1900 procedures were performed overall for all indications. 
 

Distance to Treatment Is a Major Obstacle

Even if patients have insurance plans willing to cover CAR T-cell therapy, they may not be able get care. While more than 150 US centers are certified to administer the therapy, “distance to major medical centers with CAR T capabilities is a major obstacle,” Yuliya Linhares, MD, chief of lymphoma at Miami Cancer Institute in Miami, Florida, said in an interview. 

“I have had patients who chose to not proceed with CAR T therapy due to inability to travel the distance to the medical center for pre-CAR T appointments and assessments and a lack of caretakers who are available to stay nearby,” Linhares said.

Indeed, the challenges facing patients in rural and underserved urban areas can be overwhelming, Hoda Badr, PhD, professor of medicine at Baylor College of Medicine in Houston, Texas, said in an interview.

“They must take time off work, arrange accommodations near treatment sites, and manage travel costs, all of which strain limited financial resources. The inability to afford these additional expenses can lead to delays in receiving care or patients forgoing the treatment altogether,” Badr said. She added that “the psychological and social burden of being away from family and community support systems during treatment can intensify the stress of an already difficult situation.”

A statistic tells the story of the urban/community divide. CAR T-cell therapy administration at academic centers after leukapheresis — the separation and collection of white blood cells — is reported to be at around 90%, while it’s only 47% in community-based practices that have to refer patients elsewhere, Linhares noted. 
 

Researchers Explore CAR T-Cell Therapy in the Community 

Linhares is lead author of the phase 2 trial that explored administration of lisocabtagene maraleucel in 82 patients with relapsed/refractory large B-cell lymphoma. The findings were published Sept. 30 in Blood Advances.

The OUTREACH trial, funded by Juno/Bristol-Myers Squibb, treated patients in the third line and beyond at community medical centers (outpatient-monitored, 70%; inpatient-monitored, 30%). The trial didn’t require facilities to be certified by the Foundation for the Accreditation of Cellular Therapy (FACT); all had to be non-tertiary cancer centers that weren’t associated with a university. In order to administer therapy on the outpatient basis, the centers had to have phase 1 or hematopoietic stem cell transplant capabilities.

As Linhares explained, 72% of participating centers hadn’t provided CAR T-cell therapy before, and 44% did not have FACT accreditation. “About 32% of patients received CAR T at CAR T naive sites, while 70% of patients received CAR T as outpatients. Investigators had to decide whether patients qualified for the outpatient observation or had to be admitted for the inpatient observation,” she noted.
 

Community Outcomes Were Comparable to Major Trial

As for the results, grade 3 or higher adverse events occurred at a similar frequency among outpatients and inpatients at 74% and 76%, Linhares said. There were no grade 5 adverse events, and 25% of patients treated as outpatients were never hospitalized. 

Response rates were similar to those in the major TRANSCEND trial with the objective response rates rate of 80% and complete response rates of 54%.

“Overall,” Linhares said, “our study demonstrated that with the availability of standard operating procedures, specially trained staff and a multidisciplinary team trained in CAR T toxicity management, inpatient and outpatient CAR T administration is feasible at specialized community medical centers.”

In 2023, another study examined patients with B-cell non-Hodgkin lymphoma who were treated on an outpatient basis with tisagenlecleucel. Researchers reported that outpatient therapy was “feasible and associated with similar efficacy outcomes as inpatient treatment.”

And a 2023 systematic literature review identified 11 studies that reported outpatient vs inpatient outcomes in CAR T-cell therapy and found “comparable response rates (80-82% in outpatient and 72-80% in inpatient).” Costs were cheaper in the outpatient setting. 

Research findings like these are good news, Baylor College of Medicine’s Badr said. “Outpatient administration could help to scale the availability of this therapy to a broader range of healthcare settings, including those serving underserved populations. Findings indicate promising safety profiles, which is encouraging for expanding access.”
 

Not Every Patient Can Tolerate Outpatient Care

Linhares noted that the patients who received outpatient care in the lisocabtagene maraleucel study were in better shape than those in the inpatient group. Those selected for inpatient care had “higher disease risk characteristics, including high grade B cell lymphoma histology, higher disease burden, and having received bridging therapy. This points to the fact that the investigators properly selected patients who were at a higher risk of complications for inpatient observation. Additionally, some patients stayed as inpatient due to social factors, which increases length of stay independently of disease characteristics.”

Specifically, reasons for inpatient monitoring were disease characteristics (48%) including tumor burden and risk of adverse events; psychosocial factors (32%) including lack of caregiver support or transportation; COVID-19 precautions (8%); pre-infusion adverse events (8%) of fever and vasovagal reaction; and principal investigator decision (4%) due to limited hospital experience with CAR T-cell therapy.

Texas Children’s Cancer Center’s Rouce said “certain patients, particularly those with higher risk for complications or those who require intensive monitoring, may not be suited for outpatient CAR T-cell therapy. This may be due to other comorbidities or baseline factors known to predispose to CAR T-related toxicities. However, evidence-based risk mitigation algorithms may still allow closely monitored outpatient treatment, with recognition that hospital admission for incipient side effects may be necessary.”
 

What’s Next for Access to Therapy?

Rouce noted that her institution, like many others, is offering CAR T-cell therapy on an outpatient basis. “Additionally, continued scientific innovation, such as immediately available, off-the-shelf cell therapies and inducible safety switches, will ultimately improve access,” she said. 

Linhares noted a recent advance and highlighted research that’s now in progress. “CAR Ts now have an indication as a second-line therapy in relapsed/refractory large B-cell lymphoma, and there are ongoing clinical trials that will potentially move CAR Ts into the first line,” she said. “Some trials are exploring allogeneic, readily available off-the-shelf CAR T for the treatment of minimal residual disease positive large B-cell lymphoma after completion of first-line therapy.”

These potential advances “are increasing the need for CAR T-capable medical centers,” Linhares noted. “More and more medical centers with expert hematology teams are becoming CAR T-certified, with more patients having access to CAR T.”

Still, she said, “I don’t think access is nearly as good as it should be. Many patients in rural areas are still unable to get this life-saving treatment. “However, “it is very possible that other novel targeted therapies, such as bispecific antibodies, will be used in place of CAR T in areas with poor CAR T access. Bispecific antibody efficacy in various B cell lymphoma histologies are being currently explored.”

Rouce discloses relationships with Novartis and Pfizer. Linhares reports ties with Kyowa Kirin, AbbVie, ADC, BeiGene, Genentech, Gilead, GlaxoSmithKline, Seagen, and TG. Badr has no disclosures. 
 

A version of this article appeared on Medscape.com.

A growing body of research suggests that clinicians can offer chimeric antigen receptor (CAR) T-cell therapy safely and effectively on an outpatient basis — a positive development as clinicians strive to expand access beyond metropolitan areas.

In one recent study, an industry-funded phase 2 trial, researchers found similar outcomes from outpatient and inpatient CAR T-cell therapy for relapsed/refractory large B-cell lymphoma with lisocabtagene maraleucel (Breyanzi). 

Another recent study reported that outpatient treatment of B cell non-Hodgkin lymphoma with tisagenlecleucel (Kymriah) had similar efficacy to inpatient treatment. Meanwhile, a 2023 review of CAR T-cell therapy in various settings found similar outcomes in outpatient and inpatient treatment. 

“The future of CAR T-cell therapy lies in balancing safety with accessibility,” said Rayne Rouce, MD, a pediatric oncologist at Texas Children’s Cancer Center in Houston, Texas, in an interview. “Expanding CAR T-cell therapy beyond large medical centers is a critical next step.” 
 

Great Outcomes, Low Access

Since 2017, the FDA has approved six CAR T-cell therapies, which target cancer by harnessing the power of a patient’s own T cells. As an Oregon Health & Sciences University/Knight Cancer Center website explains, T cells are removed from the patient’s body, “genetically modified to make the chimeric antigen receptor, or CAR, [which] protein binds to specific proteins on the surface of cancer cells.”

Modified cells are grown and then infused back into the body, where they “multiply and may be able to destroy all the cancer cells.”

As Rouce puts it, “CAR T-cells have revolutionized the treatment of relapsed or refractory blood cancers.” One or more of the therapies have been approved to treat types of lymphoblastic leukemia, B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, and multiple myeloma.

A 2023 review of clinical trial data reported complete response rates of 40%-54% in aggressive B-cell lymphoma, 67% in mantle cell lymphoma, and 69%-74% in indolent B cell lymphoma.

“Commercialization of CAR T-cell therapy brought hope that access would expand beyond the major academic medical centers with the highly specialized infrastructure and advanced laboratories required to manufacture and ultimately treat patients,” Rouce said. “However, it quickly became clear that patients who are underinsured or uninsured — or who live outside the network of the well-resourced institutions that house these therapies — are still unable to access these potentially life-saving therapies.”

A 2024 report estimated the cost of CAR T-cell therapy as $700,000-$1 million and said only a small percentage of those who could benefit from the treatment actually get it. For example, an estimated 10,000 patients with diffuse large B-cell lymphoma alone could benefit from CAR T therapy annually, but a survey of 200 US healthcare centers in 2021 found that 1900 procedures were performed overall for all indications. 
 

Distance to Treatment Is a Major Obstacle

Even if patients have insurance plans willing to cover CAR T-cell therapy, they may not be able get care. While more than 150 US centers are certified to administer the therapy, “distance to major medical centers with CAR T capabilities is a major obstacle,” Yuliya Linhares, MD, chief of lymphoma at Miami Cancer Institute in Miami, Florida, said in an interview. 

“I have had patients who chose to not proceed with CAR T therapy due to inability to travel the distance to the medical center for pre-CAR T appointments and assessments and a lack of caretakers who are available to stay nearby,” Linhares said.

Indeed, the challenges facing patients in rural and underserved urban areas can be overwhelming, Hoda Badr, PhD, professor of medicine at Baylor College of Medicine in Houston, Texas, said in an interview.

“They must take time off work, arrange accommodations near treatment sites, and manage travel costs, all of which strain limited financial resources. The inability to afford these additional expenses can lead to delays in receiving care or patients forgoing the treatment altogether,” Badr said. She added that “the psychological and social burden of being away from family and community support systems during treatment can intensify the stress of an already difficult situation.”

A statistic tells the story of the urban/community divide. CAR T-cell therapy administration at academic centers after leukapheresis — the separation and collection of white blood cells — is reported to be at around 90%, while it’s only 47% in community-based practices that have to refer patients elsewhere, Linhares noted. 
 

Researchers Explore CAR T-Cell Therapy in the Community 

Linhares is lead author of the phase 2 trial that explored administration of lisocabtagene maraleucel in 82 patients with relapsed/refractory large B-cell lymphoma. The findings were published Sept. 30 in Blood Advances.

The OUTREACH trial, funded by Juno/Bristol-Myers Squibb, treated patients in the third line and beyond at community medical centers (outpatient-monitored, 70%; inpatient-monitored, 30%). The trial didn’t require facilities to be certified by the Foundation for the Accreditation of Cellular Therapy (FACT); all had to be non-tertiary cancer centers that weren’t associated with a university. In order to administer therapy on the outpatient basis, the centers had to have phase 1 or hematopoietic stem cell transplant capabilities.

As Linhares explained, 72% of participating centers hadn’t provided CAR T-cell therapy before, and 44% did not have FACT accreditation. “About 32% of patients received CAR T at CAR T naive sites, while 70% of patients received CAR T as outpatients. Investigators had to decide whether patients qualified for the outpatient observation or had to be admitted for the inpatient observation,” she noted.
 

Community Outcomes Were Comparable to Major Trial

As for the results, grade 3 or higher adverse events occurred at a similar frequency among outpatients and inpatients at 74% and 76%, Linhares said. There were no grade 5 adverse events, and 25% of patients treated as outpatients were never hospitalized. 

Response rates were similar to those in the major TRANSCEND trial with the objective response rates rate of 80% and complete response rates of 54%.

“Overall,” Linhares said, “our study demonstrated that with the availability of standard operating procedures, specially trained staff and a multidisciplinary team trained in CAR T toxicity management, inpatient and outpatient CAR T administration is feasible at specialized community medical centers.”

In 2023, another study examined patients with B-cell non-Hodgkin lymphoma who were treated on an outpatient basis with tisagenlecleucel. Researchers reported that outpatient therapy was “feasible and associated with similar efficacy outcomes as inpatient treatment.”

And a 2023 systematic literature review identified 11 studies that reported outpatient vs inpatient outcomes in CAR T-cell therapy and found “comparable response rates (80-82% in outpatient and 72-80% in inpatient).” Costs were cheaper in the outpatient setting. 

Research findings like these are good news, Baylor College of Medicine’s Badr said. “Outpatient administration could help to scale the availability of this therapy to a broader range of healthcare settings, including those serving underserved populations. Findings indicate promising safety profiles, which is encouraging for expanding access.”
 

Not Every Patient Can Tolerate Outpatient Care

Linhares noted that the patients who received outpatient care in the lisocabtagene maraleucel study were in better shape than those in the inpatient group. Those selected for inpatient care had “higher disease risk characteristics, including high grade B cell lymphoma histology, higher disease burden, and having received bridging therapy. This points to the fact that the investigators properly selected patients who were at a higher risk of complications for inpatient observation. Additionally, some patients stayed as inpatient due to social factors, which increases length of stay independently of disease characteristics.”

Specifically, reasons for inpatient monitoring were disease characteristics (48%) including tumor burden and risk of adverse events; psychosocial factors (32%) including lack of caregiver support or transportation; COVID-19 precautions (8%); pre-infusion adverse events (8%) of fever and vasovagal reaction; and principal investigator decision (4%) due to limited hospital experience with CAR T-cell therapy.

Texas Children’s Cancer Center’s Rouce said “certain patients, particularly those with higher risk for complications or those who require intensive monitoring, may not be suited for outpatient CAR T-cell therapy. This may be due to other comorbidities or baseline factors known to predispose to CAR T-related toxicities. However, evidence-based risk mitigation algorithms may still allow closely monitored outpatient treatment, with recognition that hospital admission for incipient side effects may be necessary.”
 

What’s Next for Access to Therapy?

Rouce noted that her institution, like many others, is offering CAR T-cell therapy on an outpatient basis. “Additionally, continued scientific innovation, such as immediately available, off-the-shelf cell therapies and inducible safety switches, will ultimately improve access,” she said. 

Linhares noted a recent advance and highlighted research that’s now in progress. “CAR Ts now have an indication as a second-line therapy in relapsed/refractory large B-cell lymphoma, and there are ongoing clinical trials that will potentially move CAR Ts into the first line,” she said. “Some trials are exploring allogeneic, readily available off-the-shelf CAR T for the treatment of minimal residual disease positive large B-cell lymphoma after completion of first-line therapy.”

These potential advances “are increasing the need for CAR T-capable medical centers,” Linhares noted. “More and more medical centers with expert hematology teams are becoming CAR T-certified, with more patients having access to CAR T.”

Still, she said, “I don’t think access is nearly as good as it should be. Many patients in rural areas are still unable to get this life-saving treatment. “However, “it is very possible that other novel targeted therapies, such as bispecific antibodies, will be used in place of CAR T in areas with poor CAR T access. Bispecific antibody efficacy in various B cell lymphoma histologies are being currently explored.”

Rouce discloses relationships with Novartis and Pfizer. Linhares reports ties with Kyowa Kirin, AbbVie, ADC, BeiGene, Genentech, Gilead, GlaxoSmithKline, Seagen, and TG. Badr has no disclosures. 
 

A version of this article appeared on Medscape.com.

A growing body of research suggests that clinicians can offer chimeric antigen receptor (CAR) T-cell therapy safely and effectively on an outpatient basis — a positive development as clinicians strive to expand access beyond metropolitan areas.

In one recent study, an industry-funded phase 2 trial, researchers found similar outcomes from outpatient and inpatient CAR T-cell therapy for relapsed/refractory large B-cell lymphoma with lisocabtagene maraleucel (Breyanzi). 

Another recent study reported that outpatient treatment of B cell non-Hodgkin lymphoma with tisagenlecleucel (Kymriah) had similar efficacy to inpatient treatment. Meanwhile, a 2023 review of CAR T-cell therapy in various settings found similar outcomes in outpatient and inpatient treatment. 

“The future of CAR T-cell therapy lies in balancing safety with accessibility,” said Rayne Rouce, MD, a pediatric oncologist at Texas Children’s Cancer Center in Houston, Texas, in an interview. “Expanding CAR T-cell therapy beyond large medical centers is a critical next step.” 
 

Great Outcomes, Low Access

Since 2017, the FDA has approved six CAR T-cell therapies, which target cancer by harnessing the power of a patient’s own T cells. As an Oregon Health & Sciences University/Knight Cancer Center website explains, T cells are removed from the patient’s body, “genetically modified to make the chimeric antigen receptor, or CAR, [which] protein binds to specific proteins on the surface of cancer cells.”

Modified cells are grown and then infused back into the body, where they “multiply and may be able to destroy all the cancer cells.”

As Rouce puts it, “CAR T-cells have revolutionized the treatment of relapsed or refractory blood cancers.” One or more of the therapies have been approved to treat types of lymphoblastic leukemia, B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, and multiple myeloma.

A 2023 review of clinical trial data reported complete response rates of 40%-54% in aggressive B-cell lymphoma, 67% in mantle cell lymphoma, and 69%-74% in indolent B cell lymphoma.

“Commercialization of CAR T-cell therapy brought hope that access would expand beyond the major academic medical centers with the highly specialized infrastructure and advanced laboratories required to manufacture and ultimately treat patients,” Rouce said. “However, it quickly became clear that patients who are underinsured or uninsured — or who live outside the network of the well-resourced institutions that house these therapies — are still unable to access these potentially life-saving therapies.”

A 2024 report estimated the cost of CAR T-cell therapy as $700,000-$1 million and said only a small percentage of those who could benefit from the treatment actually get it. For example, an estimated 10,000 patients with diffuse large B-cell lymphoma alone could benefit from CAR T therapy annually, but a survey of 200 US healthcare centers in 2021 found that 1900 procedures were performed overall for all indications. 
 

Distance to Treatment Is a Major Obstacle

Even if patients have insurance plans willing to cover CAR T-cell therapy, they may not be able get care. While more than 150 US centers are certified to administer the therapy, “distance to major medical centers with CAR T capabilities is a major obstacle,” Yuliya Linhares, MD, chief of lymphoma at Miami Cancer Institute in Miami, Florida, said in an interview. 

“I have had patients who chose to not proceed with CAR T therapy due to inability to travel the distance to the medical center for pre-CAR T appointments and assessments and a lack of caretakers who are available to stay nearby,” Linhares said.

Indeed, the challenges facing patients in rural and underserved urban areas can be overwhelming, Hoda Badr, PhD, professor of medicine at Baylor College of Medicine in Houston, Texas, said in an interview.

“They must take time off work, arrange accommodations near treatment sites, and manage travel costs, all of which strain limited financial resources. The inability to afford these additional expenses can lead to delays in receiving care or patients forgoing the treatment altogether,” Badr said. She added that “the psychological and social burden of being away from family and community support systems during treatment can intensify the stress of an already difficult situation.”

A statistic tells the story of the urban/community divide. CAR T-cell therapy administration at academic centers after leukapheresis — the separation and collection of white blood cells — is reported to be at around 90%, while it’s only 47% in community-based practices that have to refer patients elsewhere, Linhares noted. 
 

Researchers Explore CAR T-Cell Therapy in the Community 

Linhares is lead author of the phase 2 trial that explored administration of lisocabtagene maraleucel in 82 patients with relapsed/refractory large B-cell lymphoma. The findings were published Sept. 30 in Blood Advances.

The OUTREACH trial, funded by Juno/Bristol-Myers Squibb, treated patients in the third line and beyond at community medical centers (outpatient-monitored, 70%; inpatient-monitored, 30%). The trial didn’t require facilities to be certified by the Foundation for the Accreditation of Cellular Therapy (FACT); all had to be non-tertiary cancer centers that weren’t associated with a university. In order to administer therapy on the outpatient basis, the centers had to have phase 1 or hematopoietic stem cell transplant capabilities.

As Linhares explained, 72% of participating centers hadn’t provided CAR T-cell therapy before, and 44% did not have FACT accreditation. “About 32% of patients received CAR T at CAR T naive sites, while 70% of patients received CAR T as outpatients. Investigators had to decide whether patients qualified for the outpatient observation or had to be admitted for the inpatient observation,” she noted.
 

Community Outcomes Were Comparable to Major Trial

As for the results, grade 3 or higher adverse events occurred at a similar frequency among outpatients and inpatients at 74% and 76%, Linhares said. There were no grade 5 adverse events, and 25% of patients treated as outpatients were never hospitalized. 

Response rates were similar to those in the major TRANSCEND trial with the objective response rates rate of 80% and complete response rates of 54%.

“Overall,” Linhares said, “our study demonstrated that with the availability of standard operating procedures, specially trained staff and a multidisciplinary team trained in CAR T toxicity management, inpatient and outpatient CAR T administration is feasible at specialized community medical centers.”

In 2023, another study examined patients with B-cell non-Hodgkin lymphoma who were treated on an outpatient basis with tisagenlecleucel. Researchers reported that outpatient therapy was “feasible and associated with similar efficacy outcomes as inpatient treatment.”

And a 2023 systematic literature review identified 11 studies that reported outpatient vs inpatient outcomes in CAR T-cell therapy and found “comparable response rates (80-82% in outpatient and 72-80% in inpatient).” Costs were cheaper in the outpatient setting. 

Research findings like these are good news, Baylor College of Medicine’s Badr said. “Outpatient administration could help to scale the availability of this therapy to a broader range of healthcare settings, including those serving underserved populations. Findings indicate promising safety profiles, which is encouraging for expanding access.”
 

Not Every Patient Can Tolerate Outpatient Care

Linhares noted that the patients who received outpatient care in the lisocabtagene maraleucel study were in better shape than those in the inpatient group. Those selected for inpatient care had “higher disease risk characteristics, including high grade B cell lymphoma histology, higher disease burden, and having received bridging therapy. This points to the fact that the investigators properly selected patients who were at a higher risk of complications for inpatient observation. Additionally, some patients stayed as inpatient due to social factors, which increases length of stay independently of disease characteristics.”

Specifically, reasons for inpatient monitoring were disease characteristics (48%) including tumor burden and risk of adverse events; psychosocial factors (32%) including lack of caregiver support or transportation; COVID-19 precautions (8%); pre-infusion adverse events (8%) of fever and vasovagal reaction; and principal investigator decision (4%) due to limited hospital experience with CAR T-cell therapy.

Texas Children’s Cancer Center’s Rouce said “certain patients, particularly those with higher risk for complications or those who require intensive monitoring, may not be suited for outpatient CAR T-cell therapy. This may be due to other comorbidities or baseline factors known to predispose to CAR T-related toxicities. However, evidence-based risk mitigation algorithms may still allow closely monitored outpatient treatment, with recognition that hospital admission for incipient side effects may be necessary.”
 

What’s Next for Access to Therapy?

Rouce noted that her institution, like many others, is offering CAR T-cell therapy on an outpatient basis. “Additionally, continued scientific innovation, such as immediately available, off-the-shelf cell therapies and inducible safety switches, will ultimately improve access,” she said. 

Linhares noted a recent advance and highlighted research that’s now in progress. “CAR Ts now have an indication as a second-line therapy in relapsed/refractory large B-cell lymphoma, and there are ongoing clinical trials that will potentially move CAR Ts into the first line,” she said. “Some trials are exploring allogeneic, readily available off-the-shelf CAR T for the treatment of minimal residual disease positive large B-cell lymphoma after completion of first-line therapy.”

These potential advances “are increasing the need for CAR T-capable medical centers,” Linhares noted. “More and more medical centers with expert hematology teams are becoming CAR T-certified, with more patients having access to CAR T.”

Still, she said, “I don’t think access is nearly as good as it should be. Many patients in rural areas are still unable to get this life-saving treatment. “However, “it is very possible that other novel targeted therapies, such as bispecific antibodies, will be used in place of CAR T in areas with poor CAR T access. Bispecific antibody efficacy in various B cell lymphoma histologies are being currently explored.”

Rouce discloses relationships with Novartis and Pfizer. Linhares reports ties with Kyowa Kirin, AbbVie, ADC, BeiGene, Genentech, Gilead, GlaxoSmithKline, Seagen, and TG. Badr has no disclosures. 
 

A version of this article appeared on Medscape.com.

CHICAGO — Patients who are new users of glucagon-like peptide 1 (GLP-1) receptor agonists have a low absolute risk of thyroid cancer, according to a new study presented at the annual meeting of the American Thyroid Association (ATA).

The study, presented by Juan Brito Campana, MBBS, of the Mayo Clinic in Rochester, Minnesota, used Medicare records to perform a secondary analysis of 41,000 adults with type 2 diabetes and moderate cardiovascular risk who were new users of GLP-1 receptor agonists, compared to users of other diabetes medications. 

“We took the innovative approach of applying the methodological rigor of a randomized clinical trial to the very large dataset of observational studies,” said Brito Campana.

The results showed a low absolute risk of thyroid cancer, with only 0.17% of patients in the GLP-1 group developing the disease. However, the data also showed a potential relative increase in risk during the first year of GLP-1 receptor agonist use. 

“This is likely due to increased detection rather than true incidence, as the latency period for thyroid cancer development is typically longer,” Brito Campana said. 

“We also note the limitations of the observational study design, including the short follow-up period and lack of detailed histological data. However, we believe the benefits of GLP-1 receptor agonists likely outweigh the risk of thyroid cancer.”
 

Malignancy in Bethesda III and IV Thyroid Nodules

At the same ATA session, Sapir Nachum Goldberg, MD, of the University of Pennsylvania, Philadelphia, presented the results of a retrospective record review that examined the prevalence of malignancy in Bethesda III and IV thyroid nodules with negative Thyrogen Receptor Signaling (ThyroSeq) version 3 molecular testing results.

Goldberg reported that 87% of patients with ThyroSeq negative subtype results were managed nonoperatively. “Based on our data, the true prevalence of malignancy likely lies between our low and high estimates of 3% and 23%,” she said. “We believe that the prevalence of malignancy may be higher in real-world practice than validation studies.”

Additionally, nodules with “currently negative” or “negative but limited” ThyroSeq results had a higher prevalence of malignancy (7%), compared with those with a “negative” result (2%). Factors like immediate vs delayed surgery, nodule size, and ultrasound pattern did not significantly impact malignancy prevalence.

The study results also indicated that surveillance ultrasonography is not routinely performed in up to one-third of patients, Goldberg said.

She closed by suggesting that colleagues consider the negative subtype in clinical decision-making. For “negative but limited” nodules, repeat the fine needle aspiration and, for “negative” and “currently negative” nodules, consider ultrasound follow-up as per ATA guidelines for Bethesda II cytology, she said.
 

RET-Mutated Medullary Thyroid Cancer

For patients with RET-mutated medullary thyroid cancer, Julien Hadoux, MD, PhD, of Institut de Cancérologie Gustave Roussy, Villejuif, France, presented a combined analysis of the efficacy of the RET inhibitor selpercatinib from the phase 1/2 LIBRETTO-001 and phase 3 LIBRETTO-531 trials.

This post hoc analysis used a combined cohort of 509 patients with RET-mutated advanced or metastatic medullary thyroid cancer who had received selpercatinib in the two trials.

Hadoux reported that robust and durable responses were seen across all mutation groups, including M918T, extracellular cysteine, and an “other” group composed of various uncommon RET mutations. “The median [progression-free survival] PFS was not reached for either the M918T or extracellular groups and it was 51.4 months for the Other group,” he said. 

“Selpercatinib showed superior median PFS vs control, regardless of the RET mutation. This analysis constitutes the largest catalog of RET mutations in medullary thyroid cancers treated with RET-specific inhibitors.”
 

TRK-Fusion Differentiated Thyroid Cancer

Steven Waguespack, MD, of the University of Texas MD Anderson Cancer Center, Houston, shared updated efficacy and safety data from three phase 1/2 pooled clinical trials of the tropomyosin kinase receptor (TRK) inhibitor larotrectinib in thyroid cancer. These data updated results initially published in 2022.

“Larotrectinib continues to demonstrate rapid and durable responses, extended survival, and offers a favorable safety profile in patients with TRK fusion differentiated thyroid cancer, with limited activity in anaplastic thyroid cancer,” Waguespack said. 

“Additionally, in a subset of patients, we identified some acquired on-target NTRK mutations and off-target GNAS and TP53 mutations that may give further insight into mechanisms of resistance.”

The primary endpoint was the investigator-assessed objective response rate (ORR); at 48 months, the ORR was 79% by independent review. The median PFS in patients with TRK fusion differentiated thyroid cancer was 44 months, while the median duration of response was 41 months. The 4-year overall survival rate was 86%.

Waguespack closed with a cautionary note to colleagues: “While circulating tumor DNA next-generation sequencing (NGS) analysis can be used to test for NTRK gene fusions, negative results should be followed up with tissue-based NGS,” he said.

Brito Campana and Goldberg disclosed no relevant financial relationships. Hadoux reported receiving honoraria for speaker engagements, advisory roles, or funding for CME from Eli Lilly, AAA, IPSEN, Roche, Pharma Mar, and EISAI, and research grants from Novartis, Sanofi, and Eli Lilly.

A version of this article appeared on Medscape.com.

CHICAGO — Patients who are new users of glucagon-like peptide 1 (GLP-1) receptor agonists have a low absolute risk of thyroid cancer, according to a new study presented at the annual meeting of the American Thyroid Association (ATA).

The study, presented by Juan Brito Campana, MBBS, of the Mayo Clinic in Rochester, Minnesota, used Medicare records to perform a secondary analysis of 41,000 adults with type 2 diabetes and moderate cardiovascular risk who were new users of GLP-1 receptor agonists, compared to users of other diabetes medications. 

“We took the innovative approach of applying the methodological rigor of a randomized clinical trial to the very large dataset of observational studies,” said Brito Campana.

The results showed a low absolute risk of thyroid cancer, with only 0.17% of patients in the GLP-1 group developing the disease. However, the data also showed a potential relative increase in risk during the first year of GLP-1 receptor agonist use. 

“This is likely due to increased detection rather than true incidence, as the latency period for thyroid cancer development is typically longer,” Brito Campana said. 

“We also note the limitations of the observational study design, including the short follow-up period and lack of detailed histological data. However, we believe the benefits of GLP-1 receptor agonists likely outweigh the risk of thyroid cancer.”
 

Malignancy in Bethesda III and IV Thyroid Nodules

At the same ATA session, Sapir Nachum Goldberg, MD, of the University of Pennsylvania, Philadelphia, presented the results of a retrospective record review that examined the prevalence of malignancy in Bethesda III and IV thyroid nodules with negative Thyrogen Receptor Signaling (ThyroSeq) version 3 molecular testing results.

Goldberg reported that 87% of patients with ThyroSeq negative subtype results were managed nonoperatively. “Based on our data, the true prevalence of malignancy likely lies between our low and high estimates of 3% and 23%,” she said. “We believe that the prevalence of malignancy may be higher in real-world practice than validation studies.”

Additionally, nodules with “currently negative” or “negative but limited” ThyroSeq results had a higher prevalence of malignancy (7%), compared with those with a “negative” result (2%). Factors like immediate vs delayed surgery, nodule size, and ultrasound pattern did not significantly impact malignancy prevalence.

The study results also indicated that surveillance ultrasonography is not routinely performed in up to one-third of patients, Goldberg said.

She closed by suggesting that colleagues consider the negative subtype in clinical decision-making. For “negative but limited” nodules, repeat the fine needle aspiration and, for “negative” and “currently negative” nodules, consider ultrasound follow-up as per ATA guidelines for Bethesda II cytology, she said.
 

RET-Mutated Medullary Thyroid Cancer

For patients with RET-mutated medullary thyroid cancer, Julien Hadoux, MD, PhD, of Institut de Cancérologie Gustave Roussy, Villejuif, France, presented a combined analysis of the efficacy of the RET inhibitor selpercatinib from the phase 1/2 LIBRETTO-001 and phase 3 LIBRETTO-531 trials.

This post hoc analysis used a combined cohort of 509 patients with RET-mutated advanced or metastatic medullary thyroid cancer who had received selpercatinib in the two trials.

Hadoux reported that robust and durable responses were seen across all mutation groups, including M918T, extracellular cysteine, and an “other” group composed of various uncommon RET mutations. “The median [progression-free survival] PFS was not reached for either the M918T or extracellular groups and it was 51.4 months for the Other group,” he said. 

“Selpercatinib showed superior median PFS vs control, regardless of the RET mutation. This analysis constitutes the largest catalog of RET mutations in medullary thyroid cancers treated with RET-specific inhibitors.”
 

TRK-Fusion Differentiated Thyroid Cancer

Steven Waguespack, MD, of the University of Texas MD Anderson Cancer Center, Houston, shared updated efficacy and safety data from three phase 1/2 pooled clinical trials of the tropomyosin kinase receptor (TRK) inhibitor larotrectinib in thyroid cancer. These data updated results initially published in 2022.

“Larotrectinib continues to demonstrate rapid and durable responses, extended survival, and offers a favorable safety profile in patients with TRK fusion differentiated thyroid cancer, with limited activity in anaplastic thyroid cancer,” Waguespack said. 

“Additionally, in a subset of patients, we identified some acquired on-target NTRK mutations and off-target GNAS and TP53 mutations that may give further insight into mechanisms of resistance.”

The primary endpoint was the investigator-assessed objective response rate (ORR); at 48 months, the ORR was 79% by independent review. The median PFS in patients with TRK fusion differentiated thyroid cancer was 44 months, while the median duration of response was 41 months. The 4-year overall survival rate was 86%.

Waguespack closed with a cautionary note to colleagues: “While circulating tumor DNA next-generation sequencing (NGS) analysis can be used to test for NTRK gene fusions, negative results should be followed up with tissue-based NGS,” he said.

Brito Campana and Goldberg disclosed no relevant financial relationships. Hadoux reported receiving honoraria for speaker engagements, advisory roles, or funding for CME from Eli Lilly, AAA, IPSEN, Roche, Pharma Mar, and EISAI, and research grants from Novartis, Sanofi, and Eli Lilly.

A version of this article appeared on Medscape.com.

CHICAGO — Patients who are new users of glucagon-like peptide 1 (GLP-1) receptor agonists have a low absolute risk of thyroid cancer, according to a new study presented at the annual meeting of the American Thyroid Association (ATA).

The study, presented by Juan Brito Campana, MBBS, of the Mayo Clinic in Rochester, Minnesota, used Medicare records to perform a secondary analysis of 41,000 adults with type 2 diabetes and moderate cardiovascular risk who were new users of GLP-1 receptor agonists, compared to users of other diabetes medications. 

“We took the innovative approach of applying the methodological rigor of a randomized clinical trial to the very large dataset of observational studies,” said Brito Campana.

The results showed a low absolute risk of thyroid cancer, with only 0.17% of patients in the GLP-1 group developing the disease. However, the data also showed a potential relative increase in risk during the first year of GLP-1 receptor agonist use. 

“This is likely due to increased detection rather than true incidence, as the latency period for thyroid cancer development is typically longer,” Brito Campana said. 

“We also note the limitations of the observational study design, including the short follow-up period and lack of detailed histological data. However, we believe the benefits of GLP-1 receptor agonists likely outweigh the risk of thyroid cancer.”
 

Malignancy in Bethesda III and IV Thyroid Nodules

At the same ATA session, Sapir Nachum Goldberg, MD, of the University of Pennsylvania, Philadelphia, presented the results of a retrospective record review that examined the prevalence of malignancy in Bethesda III and IV thyroid nodules with negative Thyrogen Receptor Signaling (ThyroSeq) version 3 molecular testing results.

Goldberg reported that 87% of patients with ThyroSeq negative subtype results were managed nonoperatively. “Based on our data, the true prevalence of malignancy likely lies between our low and high estimates of 3% and 23%,” she said. “We believe that the prevalence of malignancy may be higher in real-world practice than validation studies.”

Additionally, nodules with “currently negative” or “negative but limited” ThyroSeq results had a higher prevalence of malignancy (7%), compared with those with a “negative” result (2%). Factors like immediate vs delayed surgery, nodule size, and ultrasound pattern did not significantly impact malignancy prevalence.

The study results also indicated that surveillance ultrasonography is not routinely performed in up to one-third of patients, Goldberg said.

She closed by suggesting that colleagues consider the negative subtype in clinical decision-making. For “negative but limited” nodules, repeat the fine needle aspiration and, for “negative” and “currently negative” nodules, consider ultrasound follow-up as per ATA guidelines for Bethesda II cytology, she said.
 

RET-Mutated Medullary Thyroid Cancer

For patients with RET-mutated medullary thyroid cancer, Julien Hadoux, MD, PhD, of Institut de Cancérologie Gustave Roussy, Villejuif, France, presented a combined analysis of the efficacy of the RET inhibitor selpercatinib from the phase 1/2 LIBRETTO-001 and phase 3 LIBRETTO-531 trials.

This post hoc analysis used a combined cohort of 509 patients with RET-mutated advanced or metastatic medullary thyroid cancer who had received selpercatinib in the two trials.

Hadoux reported that robust and durable responses were seen across all mutation groups, including M918T, extracellular cysteine, and an “other” group composed of various uncommon RET mutations. “The median [progression-free survival] PFS was not reached for either the M918T or extracellular groups and it was 51.4 months for the Other group,” he said. 

“Selpercatinib showed superior median PFS vs control, regardless of the RET mutation. This analysis constitutes the largest catalog of RET mutations in medullary thyroid cancers treated with RET-specific inhibitors.”
 

TRK-Fusion Differentiated Thyroid Cancer

Steven Waguespack, MD, of the University of Texas MD Anderson Cancer Center, Houston, shared updated efficacy and safety data from three phase 1/2 pooled clinical trials of the tropomyosin kinase receptor (TRK) inhibitor larotrectinib in thyroid cancer. These data updated results initially published in 2022.

“Larotrectinib continues to demonstrate rapid and durable responses, extended survival, and offers a favorable safety profile in patients with TRK fusion differentiated thyroid cancer, with limited activity in anaplastic thyroid cancer,” Waguespack said. 

“Additionally, in a subset of patients, we identified some acquired on-target NTRK mutations and off-target GNAS and TP53 mutations that may give further insight into mechanisms of resistance.”

The primary endpoint was the investigator-assessed objective response rate (ORR); at 48 months, the ORR was 79% by independent review. The median PFS in patients with TRK fusion differentiated thyroid cancer was 44 months, while the median duration of response was 41 months. The 4-year overall survival rate was 86%.

Waguespack closed with a cautionary note to colleagues: “While circulating tumor DNA next-generation sequencing (NGS) analysis can be used to test for NTRK gene fusions, negative results should be followed up with tissue-based NGS,” he said.

Brito Campana and Goldberg disclosed no relevant financial relationships. Hadoux reported receiving honoraria for speaker engagements, advisory roles, or funding for CME from Eli Lilly, AAA, IPSEN, Roche, Pharma Mar, and EISAI, and research grants from Novartis, Sanofi, and Eli Lilly.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Researchers have developed an artificial intelligence (AI) tool capable of detecting and differentiating cystic and solid pancreatic lesions during endoscopic ultrasound (EUS) with high accuracy.

This was a transatlantic collaborative effort involving researchers in Portugal, Spain, the United States, and Brazil, and the AI tool “works on different platforms and different devices,” Miguel Mascarenhas, MD, PhD, with Centro Hospitalar Universitário de São João, Porto, Portugal, said in a presentation at the annual meeting of the American College of Gastroenterology.

Mascarenhas noted that pancreatic cystic lesions (PCLs) are a common incidental finding during imaging and are differentiated by whether they’re mucinous PCLs (M-PCLs) or non-mucinous PCLs (NM-PCLs). The malignancy risk is almost exclusive of PCL with a mucinous phenotype.

Pancreatic solid lesions are also prevalent, and differentiation is challenging. Pancreatic ductal adenocarcinoma (P-DAC) is the most common pancreatic solid lesion and has a poor prognosis because of late-stage disease at diagnosis. Pancreatic neuroendocrine tumors (P-NETs) are less common but have malignant potential.

EUS is the “gold standard” for pancreatic lesion evaluation, but its diagnostic accuracy is suboptimal, particularly for lesions < 10 mm, Mascarenhas noted.

With an eye toward improving diagnostic accuracy, he and colleagues developed a convolutional neural network for detecting and differentiating cystic (M-PCL and NM-PCL) and solid (P-DAC and P-NET) pancreatic lesions.

They leveraged data from 378 EUS exams with 126,000 still images — 19,528 M-PCL, 8175 NM-PCL, 64,286 P-DAC, 29,153 P-NET, and 4858 normal pancreas images.

The AI tool demonstrated 99.1% accuracy for identifying normal pancreatic tissue, and it showed 99% and 99.8% accuracy for M-PCL and NM-PCL, respectively.

For pancreatic solid lesions, P-DAC and P-NET were distinguished with 94% accuracy, with 98.7% and 83.6% sensitivity for P-DAC and P-NET, respectively.
 

Real-Time Validation Next

“AI is delivering promising results throughout medicine, but particularly in gastroenterology, which is one of the most fertile areas of AI research. This comes mostly from the deployment of deep-learning models, most of them convolutional neural networks, which are highly efficient for image analysis,” Mascarenhas told attendees.

This is the “first worldwide convolutional neural network” capable of detecting and differentiating both cystic and solid pancreatic lesions. The use of a large dataset from four centers in two continents helps minimize the impact of demographic bias, Mascarenhas added.

The study is based on still images, not full videos, he noted. As a next step, the team is conducting a multicenter study focused on real-time clinical validation of the model during EUS procedures.

“AI has the potential to improve the diagnostic accuracy of endoscopic ultrasound. We’re just on the tip of the iceberg. There is enormous potential to harness AI, and we welcome all the groups that might want to join our research,” Mascarenhas said.

 

Brennan Spiegel, MD, MSHS, AGAF, director of Health Services Research at Cedars-Sinai Medical Center, Los Angeles, who wasn’t involved in the study, is optimistic about emerging applications for AI.

“AI holds incredible promise in gastroenterology, especially for diagnosing complex pancreatic lesions where early, accurate differentiation can be lifesaving,” Spiegel said in an interview.

“This study’s high accuracy across diverse datasets is encouraging; however, as a retrospective analysis, it leaves the real-time clinical impact still to be proven. Prospective studies will be essential to confirm AI’s role in enhancing our diagnostic capabilities,” Spiegel cautioned.

“More generally, AI is rapidly transforming gastroenterology by enhancing our ability to detect, differentiate, and monitor conditions with unprecedented precision. From improving early cancer detection to guiding complex diagnostic procedures, AI stands to become an invaluable tool that complements clinical expertise. As we refine these technologies, the potential for AI to elevate both diagnostic accuracy and patient outcomes in GI is truly remarkable,” Spiegel said.

The study had no specific funding. Mascarenhas and Spiegel have declared no conflicts of interest.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Researchers have developed an artificial intelligence (AI) tool capable of detecting and differentiating cystic and solid pancreatic lesions during endoscopic ultrasound (EUS) with high accuracy.

This was a transatlantic collaborative effort involving researchers in Portugal, Spain, the United States, and Brazil, and the AI tool “works on different platforms and different devices,” Miguel Mascarenhas, MD, PhD, with Centro Hospitalar Universitário de São João, Porto, Portugal, said in a presentation at the annual meeting of the American College of Gastroenterology.

Mascarenhas noted that pancreatic cystic lesions (PCLs) are a common incidental finding during imaging and are differentiated by whether they’re mucinous PCLs (M-PCLs) or non-mucinous PCLs (NM-PCLs). The malignancy risk is almost exclusive of PCL with a mucinous phenotype.

Pancreatic solid lesions are also prevalent, and differentiation is challenging. Pancreatic ductal adenocarcinoma (P-DAC) is the most common pancreatic solid lesion and has a poor prognosis because of late-stage disease at diagnosis. Pancreatic neuroendocrine tumors (P-NETs) are less common but have malignant potential.

EUS is the “gold standard” for pancreatic lesion evaluation, but its diagnostic accuracy is suboptimal, particularly for lesions < 10 mm, Mascarenhas noted.

With an eye toward improving diagnostic accuracy, he and colleagues developed a convolutional neural network for detecting and differentiating cystic (M-PCL and NM-PCL) and solid (P-DAC and P-NET) pancreatic lesions.

They leveraged data from 378 EUS exams with 126,000 still images — 19,528 M-PCL, 8175 NM-PCL, 64,286 P-DAC, 29,153 P-NET, and 4858 normal pancreas images.

The AI tool demonstrated 99.1% accuracy for identifying normal pancreatic tissue, and it showed 99% and 99.8% accuracy for M-PCL and NM-PCL, respectively.

For pancreatic solid lesions, P-DAC and P-NET were distinguished with 94% accuracy, with 98.7% and 83.6% sensitivity for P-DAC and P-NET, respectively.
 

Real-Time Validation Next

“AI is delivering promising results throughout medicine, but particularly in gastroenterology, which is one of the most fertile areas of AI research. This comes mostly from the deployment of deep-learning models, most of them convolutional neural networks, which are highly efficient for image analysis,” Mascarenhas told attendees.

This is the “first worldwide convolutional neural network” capable of detecting and differentiating both cystic and solid pancreatic lesions. The use of a large dataset from four centers in two continents helps minimize the impact of demographic bias, Mascarenhas added.

The study is based on still images, not full videos, he noted. As a next step, the team is conducting a multicenter study focused on real-time clinical validation of the model during EUS procedures.

“AI has the potential to improve the diagnostic accuracy of endoscopic ultrasound. We’re just on the tip of the iceberg. There is enormous potential to harness AI, and we welcome all the groups that might want to join our research,” Mascarenhas said.

 

Brennan Spiegel, MD, MSHS, AGAF, director of Health Services Research at Cedars-Sinai Medical Center, Los Angeles, who wasn’t involved in the study, is optimistic about emerging applications for AI.

“AI holds incredible promise in gastroenterology, especially for diagnosing complex pancreatic lesions where early, accurate differentiation can be lifesaving,” Spiegel said in an interview.

“This study’s high accuracy across diverse datasets is encouraging; however, as a retrospective analysis, it leaves the real-time clinical impact still to be proven. Prospective studies will be essential to confirm AI’s role in enhancing our diagnostic capabilities,” Spiegel cautioned.

“More generally, AI is rapidly transforming gastroenterology by enhancing our ability to detect, differentiate, and monitor conditions with unprecedented precision. From improving early cancer detection to guiding complex diagnostic procedures, AI stands to become an invaluable tool that complements clinical expertise. As we refine these technologies, the potential for AI to elevate both diagnostic accuracy and patient outcomes in GI is truly remarkable,” Spiegel said.

The study had no specific funding. Mascarenhas and Spiegel have declared no conflicts of interest.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Researchers have developed an artificial intelligence (AI) tool capable of detecting and differentiating cystic and solid pancreatic lesions during endoscopic ultrasound (EUS) with high accuracy.

This was a transatlantic collaborative effort involving researchers in Portugal, Spain, the United States, and Brazil, and the AI tool “works on different platforms and different devices,” Miguel Mascarenhas, MD, PhD, with Centro Hospitalar Universitário de São João, Porto, Portugal, said in a presentation at the annual meeting of the American College of Gastroenterology.

Mascarenhas noted that pancreatic cystic lesions (PCLs) are a common incidental finding during imaging and are differentiated by whether they’re mucinous PCLs (M-PCLs) or non-mucinous PCLs (NM-PCLs). The malignancy risk is almost exclusive of PCL with a mucinous phenotype.

Pancreatic solid lesions are also prevalent, and differentiation is challenging. Pancreatic ductal adenocarcinoma (P-DAC) is the most common pancreatic solid lesion and has a poor prognosis because of late-stage disease at diagnosis. Pancreatic neuroendocrine tumors (P-NETs) are less common but have malignant potential.

EUS is the “gold standard” for pancreatic lesion evaluation, but its diagnostic accuracy is suboptimal, particularly for lesions < 10 mm, Mascarenhas noted.

With an eye toward improving diagnostic accuracy, he and colleagues developed a convolutional neural network for detecting and differentiating cystic (M-PCL and NM-PCL) and solid (P-DAC and P-NET) pancreatic lesions.

They leveraged data from 378 EUS exams with 126,000 still images — 19,528 M-PCL, 8175 NM-PCL, 64,286 P-DAC, 29,153 P-NET, and 4858 normal pancreas images.

The AI tool demonstrated 99.1% accuracy for identifying normal pancreatic tissue, and it showed 99% and 99.8% accuracy for M-PCL and NM-PCL, respectively.

For pancreatic solid lesions, P-DAC and P-NET were distinguished with 94% accuracy, with 98.7% and 83.6% sensitivity for P-DAC and P-NET, respectively.
 

Real-Time Validation Next

“AI is delivering promising results throughout medicine, but particularly in gastroenterology, which is one of the most fertile areas of AI research. This comes mostly from the deployment of deep-learning models, most of them convolutional neural networks, which are highly efficient for image analysis,” Mascarenhas told attendees.

This is the “first worldwide convolutional neural network” capable of detecting and differentiating both cystic and solid pancreatic lesions. The use of a large dataset from four centers in two continents helps minimize the impact of demographic bias, Mascarenhas added.

The study is based on still images, not full videos, he noted. As a next step, the team is conducting a multicenter study focused on real-time clinical validation of the model during EUS procedures.

“AI has the potential to improve the diagnostic accuracy of endoscopic ultrasound. We’re just on the tip of the iceberg. There is enormous potential to harness AI, and we welcome all the groups that might want to join our research,” Mascarenhas said.

 

Brennan Spiegel, MD, MSHS, AGAF, director of Health Services Research at Cedars-Sinai Medical Center, Los Angeles, who wasn’t involved in the study, is optimistic about emerging applications for AI.

“AI holds incredible promise in gastroenterology, especially for diagnosing complex pancreatic lesions where early, accurate differentiation can be lifesaving,” Spiegel said in an interview.

“This study’s high accuracy across diverse datasets is encouraging; however, as a retrospective analysis, it leaves the real-time clinical impact still to be proven. Prospective studies will be essential to confirm AI’s role in enhancing our diagnostic capabilities,” Spiegel cautioned.

“More generally, AI is rapidly transforming gastroenterology by enhancing our ability to detect, differentiate, and monitor conditions with unprecedented precision. From improving early cancer detection to guiding complex diagnostic procedures, AI stands to become an invaluable tool that complements clinical expertise. As we refine these technologies, the potential for AI to elevate both diagnostic accuracy and patient outcomes in GI is truly remarkable,” Spiegel said.

The study had no specific funding. Mascarenhas and Spiegel have declared no conflicts of interest.

A version of this article appeared on Medscape.com.

Last April, the US Preventive Services Task Force (USPSTF) revised its breast cancer screening guidelines to recommend average-risk women start their screening mammograms at age 40, instead of age 50, and continue every other year until age 74. 

The USPSTF’s recent recommendations align with those from major organizations, including the National Comprehensive Cancer Network and the American College of Radiology. The latest update comes from the American College of Obstetricians and Gynecologists (ACOG), which recommended a start age of 40 and continued screening either annually or every 2 years.

For USPSTF, the decision to recommend the earlier screening age, instead of keeping the choice an individualized one, was largely driven by the steady rise in breast cancer diagnoses among women in their 40s, alongside evidence that Black women are more likely to get breast cancer younger and die from the disease compared with White women. 

But is this recommendation to screen earlier a change for the better? 

Opinions vary.

USPSTF member John Wong, MD, chief of clinical decision making and a primary care physician at Tufts Medical Center in Boston, believes the new recommendation is the right move.

“It is now clear that screening every other year starting at age 40 has the potential to save about 20% more lives among all women and there is even greater potential benefit for Black women, who are much more likely to die from breast cancer,” Wong told Medscape last year. 

However, in a recent Viewpoint in JAMA Internal Medicine, experts from the University of California San Francisco expressed their reservations about shifting the recommended screening age a decade earlier.

The trio — Karla Kerlikowske, MD, Laura Esserman, MD, and Jeffrey Tice, MD — called the new recommendations “surprising” given the lack of new randomized control trial data to support the change as well as data that show breast cancer deaths have been decreasing among women, including younger women. 

More specifically, breast cancer deaths for women under 50 have decreased from 5.9 to 3.9 per 100,000 individuals between 2000 and 2020 — a decline that can likely be attributed to better treatments rather than increased screening effectiveness, the Viewpoint authors said.

However, moving the screening age earlier would not markedly improve survival for most women, the authors argued. According to USPSTF modeling, starting mammograms at age 40 instead of 50 could avert only 1.3 additional breast cancer deaths per 1000 women screened biennially and 1.8 additional breast cancer deaths among Black women.

Starting screening at 40, however, does come with an array of potential harms. These include 65 more benign biopsies per 1000 women screened, 1 in 2 women with a false-positive mammography result (503 per 1000), and 1 in 500 women with an over-diagnosed breast cancer, meaning the cancer would not have become clinically evident in their lifetime. 

The use of digital breast tomosynthesis can slightly reduce the number of false-positives and benign biopsies compared to older mammography techniques, but these small improvements did not sway the overall pro-con assessment for the Viewpoint authors.

“False-positive results require additional imaging and are associated with anxiety for patients,” the authors noted. “Women who have benign biopsies may experience the potential adverse effects of biopsies, such as bleeding, infection, and scarring unnecessarily; and over-diagnosis may lead to unnecessary treatment.”

Kenneth Lin, MD, MPH, family physician and associate director of the Lancaster General Hospital Family Medicine Residency in Pennsylvania, agreed that starting mammograms at age 40 is not a change for the better. 

Lin and colleagues conducted an analysis based on data from the USPSTF’s 2016 breast cancer screening report that similarly found 1 additional breast cancer death prevented per 1000 women screened starting at 40 vs 50, at a cost of 576 more false-positive results, 67 more benign breast biopsies, and 2 women diagnosed and treated unnecessarily. 

Overall, “there is no compelling evidence to change our clinical approach to breast cancer screening for women in their 40s: individual decision-making based on patient preferences and values,” Lin wrote in a recent Medscape commentary. 

But several experts not involved in the USPSTF recommendations agree with the change. 

The updated recommendation to begin mammograms at age 40 for women at average risk “aligns with accumulating data suggesting that earlier and more frequent screening can save more lives, and is widely seen as a positive step,” said Lisa Abramson, MD, a radiologist specializing in breast imaging with Mount Sinai Health System and Icahn School of Medicine at Mount Sinai, New York City.

Melissa Fana, MD, a breast surgical oncologist at NYU Langone Health, agreed that the revised recommendation is justified and “will undoubtedly save lives.” 

“The recent change in the screening recommendation was meant to be inclusive, and provide women, particularly women aged 40 to 49 the opportunity to screen with mammography,” Fana said.

One major argument in favor of earlier screening is that it will help address racial inequities in breast cancer diagnoses, treatment, and deaths. Despite a 5% lower incidence of breast cancer, Black women are more likely to be diagnosed with distant-stage cancer or more aggressive breast cancer subtypes, such as triple-negative, compared with White women, and are more likely to die from breast cancer.

“We hope that the earlier initiation of mammography screening across the board will have a great net benefit in outcomes for Black women especially, who have been shown to have the poorest outcomes when it comes to breast cancer, in part because of long-standing inequities in social determinants of health,” said Cherie C. Hill, MD, FACOG, an ob.gyn. at Emory Healthcare in Atlanta, who coauthored the recent ACOG recommendations.

The Viewpoint authors Kerlikowske, Esserman and Tice agreed that Black women may benefit more from earlier screening. However, earlier screening does not address the underlying disparities in treatment and follow-up care for Black women, and it is unclear whether screening alone will help improve breast cancer mortality rates for Black women, the authors noted.

There is one place where experts seem to align: the importance of educating patients about their personal risk. 

The Viewpoint authors favor a risk-based approach to help women decide whether to start screening before age 50. 

“Engaging women in informed decision-making based on their invasive and advanced breast cancer risk would be a patient-centered approach toward tailored screening, informing when to consider starting screening and how often to screen,” the experts wrote. 

For a woman to truly make an educated decision on whether she would like to screen or wait after age 40, she would at least need to know what her specific lifetime risk of developing breast cancer is, not the average risk is for American women in general, Fana told this news organization. 

“Risk assessment calculators are widely available and include factors such as family history and reproductive history, and this information can evolve over time and affect lifetime risk,” Fana noted. But “some women just do not get this information.”

Abramson explained that ob.gyns. and primary care physicians will likely play a larger role in the early assessment of breast cancer risk, including discussions about genetic testing and personal risk factors starting as early as age 25. 

“For clinicians, the emphasis may be on educating patients about their individual risk, ensuring timely mammograms, and referring higher-risk individuals for further testing or consultations with specialists,” Abramson added. 

Esserman reported being a Blue Cross Medical Advisory Panel member, an uncompensated board member of Quantum Leap Healthcare Collaborative, which funds the I-SPY trial through the University of California, San Francisco, and having an investigator-initiated trial for high-risk ductal carcinoma in situ (DCIS) funded through UCSF by Moderna for a DCIS phase 1 study. Tice and Kerlikowske reported receiving grants from the National Cancer Institute outside the submitted work. Abramson and Fana have no relevant disclosures.
 

A version of this article appeared on Medscape.com.

Last April, the US Preventive Services Task Force (USPSTF) revised its breast cancer screening guidelines to recommend average-risk women start their screening mammograms at age 40, instead of age 50, and continue every other year until age 74. 

The USPSTF’s recent recommendations align with those from major organizations, including the National Comprehensive Cancer Network and the American College of Radiology. The latest update comes from the American College of Obstetricians and Gynecologists (ACOG), which recommended a start age of 40 and continued screening either annually or every 2 years.

For USPSTF, the decision to recommend the earlier screening age, instead of keeping the choice an individualized one, was largely driven by the steady rise in breast cancer diagnoses among women in their 40s, alongside evidence that Black women are more likely to get breast cancer younger and die from the disease compared with White women. 

But is this recommendation to screen earlier a change for the better? 

Opinions vary.

USPSTF member John Wong, MD, chief of clinical decision making and a primary care physician at Tufts Medical Center in Boston, believes the new recommendation is the right move.

“It is now clear that screening every other year starting at age 40 has the potential to save about 20% more lives among all women and there is even greater potential benefit for Black women, who are much more likely to die from breast cancer,” Wong told Medscape last year. 

However, in a recent Viewpoint in JAMA Internal Medicine, experts from the University of California San Francisco expressed their reservations about shifting the recommended screening age a decade earlier.

The trio — Karla Kerlikowske, MD, Laura Esserman, MD, and Jeffrey Tice, MD — called the new recommendations “surprising” given the lack of new randomized control trial data to support the change as well as data that show breast cancer deaths have been decreasing among women, including younger women. 

More specifically, breast cancer deaths for women under 50 have decreased from 5.9 to 3.9 per 100,000 individuals between 2000 and 2020 — a decline that can likely be attributed to better treatments rather than increased screening effectiveness, the Viewpoint authors said.

However, moving the screening age earlier would not markedly improve survival for most women, the authors argued. According to USPSTF modeling, starting mammograms at age 40 instead of 50 could avert only 1.3 additional breast cancer deaths per 1000 women screened biennially and 1.8 additional breast cancer deaths among Black women.

Starting screening at 40, however, does come with an array of potential harms. These include 65 more benign biopsies per 1000 women screened, 1 in 2 women with a false-positive mammography result (503 per 1000), and 1 in 500 women with an over-diagnosed breast cancer, meaning the cancer would not have become clinically evident in their lifetime. 

The use of digital breast tomosynthesis can slightly reduce the number of false-positives and benign biopsies compared to older mammography techniques, but these small improvements did not sway the overall pro-con assessment for the Viewpoint authors.

“False-positive results require additional imaging and are associated with anxiety for patients,” the authors noted. “Women who have benign biopsies may experience the potential adverse effects of biopsies, such as bleeding, infection, and scarring unnecessarily; and over-diagnosis may lead to unnecessary treatment.”

Kenneth Lin, MD, MPH, family physician and associate director of the Lancaster General Hospital Family Medicine Residency in Pennsylvania, agreed that starting mammograms at age 40 is not a change for the better. 

Lin and colleagues conducted an analysis based on data from the USPSTF’s 2016 breast cancer screening report that similarly found 1 additional breast cancer death prevented per 1000 women screened starting at 40 vs 50, at a cost of 576 more false-positive results, 67 more benign breast biopsies, and 2 women diagnosed and treated unnecessarily. 

Overall, “there is no compelling evidence to change our clinical approach to breast cancer screening for women in their 40s: individual decision-making based on patient preferences and values,” Lin wrote in a recent Medscape commentary. 

But several experts not involved in the USPSTF recommendations agree with the change. 

The updated recommendation to begin mammograms at age 40 for women at average risk “aligns with accumulating data suggesting that earlier and more frequent screening can save more lives, and is widely seen as a positive step,” said Lisa Abramson, MD, a radiologist specializing in breast imaging with Mount Sinai Health System and Icahn School of Medicine at Mount Sinai, New York City.

Melissa Fana, MD, a breast surgical oncologist at NYU Langone Health, agreed that the revised recommendation is justified and “will undoubtedly save lives.” 

“The recent change in the screening recommendation was meant to be inclusive, and provide women, particularly women aged 40 to 49 the opportunity to screen with mammography,” Fana said.

One major argument in favor of earlier screening is that it will help address racial inequities in breast cancer diagnoses, treatment, and deaths. Despite a 5% lower incidence of breast cancer, Black women are more likely to be diagnosed with distant-stage cancer or more aggressive breast cancer subtypes, such as triple-negative, compared with White women, and are more likely to die from breast cancer.

“We hope that the earlier initiation of mammography screening across the board will have a great net benefit in outcomes for Black women especially, who have been shown to have the poorest outcomes when it comes to breast cancer, in part because of long-standing inequities in social determinants of health,” said Cherie C. Hill, MD, FACOG, an ob.gyn. at Emory Healthcare in Atlanta, who coauthored the recent ACOG recommendations.

The Viewpoint authors Kerlikowske, Esserman and Tice agreed that Black women may benefit more from earlier screening. However, earlier screening does not address the underlying disparities in treatment and follow-up care for Black women, and it is unclear whether screening alone will help improve breast cancer mortality rates for Black women, the authors noted.

There is one place where experts seem to align: the importance of educating patients about their personal risk. 

The Viewpoint authors favor a risk-based approach to help women decide whether to start screening before age 50. 

“Engaging women in informed decision-making based on their invasive and advanced breast cancer risk would be a patient-centered approach toward tailored screening, informing when to consider starting screening and how often to screen,” the experts wrote. 

For a woman to truly make an educated decision on whether she would like to screen or wait after age 40, she would at least need to know what her specific lifetime risk of developing breast cancer is, not the average risk is for American women in general, Fana told this news organization. 

“Risk assessment calculators are widely available and include factors such as family history and reproductive history, and this information can evolve over time and affect lifetime risk,” Fana noted. But “some women just do not get this information.”

Abramson explained that ob.gyns. and primary care physicians will likely play a larger role in the early assessment of breast cancer risk, including discussions about genetic testing and personal risk factors starting as early as age 25. 

“For clinicians, the emphasis may be on educating patients about their individual risk, ensuring timely mammograms, and referring higher-risk individuals for further testing or consultations with specialists,” Abramson added. 

Esserman reported being a Blue Cross Medical Advisory Panel member, an uncompensated board member of Quantum Leap Healthcare Collaborative, which funds the I-SPY trial through the University of California, San Francisco, and having an investigator-initiated trial for high-risk ductal carcinoma in situ (DCIS) funded through UCSF by Moderna for a DCIS phase 1 study. Tice and Kerlikowske reported receiving grants from the National Cancer Institute outside the submitted work. Abramson and Fana have no relevant disclosures.
 

A version of this article appeared on Medscape.com.

Last April, the US Preventive Services Task Force (USPSTF) revised its breast cancer screening guidelines to recommend average-risk women start their screening mammograms at age 40, instead of age 50, and continue every other year until age 74. 

The USPSTF’s recent recommendations align with those from major organizations, including the National Comprehensive Cancer Network and the American College of Radiology. The latest update comes from the American College of Obstetricians and Gynecologists (ACOG), which recommended a start age of 40 and continued screening either annually or every 2 years.

For USPSTF, the decision to recommend the earlier screening age, instead of keeping the choice an individualized one, was largely driven by the steady rise in breast cancer diagnoses among women in their 40s, alongside evidence that Black women are more likely to get breast cancer younger and die from the disease compared with White women. 

But is this recommendation to screen earlier a change for the better? 

Opinions vary.

USPSTF member John Wong, MD, chief of clinical decision making and a primary care physician at Tufts Medical Center in Boston, believes the new recommendation is the right move.

“It is now clear that screening every other year starting at age 40 has the potential to save about 20% more lives among all women and there is even greater potential benefit for Black women, who are much more likely to die from breast cancer,” Wong told Medscape last year. 

However, in a recent Viewpoint in JAMA Internal Medicine, experts from the University of California San Francisco expressed their reservations about shifting the recommended screening age a decade earlier.

The trio — Karla Kerlikowske, MD, Laura Esserman, MD, and Jeffrey Tice, MD — called the new recommendations “surprising” given the lack of new randomized control trial data to support the change as well as data that show breast cancer deaths have been decreasing among women, including younger women. 

More specifically, breast cancer deaths for women under 50 have decreased from 5.9 to 3.9 per 100,000 individuals between 2000 and 2020 — a decline that can likely be attributed to better treatments rather than increased screening effectiveness, the Viewpoint authors said.

However, moving the screening age earlier would not markedly improve survival for most women, the authors argued. According to USPSTF modeling, starting mammograms at age 40 instead of 50 could avert only 1.3 additional breast cancer deaths per 1000 women screened biennially and 1.8 additional breast cancer deaths among Black women.

Starting screening at 40, however, does come with an array of potential harms. These include 65 more benign biopsies per 1000 women screened, 1 in 2 women with a false-positive mammography result (503 per 1000), and 1 in 500 women with an over-diagnosed breast cancer, meaning the cancer would not have become clinically evident in their lifetime. 

The use of digital breast tomosynthesis can slightly reduce the number of false-positives and benign biopsies compared to older mammography techniques, but these small improvements did not sway the overall pro-con assessment for the Viewpoint authors.

“False-positive results require additional imaging and are associated with anxiety for patients,” the authors noted. “Women who have benign biopsies may experience the potential adverse effects of biopsies, such as bleeding, infection, and scarring unnecessarily; and over-diagnosis may lead to unnecessary treatment.”

Kenneth Lin, MD, MPH, family physician and associate director of the Lancaster General Hospital Family Medicine Residency in Pennsylvania, agreed that starting mammograms at age 40 is not a change for the better. 

Lin and colleagues conducted an analysis based on data from the USPSTF’s 2016 breast cancer screening report that similarly found 1 additional breast cancer death prevented per 1000 women screened starting at 40 vs 50, at a cost of 576 more false-positive results, 67 more benign breast biopsies, and 2 women diagnosed and treated unnecessarily. 

Overall, “there is no compelling evidence to change our clinical approach to breast cancer screening for women in their 40s: individual decision-making based on patient preferences and values,” Lin wrote in a recent Medscape commentary. 

But several experts not involved in the USPSTF recommendations agree with the change. 

The updated recommendation to begin mammograms at age 40 for women at average risk “aligns with accumulating data suggesting that earlier and more frequent screening can save more lives, and is widely seen as a positive step,” said Lisa Abramson, MD, a radiologist specializing in breast imaging with Mount Sinai Health System and Icahn School of Medicine at Mount Sinai, New York City.

Melissa Fana, MD, a breast surgical oncologist at NYU Langone Health, agreed that the revised recommendation is justified and “will undoubtedly save lives.” 

“The recent change in the screening recommendation was meant to be inclusive, and provide women, particularly women aged 40 to 49 the opportunity to screen with mammography,” Fana said.

One major argument in favor of earlier screening is that it will help address racial inequities in breast cancer diagnoses, treatment, and deaths. Despite a 5% lower incidence of breast cancer, Black women are more likely to be diagnosed with distant-stage cancer or more aggressive breast cancer subtypes, such as triple-negative, compared with White women, and are more likely to die from breast cancer.

“We hope that the earlier initiation of mammography screening across the board will have a great net benefit in outcomes for Black women especially, who have been shown to have the poorest outcomes when it comes to breast cancer, in part because of long-standing inequities in social determinants of health,” said Cherie C. Hill, MD, FACOG, an ob.gyn. at Emory Healthcare in Atlanta, who coauthored the recent ACOG recommendations.

The Viewpoint authors Kerlikowske, Esserman and Tice agreed that Black women may benefit more from earlier screening. However, earlier screening does not address the underlying disparities in treatment and follow-up care for Black women, and it is unclear whether screening alone will help improve breast cancer mortality rates for Black women, the authors noted.

There is one place where experts seem to align: the importance of educating patients about their personal risk. 

The Viewpoint authors favor a risk-based approach to help women decide whether to start screening before age 50. 

“Engaging women in informed decision-making based on their invasive and advanced breast cancer risk would be a patient-centered approach toward tailored screening, informing when to consider starting screening and how often to screen,” the experts wrote. 

For a woman to truly make an educated decision on whether she would like to screen or wait after age 40, she would at least need to know what her specific lifetime risk of developing breast cancer is, not the average risk is for American women in general, Fana told this news organization. 

“Risk assessment calculators are widely available and include factors such as family history and reproductive history, and this information can evolve over time and affect lifetime risk,” Fana noted. But “some women just do not get this information.”

Abramson explained that ob.gyns. and primary care physicians will likely play a larger role in the early assessment of breast cancer risk, including discussions about genetic testing and personal risk factors starting as early as age 25. 

“For clinicians, the emphasis may be on educating patients about their individual risk, ensuring timely mammograms, and referring higher-risk individuals for further testing or consultations with specialists,” Abramson added. 

Esserman reported being a Blue Cross Medical Advisory Panel member, an uncompensated board member of Quantum Leap Healthcare Collaborative, which funds the I-SPY trial through the University of California, San Francisco, and having an investigator-initiated trial for high-risk ductal carcinoma in situ (DCIS) funded through UCSF by Moderna for a DCIS phase 1 study. Tice and Kerlikowske reported receiving grants from the National Cancer Institute outside the submitted work. Abramson and Fana have no relevant disclosures.
 

A version of this article appeared on Medscape.com.

US veterans were nearly three times more likely to develop skin cancer than the general population, according to a large cross-sectional analysis of recent national data.

“US veterans are known to have increased risk of cancers and cancer morbidity compared to the general US population,” one of the study authors, Sepideh Ashrafzadeh, MD, a third-year dermatology resident at Massachusetts General Hospital, Boston, told this news organization following the annual meeting of the American Society for Dermatologic Surgery, where the results were presented. “There have been several studies that have shown that US veterans have an increased prevalence of melanoma compared to nonveterans,” she said, noting, however, that no study has investigated the prevalence of nonmelanoma skin cancers (NMSCs), which include basal cell carcinomas and squamous cell carcinomas, compared with the general population.

Dr. Ashrafzadeh

To address this knowledge gap, the researchers performed a national cross-sectional study of adults aged 18 years or older from the 2019-2023 National Health Interview Surveys to examine the prevalence of melanoma and NMSCs among veterans compared with the general US population. They aggregated and tabulated the data by veteran status, defined as having served at any point in the US armed forces, reserves, or national guard, and by demographic and socioeconomic status variables. Next, they performed multivariate logistic regression for skin cancer risk adjusted for age, sex, race, ethnicity, urbanicity, and disability status.

The study population consisted of 14,301 veterans and 209,936 nonveterans. Compared with nonveterans, veterans were more likely to have been diagnosed with skin cancer at some point in their lives (7% vs 2.4%; P < .001); had a higher mean age of skin cancer diagnosis (61.1 vs 55.8 years; P < .001); were more likely to have been diagnosed with melanoma (2.8% vs 0.9%; P < .001), and were more likely to have been diagnosed with NMSC (4.4% vs 1.6%; P < .001).

The researchers found that older age, White race, non-Hispanic ethnicity, and veteran status were all associated with higher odds of developing NMSCs, even after adjusting for relevant covariates. Specifically, veterans had 1.23 higher odds of developing NMSC than the general population, while two factors were protective for developing NMSCs: Living in a rural setting (adjusted odds ratio [aOR], 0.78) and receiving supplemental security income or disability income (aOR, 0.69).

In another part of the study, the researchers evaluated demographic and socioeconomic variables associated with developing melanoma among veterans. These included the following: Male (aOR, 1.16), older age (50-64 years: aOR, 6.82; 65-74 years: aOR, 12.55; and 75 years or older: aOR, 16.16), White race (aOR, 9.24), and non-Hispanic ethnicity (aOR, 7.15).

“Veterans may have occupational risks such as sun and chemical exposure, as well as behavioral habits for sun protection, that may contribute to their elevated risk of melanoma and NMSCs,” Ashrafzadeh said. “Therefore, US veterans would benefit from targeted and regular skin cancer screenings, sun protective preventative resources such as hats and sunscreen, and access to medical and surgical care for diagnosis and treatment of skin cancers.”

Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Connecticut, who was asked to comment on the findings, said that a key strength of the study is that it drew from a nationally representative sample. “A limitation is that skin cancer was self-reported rather than based on documented medical histories,” Ko said. “The study confirms that skin cancer risk is higher in older individuals (> 75 as compared to < 50) and in individuals of self-reported white race and non-Hispanic ethnicity,” she added.

Neither the researchers nor Ko reported having relevant disclosures.
 

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

US veterans were nearly three times more likely to develop skin cancer than the general population, according to a large cross-sectional analysis of recent national data.

“US veterans are known to have increased risk of cancers and cancer morbidity compared to the general US population,” one of the study authors, Sepideh Ashrafzadeh, MD, a third-year dermatology resident at Massachusetts General Hospital, Boston, told this news organization following the annual meeting of the American Society for Dermatologic Surgery, where the results were presented. “There have been several studies that have shown that US veterans have an increased prevalence of melanoma compared to nonveterans,” she said, noting, however, that no study has investigated the prevalence of nonmelanoma skin cancers (NMSCs), which include basal cell carcinomas and squamous cell carcinomas, compared with the general population.

Dr. Ashrafzadeh

To address this knowledge gap, the researchers performed a national cross-sectional study of adults aged 18 years or older from the 2019-2023 National Health Interview Surveys to examine the prevalence of melanoma and NMSCs among veterans compared with the general US population. They aggregated and tabulated the data by veteran status, defined as having served at any point in the US armed forces, reserves, or national guard, and by demographic and socioeconomic status variables. Next, they performed multivariate logistic regression for skin cancer risk adjusted for age, sex, race, ethnicity, urbanicity, and disability status.

The study population consisted of 14,301 veterans and 209,936 nonveterans. Compared with nonveterans, veterans were more likely to have been diagnosed with skin cancer at some point in their lives (7% vs 2.4%; P < .001); had a higher mean age of skin cancer diagnosis (61.1 vs 55.8 years; P < .001); were more likely to have been diagnosed with melanoma (2.8% vs 0.9%; P < .001), and were more likely to have been diagnosed with NMSC (4.4% vs 1.6%; P < .001).

The researchers found that older age, White race, non-Hispanic ethnicity, and veteran status were all associated with higher odds of developing NMSCs, even after adjusting for relevant covariates. Specifically, veterans had 1.23 higher odds of developing NMSC than the general population, while two factors were protective for developing NMSCs: Living in a rural setting (adjusted odds ratio [aOR], 0.78) and receiving supplemental security income or disability income (aOR, 0.69).

In another part of the study, the researchers evaluated demographic and socioeconomic variables associated with developing melanoma among veterans. These included the following: Male (aOR, 1.16), older age (50-64 years: aOR, 6.82; 65-74 years: aOR, 12.55; and 75 years or older: aOR, 16.16), White race (aOR, 9.24), and non-Hispanic ethnicity (aOR, 7.15).

“Veterans may have occupational risks such as sun and chemical exposure, as well as behavioral habits for sun protection, that may contribute to their elevated risk of melanoma and NMSCs,” Ashrafzadeh said. “Therefore, US veterans would benefit from targeted and regular skin cancer screenings, sun protective preventative resources such as hats and sunscreen, and access to medical and surgical care for diagnosis and treatment of skin cancers.”

Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Connecticut, who was asked to comment on the findings, said that a key strength of the study is that it drew from a nationally representative sample. “A limitation is that skin cancer was self-reported rather than based on documented medical histories,” Ko said. “The study confirms that skin cancer risk is higher in older individuals (> 75 as compared to < 50) and in individuals of self-reported white race and non-Hispanic ethnicity,” she added.

Neither the researchers nor Ko reported having relevant disclosures.
 

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

US veterans were nearly three times more likely to develop skin cancer than the general population, according to a large cross-sectional analysis of recent national data.

“US veterans are known to have increased risk of cancers and cancer morbidity compared to the general US population,” one of the study authors, Sepideh Ashrafzadeh, MD, a third-year dermatology resident at Massachusetts General Hospital, Boston, told this news organization following the annual meeting of the American Society for Dermatologic Surgery, where the results were presented. “There have been several studies that have shown that US veterans have an increased prevalence of melanoma compared to nonveterans,” she said, noting, however, that no study has investigated the prevalence of nonmelanoma skin cancers (NMSCs), which include basal cell carcinomas and squamous cell carcinomas, compared with the general population.

Dr. Ashrafzadeh

To address this knowledge gap, the researchers performed a national cross-sectional study of adults aged 18 years or older from the 2019-2023 National Health Interview Surveys to examine the prevalence of melanoma and NMSCs among veterans compared with the general US population. They aggregated and tabulated the data by veteran status, defined as having served at any point in the US armed forces, reserves, or national guard, and by demographic and socioeconomic status variables. Next, they performed multivariate logistic regression for skin cancer risk adjusted for age, sex, race, ethnicity, urbanicity, and disability status.

The study population consisted of 14,301 veterans and 209,936 nonveterans. Compared with nonveterans, veterans were more likely to have been diagnosed with skin cancer at some point in their lives (7% vs 2.4%; P < .001); had a higher mean age of skin cancer diagnosis (61.1 vs 55.8 years; P < .001); were more likely to have been diagnosed with melanoma (2.8% vs 0.9%; P < .001), and were more likely to have been diagnosed with NMSC (4.4% vs 1.6%; P < .001).

The researchers found that older age, White race, non-Hispanic ethnicity, and veteran status were all associated with higher odds of developing NMSCs, even after adjusting for relevant covariates. Specifically, veterans had 1.23 higher odds of developing NMSC than the general population, while two factors were protective for developing NMSCs: Living in a rural setting (adjusted odds ratio [aOR], 0.78) and receiving supplemental security income or disability income (aOR, 0.69).

In another part of the study, the researchers evaluated demographic and socioeconomic variables associated with developing melanoma among veterans. These included the following: Male (aOR, 1.16), older age (50-64 years: aOR, 6.82; 65-74 years: aOR, 12.55; and 75 years or older: aOR, 16.16), White race (aOR, 9.24), and non-Hispanic ethnicity (aOR, 7.15).

“Veterans may have occupational risks such as sun and chemical exposure, as well as behavioral habits for sun protection, that may contribute to their elevated risk of melanoma and NMSCs,” Ashrafzadeh said. “Therefore, US veterans would benefit from targeted and regular skin cancer screenings, sun protective preventative resources such as hats and sunscreen, and access to medical and surgical care for diagnosis and treatment of skin cancers.”

Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Connecticut, who was asked to comment on the findings, said that a key strength of the study is that it drew from a nationally representative sample. “A limitation is that skin cancer was self-reported rather than based on documented medical histories,” Ko said. “The study confirms that skin cancer risk is higher in older individuals (> 75 as compared to < 50) and in individuals of self-reported white race and non-Hispanic ethnicity,” she added.

Neither the researchers nor Ko reported having relevant disclosures.
 

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

About 7 of every 10 veterans who die by suicide involve the use of a firearm. A reason for this high rate is access, as half of veterans report owning ≥ 1 personal firearms. Of those individuals, more than half report storing firearms loaded and/or unsecured and one-third of veterans who store their firearms loaded and unlocked do not own a lockbox or safe. 

Suicide death prevention has improved as firearms have become more difficult to obtain. That’s why Navy veteran Rep. Chris Deluzio (D-PA), former FBI Special Agent and federal prosecutor Rep. Brian Fitzpatrick (R-PA), and Rep. Greg Landsman (D-OH) have teamed up to introduce the Saving Our Veterans Lives Act of 2024. Under the proposed act, any veteran would be able to get a free lockbox from the US Department of Veterans Affairs (VA).

Suicidal crises can be brief. According to the VA, if a person experiencing a suicidal crisis can’t access the method they planned to use, they generally do not seek out other lethal means. Lockboxes are a way of “putting space between thought and trigger,” the VA said.

The VA Suicide Prevention Program distributes free firearm cable locks to any veteran who requests one. However, many veterans favor lockboxes and safes to secure their guns. A VA pilot program offers free lockboxes to veterans enrolled in the Veterans Health Administration who are at an elevated risk for suicide. The program is set to launch in late 2024 and is a collaboration between the Rocky Mountain Mental Illness Research, Education, and Clinical Center for Suicide Prevention, VA National Prosthetics Service, and VA Office of Suicide Prevention.

The proposed bill would make the lockboxes (which typically cost between $25 and $350) free to any veteran, regardless of VA enrollment status or diagnosis. It ensures “sufficient funding for many tens of thousands of lockboxes to be distributed.” The bill would also direct the VA to create a public education campaign on the availability of lockboxes and the importance of secure firearm storage in suicide prevention.

“The alarming and tragic reality is that our veterans face a suicide rate 57% higher than that of civilians,” Rep. Fitzpatrick said. “This commonsense, bipartisan initiative is more than a solution—it's a lifeline.”

The representatives report that the bill has been endorsed by an “unprecedented” number of organizations, including the National Shooting Sports Foundation, Disabled American Veterans, The American Legion, GIFFORDS, Everytown for Gun Safety, Brady, American Psychological Association, American Foundation for Suicide Prevention, and Association of VA Psychologist Leaders.

“Did you know that in some cases only 10 minutes elapse between an individual having suicidal ideation and acting?” American Legion National Commander James LaCoursiere said in the representatives’ press release. “The Saving Our Veterans Lives Act is an important part of preventing suicide as it will provide veterans with the information and means to securely store their firearms to prevent suicide, while still protecting their Second Amendment rights. The Legion commends Rep. Deluzio and his team for bringing this bill forward and for their continued dedication to the welfare of our nation’s veterans.” 

"I hear colleagues all the time talk about veteran suicide," Rep. Deluzio said in an interview with Military.com. "It is a problem in my community. It's a problem across the country. Let's take action. This is a chance where we can do it that I think can cut through the politics that normally divide us on these [gun] issues. And I think the coalition supporting the bill tells you, we've got a path to pass it."

About 7 of every 10 veterans who die by suicide involve the use of a firearm. A reason for this high rate is access, as half of veterans report owning ≥ 1 personal firearms. Of those individuals, more than half report storing firearms loaded and/or unsecured and one-third of veterans who store their firearms loaded and unlocked do not own a lockbox or safe. 

Suicide death prevention has improved as firearms have become more difficult to obtain. That’s why Navy veteran Rep. Chris Deluzio (D-PA), former FBI Special Agent and federal prosecutor Rep. Brian Fitzpatrick (R-PA), and Rep. Greg Landsman (D-OH) have teamed up to introduce the Saving Our Veterans Lives Act of 2024. Under the proposed act, any veteran would be able to get a free lockbox from the US Department of Veterans Affairs (VA).

Suicidal crises can be brief. According to the VA, if a person experiencing a suicidal crisis can’t access the method they planned to use, they generally do not seek out other lethal means. Lockboxes are a way of “putting space between thought and trigger,” the VA said.

The VA Suicide Prevention Program distributes free firearm cable locks to any veteran who requests one. However, many veterans favor lockboxes and safes to secure their guns. A VA pilot program offers free lockboxes to veterans enrolled in the Veterans Health Administration who are at an elevated risk for suicide. The program is set to launch in late 2024 and is a collaboration between the Rocky Mountain Mental Illness Research, Education, and Clinical Center for Suicide Prevention, VA National Prosthetics Service, and VA Office of Suicide Prevention.

The proposed bill would make the lockboxes (which typically cost between $25 and $350) free to any veteran, regardless of VA enrollment status or diagnosis. It ensures “sufficient funding for many tens of thousands of lockboxes to be distributed.” The bill would also direct the VA to create a public education campaign on the availability of lockboxes and the importance of secure firearm storage in suicide prevention.

“The alarming and tragic reality is that our veterans face a suicide rate 57% higher than that of civilians,” Rep. Fitzpatrick said. “This commonsense, bipartisan initiative is more than a solution—it's a lifeline.”

The representatives report that the bill has been endorsed by an “unprecedented” number of organizations, including the National Shooting Sports Foundation, Disabled American Veterans, The American Legion, GIFFORDS, Everytown for Gun Safety, Brady, American Psychological Association, American Foundation for Suicide Prevention, and Association of VA Psychologist Leaders.

“Did you know that in some cases only 10 minutes elapse between an individual having suicidal ideation and acting?” American Legion National Commander James LaCoursiere said in the representatives’ press release. “The Saving Our Veterans Lives Act is an important part of preventing suicide as it will provide veterans with the information and means to securely store their firearms to prevent suicide, while still protecting their Second Amendment rights. The Legion commends Rep. Deluzio and his team for bringing this bill forward and for their continued dedication to the welfare of our nation’s veterans.” 

"I hear colleagues all the time talk about veteran suicide," Rep. Deluzio said in an interview with Military.com. "It is a problem in my community. It's a problem across the country. Let's take action. This is a chance where we can do it that I think can cut through the politics that normally divide us on these [gun] issues. And I think the coalition supporting the bill tells you, we've got a path to pass it."

About 7 of every 10 veterans who die by suicide involve the use of a firearm. A reason for this high rate is access, as half of veterans report owning ≥ 1 personal firearms. Of those individuals, more than half report storing firearms loaded and/or unsecured and one-third of veterans who store their firearms loaded and unlocked do not own a lockbox or safe. 

Suicide death prevention has improved as firearms have become more difficult to obtain. That’s why Navy veteran Rep. Chris Deluzio (D-PA), former FBI Special Agent and federal prosecutor Rep. Brian Fitzpatrick (R-PA), and Rep. Greg Landsman (D-OH) have teamed up to introduce the Saving Our Veterans Lives Act of 2024. Under the proposed act, any veteran would be able to get a free lockbox from the US Department of Veterans Affairs (VA).

Suicidal crises can be brief. According to the VA, if a person experiencing a suicidal crisis can’t access the method they planned to use, they generally do not seek out other lethal means. Lockboxes are a way of “putting space between thought and trigger,” the VA said.

The VA Suicide Prevention Program distributes free firearm cable locks to any veteran who requests one. However, many veterans favor lockboxes and safes to secure their guns. A VA pilot program offers free lockboxes to veterans enrolled in the Veterans Health Administration who are at an elevated risk for suicide. The program is set to launch in late 2024 and is a collaboration between the Rocky Mountain Mental Illness Research, Education, and Clinical Center for Suicide Prevention, VA National Prosthetics Service, and VA Office of Suicide Prevention.

The proposed bill would make the lockboxes (which typically cost between $25 and $350) free to any veteran, regardless of VA enrollment status or diagnosis. It ensures “sufficient funding for many tens of thousands of lockboxes to be distributed.” The bill would also direct the VA to create a public education campaign on the availability of lockboxes and the importance of secure firearm storage in suicide prevention.

“The alarming and tragic reality is that our veterans face a suicide rate 57% higher than that of civilians,” Rep. Fitzpatrick said. “This commonsense, bipartisan initiative is more than a solution—it's a lifeline.”

The representatives report that the bill has been endorsed by an “unprecedented” number of organizations, including the National Shooting Sports Foundation, Disabled American Veterans, The American Legion, GIFFORDS, Everytown for Gun Safety, Brady, American Psychological Association, American Foundation for Suicide Prevention, and Association of VA Psychologist Leaders.

“Did you know that in some cases only 10 minutes elapse between an individual having suicidal ideation and acting?” American Legion National Commander James LaCoursiere said in the representatives’ press release. “The Saving Our Veterans Lives Act is an important part of preventing suicide as it will provide veterans with the information and means to securely store their firearms to prevent suicide, while still protecting their Second Amendment rights. The Legion commends Rep. Deluzio and his team for bringing this bill forward and for their continued dedication to the welfare of our nation’s veterans.” 

"I hear colleagues all the time talk about veteran suicide," Rep. Deluzio said in an interview with Military.com. "It is a problem in my community. It's a problem across the country. Let's take action. This is a chance where we can do it that I think can cut through the politics that normally divide us on these [gun] issues. And I think the coalition supporting the bill tells you, we've got a path to pass it."

NEW YORK — In a three-way debate on whether to prioritize chimeric antigen receptor (CAR) T-cell therapy, bispecific antibodies (BsAbs), or one of the novel oral targeted therapies for relapsed/refractory follicular lymphoma (R/R FL), no expert conceded.

Acknowledging that hers was the weakest position, even the specialist who defended novel targeted therapies mounted a staunch defense of real-world patients being treated outside of tertiary centers.

“I was told by many of my colleagues that I got the short end of the stick in this debate, but I am actually here to convince everybody that targeted therapies continue to play an important role, despite the fact that they are the least sexy of these treatment options,” said Joanna Rhodes, MD, director of the Lymphoma Program at Rutgers Cancer Institute, Hoboken, New Jersey.
 

Targeted Therapies Still Relevant to Advanced FL

Although even the newest or coming targeted therapies, such as the EZH2 inhibitor tazemetostat or next-generation Bruton tyrosine kinase inhibitors, are not likely to achieve the deep responses and long-term progression-free survival possible with BsAbs or CAR T-cell therapy, the sustained disease control they offer for many patients with R/R FL is not trivial, according to Rhodes.

“The majority of these [advanced follicular lymphoma] patients are being managed in the community,” Rhodes argued at the 2024 Lymphoma, Leukemia, & Myeloma Congress. Access to tertiary centers where the most advanced therapies are available in some cases might not even be feasible. 

Moreover, there are barriers to CAR T cells and BsAbs even at centers where these are available, Rhodes said. On a long list of barriers, lack of caregiver support is an example of one common disqualification at her own institution. 

The experience with CAR T cells in R/R FL has been relatively short, so Rhodes used data on CAR T cells for B-cell lymphoma to make her point. It is not just that the proportion of eligible patients is limited. 

“The majority of B-cell lymphoma patients who are eligible for CAR T cells are not getting them,” she said. “It will be the same for FL.”

In other words, Rhodes indicated that it is premature to count out targeted oral agents or lenalidomide despite the excitement surrounding BsAbs and CAR T cells. The targeted agents and immunomodulatory drugs remain appropriate choices for patients unable or unwilling to travel to tertiary centers for treatment, for frail patients, and for well-informed patients who understand their options and still consider better tolerated therapies to be more consistent with their perception of an adequate risk-benefit ratio. 
 

BsAbs Vie With CAR T Cells in Advanced FL

Hers might be a valid summary, but it did not derail arguments about whether CAR T-cell therapy should be prioritized over BsAbs or the other way around for patients who are candidates for both. 

There are two BsAbs currently approved for R/R FL: glofitamab and mosunetuzumab. More are coming, according to Nina Wagner-Johnston, MD, director of hematologic malignancies at Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, Maryland. She provided several reasons why BsAbs might be considered before CAR T-cell therapies in at least some individuals. 

“The biggest advantage is that these therapies…are off the shelf,” she said. This avoids the delay of T-cell manufacturing, the potential need for bridging therapies, and the need for conditioning regimens. With more experience, BsAbs offer the potential for treatment even in a community-practice setting, particularly for maintenance dosing.

“I do think this is a safe treatment in patients who are elderly or unfit,” Wagner-Johnston said, suggesting she tends to lean toward prioritizing BsAbs over CAR T cells when the ability to tolerate an aggressive strategy is a concern. She specified that these drugs are associated with a low relative incidence of grade 3 or higher cytokine release syndrome or immune effector cell–associated neurotoxicity syndrome, and faster B-cell aplasia recovery. 

The third participant in the debate, who described the efficacy and safety of the three currently approved CAR T-cell therapies for R/R FL, did not agree with this characterization. Daniel J. Landsburg, MD, associate professor of clinical medicine at the University of Pennsylvania, Philadelphia, acknowledged that BsAb agents have an important role to play in the advanced FL setting, but he thinks that CAR T-cell therapies should be prioritized in at least some patients. 

In particular, he would not rule out CAR T-cell therapy in patients with comorbidities or other characteristics that raise questions about fitness for aggressive treatment. 

“In fact, you might want to treat a frail patient just one time with CAR T-cell therapy rather than dose after dose with a bispecific drug,” he said. 
 

No Data to Compare BsAbs and CAR T-Cells Directly

Both agreed that there have been no trials directly comparing a BsAb therapy vs CAR T cells, so there is no definitive answer, and Landsburg was reluctant to take a hard line on reserving BsAbs until after CAR T-cell therapy has been tried.

“Because BsAbs and CAR Ts are approved in the third-line setting, you might consider debulking a patient getting ready for a CAR T with a bispecific,” Landsburg said. However, he acknowledged that the next step becomes complex if patients achieved a complete response after just a few BsAb doses.

“Do you stop what is already working?” Landsburg asked rhetorically, suggesting that the best way forward is not always clear.

For R/R FL, currently there are three approved products: axicabtagene ciloleucel (Yescarta), tisagenlecleucel (Kymriah), and lisocabtagene maraleucel (Breyanzi). The entry criteria and design of the three pivotal trials differed, so their specific indications vary. Looking across the trials, Landsburg suggested that there might be differences in activity as defined by objective response rates or risk for cytokine release syndrome, but these remain theoretical without head-to-head comparisons.

“My suspicion is we are going to see very similar — quote, unquote — long-term survival curves for patients treated with any of these therapies,” he said, noting that progression-free survival at 3 years has been in the vicinity of 50% for the trials that have had long enough follow-up to judge.

Rather than trying to pick the best agent, he suggested that it makes more sense now to concentrate on strategies to improve response irrespective of CAR T-cell product; these include paying attention to total metabolic tumor volume at the time of infusion, optimizing bridging therapies, and thinking about T-cell fitness, which might be impaired in some patients by recent exposure to bendamustine.

Overall, with multiple ongoing studies with both CAR T-cell therapies and BsAbs in R/R FL — as well with targeted small-molecule agents and immunomodulatory drugs — all of the debate participants acknowledged that choices in R/R FL will evolve. 

“I actually think that combinations will be the future,” Wagner-Johnston said. Singling out tazemetostat and a BsAb and one approach that seems promising, she also predicted that some of the therapies in advanced disease are likely to be moved forward to earlier stages of FL therapy.

Rhodes reported ties with AbbVie, AstraZeneca, ADC Therapeutics, BeiGene, Bristol Myers Squibb, Epizyme, Genentech, Genmab, Janssen, Loxo Oncology, MorphoSys, Pharmacyclics, and Pfizer. Wagner-Johnston disclosed relationships with Cuno Science, Dava Oncology, Epizyme, Grünenthal, Karyopharm, and Seagen. Landsburg reported ties with ADC Therapeutics, Calithera, Curis, Epizyme, Karyopharm, MorphoSys, and Novartis.
 

A version of this article appeared on Medscape.com.

NEW YORK — In a three-way debate on whether to prioritize chimeric antigen receptor (CAR) T-cell therapy, bispecific antibodies (BsAbs), or one of the novel oral targeted therapies for relapsed/refractory follicular lymphoma (R/R FL), no expert conceded.

Acknowledging that hers was the weakest position, even the specialist who defended novel targeted therapies mounted a staunch defense of real-world patients being treated outside of tertiary centers.

“I was told by many of my colleagues that I got the short end of the stick in this debate, but I am actually here to convince everybody that targeted therapies continue to play an important role, despite the fact that they are the least sexy of these treatment options,” said Joanna Rhodes, MD, director of the Lymphoma Program at Rutgers Cancer Institute, Hoboken, New Jersey.
 

Targeted Therapies Still Relevant to Advanced FL

Although even the newest or coming targeted therapies, such as the EZH2 inhibitor tazemetostat or next-generation Bruton tyrosine kinase inhibitors, are not likely to achieve the deep responses and long-term progression-free survival possible with BsAbs or CAR T-cell therapy, the sustained disease control they offer for many patients with R/R FL is not trivial, according to Rhodes.

“The majority of these [advanced follicular lymphoma] patients are being managed in the community,” Rhodes argued at the 2024 Lymphoma, Leukemia, & Myeloma Congress. Access to tertiary centers where the most advanced therapies are available in some cases might not even be feasible. 

Moreover, there are barriers to CAR T cells and BsAbs even at centers where these are available, Rhodes said. On a long list of barriers, lack of caregiver support is an example of one common disqualification at her own institution. 

The experience with CAR T cells in R/R FL has been relatively short, so Rhodes used data on CAR T cells for B-cell lymphoma to make her point. It is not just that the proportion of eligible patients is limited. 

“The majority of B-cell lymphoma patients who are eligible for CAR T cells are not getting them,” she said. “It will be the same for FL.”

In other words, Rhodes indicated that it is premature to count out targeted oral agents or lenalidomide despite the excitement surrounding BsAbs and CAR T cells. The targeted agents and immunomodulatory drugs remain appropriate choices for patients unable or unwilling to travel to tertiary centers for treatment, for frail patients, and for well-informed patients who understand their options and still consider better tolerated therapies to be more consistent with their perception of an adequate risk-benefit ratio. 
 

BsAbs Vie With CAR T Cells in Advanced FL

Hers might be a valid summary, but it did not derail arguments about whether CAR T-cell therapy should be prioritized over BsAbs or the other way around for patients who are candidates for both. 

There are two BsAbs currently approved for R/R FL: glofitamab and mosunetuzumab. More are coming, according to Nina Wagner-Johnston, MD, director of hematologic malignancies at Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, Maryland. She provided several reasons why BsAbs might be considered before CAR T-cell therapies in at least some individuals. 

“The biggest advantage is that these therapies…are off the shelf,” she said. This avoids the delay of T-cell manufacturing, the potential need for bridging therapies, and the need for conditioning regimens. With more experience, BsAbs offer the potential for treatment even in a community-practice setting, particularly for maintenance dosing.

“I do think this is a safe treatment in patients who are elderly or unfit,” Wagner-Johnston said, suggesting she tends to lean toward prioritizing BsAbs over CAR T cells when the ability to tolerate an aggressive strategy is a concern. She specified that these drugs are associated with a low relative incidence of grade 3 or higher cytokine release syndrome or immune effector cell–associated neurotoxicity syndrome, and faster B-cell aplasia recovery. 

The third participant in the debate, who described the efficacy and safety of the three currently approved CAR T-cell therapies for R/R FL, did not agree with this characterization. Daniel J. Landsburg, MD, associate professor of clinical medicine at the University of Pennsylvania, Philadelphia, acknowledged that BsAb agents have an important role to play in the advanced FL setting, but he thinks that CAR T-cell therapies should be prioritized in at least some patients. 

In particular, he would not rule out CAR T-cell therapy in patients with comorbidities or other characteristics that raise questions about fitness for aggressive treatment. 

“In fact, you might want to treat a frail patient just one time with CAR T-cell therapy rather than dose after dose with a bispecific drug,” he said. 
 

No Data to Compare BsAbs and CAR T-Cells Directly

Both agreed that there have been no trials directly comparing a BsAb therapy vs CAR T cells, so there is no definitive answer, and Landsburg was reluctant to take a hard line on reserving BsAbs until after CAR T-cell therapy has been tried.

“Because BsAbs and CAR Ts are approved in the third-line setting, you might consider debulking a patient getting ready for a CAR T with a bispecific,” Landsburg said. However, he acknowledged that the next step becomes complex if patients achieved a complete response after just a few BsAb doses.

“Do you stop what is already working?” Landsburg asked rhetorically, suggesting that the best way forward is not always clear.

For R/R FL, currently there are three approved products: axicabtagene ciloleucel (Yescarta), tisagenlecleucel (Kymriah), and lisocabtagene maraleucel (Breyanzi). The entry criteria and design of the three pivotal trials differed, so their specific indications vary. Looking across the trials, Landsburg suggested that there might be differences in activity as defined by objective response rates or risk for cytokine release syndrome, but these remain theoretical without head-to-head comparisons.

“My suspicion is we are going to see very similar — quote, unquote — long-term survival curves for patients treated with any of these therapies,” he said, noting that progression-free survival at 3 years has been in the vicinity of 50% for the trials that have had long enough follow-up to judge.

Rather than trying to pick the best agent, he suggested that it makes more sense now to concentrate on strategies to improve response irrespective of CAR T-cell product; these include paying attention to total metabolic tumor volume at the time of infusion, optimizing bridging therapies, and thinking about T-cell fitness, which might be impaired in some patients by recent exposure to bendamustine.

Overall, with multiple ongoing studies with both CAR T-cell therapies and BsAbs in R/R FL — as well with targeted small-molecule agents and immunomodulatory drugs — all of the debate participants acknowledged that choices in R/R FL will evolve. 

“I actually think that combinations will be the future,” Wagner-Johnston said. Singling out tazemetostat and a BsAb and one approach that seems promising, she also predicted that some of the therapies in advanced disease are likely to be moved forward to earlier stages of FL therapy.

Rhodes reported ties with AbbVie, AstraZeneca, ADC Therapeutics, BeiGene, Bristol Myers Squibb, Epizyme, Genentech, Genmab, Janssen, Loxo Oncology, MorphoSys, Pharmacyclics, and Pfizer. Wagner-Johnston disclosed relationships with Cuno Science, Dava Oncology, Epizyme, Grünenthal, Karyopharm, and Seagen. Landsburg reported ties with ADC Therapeutics, Calithera, Curis, Epizyme, Karyopharm, MorphoSys, and Novartis.
 

A version of this article appeared on Medscape.com.

NEW YORK — In a three-way debate on whether to prioritize chimeric antigen receptor (CAR) T-cell therapy, bispecific antibodies (BsAbs), or one of the novel oral targeted therapies for relapsed/refractory follicular lymphoma (R/R FL), no expert conceded.

Acknowledging that hers was the weakest position, even the specialist who defended novel targeted therapies mounted a staunch defense of real-world patients being treated outside of tertiary centers.

“I was told by many of my colleagues that I got the short end of the stick in this debate, but I am actually here to convince everybody that targeted therapies continue to play an important role, despite the fact that they are the least sexy of these treatment options,” said Joanna Rhodes, MD, director of the Lymphoma Program at Rutgers Cancer Institute, Hoboken, New Jersey.
 

Targeted Therapies Still Relevant to Advanced FL

Although even the newest or coming targeted therapies, such as the EZH2 inhibitor tazemetostat or next-generation Bruton tyrosine kinase inhibitors, are not likely to achieve the deep responses and long-term progression-free survival possible with BsAbs or CAR T-cell therapy, the sustained disease control they offer for many patients with R/R FL is not trivial, according to Rhodes.

“The majority of these [advanced follicular lymphoma] patients are being managed in the community,” Rhodes argued at the 2024 Lymphoma, Leukemia, & Myeloma Congress. Access to tertiary centers where the most advanced therapies are available in some cases might not even be feasible. 

Moreover, there are barriers to CAR T cells and BsAbs even at centers where these are available, Rhodes said. On a long list of barriers, lack of caregiver support is an example of one common disqualification at her own institution. 

The experience with CAR T cells in R/R FL has been relatively short, so Rhodes used data on CAR T cells for B-cell lymphoma to make her point. It is not just that the proportion of eligible patients is limited. 

“The majority of B-cell lymphoma patients who are eligible for CAR T cells are not getting them,” she said. “It will be the same for FL.”

In other words, Rhodes indicated that it is premature to count out targeted oral agents or lenalidomide despite the excitement surrounding BsAbs and CAR T cells. The targeted agents and immunomodulatory drugs remain appropriate choices for patients unable or unwilling to travel to tertiary centers for treatment, for frail patients, and for well-informed patients who understand their options and still consider better tolerated therapies to be more consistent with their perception of an adequate risk-benefit ratio. 
 

BsAbs Vie With CAR T Cells in Advanced FL

Hers might be a valid summary, but it did not derail arguments about whether CAR T-cell therapy should be prioritized over BsAbs or the other way around for patients who are candidates for both. 

There are two BsAbs currently approved for R/R FL: glofitamab and mosunetuzumab. More are coming, according to Nina Wagner-Johnston, MD, director of hematologic malignancies at Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, Maryland. She provided several reasons why BsAbs might be considered before CAR T-cell therapies in at least some individuals. 

“The biggest advantage is that these therapies…are off the shelf,” she said. This avoids the delay of T-cell manufacturing, the potential need for bridging therapies, and the need for conditioning regimens. With more experience, BsAbs offer the potential for treatment even in a community-practice setting, particularly for maintenance dosing.

“I do think this is a safe treatment in patients who are elderly or unfit,” Wagner-Johnston said, suggesting she tends to lean toward prioritizing BsAbs over CAR T cells when the ability to tolerate an aggressive strategy is a concern. She specified that these drugs are associated with a low relative incidence of grade 3 or higher cytokine release syndrome or immune effector cell–associated neurotoxicity syndrome, and faster B-cell aplasia recovery. 

The third participant in the debate, who described the efficacy and safety of the three currently approved CAR T-cell therapies for R/R FL, did not agree with this characterization. Daniel J. Landsburg, MD, associate professor of clinical medicine at the University of Pennsylvania, Philadelphia, acknowledged that BsAb agents have an important role to play in the advanced FL setting, but he thinks that CAR T-cell therapies should be prioritized in at least some patients. 

In particular, he would not rule out CAR T-cell therapy in patients with comorbidities or other characteristics that raise questions about fitness for aggressive treatment. 

“In fact, you might want to treat a frail patient just one time with CAR T-cell therapy rather than dose after dose with a bispecific drug,” he said. 
 

No Data to Compare BsAbs and CAR T-Cells Directly

Both agreed that there have been no trials directly comparing a BsAb therapy vs CAR T cells, so there is no definitive answer, and Landsburg was reluctant to take a hard line on reserving BsAbs until after CAR T-cell therapy has been tried.

“Because BsAbs and CAR Ts are approved in the third-line setting, you might consider debulking a patient getting ready for a CAR T with a bispecific,” Landsburg said. However, he acknowledged that the next step becomes complex if patients achieved a complete response after just a few BsAb doses.

“Do you stop what is already working?” Landsburg asked rhetorically, suggesting that the best way forward is not always clear.

For R/R FL, currently there are three approved products: axicabtagene ciloleucel (Yescarta), tisagenlecleucel (Kymriah), and lisocabtagene maraleucel (Breyanzi). The entry criteria and design of the three pivotal trials differed, so their specific indications vary. Looking across the trials, Landsburg suggested that there might be differences in activity as defined by objective response rates or risk for cytokine release syndrome, but these remain theoretical without head-to-head comparisons.

“My suspicion is we are going to see very similar — quote, unquote — long-term survival curves for patients treated with any of these therapies,” he said, noting that progression-free survival at 3 years has been in the vicinity of 50% for the trials that have had long enough follow-up to judge.

Rather than trying to pick the best agent, he suggested that it makes more sense now to concentrate on strategies to improve response irrespective of CAR T-cell product; these include paying attention to total metabolic tumor volume at the time of infusion, optimizing bridging therapies, and thinking about T-cell fitness, which might be impaired in some patients by recent exposure to bendamustine.

Overall, with multiple ongoing studies with both CAR T-cell therapies and BsAbs in R/R FL — as well with targeted small-molecule agents and immunomodulatory drugs — all of the debate participants acknowledged that choices in R/R FL will evolve. 

“I actually think that combinations will be the future,” Wagner-Johnston said. Singling out tazemetostat and a BsAb and one approach that seems promising, she also predicted that some of the therapies in advanced disease are likely to be moved forward to earlier stages of FL therapy.

Rhodes reported ties with AbbVie, AstraZeneca, ADC Therapeutics, BeiGene, Bristol Myers Squibb, Epizyme, Genentech, Genmab, Janssen, Loxo Oncology, MorphoSys, Pharmacyclics, and Pfizer. Wagner-Johnston disclosed relationships with Cuno Science, Dava Oncology, Epizyme, Grünenthal, Karyopharm, and Seagen. Landsburg reported ties with ADC Therapeutics, Calithera, Curis, Epizyme, Karyopharm, MorphoSys, and Novartis.
 

A version of this article appeared on Medscape.com.

Many patients use cannabis to manage their cancer-related symptoms. However, research indicates that patients often do so without speaking to their oncologists first, and oncologists may be hesitant to broach the topic with their patients.

Updated guidelines from the American Society of Clinical Oncology (ASCO) on the use of cannabis and cannabinoids in adults with cancer stress that it’s an important conversation to have.

According to the ASCO expert panel, access to and use of cannabis alongside cancer care have outpaced the science on evidence-based indications, and overall high-quality data on the effects of cannabis during cancer care are lacking. While several observational studies support cannabis use to help ease chemotherapy-related nausea and vomiting, the literature remains more divided on other potential benefits, such as alleviating cancer pain and sleep problems, and some evidence points to potential downsides of cannabis use.

Oncologists should “absolutely talk to patients” about cannabis, Brooke Worster, MD, medical director for the Master of Science in Medical Cannabis Science & Business program at Thomas Jefferson University, Philadelphia, told Medscape Medical News.

“Patients are interested, and they are going to find access to information. As a medical professional, it’s our job to help guide them through these spaces in a safe, nonjudgmental way.”

But, Worster noted, oncologists don’t have to be experts on cannabis to begin the conversation with patients.

So, “let yourself off the hook,” Worster urged.

Plus, avoiding the conversation won’t stop patients from using cannabis. In a recent study, Worster and her colleagues found that nearly one third of patients at 12 National Cancer Institute-designated cancer centers had used cannabis since their diagnosis — most often for sleep disturbance, pain, stress, and anxiety. Most (60%) felt somewhat or extremely comfortable talking to their healthcare provider about it, but only 21.5% said they had done so. Even fewer — about 10% — had talked to their treating oncologist.

Because patients may not discuss cannabis use, it’s especially important for oncologists to open up a line of communication, said Worster, also the enterprise director of supportive oncology at the Thomas Jefferson University.
 

Evidence on Cannabis During Cancer Care

A substantial proportion of people with cancer believe cannabis can help manage cancer-related symptoms.

In Worster’s recent survey study, regardless of whether patients had used cannabis, almost 90% of those surveyed reported a perceived benefit. Although 65% also reported perceived risks for cannabis use, including difficulty concentrating, lung damage, and impaired memory, the perceived benefits outweighed the risks.

Despite generally positive perceptions, the overall literature on the benefits of cannabis in patients with cancer paints a less clear picture.

The ASCO guidelines, which were based on 13 systematic reviews and five additional primary studies, reported that cannabis can improve refractory, chemotherapy-induced nausea or vomiting when added to guideline-concordant antiemetic regimens, but that there is no clear evidence of benefit or harm for other supportive care outcomes.

The “certainty of evidence for most outcomes was low or very low,” the ASCO authors wrote.

The ASCO experts explained that, outside the context of a clinical trial, the evidence is not sufficient to recommend cannabis or cannabinoids for managing cancer pain, sleep issues, appetite loss, or anxiety and depression. For these outcomes, some studies indicate a benefit, while others don’t.

Real-world data from a large registry study, for instance, have indicated that medical cannabis is “a safe and effective complementary treatment for pain relief in patients with cancer.” However, a 2020 meta-analysis found that, in studies with a low risk for bias, adding cannabinoids to opioids did not reduce cancer pain in adults with advanced cancer.

There can be downsides to cannabis use, too. In one recent study, some patients reported feeling worse physically and psychologically compared with those who didn’t use cannabis. Another study found that oral cannabis was associated with “bothersome” side effects, including sedation, dizziness, and transient anxiety.

The ASCO guidelines also made it clear that cannabis or cannabinoids should not be used as cancer-directed treatment, outside of a clinical trial.
 

Talking to Patients About Cannabis

Given the level of evidence and patient interest in cannabis, it is important for oncologists to raise the topic of cannabis use with their patients.

To help inform decision-making and approaches to care, the ASCO guidelines suggest that oncologists can guide care themselves or direct patients to appropriate “unbiased, evidence-based” resources. For those who use cannabis or cannabinoids outside of evidence-based indications or clinician recommendations, it’s important to explore patients’ goals, educate them, and try to minimize harm.

One strategy for broaching the topic, Worster suggested, is to simply ask patients if they have tried or considered trying cannabis to control symptoms like nausea and vomiting, loss of appetite, or cancer pain.

The conversation with patients should then include an overview of the potential benefits and potential risks for cannabis use as well as risk reduction strategies, Worster noted.

But “approach it in an open and nonjudgmental frame of mind,” she said. “Just have a conversation.”

Discussing the formulation and concentration of tetrahydrocannabinol (THC) and cannabidiol (CBD) in products matters as well.

Will the product be inhaled, ingested, or topical? Inhaled cannabis is not ideal but is sometimes what patients have access to, Worster explained. Inhaled formulations tend to have faster onset, which might be preferable for treating chemotherapy-related nausea and vomiting, whereas edible formulations may take a while to start working.

It’s also important to warn patients about taking too much, she said, explaining that inhaling THC at higher doses can increase the risk for cardiovascular effects, anxiety, paranoia, panic, and psychosis.

CBD, on the other hand, is anti-inflammatory, but early data suggest it may blunt immune responses in high doses and should be used cautiously by patients receiving immunotherapy.

Worster noted that as laws change and the science advances, new cannabis products and formulations will emerge, as will artificial intelligence tools for helping to guide patients and clinicians in optimal use of cannabis for cancer care. State websites are a particularly helpful tool for providing state-specific medical education related to cannabis laws and use, as well, she said.

The bottom line, she said, is that talking to patients about the ins and outs of cannabis use “really matters.”

Worster disclosed that she is a medical consultant for EO Care.
 

A version of this article appeared on Medscape.com.

Many patients use cannabis to manage their cancer-related symptoms. However, research indicates that patients often do so without speaking to their oncologists first, and oncologists may be hesitant to broach the topic with their patients.

Updated guidelines from the American Society of Clinical Oncology (ASCO) on the use of cannabis and cannabinoids in adults with cancer stress that it’s an important conversation to have.

According to the ASCO expert panel, access to and use of cannabis alongside cancer care have outpaced the science on evidence-based indications, and overall high-quality data on the effects of cannabis during cancer care are lacking. While several observational studies support cannabis use to help ease chemotherapy-related nausea and vomiting, the literature remains more divided on other potential benefits, such as alleviating cancer pain and sleep problems, and some evidence points to potential downsides of cannabis use.

Oncologists should “absolutely talk to patients” about cannabis, Brooke Worster, MD, medical director for the Master of Science in Medical Cannabis Science & Business program at Thomas Jefferson University, Philadelphia, told Medscape Medical News.

“Patients are interested, and they are going to find access to information. As a medical professional, it’s our job to help guide them through these spaces in a safe, nonjudgmental way.”

But, Worster noted, oncologists don’t have to be experts on cannabis to begin the conversation with patients.

So, “let yourself off the hook,” Worster urged.

Plus, avoiding the conversation won’t stop patients from using cannabis. In a recent study, Worster and her colleagues found that nearly one third of patients at 12 National Cancer Institute-designated cancer centers had used cannabis since their diagnosis — most often for sleep disturbance, pain, stress, and anxiety. Most (60%) felt somewhat or extremely comfortable talking to their healthcare provider about it, but only 21.5% said they had done so. Even fewer — about 10% — had talked to their treating oncologist.

Because patients may not discuss cannabis use, it’s especially important for oncologists to open up a line of communication, said Worster, also the enterprise director of supportive oncology at the Thomas Jefferson University.
 

Evidence on Cannabis During Cancer Care

A substantial proportion of people with cancer believe cannabis can help manage cancer-related symptoms.

In Worster’s recent survey study, regardless of whether patients had used cannabis, almost 90% of those surveyed reported a perceived benefit. Although 65% also reported perceived risks for cannabis use, including difficulty concentrating, lung damage, and impaired memory, the perceived benefits outweighed the risks.

Despite generally positive perceptions, the overall literature on the benefits of cannabis in patients with cancer paints a less clear picture.

The ASCO guidelines, which were based on 13 systematic reviews and five additional primary studies, reported that cannabis can improve refractory, chemotherapy-induced nausea or vomiting when added to guideline-concordant antiemetic regimens, but that there is no clear evidence of benefit or harm for other supportive care outcomes.

The “certainty of evidence for most outcomes was low or very low,” the ASCO authors wrote.

The ASCO experts explained that, outside the context of a clinical trial, the evidence is not sufficient to recommend cannabis or cannabinoids for managing cancer pain, sleep issues, appetite loss, or anxiety and depression. For these outcomes, some studies indicate a benefit, while others don’t.

Real-world data from a large registry study, for instance, have indicated that medical cannabis is “a safe and effective complementary treatment for pain relief in patients with cancer.” However, a 2020 meta-analysis found that, in studies with a low risk for bias, adding cannabinoids to opioids did not reduce cancer pain in adults with advanced cancer.

There can be downsides to cannabis use, too. In one recent study, some patients reported feeling worse physically and psychologically compared with those who didn’t use cannabis. Another study found that oral cannabis was associated with “bothersome” side effects, including sedation, dizziness, and transient anxiety.

The ASCO guidelines also made it clear that cannabis or cannabinoids should not be used as cancer-directed treatment, outside of a clinical trial.
 

Talking to Patients About Cannabis

Given the level of evidence and patient interest in cannabis, it is important for oncologists to raise the topic of cannabis use with their patients.

To help inform decision-making and approaches to care, the ASCO guidelines suggest that oncologists can guide care themselves or direct patients to appropriate “unbiased, evidence-based” resources. For those who use cannabis or cannabinoids outside of evidence-based indications or clinician recommendations, it’s important to explore patients’ goals, educate them, and try to minimize harm.

One strategy for broaching the topic, Worster suggested, is to simply ask patients if they have tried or considered trying cannabis to control symptoms like nausea and vomiting, loss of appetite, or cancer pain.

The conversation with patients should then include an overview of the potential benefits and potential risks for cannabis use as well as risk reduction strategies, Worster noted.

But “approach it in an open and nonjudgmental frame of mind,” she said. “Just have a conversation.”

Discussing the formulation and concentration of tetrahydrocannabinol (THC) and cannabidiol (CBD) in products matters as well.

Will the product be inhaled, ingested, or topical? Inhaled cannabis is not ideal but is sometimes what patients have access to, Worster explained. Inhaled formulations tend to have faster onset, which might be preferable for treating chemotherapy-related nausea and vomiting, whereas edible formulations may take a while to start working.

It’s also important to warn patients about taking too much, she said, explaining that inhaling THC at higher doses can increase the risk for cardiovascular effects, anxiety, paranoia, panic, and psychosis.

CBD, on the other hand, is anti-inflammatory, but early data suggest it may blunt immune responses in high doses and should be used cautiously by patients receiving immunotherapy.

Worster noted that as laws change and the science advances, new cannabis products and formulations will emerge, as will artificial intelligence tools for helping to guide patients and clinicians in optimal use of cannabis for cancer care. State websites are a particularly helpful tool for providing state-specific medical education related to cannabis laws and use, as well, she said.

The bottom line, she said, is that talking to patients about the ins and outs of cannabis use “really matters.”

Worster disclosed that she is a medical consultant for EO Care.
 

A version of this article appeared on Medscape.com.

Many patients use cannabis to manage their cancer-related symptoms. However, research indicates that patients often do so without speaking to their oncologists first, and oncologists may be hesitant to broach the topic with their patients.

Updated guidelines from the American Society of Clinical Oncology (ASCO) on the use of cannabis and cannabinoids in adults with cancer stress that it’s an important conversation to have.

According to the ASCO expert panel, access to and use of cannabis alongside cancer care have outpaced the science on evidence-based indications, and overall high-quality data on the effects of cannabis during cancer care are lacking. While several observational studies support cannabis use to help ease chemotherapy-related nausea and vomiting, the literature remains more divided on other potential benefits, such as alleviating cancer pain and sleep problems, and some evidence points to potential downsides of cannabis use.

Oncologists should “absolutely talk to patients” about cannabis, Brooke Worster, MD, medical director for the Master of Science in Medical Cannabis Science & Business program at Thomas Jefferson University, Philadelphia, told Medscape Medical News.

“Patients are interested, and they are going to find access to information. As a medical professional, it’s our job to help guide them through these spaces in a safe, nonjudgmental way.”

But, Worster noted, oncologists don’t have to be experts on cannabis to begin the conversation with patients.

So, “let yourself off the hook,” Worster urged.

Plus, avoiding the conversation won’t stop patients from using cannabis. In a recent study, Worster and her colleagues found that nearly one third of patients at 12 National Cancer Institute-designated cancer centers had used cannabis since their diagnosis — most often for sleep disturbance, pain, stress, and anxiety. Most (60%) felt somewhat or extremely comfortable talking to their healthcare provider about it, but only 21.5% said they had done so. Even fewer — about 10% — had talked to their treating oncologist.

Because patients may not discuss cannabis use, it’s especially important for oncologists to open up a line of communication, said Worster, also the enterprise director of supportive oncology at the Thomas Jefferson University.
 

Evidence on Cannabis During Cancer Care

A substantial proportion of people with cancer believe cannabis can help manage cancer-related symptoms.

In Worster’s recent survey study, regardless of whether patients had used cannabis, almost 90% of those surveyed reported a perceived benefit. Although 65% also reported perceived risks for cannabis use, including difficulty concentrating, lung damage, and impaired memory, the perceived benefits outweighed the risks.

Despite generally positive perceptions, the overall literature on the benefits of cannabis in patients with cancer paints a less clear picture.

The ASCO guidelines, which were based on 13 systematic reviews and five additional primary studies, reported that cannabis can improve refractory, chemotherapy-induced nausea or vomiting when added to guideline-concordant antiemetic regimens, but that there is no clear evidence of benefit or harm for other supportive care outcomes.

The “certainty of evidence for most outcomes was low or very low,” the ASCO authors wrote.

The ASCO experts explained that, outside the context of a clinical trial, the evidence is not sufficient to recommend cannabis or cannabinoids for managing cancer pain, sleep issues, appetite loss, or anxiety and depression. For these outcomes, some studies indicate a benefit, while others don’t.

Real-world data from a large registry study, for instance, have indicated that medical cannabis is “a safe and effective complementary treatment for pain relief in patients with cancer.” However, a 2020 meta-analysis found that, in studies with a low risk for bias, adding cannabinoids to opioids did not reduce cancer pain in adults with advanced cancer.

There can be downsides to cannabis use, too. In one recent study, some patients reported feeling worse physically and psychologically compared with those who didn’t use cannabis. Another study found that oral cannabis was associated with “bothersome” side effects, including sedation, dizziness, and transient anxiety.

The ASCO guidelines also made it clear that cannabis or cannabinoids should not be used as cancer-directed treatment, outside of a clinical trial.
 

Talking to Patients About Cannabis

Given the level of evidence and patient interest in cannabis, it is important for oncologists to raise the topic of cannabis use with their patients.

To help inform decision-making and approaches to care, the ASCO guidelines suggest that oncologists can guide care themselves or direct patients to appropriate “unbiased, evidence-based” resources. For those who use cannabis or cannabinoids outside of evidence-based indications or clinician recommendations, it’s important to explore patients’ goals, educate them, and try to minimize harm.

One strategy for broaching the topic, Worster suggested, is to simply ask patients if they have tried or considered trying cannabis to control symptoms like nausea and vomiting, loss of appetite, or cancer pain.

The conversation with patients should then include an overview of the potential benefits and potential risks for cannabis use as well as risk reduction strategies, Worster noted.

But “approach it in an open and nonjudgmental frame of mind,” she said. “Just have a conversation.”

Discussing the formulation and concentration of tetrahydrocannabinol (THC) and cannabidiol (CBD) in products matters as well.

Will the product be inhaled, ingested, or topical? Inhaled cannabis is not ideal but is sometimes what patients have access to, Worster explained. Inhaled formulations tend to have faster onset, which might be preferable for treating chemotherapy-related nausea and vomiting, whereas edible formulations may take a while to start working.

It’s also important to warn patients about taking too much, she said, explaining that inhaling THC at higher doses can increase the risk for cardiovascular effects, anxiety, paranoia, panic, and psychosis.

CBD, on the other hand, is anti-inflammatory, but early data suggest it may blunt immune responses in high doses and should be used cautiously by patients receiving immunotherapy.

Worster noted that as laws change and the science advances, new cannabis products and formulations will emerge, as will artificial intelligence tools for helping to guide patients and clinicians in optimal use of cannabis for cancer care. State websites are a particularly helpful tool for providing state-specific medical education related to cannabis laws and use, as well, she said.

The bottom line, she said, is that talking to patients about the ins and outs of cannabis use “really matters.”

Worster disclosed that she is a medical consultant for EO Care.
 

A version of this article appeared on Medscape.com.