For patients with intermediate- or low-risk localized prostate cancer, intensity-modulated radiation therapy (IMRT) and proton beam therapy are both safe and effective options, according to results of the phase 3 randomized controlled PARTIQoL trial.

With both techniques, disease control rates were over 90%, with virtually no difference in bowel function or other quality-of-life ratings after 2 years, reported Jason Efstathiou, MD, PhD, with Massachusetts General Hospital, Boston, at the annual meeting of the American Society for Radiation Oncology (ASTRO).

“This is a tremendous study [that] really shows us we have two great options, with equal results across the board for both control rates and toxicity rates,” said Sameer Keole, MD, incoming ASTRO president, during a press briefing.

“These control rates are phenomenal, and the complication rates were very low,” continued Dr. Keole, with the Mayo Clinic in Phoenix, Arizona. “I think men can go and seek definitive treatment when it’s appropriate with a radiation oncologist and know that whether it’s proton therapy or IMRT; it’s an excellent treatment option.”

Overall, about 70% of new cases of prostate cancer each year are localized disease, which represents about 200,000 patients in the United States each year, Dr. Efstathiou explained. These patients have several treatment options, including different choices for external beam radiation therapy.

“Because many of these patients are going to survive their cancer and live many years after treatment, quality of life becomes paramount because they’re at risk for long-term posttreatment morbidity,” Dr. Efstathiou said. “Quality of life will inform their decision-making.”

Dr. Efstathiou noted that proton beam therapy comes with certain dosimetric advantages with the potential to reduce morbidity and improve cancer outcomes, but it is generally more resource intensive and costly than IMRT.

The PARTIQoL multicenter, phase 3, randomized trial compared patient-reported quality of life after external beam radiation using either IMRT or proton beam therapy to determine whether one performs better on the local control and toxicity fronts.

After stratifying by institution, age (< 65 years vs ≥ 65 years), rectal spacer use (no vs yes), and moderate hypofractionation (no vs yes), participants were randomized to either proton beam therapy or IMRT.

Patients were followed longitudinally for 60 months after completing radiotherapy. The primary endpoint was bowel function at 24 months using the Expanded Prostate Cancer Index Composite (EPIC) instrument. Secondary outcomes included urinary and erectile function, sexual function, toxicity and efficacy, or disease control endpoints.

Of the 450 patients randomized, 221 of 226 (97.8%) randomized to proton beam therapy and 216 of 224 (96.4%) randomized to IMRT started on their respective treatments, and 167 and 162, respectively, completed the EPIC at 24 months. This represents about a 27% rate of missing data, which “was much better than anticipated,” Dr. Efstathiou noted.

For the primary endpoint, there was no difference between proton beam therapy and IMRT in mean change of the EPIC bowel score at 24 months, with both treatment groups showing only a small, clinically nonrelevant decline from baseline. There was only about a 2% decrease on a 100-point scale in bowel quality of life after 2 years, Dr. Efstathiou reported.

Similarly, the team noted no difference in bowel function at earlier or later time points. “We see some small fluctuations, but at no time point did these reach statistical significance,” he noted.

There were also no differences observed in the other domains at any point, including urinary incontinence, urinary irritation, or sexual function.

Turning to disease control, Dr. Efstathiou and colleagues found no difference between the two groups in progression-free survival. The progression-free survival rate was 99% at 24 months and 93.7% at 60 months with IMRT, compared with 98.1% at 24 months and 93.4% at 60 months with proton beam therapy.

When looking at key subgroups or factors, the team reported no sustained difference in any quality-of-life domain or in cancer control.

Patient monitoring over a longer follow-up period is ongoing. Dr. Efstathiou noted that the PARTIQoL trial was limited to localized low- and intermediate-risk prostate cancer patients receiving either conventionally or moderately hypofractionated therapy. The trial also did not address the full range of disease scope, including higher risk disease, nodal therapy, concurrent use of hormonal therapy or other systemic therapy, local recurrent situations, or retreatment situations.

Dr. Efstathiou noted that because both proton therapy and IMRT continue to evolve, there is ongoing work to optimize the delivery of both.

Overall, the PARTIQoL trial results demonstrate “equivalent outcomes, with superb cancer control rates and extremely low toxicity from both treatments,” Jessica Karen Wong, MD, MEng, who wasn’t involved in the study, told this news organization.

“Both are excellent treatments for low- and intermediate-risk prostate cancer patients,” said Dr. Wong, Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. “This study corroborates prior single and multi-institutional experiences with the statistical power and rigorous methods of a clinical trial. Dr Efstathiou and authors should be commended for this comprehensive and well-run trial.”

Discussant for the study, Curtiland Deville, MD, of Johns Hopkins University School of Medicine, Baltimore, Maryland, agreed that patients in the trial did “exceedingly well,” regardless of whether patients received IMRT or proton therapy.

Dr. Deville said the “fundamental question regarding the use of proton therapy for prostate cancer remains — is there a clinical benefit to protons that justifies their increased costs in this setting? In a cost-neutral setting, it may still be considered very reasonable to deliver proton therapy for prostate cancer.”

In his view, this study is “practice informing” but not yet “practice changing as we await the imminent findings of the COMPARE trial,” which uses a pragmatic design powered to assess the co-primary patient-reported outcome endpoints of EPIC bowel summary, urinary function, and sexual function scores at 2 years, and which enrolled over 2500 patients.

The study has no commercial funding. Dr. Efstathiou disclosed various relationships with IBA Proton Therapy, Blue Earth Diagnostics, Boston Scientific, AstraZeneca, Genentech, Lantheus/Progenics, Astellas/Pfizer, Elekta, Uptodate, Merck, Roivant Pharma, Myovant Sciences, EMD Serono, Bayer Healthcare, Janssen, Pfizer, Progenics Pharmaceuticals, Gilead, Angiodynamics, and Clarity Pharmaceuticals. Dr. Keole and Dr. Wong had no relevant disclosures. Dr. Deville is deputy editor of the ASTRO Red Journal.

A version of this article appeared on Medscape.com.

For patients with intermediate- or low-risk localized prostate cancer, intensity-modulated radiation therapy (IMRT) and proton beam therapy are both safe and effective options, according to results of the phase 3 randomized controlled PARTIQoL trial.

With both techniques, disease control rates were over 90%, with virtually no difference in bowel function or other quality-of-life ratings after 2 years, reported Jason Efstathiou, MD, PhD, with Massachusetts General Hospital, Boston, at the annual meeting of the American Society for Radiation Oncology (ASTRO).

“This is a tremendous study [that] really shows us we have two great options, with equal results across the board for both control rates and toxicity rates,” said Sameer Keole, MD, incoming ASTRO president, during a press briefing.

“These control rates are phenomenal, and the complication rates were very low,” continued Dr. Keole, with the Mayo Clinic in Phoenix, Arizona. “I think men can go and seek definitive treatment when it’s appropriate with a radiation oncologist and know that whether it’s proton therapy or IMRT; it’s an excellent treatment option.”

Overall, about 70% of new cases of prostate cancer each year are localized disease, which represents about 200,000 patients in the United States each year, Dr. Efstathiou explained. These patients have several treatment options, including different choices for external beam radiation therapy.

“Because many of these patients are going to survive their cancer and live many years after treatment, quality of life becomes paramount because they’re at risk for long-term posttreatment morbidity,” Dr. Efstathiou said. “Quality of life will inform their decision-making.”

Dr. Efstathiou noted that proton beam therapy comes with certain dosimetric advantages with the potential to reduce morbidity and improve cancer outcomes, but it is generally more resource intensive and costly than IMRT.

The PARTIQoL multicenter, phase 3, randomized trial compared patient-reported quality of life after external beam radiation using either IMRT or proton beam therapy to determine whether one performs better on the local control and toxicity fronts.

After stratifying by institution, age (< 65 years vs ≥ 65 years), rectal spacer use (no vs yes), and moderate hypofractionation (no vs yes), participants were randomized to either proton beam therapy or IMRT.

Patients were followed longitudinally for 60 months after completing radiotherapy. The primary endpoint was bowel function at 24 months using the Expanded Prostate Cancer Index Composite (EPIC) instrument. Secondary outcomes included urinary and erectile function, sexual function, toxicity and efficacy, or disease control endpoints.

Of the 450 patients randomized, 221 of 226 (97.8%) randomized to proton beam therapy and 216 of 224 (96.4%) randomized to IMRT started on their respective treatments, and 167 and 162, respectively, completed the EPIC at 24 months. This represents about a 27% rate of missing data, which “was much better than anticipated,” Dr. Efstathiou noted.

For the primary endpoint, there was no difference between proton beam therapy and IMRT in mean change of the EPIC bowel score at 24 months, with both treatment groups showing only a small, clinically nonrelevant decline from baseline. There was only about a 2% decrease on a 100-point scale in bowel quality of life after 2 years, Dr. Efstathiou reported.

Similarly, the team noted no difference in bowel function at earlier or later time points. “We see some small fluctuations, but at no time point did these reach statistical significance,” he noted.

There were also no differences observed in the other domains at any point, including urinary incontinence, urinary irritation, or sexual function.

Turning to disease control, Dr. Efstathiou and colleagues found no difference between the two groups in progression-free survival. The progression-free survival rate was 99% at 24 months and 93.7% at 60 months with IMRT, compared with 98.1% at 24 months and 93.4% at 60 months with proton beam therapy.

When looking at key subgroups or factors, the team reported no sustained difference in any quality-of-life domain or in cancer control.

Patient monitoring over a longer follow-up period is ongoing. Dr. Efstathiou noted that the PARTIQoL trial was limited to localized low- and intermediate-risk prostate cancer patients receiving either conventionally or moderately hypofractionated therapy. The trial also did not address the full range of disease scope, including higher risk disease, nodal therapy, concurrent use of hormonal therapy or other systemic therapy, local recurrent situations, or retreatment situations.

Dr. Efstathiou noted that because both proton therapy and IMRT continue to evolve, there is ongoing work to optimize the delivery of both.

Overall, the PARTIQoL trial results demonstrate “equivalent outcomes, with superb cancer control rates and extremely low toxicity from both treatments,” Jessica Karen Wong, MD, MEng, who wasn’t involved in the study, told this news organization.

“Both are excellent treatments for low- and intermediate-risk prostate cancer patients,” said Dr. Wong, Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. “This study corroborates prior single and multi-institutional experiences with the statistical power and rigorous methods of a clinical trial. Dr Efstathiou and authors should be commended for this comprehensive and well-run trial.”

Discussant for the study, Curtiland Deville, MD, of Johns Hopkins University School of Medicine, Baltimore, Maryland, agreed that patients in the trial did “exceedingly well,” regardless of whether patients received IMRT or proton therapy.

Dr. Deville said the “fundamental question regarding the use of proton therapy for prostate cancer remains — is there a clinical benefit to protons that justifies their increased costs in this setting? In a cost-neutral setting, it may still be considered very reasonable to deliver proton therapy for prostate cancer.”

In his view, this study is “practice informing” but not yet “practice changing as we await the imminent findings of the COMPARE trial,” which uses a pragmatic design powered to assess the co-primary patient-reported outcome endpoints of EPIC bowel summary, urinary function, and sexual function scores at 2 years, and which enrolled over 2500 patients.

The study has no commercial funding. Dr. Efstathiou disclosed various relationships with IBA Proton Therapy, Blue Earth Diagnostics, Boston Scientific, AstraZeneca, Genentech, Lantheus/Progenics, Astellas/Pfizer, Elekta, Uptodate, Merck, Roivant Pharma, Myovant Sciences, EMD Serono, Bayer Healthcare, Janssen, Pfizer, Progenics Pharmaceuticals, Gilead, Angiodynamics, and Clarity Pharmaceuticals. Dr. Keole and Dr. Wong had no relevant disclosures. Dr. Deville is deputy editor of the ASTRO Red Journal.

A version of this article appeared on Medscape.com.

For patients with intermediate- or low-risk localized prostate cancer, intensity-modulated radiation therapy (IMRT) and proton beam therapy are both safe and effective options, according to results of the phase 3 randomized controlled PARTIQoL trial.

With both techniques, disease control rates were over 90%, with virtually no difference in bowel function or other quality-of-life ratings after 2 years, reported Jason Efstathiou, MD, PhD, with Massachusetts General Hospital, Boston, at the annual meeting of the American Society for Radiation Oncology (ASTRO).

“This is a tremendous study [that] really shows us we have two great options, with equal results across the board for both control rates and toxicity rates,” said Sameer Keole, MD, incoming ASTRO president, during a press briefing.

“These control rates are phenomenal, and the complication rates were very low,” continued Dr. Keole, with the Mayo Clinic in Phoenix, Arizona. “I think men can go and seek definitive treatment when it’s appropriate with a radiation oncologist and know that whether it’s proton therapy or IMRT; it’s an excellent treatment option.”

Overall, about 70% of new cases of prostate cancer each year are localized disease, which represents about 200,000 patients in the United States each year, Dr. Efstathiou explained. These patients have several treatment options, including different choices for external beam radiation therapy.

“Because many of these patients are going to survive their cancer and live many years after treatment, quality of life becomes paramount because they’re at risk for long-term posttreatment morbidity,” Dr. Efstathiou said. “Quality of life will inform their decision-making.”

Dr. Efstathiou noted that proton beam therapy comes with certain dosimetric advantages with the potential to reduce morbidity and improve cancer outcomes, but it is generally more resource intensive and costly than IMRT.

The PARTIQoL multicenter, phase 3, randomized trial compared patient-reported quality of life after external beam radiation using either IMRT or proton beam therapy to determine whether one performs better on the local control and toxicity fronts.

After stratifying by institution, age (< 65 years vs ≥ 65 years), rectal spacer use (no vs yes), and moderate hypofractionation (no vs yes), participants were randomized to either proton beam therapy or IMRT.

Patients were followed longitudinally for 60 months after completing radiotherapy. The primary endpoint was bowel function at 24 months using the Expanded Prostate Cancer Index Composite (EPIC) instrument. Secondary outcomes included urinary and erectile function, sexual function, toxicity and efficacy, or disease control endpoints.

Of the 450 patients randomized, 221 of 226 (97.8%) randomized to proton beam therapy and 216 of 224 (96.4%) randomized to IMRT started on their respective treatments, and 167 and 162, respectively, completed the EPIC at 24 months. This represents about a 27% rate of missing data, which “was much better than anticipated,” Dr. Efstathiou noted.

For the primary endpoint, there was no difference between proton beam therapy and IMRT in mean change of the EPIC bowel score at 24 months, with both treatment groups showing only a small, clinically nonrelevant decline from baseline. There was only about a 2% decrease on a 100-point scale in bowel quality of life after 2 years, Dr. Efstathiou reported.

Similarly, the team noted no difference in bowel function at earlier or later time points. “We see some small fluctuations, but at no time point did these reach statistical significance,” he noted.

There were also no differences observed in the other domains at any point, including urinary incontinence, urinary irritation, or sexual function.

Turning to disease control, Dr. Efstathiou and colleagues found no difference between the two groups in progression-free survival. The progression-free survival rate was 99% at 24 months and 93.7% at 60 months with IMRT, compared with 98.1% at 24 months and 93.4% at 60 months with proton beam therapy.

When looking at key subgroups or factors, the team reported no sustained difference in any quality-of-life domain or in cancer control.

Patient monitoring over a longer follow-up period is ongoing. Dr. Efstathiou noted that the PARTIQoL trial was limited to localized low- and intermediate-risk prostate cancer patients receiving either conventionally or moderately hypofractionated therapy. The trial also did not address the full range of disease scope, including higher risk disease, nodal therapy, concurrent use of hormonal therapy or other systemic therapy, local recurrent situations, or retreatment situations.

Dr. Efstathiou noted that because both proton therapy and IMRT continue to evolve, there is ongoing work to optimize the delivery of both.

Overall, the PARTIQoL trial results demonstrate “equivalent outcomes, with superb cancer control rates and extremely low toxicity from both treatments,” Jessica Karen Wong, MD, MEng, who wasn’t involved in the study, told this news organization.

“Both are excellent treatments for low- and intermediate-risk prostate cancer patients,” said Dr. Wong, Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. “This study corroborates prior single and multi-institutional experiences with the statistical power and rigorous methods of a clinical trial. Dr Efstathiou and authors should be commended for this comprehensive and well-run trial.”

Discussant for the study, Curtiland Deville, MD, of Johns Hopkins University School of Medicine, Baltimore, Maryland, agreed that patients in the trial did “exceedingly well,” regardless of whether patients received IMRT or proton therapy.

Dr. Deville said the “fundamental question regarding the use of proton therapy for prostate cancer remains — is there a clinical benefit to protons that justifies their increased costs in this setting? In a cost-neutral setting, it may still be considered very reasonable to deliver proton therapy for prostate cancer.”

In his view, this study is “practice informing” but not yet “practice changing as we await the imminent findings of the COMPARE trial,” which uses a pragmatic design powered to assess the co-primary patient-reported outcome endpoints of EPIC bowel summary, urinary function, and sexual function scores at 2 years, and which enrolled over 2500 patients.

The study has no commercial funding. Dr. Efstathiou disclosed various relationships with IBA Proton Therapy, Blue Earth Diagnostics, Boston Scientific, AstraZeneca, Genentech, Lantheus/Progenics, Astellas/Pfizer, Elekta, Uptodate, Merck, Roivant Pharma, Myovant Sciences, EMD Serono, Bayer Healthcare, Janssen, Pfizer, Progenics Pharmaceuticals, Gilead, Angiodynamics, and Clarity Pharmaceuticals. Dr. Keole and Dr. Wong had no relevant disclosures. Dr. Deville is deputy editor of the ASTRO Red Journal.

A version of this article appeared on Medscape.com.

Neoadjuvant concurrent chemoradiotherapy significantly improves survival outcomes over adjuvant sequential chemoradiotherapy (ASCRT) in patients with locally advanced esophageal squamous cell carcinoma, confirmed the first randomized trial to directly compare the two approaches.

Yaoyao Zhu, MD, Department of Radiation Oncology, Shanghai Pulmonary Hospital, Shanghai, China, presented the new research at the annual World Conference on Lung Cancer on September 10.

Based on the findings, neoadjuvant concurrent chemoradiotherapy (NCCRT) followed by surgical resection “should be regarded as the standard of care for patients with locally advanced esophageal squamous cell carcinoma (ESCC) in the Chinese population,” Dr. Zhu said.
 

Different Approaches in ESCC

Dr. Zhu began her presentation by underscoring that in Western countries, NCCRT followed by surgery has been the standard treatment for locally advanced, resectable esophageal cancer since the publication of the CROSS trial in 2012, which compared neoadjuvant therapy plus surgery with surgery alone.

This demonstrated that preoperative chemoradiotherapy improved survival by 34% in patients with potentially curable esophageal or esophagogastric junction cancer, while adverse event rates were deemed “acceptable.”

In contrast, in most centers in China, clinicians opt for performing surgery followed by ASCRT.

Dr. Zhu pointed out that as previous randomized controlled trials have used surgery alone as the comparator arm, it has not been shown definitively that NCCRT plus surgery is superior to surgery followed by ASCRT.

The researchers, therefore, conducted the NEOTERIC trial, which enrolled patients with clinically resectable, locally advanced ESCC, defined as clinical stage T1-2N1M0 or T3-4N0-1M0.

They were randomized to one of two arms. The NCCRT arm involved 6 weeks of carboplatin plus paclitaxel chemotherapy alongside radiotherapy delivered as 50.4 Gy over 28 fractions. After an interval of 4-6 weeks, the patients underwent surgery, followed by an optional two cycles of carboplatin plus paclitaxel 4-6 weeks later.

In the ASCRT arm, patients underwent surgery straightaway, waited for 4-6 weeks, then had two cycles of carboplatin plus paclitaxel 3 weeks apart, followed by the same radiotherapy regimen as in the first arm. About 2-4 weeks later, patients could then undergo another two cycles of carboplatin plus paclitaxel.
 

More Than Doubling of Survival Outcomes

One hundred patients were assigned to NCCRT and 104 to ASCRT. There were no significant differences between the groups in terms of their baseline characteristics.

The vast majority of patients were men, just over two thirds were smokers, and the median age was around 60 years. The median tumor length was approximately 5 cm, and around half of tumors were located in the middle third of the esophagus.

Median disease-free survival was markedly longer with NCCRT, at 51.0 months vs 14.0 months in the ASCRT arm (P = .01). Similarly, median overall survival was far longer with neoadjuvant therapy, at 79.0 months, vs 38.0 months when waiting until after surgery to provide chemoradiotherapy (P = .025).

There were no significant differences in postsurgical complications between the two arms, and no significant differences in rates of grade 3-4 hematologic and nonhematologic toxicities. There were also no chemoradiotherapy-related deaths.

The most common toxicities across the two study arms were esophagitis, neutropenia, thrombocytopenia, and leukopenia.

Overall, the rates of recurrence were significantly lower with NCCRT than with ASCRT (58.0% vs 66.3%; P = .020). This included significant reductions in both locoregional (P = .012) and distant recurrence (P = .009).

Jaffer A. Ajani, MD, University of Texas MD Anderson Cancer Center, Houston, underlined that the experimental arm of the trial, with neoadjuvant chemoradiotherapy, “has been the standard of care in the United States for a long time, particularly for squamous carcinoma.”

However, he said in an interview that it is not a standard of care in China and clinicians continue with adjuvant therapy. This is despite a recent study conducted in Hong Kong that concluded that patients should not be given any treatment after surgery “because they do worse” than those given neoadjuvant therapy, he continued.

While Dr. Ajani noted that the current analysis is underpowered to provide a definitive conclusion, it remains “an important study for Chinese patients.

“Hopefully, it will be well advertised in China, and all the providers switch [to NCCRT]. This could push them to abandon what in the West was considered harmful.”

Dr. Ajani explained the reason neoadjuvant therapy performs better than adjuvant chemoradiotherapy is it “may be mopping up some of the micro metastatic disease, which is difficult to do after surgery,” especially as many patients cannot tolerate postoperative treatment.

“It may be that the majority of patients don’t even get [adjuvant therapy], and those who get it don’t seem to benefit.”

Vishwanath Sathyanarayanan, MD, PhD, Senior Consultant, Professor and Academic Advisor, Department of Medical Oncology, Apollo Cancer Centers, Bangalore, India, agreed that the study reinforces that “NCCRT continues to remain the standard of care in locally advanced resectable esophageal squamous cell carcinoma.”

Consequently, there are “no implications for clinical practice” for providers in the West from these study results, “particularly as NCCRT significantly improves outcomes vs ASCRT with a similar toxicity profile,” he said in an interview.

No funding was declared. Dr. Zhu declared no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Neoadjuvant concurrent chemoradiotherapy significantly improves survival outcomes over adjuvant sequential chemoradiotherapy (ASCRT) in patients with locally advanced esophageal squamous cell carcinoma, confirmed the first randomized trial to directly compare the two approaches.

Yaoyao Zhu, MD, Department of Radiation Oncology, Shanghai Pulmonary Hospital, Shanghai, China, presented the new research at the annual World Conference on Lung Cancer on September 10.

Based on the findings, neoadjuvant concurrent chemoradiotherapy (NCCRT) followed by surgical resection “should be regarded as the standard of care for patients with locally advanced esophageal squamous cell carcinoma (ESCC) in the Chinese population,” Dr. Zhu said.
 

Different Approaches in ESCC

Dr. Zhu began her presentation by underscoring that in Western countries, NCCRT followed by surgery has been the standard treatment for locally advanced, resectable esophageal cancer since the publication of the CROSS trial in 2012, which compared neoadjuvant therapy plus surgery with surgery alone.

This demonstrated that preoperative chemoradiotherapy improved survival by 34% in patients with potentially curable esophageal or esophagogastric junction cancer, while adverse event rates were deemed “acceptable.”

In contrast, in most centers in China, clinicians opt for performing surgery followed by ASCRT.

Dr. Zhu pointed out that as previous randomized controlled trials have used surgery alone as the comparator arm, it has not been shown definitively that NCCRT plus surgery is superior to surgery followed by ASCRT.

The researchers, therefore, conducted the NEOTERIC trial, which enrolled patients with clinically resectable, locally advanced ESCC, defined as clinical stage T1-2N1M0 or T3-4N0-1M0.

They were randomized to one of two arms. The NCCRT arm involved 6 weeks of carboplatin plus paclitaxel chemotherapy alongside radiotherapy delivered as 50.4 Gy over 28 fractions. After an interval of 4-6 weeks, the patients underwent surgery, followed by an optional two cycles of carboplatin plus paclitaxel 4-6 weeks later.

In the ASCRT arm, patients underwent surgery straightaway, waited for 4-6 weeks, then had two cycles of carboplatin plus paclitaxel 3 weeks apart, followed by the same radiotherapy regimen as in the first arm. About 2-4 weeks later, patients could then undergo another two cycles of carboplatin plus paclitaxel.
 

More Than Doubling of Survival Outcomes

One hundred patients were assigned to NCCRT and 104 to ASCRT. There were no significant differences between the groups in terms of their baseline characteristics.

The vast majority of patients were men, just over two thirds were smokers, and the median age was around 60 years. The median tumor length was approximately 5 cm, and around half of tumors were located in the middle third of the esophagus.

Median disease-free survival was markedly longer with NCCRT, at 51.0 months vs 14.0 months in the ASCRT arm (P = .01). Similarly, median overall survival was far longer with neoadjuvant therapy, at 79.0 months, vs 38.0 months when waiting until after surgery to provide chemoradiotherapy (P = .025).

There were no significant differences in postsurgical complications between the two arms, and no significant differences in rates of grade 3-4 hematologic and nonhematologic toxicities. There were also no chemoradiotherapy-related deaths.

The most common toxicities across the two study arms were esophagitis, neutropenia, thrombocytopenia, and leukopenia.

Overall, the rates of recurrence were significantly lower with NCCRT than with ASCRT (58.0% vs 66.3%; P = .020). This included significant reductions in both locoregional (P = .012) and distant recurrence (P = .009).

Jaffer A. Ajani, MD, University of Texas MD Anderson Cancer Center, Houston, underlined that the experimental arm of the trial, with neoadjuvant chemoradiotherapy, “has been the standard of care in the United States for a long time, particularly for squamous carcinoma.”

However, he said in an interview that it is not a standard of care in China and clinicians continue with adjuvant therapy. This is despite a recent study conducted in Hong Kong that concluded that patients should not be given any treatment after surgery “because they do worse” than those given neoadjuvant therapy, he continued.

While Dr. Ajani noted that the current analysis is underpowered to provide a definitive conclusion, it remains “an important study for Chinese patients.

“Hopefully, it will be well advertised in China, and all the providers switch [to NCCRT]. This could push them to abandon what in the West was considered harmful.”

Dr. Ajani explained the reason neoadjuvant therapy performs better than adjuvant chemoradiotherapy is it “may be mopping up some of the micro metastatic disease, which is difficult to do after surgery,” especially as many patients cannot tolerate postoperative treatment.

“It may be that the majority of patients don’t even get [adjuvant therapy], and those who get it don’t seem to benefit.”

Vishwanath Sathyanarayanan, MD, PhD, Senior Consultant, Professor and Academic Advisor, Department of Medical Oncology, Apollo Cancer Centers, Bangalore, India, agreed that the study reinforces that “NCCRT continues to remain the standard of care in locally advanced resectable esophageal squamous cell carcinoma.”

Consequently, there are “no implications for clinical practice” for providers in the West from these study results, “particularly as NCCRT significantly improves outcomes vs ASCRT with a similar toxicity profile,” he said in an interview.

No funding was declared. Dr. Zhu declared no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Neoadjuvant concurrent chemoradiotherapy significantly improves survival outcomes over adjuvant sequential chemoradiotherapy (ASCRT) in patients with locally advanced esophageal squamous cell carcinoma, confirmed the first randomized trial to directly compare the two approaches.

Yaoyao Zhu, MD, Department of Radiation Oncology, Shanghai Pulmonary Hospital, Shanghai, China, presented the new research at the annual World Conference on Lung Cancer on September 10.

Based on the findings, neoadjuvant concurrent chemoradiotherapy (NCCRT) followed by surgical resection “should be regarded as the standard of care for patients with locally advanced esophageal squamous cell carcinoma (ESCC) in the Chinese population,” Dr. Zhu said.
 

Different Approaches in ESCC

Dr. Zhu began her presentation by underscoring that in Western countries, NCCRT followed by surgery has been the standard treatment for locally advanced, resectable esophageal cancer since the publication of the CROSS trial in 2012, which compared neoadjuvant therapy plus surgery with surgery alone.

This demonstrated that preoperative chemoradiotherapy improved survival by 34% in patients with potentially curable esophageal or esophagogastric junction cancer, while adverse event rates were deemed “acceptable.”

In contrast, in most centers in China, clinicians opt for performing surgery followed by ASCRT.

Dr. Zhu pointed out that as previous randomized controlled trials have used surgery alone as the comparator arm, it has not been shown definitively that NCCRT plus surgery is superior to surgery followed by ASCRT.

The researchers, therefore, conducted the NEOTERIC trial, which enrolled patients with clinically resectable, locally advanced ESCC, defined as clinical stage T1-2N1M0 or T3-4N0-1M0.

They were randomized to one of two arms. The NCCRT arm involved 6 weeks of carboplatin plus paclitaxel chemotherapy alongside radiotherapy delivered as 50.4 Gy over 28 fractions. After an interval of 4-6 weeks, the patients underwent surgery, followed by an optional two cycles of carboplatin plus paclitaxel 4-6 weeks later.

In the ASCRT arm, patients underwent surgery straightaway, waited for 4-6 weeks, then had two cycles of carboplatin plus paclitaxel 3 weeks apart, followed by the same radiotherapy regimen as in the first arm. About 2-4 weeks later, patients could then undergo another two cycles of carboplatin plus paclitaxel.
 

More Than Doubling of Survival Outcomes

One hundred patients were assigned to NCCRT and 104 to ASCRT. There were no significant differences between the groups in terms of their baseline characteristics.

The vast majority of patients were men, just over two thirds were smokers, and the median age was around 60 years. The median tumor length was approximately 5 cm, and around half of tumors were located in the middle third of the esophagus.

Median disease-free survival was markedly longer with NCCRT, at 51.0 months vs 14.0 months in the ASCRT arm (P = .01). Similarly, median overall survival was far longer with neoadjuvant therapy, at 79.0 months, vs 38.0 months when waiting until after surgery to provide chemoradiotherapy (P = .025).

There were no significant differences in postsurgical complications between the two arms, and no significant differences in rates of grade 3-4 hematologic and nonhematologic toxicities. There were also no chemoradiotherapy-related deaths.

The most common toxicities across the two study arms were esophagitis, neutropenia, thrombocytopenia, and leukopenia.

Overall, the rates of recurrence were significantly lower with NCCRT than with ASCRT (58.0% vs 66.3%; P = .020). This included significant reductions in both locoregional (P = .012) and distant recurrence (P = .009).

Jaffer A. Ajani, MD, University of Texas MD Anderson Cancer Center, Houston, underlined that the experimental arm of the trial, with neoadjuvant chemoradiotherapy, “has been the standard of care in the United States for a long time, particularly for squamous carcinoma.”

However, he said in an interview that it is not a standard of care in China and clinicians continue with adjuvant therapy. This is despite a recent study conducted in Hong Kong that concluded that patients should not be given any treatment after surgery “because they do worse” than those given neoadjuvant therapy, he continued.

While Dr. Ajani noted that the current analysis is underpowered to provide a definitive conclusion, it remains “an important study for Chinese patients.

“Hopefully, it will be well advertised in China, and all the providers switch [to NCCRT]. This could push them to abandon what in the West was considered harmful.”

Dr. Ajani explained the reason neoadjuvant therapy performs better than adjuvant chemoradiotherapy is it “may be mopping up some of the micro metastatic disease, which is difficult to do after surgery,” especially as many patients cannot tolerate postoperative treatment.

“It may be that the majority of patients don’t even get [adjuvant therapy], and those who get it don’t seem to benefit.”

Vishwanath Sathyanarayanan, MD, PhD, Senior Consultant, Professor and Academic Advisor, Department of Medical Oncology, Apollo Cancer Centers, Bangalore, India, agreed that the study reinforces that “NCCRT continues to remain the standard of care in locally advanced resectable esophageal squamous cell carcinoma.”

Consequently, there are “no implications for clinical practice” for providers in the West from these study results, “particularly as NCCRT significantly improves outcomes vs ASCRT with a similar toxicity profile,” he said in an interview.

No funding was declared. Dr. Zhu declared no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

A single infusion of the chimeric antigen receptor (CAR) T-cell therapy ciltacabtagene autoleucel, or cilta-cel (CARVYKTI, Janssen Biotech, Inc.), reduces the risk for death by 45% vs standard-of-care (SoC) therapies in patients with lenalidomide-refractory multiple myeloma, according to the latest data from the phase 3 CARTITUDE-4 study.

“Cilta-cel is the first CAR T-cell therapy to demonstrate an overall survival benefit in multiple myeloma,” María-Victoria Mateos, MD, PhD, said during a presentation of the updated CARTITUDE-4 data at the annual meeting of the International Myeloma Society in late September.

A prespecified overall survival (OS) analysis at a median follow-up of 34 months showed that median OS was not reached in either the cilta-cel or SoC therapy arm (hazard ratio [HR], 0.55). The 30-month OS rates were 76% and 64% in the arms, respectively, said Dr. Mateos, a professor at the University Hospital of Salamanca, Spain.

The significant OS benefit was sustained across all prespecified subgroups, she noted.

The US Food and Drug Administration first approved cilta-cel in 2022 for use after at least four prior lines of therapy in patients with lenalidomide-resistant multiple myeloma based on findings from the CARTITUDE-1 trial. In April 2024, based on progression-free survival (PFS) findings at median follow-up of 16 months in CARTITUDE-4 (HR for progression/death vs SoC, 0.26), that approval was expanded to include patients with lenalidomide-refractory multiple myeloma after one or more prior lines of therapy.

“CARVYKTI demonstrated remarkable efficacy as a personalized, one-time infusion in the earlier treatment of relapsed/refractory multiple myeloma as shown through the CARTITUDE-4 study results,” study coauthor Binod Dhakal, MD, of the Medical College of Wisconsin, in Milwaukee, stated in a press release announcing that expansion. “With this approval, I’m excited for patients who may have the opportunity for a treatment-free period for their multiple myeloma as early as first relapse, with the hope of eliminating the burden of having to be on continuous treatment while living with this challenging disease.”

At the latest analysis, PFS was not reached in the cilta-cel arm and was 11.79 months with SoC, Dr. Mateos said.

The 30-month PFS rates were 59% and 26%, respectively (HR, 0.29), and the PFS benefit was observed across prespecified subgroups.

Patients in the cilta-cel arm also had better complete response rates (77% vs 24%), overall response rates (85% vs 67%), and minimal residual disease-negativity rates (62% vs 18%).

Median duration of response was not reached with cilta-cel and was 18.69 months with SoC, and median time to symptom worsening was not reached vs 34.33 months, respectively.

Safety at the latest update was consistent with prior analyses.

The CARTITUDE findings continue to support the overall benefit-risk profile of cilta-cel vs SoC in patients with lenalidomide-refractory multiple myeloma as early as after the first relapse, Dr. Mateos concluded.

Despite the “compelling efficacy” of cilta-cel, there remains a need for “a safer and equally (if not more) effective CAR-T product” in this setting, Manni Mohyuddin, MD, told this news organization.

“The trial does not change my practice,” said Dr. Mohyuddin, an assistant professor in the multiple myeloma program at Huntsman Cancer Institute, University of Utah, Salt Lake City.

“We must recognize that the control arm [in CARTITUDE-4] isn’t the best available standard of care,” he explained, noting that carfilzomib-containing triplets were not allowed. “Furthermore, overall survival is dependent on access to good therapies upon relapse, and patients in the control arm did not cross over to get cilta-cel at the time of relapse.

“We do not know if overall survival benefit would have been present if the control arm was better and if there was access to better post-protocol therapy.”

Toxicity is also a concern, he said.

“I think of it as high risk-high reward. There was a sevenfold increased incidence of secondary hematological malignancies in the cilta-cel arm compared to standard of care — this is a very concerning signal that dampens my enthusiasm to use this drug early for everyone,” he added.

For example, although Parkinsonism was rare, it generally did not resolve and lasted years, resolving in only 13% of affected patients, with a median time to resolution of 523 days.

“These are horrible odds, and for many patients there may be safer options,” he noted, adding that “cilta-cel is an option I would consider for some relapses (very early relapse while still on multi-agent therapy, high-risk disease), but otherwise I think personally it’s too toxic for most first relapses.”

Dr. Mateos reported relationships with AbbVie, Amgen, BMS, GSK, Janssen, Kite, Oncopeptides, Pfizer, Regeneron, Roche, Sanofi, Stemline Therapeutics, and Takeda. Dr. Mohyuddin had no disclosures.
 

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

A single infusion of the chimeric antigen receptor (CAR) T-cell therapy ciltacabtagene autoleucel, or cilta-cel (CARVYKTI, Janssen Biotech, Inc.), reduces the risk for death by 45% vs standard-of-care (SoC) therapies in patients with lenalidomide-refractory multiple myeloma, according to the latest data from the phase 3 CARTITUDE-4 study.

“Cilta-cel is the first CAR T-cell therapy to demonstrate an overall survival benefit in multiple myeloma,” María-Victoria Mateos, MD, PhD, said during a presentation of the updated CARTITUDE-4 data at the annual meeting of the International Myeloma Society in late September.

A prespecified overall survival (OS) analysis at a median follow-up of 34 months showed that median OS was not reached in either the cilta-cel or SoC therapy arm (hazard ratio [HR], 0.55). The 30-month OS rates were 76% and 64% in the arms, respectively, said Dr. Mateos, a professor at the University Hospital of Salamanca, Spain.

The significant OS benefit was sustained across all prespecified subgroups, she noted.

The US Food and Drug Administration first approved cilta-cel in 2022 for use after at least four prior lines of therapy in patients with lenalidomide-resistant multiple myeloma based on findings from the CARTITUDE-1 trial. In April 2024, based on progression-free survival (PFS) findings at median follow-up of 16 months in CARTITUDE-4 (HR for progression/death vs SoC, 0.26), that approval was expanded to include patients with lenalidomide-refractory multiple myeloma after one or more prior lines of therapy.

“CARVYKTI demonstrated remarkable efficacy as a personalized, one-time infusion in the earlier treatment of relapsed/refractory multiple myeloma as shown through the CARTITUDE-4 study results,” study coauthor Binod Dhakal, MD, of the Medical College of Wisconsin, in Milwaukee, stated in a press release announcing that expansion. “With this approval, I’m excited for patients who may have the opportunity for a treatment-free period for their multiple myeloma as early as first relapse, with the hope of eliminating the burden of having to be on continuous treatment while living with this challenging disease.”

At the latest analysis, PFS was not reached in the cilta-cel arm and was 11.79 months with SoC, Dr. Mateos said.

The 30-month PFS rates were 59% and 26%, respectively (HR, 0.29), and the PFS benefit was observed across prespecified subgroups.

Patients in the cilta-cel arm also had better complete response rates (77% vs 24%), overall response rates (85% vs 67%), and minimal residual disease-negativity rates (62% vs 18%).

Median duration of response was not reached with cilta-cel and was 18.69 months with SoC, and median time to symptom worsening was not reached vs 34.33 months, respectively.

Safety at the latest update was consistent with prior analyses.

The CARTITUDE findings continue to support the overall benefit-risk profile of cilta-cel vs SoC in patients with lenalidomide-refractory multiple myeloma as early as after the first relapse, Dr. Mateos concluded.

Despite the “compelling efficacy” of cilta-cel, there remains a need for “a safer and equally (if not more) effective CAR-T product” in this setting, Manni Mohyuddin, MD, told this news organization.

“The trial does not change my practice,” said Dr. Mohyuddin, an assistant professor in the multiple myeloma program at Huntsman Cancer Institute, University of Utah, Salt Lake City.

“We must recognize that the control arm [in CARTITUDE-4] isn’t the best available standard of care,” he explained, noting that carfilzomib-containing triplets were not allowed. “Furthermore, overall survival is dependent on access to good therapies upon relapse, and patients in the control arm did not cross over to get cilta-cel at the time of relapse.

“We do not know if overall survival benefit would have been present if the control arm was better and if there was access to better post-protocol therapy.”

Toxicity is also a concern, he said.

“I think of it as high risk-high reward. There was a sevenfold increased incidence of secondary hematological malignancies in the cilta-cel arm compared to standard of care — this is a very concerning signal that dampens my enthusiasm to use this drug early for everyone,” he added.

For example, although Parkinsonism was rare, it generally did not resolve and lasted years, resolving in only 13% of affected patients, with a median time to resolution of 523 days.

“These are horrible odds, and for many patients there may be safer options,” he noted, adding that “cilta-cel is an option I would consider for some relapses (very early relapse while still on multi-agent therapy, high-risk disease), but otherwise I think personally it’s too toxic for most first relapses.”

Dr. Mateos reported relationships with AbbVie, Amgen, BMS, GSK, Janssen, Kite, Oncopeptides, Pfizer, Regeneron, Roche, Sanofi, Stemline Therapeutics, and Takeda. Dr. Mohyuddin had no disclosures.
 

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

A single infusion of the chimeric antigen receptor (CAR) T-cell therapy ciltacabtagene autoleucel, or cilta-cel (CARVYKTI, Janssen Biotech, Inc.), reduces the risk for death by 45% vs standard-of-care (SoC) therapies in patients with lenalidomide-refractory multiple myeloma, according to the latest data from the phase 3 CARTITUDE-4 study.

“Cilta-cel is the first CAR T-cell therapy to demonstrate an overall survival benefit in multiple myeloma,” María-Victoria Mateos, MD, PhD, said during a presentation of the updated CARTITUDE-4 data at the annual meeting of the International Myeloma Society in late September.

A prespecified overall survival (OS) analysis at a median follow-up of 34 months showed that median OS was not reached in either the cilta-cel or SoC therapy arm (hazard ratio [HR], 0.55). The 30-month OS rates were 76% and 64% in the arms, respectively, said Dr. Mateos, a professor at the University Hospital of Salamanca, Spain.

The significant OS benefit was sustained across all prespecified subgroups, she noted.

The US Food and Drug Administration first approved cilta-cel in 2022 for use after at least four prior lines of therapy in patients with lenalidomide-resistant multiple myeloma based on findings from the CARTITUDE-1 trial. In April 2024, based on progression-free survival (PFS) findings at median follow-up of 16 months in CARTITUDE-4 (HR for progression/death vs SoC, 0.26), that approval was expanded to include patients with lenalidomide-refractory multiple myeloma after one or more prior lines of therapy.

“CARVYKTI demonstrated remarkable efficacy as a personalized, one-time infusion in the earlier treatment of relapsed/refractory multiple myeloma as shown through the CARTITUDE-4 study results,” study coauthor Binod Dhakal, MD, of the Medical College of Wisconsin, in Milwaukee, stated in a press release announcing that expansion. “With this approval, I’m excited for patients who may have the opportunity for a treatment-free period for their multiple myeloma as early as first relapse, with the hope of eliminating the burden of having to be on continuous treatment while living with this challenging disease.”

At the latest analysis, PFS was not reached in the cilta-cel arm and was 11.79 months with SoC, Dr. Mateos said.

The 30-month PFS rates were 59% and 26%, respectively (HR, 0.29), and the PFS benefit was observed across prespecified subgroups.

Patients in the cilta-cel arm also had better complete response rates (77% vs 24%), overall response rates (85% vs 67%), and minimal residual disease-negativity rates (62% vs 18%).

Median duration of response was not reached with cilta-cel and was 18.69 months with SoC, and median time to symptom worsening was not reached vs 34.33 months, respectively.

Safety at the latest update was consistent with prior analyses.

The CARTITUDE findings continue to support the overall benefit-risk profile of cilta-cel vs SoC in patients with lenalidomide-refractory multiple myeloma as early as after the first relapse, Dr. Mateos concluded.

Despite the “compelling efficacy” of cilta-cel, there remains a need for “a safer and equally (if not more) effective CAR-T product” in this setting, Manni Mohyuddin, MD, told this news organization.

“The trial does not change my practice,” said Dr. Mohyuddin, an assistant professor in the multiple myeloma program at Huntsman Cancer Institute, University of Utah, Salt Lake City.

“We must recognize that the control arm [in CARTITUDE-4] isn’t the best available standard of care,” he explained, noting that carfilzomib-containing triplets were not allowed. “Furthermore, overall survival is dependent on access to good therapies upon relapse, and patients in the control arm did not cross over to get cilta-cel at the time of relapse.

“We do not know if overall survival benefit would have been present if the control arm was better and if there was access to better post-protocol therapy.”

Toxicity is also a concern, he said.

“I think of it as high risk-high reward. There was a sevenfold increased incidence of secondary hematological malignancies in the cilta-cel arm compared to standard of care — this is a very concerning signal that dampens my enthusiasm to use this drug early for everyone,” he added.

For example, although Parkinsonism was rare, it generally did not resolve and lasted years, resolving in only 13% of affected patients, with a median time to resolution of 523 days.

“These are horrible odds, and for many patients there may be safer options,” he noted, adding that “cilta-cel is an option I would consider for some relapses (very early relapse while still on multi-agent therapy, high-risk disease), but otherwise I think personally it’s too toxic for most first relapses.”

Dr. Mateos reported relationships with AbbVie, Amgen, BMS, GSK, Janssen, Kite, Oncopeptides, Pfizer, Regeneron, Roche, Sanofi, Stemline Therapeutics, and Takeda. Dr. Mohyuddin had no disclosures.
 

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

A new approach to using stem cell–derived pancreatic islets has allowed a patient with type 1 diabetes (T1D) to come off insulin for 1 year.

The chemically induced pluripotent stem cell–derived islets came from the somatic cells of the patient, a 25-year-old woman who had lived for 11 years with unstable T1D with less than 50% time-in-target glucose range despite intensive insulin therapy. By 1 year following the transplantation of the cells into her abdomen, her glucose levels were nearly 100% in range, and her hemoglobin A1c had come down from 7.4%-8.0% to nondiabetic range (~5%).

Of note, she was already under immunosuppression for a prior liver transplant and remained on it throughout. There were no major safety concerns.

“We are very encouraged by the positive clinical findings seen in this first patient using this combination of technologies. These findings set a strong foundation for further development of stem cell–derived islet transplantation as a feasible treatment modality for diabetes,” study authors Soon Yi Liew, PhD, and Hongkui Deng, PhD, both of Peking University Health Science Center, Beijing, China, told this news organization in an email. Dr. Deng, the lead author, is the director of the university’s Institute of Stem Cell Research.

The findings were published in Cell.
 

What’s New With This Approach?

The use of the patient’s own cells is one of several ways in which this approach differs from other ongoing efforts in treating T1D with pluripotent stem cell–derived islets, such as those of the companies Vertex and Sernova, Dr. Liew and Dr. Deng explained.

Another difference is that “the patient-specific stem cell–derived islets used in this study were produced from induced pluripotent stem cells generated using chemical reprogramming, which is a nontransgenic approach to inducing pluripotent stem cells from somatic cells that uses only small molecules, different from the conventional method of viral transduction of transcription factors. ... Employing small molecules as reprogramming factors provides a greater degree of control — small molecules have defined structures easily manufactured and standardized, are not genome integrating, and are cost effective,” Dr. Liew and Dr. Deng said.

A third difference, they noted, is the placement of the stem cell–derived islets underneath the abdominal anterior rectus sheath of the patient, as opposed to the more commonly used hepatic portal vein. In addition to better ease of visualization, prior evidence suggested that this approach could lead to an improved engraftment and graft function and could circumvent graft loss from blood-mediated inflammatory responses associated with the liver site.

Moreover, they added, “to our knowledge, the rapidity with which insulin-independence was achieved post transplantation of stem cell–derived islets, 75 days post-transplantation, is also a first.”
 

Immunosuppression Remains a Challenge

Asked to comment, David M. Harlan, MD, the William and Doris Krupp professor of medicine and codirector of the Diabetes Center of Excellence at the University of Massachusetts Chan Medical School, Worcester, told this news organization, “on the one hand, it seems like a great breakthrough that you could take each individual cells and use those to make islets, but ... that process takes a long time, is very, very expensive, and then the T1D recipient still needs to be immunosuppressed. From a business point of view, I just don’t see it as getting any legs.”

Dr. Harlan, who had been involved in the islet transplantation field for several decades, pointed out that the additional autoimmunity of T1D poses a challenge beyond that of the body’s immune reaction to foreign tissue. “Because transplants have been around since the 1950s, we know a lot about how to prevent allogeneic rejection, from one person to another, but we know very little about how to prevent autoimmunity, so that’s still a very difficult nut to crack. I actually think the major effort should be focused on making the beta cells more hardy [via genetic modification] as opposed to focusing on the immune system. And there’s a lot of data to support that now, and that’s what we’re working on.”

Indeed, Dr. Liew and Dr. Deng said, “New immunomodulatory strategies to address graft longevity without immunosuppression remain to be established and tested. With reports of therapeutic efficacy of stem cell–derived islet transplantation such as with our study, stem cell–derived therapy without need for immunosuppression would be a meaningful next step in the treatment of this disease.”

The team has now performed the same procedure in two more patients and will report their data “in due course.”

Dr. Liew had no disclosures. Dr. Deng is a scientific adviser at Hangzhou Reprogenix Bioscience. Two coauthors are employees of Hangzhou Reprogenix Bioscience. Another is a former employee of Hangzhou Reprogenix Bioscience and is now affiliated with the Hangzhou Institute of Medicine, Chinese Academy of Sciences. Four coauthors have patent applications related to this work. Dr. Harlan is chief scientific officer and cofounder of Stability Health. He had no other disclosures.
 

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

A new approach to using stem cell–derived pancreatic islets has allowed a patient with type 1 diabetes (T1D) to come off insulin for 1 year.

The chemically induced pluripotent stem cell–derived islets came from the somatic cells of the patient, a 25-year-old woman who had lived for 11 years with unstable T1D with less than 50% time-in-target glucose range despite intensive insulin therapy. By 1 year following the transplantation of the cells into her abdomen, her glucose levels were nearly 100% in range, and her hemoglobin A1c had come down from 7.4%-8.0% to nondiabetic range (~5%).

Of note, she was already under immunosuppression for a prior liver transplant and remained on it throughout. There were no major safety concerns.

“We are very encouraged by the positive clinical findings seen in this first patient using this combination of technologies. These findings set a strong foundation for further development of stem cell–derived islet transplantation as a feasible treatment modality for diabetes,” study authors Soon Yi Liew, PhD, and Hongkui Deng, PhD, both of Peking University Health Science Center, Beijing, China, told this news organization in an email. Dr. Deng, the lead author, is the director of the university’s Institute of Stem Cell Research.

The findings were published in Cell.
 

What’s New With This Approach?

The use of the patient’s own cells is one of several ways in which this approach differs from other ongoing efforts in treating T1D with pluripotent stem cell–derived islets, such as those of the companies Vertex and Sernova, Dr. Liew and Dr. Deng explained.

Another difference is that “the patient-specific stem cell–derived islets used in this study were produced from induced pluripotent stem cells generated using chemical reprogramming, which is a nontransgenic approach to inducing pluripotent stem cells from somatic cells that uses only small molecules, different from the conventional method of viral transduction of transcription factors. ... Employing small molecules as reprogramming factors provides a greater degree of control — small molecules have defined structures easily manufactured and standardized, are not genome integrating, and are cost effective,” Dr. Liew and Dr. Deng said.

A third difference, they noted, is the placement of the stem cell–derived islets underneath the abdominal anterior rectus sheath of the patient, as opposed to the more commonly used hepatic portal vein. In addition to better ease of visualization, prior evidence suggested that this approach could lead to an improved engraftment and graft function and could circumvent graft loss from blood-mediated inflammatory responses associated with the liver site.

Moreover, they added, “to our knowledge, the rapidity with which insulin-independence was achieved post transplantation of stem cell–derived islets, 75 days post-transplantation, is also a first.”
 

Immunosuppression Remains a Challenge

Asked to comment, David M. Harlan, MD, the William and Doris Krupp professor of medicine and codirector of the Diabetes Center of Excellence at the University of Massachusetts Chan Medical School, Worcester, told this news organization, “on the one hand, it seems like a great breakthrough that you could take each individual cells and use those to make islets, but ... that process takes a long time, is very, very expensive, and then the T1D recipient still needs to be immunosuppressed. From a business point of view, I just don’t see it as getting any legs.”

Dr. Harlan, who had been involved in the islet transplantation field for several decades, pointed out that the additional autoimmunity of T1D poses a challenge beyond that of the body’s immune reaction to foreign tissue. “Because transplants have been around since the 1950s, we know a lot about how to prevent allogeneic rejection, from one person to another, but we know very little about how to prevent autoimmunity, so that’s still a very difficult nut to crack. I actually think the major effort should be focused on making the beta cells more hardy [via genetic modification] as opposed to focusing on the immune system. And there’s a lot of data to support that now, and that’s what we’re working on.”

Indeed, Dr. Liew and Dr. Deng said, “New immunomodulatory strategies to address graft longevity without immunosuppression remain to be established and tested. With reports of therapeutic efficacy of stem cell–derived islet transplantation such as with our study, stem cell–derived therapy without need for immunosuppression would be a meaningful next step in the treatment of this disease.”

The team has now performed the same procedure in two more patients and will report their data “in due course.”

Dr. Liew had no disclosures. Dr. Deng is a scientific adviser at Hangzhou Reprogenix Bioscience. Two coauthors are employees of Hangzhou Reprogenix Bioscience. Another is a former employee of Hangzhou Reprogenix Bioscience and is now affiliated with the Hangzhou Institute of Medicine, Chinese Academy of Sciences. Four coauthors have patent applications related to this work. Dr. Harlan is chief scientific officer and cofounder of Stability Health. He had no other disclosures.
 

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

A new approach to using stem cell–derived pancreatic islets has allowed a patient with type 1 diabetes (T1D) to come off insulin for 1 year.

The chemically induced pluripotent stem cell–derived islets came from the somatic cells of the patient, a 25-year-old woman who had lived for 11 years with unstable T1D with less than 50% time-in-target glucose range despite intensive insulin therapy. By 1 year following the transplantation of the cells into her abdomen, her glucose levels were nearly 100% in range, and her hemoglobin A1c had come down from 7.4%-8.0% to nondiabetic range (~5%).

Of note, she was already under immunosuppression for a prior liver transplant and remained on it throughout. There were no major safety concerns.

“We are very encouraged by the positive clinical findings seen in this first patient using this combination of technologies. These findings set a strong foundation for further development of stem cell–derived islet transplantation as a feasible treatment modality for diabetes,” study authors Soon Yi Liew, PhD, and Hongkui Deng, PhD, both of Peking University Health Science Center, Beijing, China, told this news organization in an email. Dr. Deng, the lead author, is the director of the university’s Institute of Stem Cell Research.

The findings were published in Cell.
 

What’s New With This Approach?

The use of the patient’s own cells is one of several ways in which this approach differs from other ongoing efforts in treating T1D with pluripotent stem cell–derived islets, such as those of the companies Vertex and Sernova, Dr. Liew and Dr. Deng explained.

Another difference is that “the patient-specific stem cell–derived islets used in this study were produced from induced pluripotent stem cells generated using chemical reprogramming, which is a nontransgenic approach to inducing pluripotent stem cells from somatic cells that uses only small molecules, different from the conventional method of viral transduction of transcription factors. ... Employing small molecules as reprogramming factors provides a greater degree of control — small molecules have defined structures easily manufactured and standardized, are not genome integrating, and are cost effective,” Dr. Liew and Dr. Deng said.

A third difference, they noted, is the placement of the stem cell–derived islets underneath the abdominal anterior rectus sheath of the patient, as opposed to the more commonly used hepatic portal vein. In addition to better ease of visualization, prior evidence suggested that this approach could lead to an improved engraftment and graft function and could circumvent graft loss from blood-mediated inflammatory responses associated with the liver site.

Moreover, they added, “to our knowledge, the rapidity with which insulin-independence was achieved post transplantation of stem cell–derived islets, 75 days post-transplantation, is also a first.”
 

Immunosuppression Remains a Challenge

Asked to comment, David M. Harlan, MD, the William and Doris Krupp professor of medicine and codirector of the Diabetes Center of Excellence at the University of Massachusetts Chan Medical School, Worcester, told this news organization, “on the one hand, it seems like a great breakthrough that you could take each individual cells and use those to make islets, but ... that process takes a long time, is very, very expensive, and then the T1D recipient still needs to be immunosuppressed. From a business point of view, I just don’t see it as getting any legs.”

Dr. Harlan, who had been involved in the islet transplantation field for several decades, pointed out that the additional autoimmunity of T1D poses a challenge beyond that of the body’s immune reaction to foreign tissue. “Because transplants have been around since the 1950s, we know a lot about how to prevent allogeneic rejection, from one person to another, but we know very little about how to prevent autoimmunity, so that’s still a very difficult nut to crack. I actually think the major effort should be focused on making the beta cells more hardy [via genetic modification] as opposed to focusing on the immune system. And there’s a lot of data to support that now, and that’s what we’re working on.”

Indeed, Dr. Liew and Dr. Deng said, “New immunomodulatory strategies to address graft longevity without immunosuppression remain to be established and tested. With reports of therapeutic efficacy of stem cell–derived islet transplantation such as with our study, stem cell–derived therapy without need for immunosuppression would be a meaningful next step in the treatment of this disease.”

The team has now performed the same procedure in two more patients and will report their data “in due course.”

Dr. Liew had no disclosures. Dr. Deng is a scientific adviser at Hangzhou Reprogenix Bioscience. Two coauthors are employees of Hangzhou Reprogenix Bioscience. Another is a former employee of Hangzhou Reprogenix Bioscience and is now affiliated with the Hangzhou Institute of Medicine, Chinese Academy of Sciences. Four coauthors have patent applications related to this work. Dr. Harlan is chief scientific officer and cofounder of Stability Health. He had no other disclosures.
 

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

In the treatment of patients with newly diagnosed multiple myeloma (MM) who are not eligible for stem cell transplant or are transplant-deferred, adding subcutaneous daratumumab to bortezomib/lenalidomide/dexamethasone (D-VRd) significantly improves minimal residual disease (MRD) outcomes among patients, the first results from the phase 3 CEPHEUS trial showed.

“CEPHEUS is the first phase 3 daratumumab trial with a primary endpoint of MRD negativity,” said first author Saad Z. Usmani, MD, of Memorial Sloan Kettering Cancer Center, New York City, in presenting late-breaking findings at the annual meeting of the International Myeloma Society in Rio de Janeiro, Brazil in late September.

“We found that adding daratumumab to VRd significantly improved depth and duration of response,” Dr. Usmani said. “[The quadruplet regimen] has the potential to improve clinical outcomes for transplant-ineligible or transplant-deferred patients with newly diagnosed MM who can tolerate bortezomib.”

For newly diagnosed patients with MM who are not eligible for a stem cell transplant, the triplet MAIA regimen of daratumumab, lenalidomide, and dexamethasone is a recommended standard of care, having shown a median overall survival of 7.5 years.

However, for those who are transplant eligible, the PERSEUS regimen of D-VRd followed by daratumumab/lenalidomide maintenance, has shown significant progress-free survival benefits compared with the standard of care.

For the ongoing, multicenter, open-label CEPHEUS study, Dr. Usmani and his colleagues investigated the efficacy of the quadruplet D-VRd regimen compared with VRd alone among newly diagnosed patients who are transplant-ineligible or deferred (not planned as initial therapy).

In the trial, 395 adult patients with transplant-ineligible or transplant-deferred newly diagnosed MM all were initially treated with eight 21-day cycles of VRd, followed by 28-day cycles of lenalidomide until disease progression.

The patients were then randomized to VRd either with (n = 197) or without (n = 198) subcutaneous daratumumab.

Those receiving daratumumab received the subcutaneous therapy weekly in cycles 1 and 2, every 3 weeks in cycles 3-8, and every 4 weeks in cycles 9 or more, until disease progression.

The patients had a median age of 70 years; 28.1% had International Staging System stage III disease, and 13.2% had high-risk cytogenetics.

For the primary endpoint, with a median follow-up of 58.7 months, those in the daratumumab group had a significantly higher rate of being MRD-negative (60.9%) than the VRd-only group (39.4%; odds ratio [OR], 2.37; P < .0001).

Likewise, progression-free survival (PFS) was significantly improved with the daratumumab regimen vs VRd (hazard ratio [HR], 0.57; P = .0005).

A median PFS was not reached for daratumumab plus VRd, compared with 52.6 months for the VRd group, while estimated 54-month PFS rates were 68.1% vs 49.5%, respectively.

A complete response or better was achieved among 81.2% in the daratumumab regimen vs 61.6% with VRd alone (P < .0001) and a sustained rate of MRD-negativity was achieved in 48.7% vs 26.3%, respectively (P < .0001).

There was a trend of overall survival in favor of daratumumab plus VRd (HR, 0.85), with an HR of 0.69 in a sensitivity analysis adjusting for deaths related to COVID-19.

Patients in the daratumumab group had a substantially longer median duration of treatment (56.3 months) than the VRd-only group (34.3 months), with the most common reason for treatment discontinuation being disease progression.

The benefit of daratumumab was generally consistent across the study’s prespecified subgroups, and the relative dose intensity of VRd was not affected by combination with daratumumab.

In terms of safety, treatment-emergent adverse events (TEAEs) were consistent with the known profile of daratumumab and VRd, with grade 5 TEAEs comparable between the two groups after adjusting for treatment exposure.

Quality of life, as measured by EORTC QLQ-C30 score, was improved in both arms over time, with no detriment related to treatment with daratumumab.

Of note, frail patients were not included in the trial. Asked in the Q and A why they were excluded, Dr. Usmani explained that “all of these options are wonderful for our patients, and we are entering a phase where quadruplet therapies will become a mainstay for majority of patients.

“But we have to be careful as we think about not overtreating patients or giving too many side effects of therapies, and that’s why it made sense for us to exclude the frail patients.”

Along those lines, he noted that a key concern in the CEPHEUS trial was tolerance of bortezomib.

“Peripheral sensory neuropathy tends to occur in about half of the patients receiving bortezomib, and about half of that number is grade 2 or higher,” he noted in an interview.

“In some patients, the symptoms do not completely resolve. [Therefore], in transplant-ineligible patients, quadruple regimens may be more relevant for the fit or intermediate-fit patients.”

He concluded that “the CEPHEUS trial compliments the MAIA regimen in supporting a daratumumab-based quadruplet or triplet standard-of-care option across transplant-ineligible patients and those deferring transplant.”

Commenting on the study, Philippe Moreau, MD, who is president of the IMS, noted that “the CEPHEUS study is important because [determining] the best treatment upfront for elderly patients is very important.”

“We need confirmation of the very good results achieved with the IMROZ trial, which showed an estimated 5-year PFS of 63.2%, said Dr. Moreau, professor of clinical hematology and head of the translational research program in hematology and oncology at the University Hospital of Nantes, France.

“If we can achieve the same results, we will have the confirmation that quadruplet is probably here to stay,” Dr. Moreau said.

Dr. Usmani disclosed relationships with Abbvie, Amgen, BioPharma, Bristol Myers Squibb, Celgene, GSK, Janssen, Merck, Pharmacyclics, Sanofi, Seattle Genetics, SkylineOx, and Takeda.
 

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

In the treatment of patients with newly diagnosed multiple myeloma (MM) who are not eligible for stem cell transplant or are transplant-deferred, adding subcutaneous daratumumab to bortezomib/lenalidomide/dexamethasone (D-VRd) significantly improves minimal residual disease (MRD) outcomes among patients, the first results from the phase 3 CEPHEUS trial showed.

“CEPHEUS is the first phase 3 daratumumab trial with a primary endpoint of MRD negativity,” said first author Saad Z. Usmani, MD, of Memorial Sloan Kettering Cancer Center, New York City, in presenting late-breaking findings at the annual meeting of the International Myeloma Society in Rio de Janeiro, Brazil in late September.

“We found that adding daratumumab to VRd significantly improved depth and duration of response,” Dr. Usmani said. “[The quadruplet regimen] has the potential to improve clinical outcomes for transplant-ineligible or transplant-deferred patients with newly diagnosed MM who can tolerate bortezomib.”

For newly diagnosed patients with MM who are not eligible for a stem cell transplant, the triplet MAIA regimen of daratumumab, lenalidomide, and dexamethasone is a recommended standard of care, having shown a median overall survival of 7.5 years.

However, for those who are transplant eligible, the PERSEUS regimen of D-VRd followed by daratumumab/lenalidomide maintenance, has shown significant progress-free survival benefits compared with the standard of care.

For the ongoing, multicenter, open-label CEPHEUS study, Dr. Usmani and his colleagues investigated the efficacy of the quadruplet D-VRd regimen compared with VRd alone among newly diagnosed patients who are transplant-ineligible or deferred (not planned as initial therapy).

In the trial, 395 adult patients with transplant-ineligible or transplant-deferred newly diagnosed MM all were initially treated with eight 21-day cycles of VRd, followed by 28-day cycles of lenalidomide until disease progression.

The patients were then randomized to VRd either with (n = 197) or without (n = 198) subcutaneous daratumumab.

Those receiving daratumumab received the subcutaneous therapy weekly in cycles 1 and 2, every 3 weeks in cycles 3-8, and every 4 weeks in cycles 9 or more, until disease progression.

The patients had a median age of 70 years; 28.1% had International Staging System stage III disease, and 13.2% had high-risk cytogenetics.

For the primary endpoint, with a median follow-up of 58.7 months, those in the daratumumab group had a significantly higher rate of being MRD-negative (60.9%) than the VRd-only group (39.4%; odds ratio [OR], 2.37; P < .0001).

Likewise, progression-free survival (PFS) was significantly improved with the daratumumab regimen vs VRd (hazard ratio [HR], 0.57; P = .0005).

A median PFS was not reached for daratumumab plus VRd, compared with 52.6 months for the VRd group, while estimated 54-month PFS rates were 68.1% vs 49.5%, respectively.

A complete response or better was achieved among 81.2% in the daratumumab regimen vs 61.6% with VRd alone (P < .0001) and a sustained rate of MRD-negativity was achieved in 48.7% vs 26.3%, respectively (P < .0001).

There was a trend of overall survival in favor of daratumumab plus VRd (HR, 0.85), with an HR of 0.69 in a sensitivity analysis adjusting for deaths related to COVID-19.

Patients in the daratumumab group had a substantially longer median duration of treatment (56.3 months) than the VRd-only group (34.3 months), with the most common reason for treatment discontinuation being disease progression.

The benefit of daratumumab was generally consistent across the study’s prespecified subgroups, and the relative dose intensity of VRd was not affected by combination with daratumumab.

In terms of safety, treatment-emergent adverse events (TEAEs) were consistent with the known profile of daratumumab and VRd, with grade 5 TEAEs comparable between the two groups after adjusting for treatment exposure.

Quality of life, as measured by EORTC QLQ-C30 score, was improved in both arms over time, with no detriment related to treatment with daratumumab.

Of note, frail patients were not included in the trial. Asked in the Q and A why they were excluded, Dr. Usmani explained that “all of these options are wonderful for our patients, and we are entering a phase where quadruplet therapies will become a mainstay for majority of patients.

“But we have to be careful as we think about not overtreating patients or giving too many side effects of therapies, and that’s why it made sense for us to exclude the frail patients.”

Along those lines, he noted that a key concern in the CEPHEUS trial was tolerance of bortezomib.

“Peripheral sensory neuropathy tends to occur in about half of the patients receiving bortezomib, and about half of that number is grade 2 or higher,” he noted in an interview.

“In some patients, the symptoms do not completely resolve. [Therefore], in transplant-ineligible patients, quadruple regimens may be more relevant for the fit or intermediate-fit patients.”

He concluded that “the CEPHEUS trial compliments the MAIA regimen in supporting a daratumumab-based quadruplet or triplet standard-of-care option across transplant-ineligible patients and those deferring transplant.”

Commenting on the study, Philippe Moreau, MD, who is president of the IMS, noted that “the CEPHEUS study is important because [determining] the best treatment upfront for elderly patients is very important.”

“We need confirmation of the very good results achieved with the IMROZ trial, which showed an estimated 5-year PFS of 63.2%, said Dr. Moreau, professor of clinical hematology and head of the translational research program in hematology and oncology at the University Hospital of Nantes, France.

“If we can achieve the same results, we will have the confirmation that quadruplet is probably here to stay,” Dr. Moreau said.

Dr. Usmani disclosed relationships with Abbvie, Amgen, BioPharma, Bristol Myers Squibb, Celgene, GSK, Janssen, Merck, Pharmacyclics, Sanofi, Seattle Genetics, SkylineOx, and Takeda.
 

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

In the treatment of patients with newly diagnosed multiple myeloma (MM) who are not eligible for stem cell transplant or are transplant-deferred, adding subcutaneous daratumumab to bortezomib/lenalidomide/dexamethasone (D-VRd) significantly improves minimal residual disease (MRD) outcomes among patients, the first results from the phase 3 CEPHEUS trial showed.

“CEPHEUS is the first phase 3 daratumumab trial with a primary endpoint of MRD negativity,” said first author Saad Z. Usmani, MD, of Memorial Sloan Kettering Cancer Center, New York City, in presenting late-breaking findings at the annual meeting of the International Myeloma Society in Rio de Janeiro, Brazil in late September.

“We found that adding daratumumab to VRd significantly improved depth and duration of response,” Dr. Usmani said. “[The quadruplet regimen] has the potential to improve clinical outcomes for transplant-ineligible or transplant-deferred patients with newly diagnosed MM who can tolerate bortezomib.”

For newly diagnosed patients with MM who are not eligible for a stem cell transplant, the triplet MAIA regimen of daratumumab, lenalidomide, and dexamethasone is a recommended standard of care, having shown a median overall survival of 7.5 years.

However, for those who are transplant eligible, the PERSEUS regimen of D-VRd followed by daratumumab/lenalidomide maintenance, has shown significant progress-free survival benefits compared with the standard of care.

For the ongoing, multicenter, open-label CEPHEUS study, Dr. Usmani and his colleagues investigated the efficacy of the quadruplet D-VRd regimen compared with VRd alone among newly diagnosed patients who are transplant-ineligible or deferred (not planned as initial therapy).

In the trial, 395 adult patients with transplant-ineligible or transplant-deferred newly diagnosed MM all were initially treated with eight 21-day cycles of VRd, followed by 28-day cycles of lenalidomide until disease progression.

The patients were then randomized to VRd either with (n = 197) or without (n = 198) subcutaneous daratumumab.

Those receiving daratumumab received the subcutaneous therapy weekly in cycles 1 and 2, every 3 weeks in cycles 3-8, and every 4 weeks in cycles 9 or more, until disease progression.

The patients had a median age of 70 years; 28.1% had International Staging System stage III disease, and 13.2% had high-risk cytogenetics.

For the primary endpoint, with a median follow-up of 58.7 months, those in the daratumumab group had a significantly higher rate of being MRD-negative (60.9%) than the VRd-only group (39.4%; odds ratio [OR], 2.37; P < .0001).

Likewise, progression-free survival (PFS) was significantly improved with the daratumumab regimen vs VRd (hazard ratio [HR], 0.57; P = .0005).

A median PFS was not reached for daratumumab plus VRd, compared with 52.6 months for the VRd group, while estimated 54-month PFS rates were 68.1% vs 49.5%, respectively.

A complete response or better was achieved among 81.2% in the daratumumab regimen vs 61.6% with VRd alone (P < .0001) and a sustained rate of MRD-negativity was achieved in 48.7% vs 26.3%, respectively (P < .0001).

There was a trend of overall survival in favor of daratumumab plus VRd (HR, 0.85), with an HR of 0.69 in a sensitivity analysis adjusting for deaths related to COVID-19.

Patients in the daratumumab group had a substantially longer median duration of treatment (56.3 months) than the VRd-only group (34.3 months), with the most common reason for treatment discontinuation being disease progression.

The benefit of daratumumab was generally consistent across the study’s prespecified subgroups, and the relative dose intensity of VRd was not affected by combination with daratumumab.

In terms of safety, treatment-emergent adverse events (TEAEs) were consistent with the known profile of daratumumab and VRd, with grade 5 TEAEs comparable between the two groups after adjusting for treatment exposure.

Quality of life, as measured by EORTC QLQ-C30 score, was improved in both arms over time, with no detriment related to treatment with daratumumab.

Of note, frail patients were not included in the trial. Asked in the Q and A why they were excluded, Dr. Usmani explained that “all of these options are wonderful for our patients, and we are entering a phase where quadruplet therapies will become a mainstay for majority of patients.

“But we have to be careful as we think about not overtreating patients or giving too many side effects of therapies, and that’s why it made sense for us to exclude the frail patients.”

Along those lines, he noted that a key concern in the CEPHEUS trial was tolerance of bortezomib.

“Peripheral sensory neuropathy tends to occur in about half of the patients receiving bortezomib, and about half of that number is grade 2 or higher,” he noted in an interview.

“In some patients, the symptoms do not completely resolve. [Therefore], in transplant-ineligible patients, quadruple regimens may be more relevant for the fit or intermediate-fit patients.”

He concluded that “the CEPHEUS trial compliments the MAIA regimen in supporting a daratumumab-based quadruplet or triplet standard-of-care option across transplant-ineligible patients and those deferring transplant.”

Commenting on the study, Philippe Moreau, MD, who is president of the IMS, noted that “the CEPHEUS study is important because [determining] the best treatment upfront for elderly patients is very important.”

“We need confirmation of the very good results achieved with the IMROZ trial, which showed an estimated 5-year PFS of 63.2%, said Dr. Moreau, professor of clinical hematology and head of the translational research program in hematology and oncology at the University Hospital of Nantes, France.

“If we can achieve the same results, we will have the confirmation that quadruplet is probably here to stay,” Dr. Moreau said.

Dr. Usmani disclosed relationships with Abbvie, Amgen, BioPharma, Bristol Myers Squibb, Celgene, GSK, Janssen, Merck, Pharmacyclics, Sanofi, Seattle Genetics, SkylineOx, and Takeda.
 

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

Newly issued guidelines for cancer screening in patients with dermatomyositis had 100% sensitivity in a single institution’s cohort, though most of the cancers found would have been detected with standard cancer screenings recommended for the general population, according to a research letter published in JAMA Dermatology.

“These early results emphasize the continued need to refine risk assessment and cancer screening for patients with dermatomyositis while balancing resource use and outcomes,” concluded Caroline J. Stone and her colleagues at the Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.

dermatology.cdlib.org/CC BY-SA 3.0/wikimedia

Patients with dermatomyositis have approximately a 4.7 times greater risk for cancer than those without it, according to a 2016 meta-analysis. Despite the well-established link between cancer and dermatomyositis, cancer in people with idiopathic inflammatory myopathies is commonly diagnosed at a later stage and is the leading cause of death in people with these conditions.
 

Guidelines First Presented in 2022 and Published in 2023

A wide variability in screening practices eventually led the International Myositis Assessment & Clinical Studies Group (IMACS) to present the first evidence-based and consensus-based guidelines for cancer screening of patients with idiopathic inflammatory myopathies, including those with dermatomyositis, at the 2022 annual meeting of the American College of Rheumatology and publish them in 2023 in Nature Reviews Rheumatology. The guidelines advise low-risk patients to undergo basic cancer screening with routine blood and urine studies, liver function tests, plain chest radiography, and age- and sex-appropriate cancer screening.

Intermediate- and high-risk patients are recommended to undergo enhanced screening that can include mammography, Pap tests, endoscopy/colonoscopy, pelvic and transvaginal ultrasonography, prostate-specific antigen or cancer antigen 125 blood tests, fecal occult blood tests, and CT of the neck, thorax, abdomen, and pelvis.

But because the guidelines are new, little evidence exists regarding their validation in real-world cohorts. Researchers, therefore, assessed the IMACS guidelines in 370 patients, aged 18-80 years, who visited the University of Pennsylvania rheumatology-dermatology specialty clinic between July 2008 and January 2024. All participants had dermatomyositis and at least 3 years of follow-up and were an average 48 years old. The vast majority were women (87%) and White participants (89%).

Most (68.6%) had myositis-specific autoantibody test results, one of the factors included in the guidelines for determining whether the patient should be classified as low, intermediate, or high risk. Other factors for risk stratification included myositis subtype, age at disease onset, and clinical features. About half (49.2%) had classic dermatomyositis, 42.4% had amyopathic dermatomyositis, 3.8% had juvenile dermatomyositis, 3.2% had hypomyopathic dermatomyositis, 0.8% had antisynthetase syndrome, and 0.5% had immune-mediated necrotizing myopathy.

Just over half the patients (54%) were classified as high risk, while 37.3% were classified as intermediate risk and 8.9% as low risk using the guidelines. Among the 18 patients (4.9%) with paraneoplastic dermatomyositis, 15 were classified as high risk and 3 as intermediate risk.

Of the patients diagnosed with cancer, 55% of cases were diagnosed about a year before their dermatomyositis diagnosis. In three patients, symptoms “suggestive of cancer at the time of dermatomyositis diagnosis, including lymphadenopathy and unexplained weight loss,” led to diagnostic testing that found an underlying cancer.

In the eight patients diagnosed with cancer after their dermatomyositis diagnosis, 75% of the cancers were identified during the first year of follow-up and 25% in the second year. Five were identified based on basic cancer screening and three on enhanced screening.

A total of 11 patients (3%) developed intravenous contrast allergies, and no other adverse events were reported to be associated with cancer screening, but the study was not designed to capture other types of adverse screening effects, such as cost, quality of life, or risk from radiation exposure.

The most common neoplasm identified was breast cancer, found in nine (50%) of the patients using mammography. Two patients had lung cancer identified with chest radiography and two had ovarian cancer identified with abdominal radiography and CT. The remaining five patients included one each with bladder cancer, papillary thyroid cancer, renal cell carcinoma, non-Hodgkin lymphoma, and adenocarcinoma with unknown primary.

The sensitivity of the guidelines in detecting cancer related to dermatomyositis was 100%, though the authors noted that the “IMACS risk-stratification scheme may overestimate cancer risk and encourage enhanced screening protocols of unclear benefit.” Most of the cancers found after dermatomyositis diagnosis were detected with routine age- and sex-related screening that already falls under basic cancer screening recommendations for the general population. Nonetheless, 90% of the participants fell into the intermediate- and high-risk groups, warranting a more comprehensive and costly enhanced screening protocol.
 

Will the Guidelines Lead to Overscreening? 

The 4.9% cancer prevalence is considerably lower than the typical 15%-25% prevalence among patients with dermatomyositis, but the findings, regardless, suggest the guidelines will lead to overscreening, wrote Andrea D. Maderal, MD, University of Miami Miller School of Medicine in Florida, and Alisa Femia, MD, New York University Grossman School of Medicine, New York City, in an accompanying editorial. Given that the median age in patients with cancer in the study was 58 years — 18 years older than the age cutoff for high-risk criteria — one way to refine the guidelines may be to increase the age for the high-risk category, they suggested.

“While these guidelines led to many ultimately unnecessary screening tests based on currently recommended designations of intermediate-risk and high-risk patients, these guidelines reflect a more conservative approach to screening than was previously performed,” Dr. Maderal and Dr. Femia wrote.

Jeff Gehlhausen, MD, PhD, an assistant professor of dermatology at Yale School of Medicine, New Haven, Connecticut, said he is not concerned about overscreening in patients, however, and is “very enthusiastic” about the findings.

“Patients are very anxious for good reason,” given the typical cancer prevalence of 25% in this population, he said in an interview. “I think therein lies the challenge — with that risk, what is ‘enough’ screening?” Yet this “incredibly impressive” study “provides real insights into the applicability of the IMACS screenings to our dermatomyositis management,” including relevance to his own patients. “Their findings are instructive for how to better evaluate these patients in a more mindful fashion,” he said, and they are particularly welcome, given how widely variable practice has historically been before the guidelines were issued.

“This question has been an outstanding one for decades, and nearly every doctor has a different answer,” Dr. Gehlhausen said. “The introduction of the guidelines alone are now much more actionable with this study, and that’s why it’s such an important one for our community.”

Benedict Wu, DO, PhD, director of Inpatient Dermatology and an assistant professor at Montefiore Einstein and a member of the Montefiore Einstein Comprehensive Cancer Center in New York City, similarly regarded the findings as reassuring, though he was surprised at the low prevalence of cancer in the patients.

“The most reassuring finding was that the detection of most malignancies was possible by using routine age- and sex-related screening combined with basic cancer screening,” Wu said in an interview. “Basic cancer screening can reduce costs while keeping patients safe.”

He also found it reassuring that all the paraneoplastic dermatomyositis was in intermediate- or high-risk patients, and while he does not see the IMACS guidelines as overestimating cancer risk, he does think “the risk stratification and recommended screening tests could be revised to be less ‘aggressive.’ ” 

The overall low rate of cancer in the group “calls into question the need for stringent and annual cancer screening,” he said. “In this large cohort of patients, the fact that malignancy was detected within 2 years of dermatomyositis diagnosis will help guide us with long-term screening recommendations.”

Despite the study’s small size and single-center design, the demographics of the patients nearly represents exactly what is found in the United States more broadly, Wu noted. He also drew attention to how many patients lacked the myositis antibody profile performed, and he agreed with the authors that more extensive and prospective studies need to be conducted. He also emphasized the need to keep in mind that “the primary goal of dermatomyositis management should focus on controlling/reducing the disease burden.”

The research was funded by the National Institutes of Health and the US Department of Veterans Affairs. The authors had no disclosures. Dr. Maderal reported personal fees from argenx. No disclosures were noted for Dr. Gehlhausen and Dr. Wu.

A version of this article appeared on Medscape.com.

Newly issued guidelines for cancer screening in patients with dermatomyositis had 100% sensitivity in a single institution’s cohort, though most of the cancers found would have been detected with standard cancer screenings recommended for the general population, according to a research letter published in JAMA Dermatology.

“These early results emphasize the continued need to refine risk assessment and cancer screening for patients with dermatomyositis while balancing resource use and outcomes,” concluded Caroline J. Stone and her colleagues at the Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.

dermatology.cdlib.org/CC BY-SA 3.0/wikimedia

Patients with dermatomyositis have approximately a 4.7 times greater risk for cancer than those without it, according to a 2016 meta-analysis. Despite the well-established link between cancer and dermatomyositis, cancer in people with idiopathic inflammatory myopathies is commonly diagnosed at a later stage and is the leading cause of death in people with these conditions.
 

Guidelines First Presented in 2022 and Published in 2023

A wide variability in screening practices eventually led the International Myositis Assessment & Clinical Studies Group (IMACS) to present the first evidence-based and consensus-based guidelines for cancer screening of patients with idiopathic inflammatory myopathies, including those with dermatomyositis, at the 2022 annual meeting of the American College of Rheumatology and publish them in 2023 in Nature Reviews Rheumatology. The guidelines advise low-risk patients to undergo basic cancer screening with routine blood and urine studies, liver function tests, plain chest radiography, and age- and sex-appropriate cancer screening.

Intermediate- and high-risk patients are recommended to undergo enhanced screening that can include mammography, Pap tests, endoscopy/colonoscopy, pelvic and transvaginal ultrasonography, prostate-specific antigen or cancer antigen 125 blood tests, fecal occult blood tests, and CT of the neck, thorax, abdomen, and pelvis.

But because the guidelines are new, little evidence exists regarding their validation in real-world cohorts. Researchers, therefore, assessed the IMACS guidelines in 370 patients, aged 18-80 years, who visited the University of Pennsylvania rheumatology-dermatology specialty clinic between July 2008 and January 2024. All participants had dermatomyositis and at least 3 years of follow-up and were an average 48 years old. The vast majority were women (87%) and White participants (89%).

Most (68.6%) had myositis-specific autoantibody test results, one of the factors included in the guidelines for determining whether the patient should be classified as low, intermediate, or high risk. Other factors for risk stratification included myositis subtype, age at disease onset, and clinical features. About half (49.2%) had classic dermatomyositis, 42.4% had amyopathic dermatomyositis, 3.8% had juvenile dermatomyositis, 3.2% had hypomyopathic dermatomyositis, 0.8% had antisynthetase syndrome, and 0.5% had immune-mediated necrotizing myopathy.

Just over half the patients (54%) were classified as high risk, while 37.3% were classified as intermediate risk and 8.9% as low risk using the guidelines. Among the 18 patients (4.9%) with paraneoplastic dermatomyositis, 15 were classified as high risk and 3 as intermediate risk.

Of the patients diagnosed with cancer, 55% of cases were diagnosed about a year before their dermatomyositis diagnosis. In three patients, symptoms “suggestive of cancer at the time of dermatomyositis diagnosis, including lymphadenopathy and unexplained weight loss,” led to diagnostic testing that found an underlying cancer.

In the eight patients diagnosed with cancer after their dermatomyositis diagnosis, 75% of the cancers were identified during the first year of follow-up and 25% in the second year. Five were identified based on basic cancer screening and three on enhanced screening.

A total of 11 patients (3%) developed intravenous contrast allergies, and no other adverse events were reported to be associated with cancer screening, but the study was not designed to capture other types of adverse screening effects, such as cost, quality of life, or risk from radiation exposure.

The most common neoplasm identified was breast cancer, found in nine (50%) of the patients using mammography. Two patients had lung cancer identified with chest radiography and two had ovarian cancer identified with abdominal radiography and CT. The remaining five patients included one each with bladder cancer, papillary thyroid cancer, renal cell carcinoma, non-Hodgkin lymphoma, and adenocarcinoma with unknown primary.

The sensitivity of the guidelines in detecting cancer related to dermatomyositis was 100%, though the authors noted that the “IMACS risk-stratification scheme may overestimate cancer risk and encourage enhanced screening protocols of unclear benefit.” Most of the cancers found after dermatomyositis diagnosis were detected with routine age- and sex-related screening that already falls under basic cancer screening recommendations for the general population. Nonetheless, 90% of the participants fell into the intermediate- and high-risk groups, warranting a more comprehensive and costly enhanced screening protocol.
 

Will the Guidelines Lead to Overscreening? 

The 4.9% cancer prevalence is considerably lower than the typical 15%-25% prevalence among patients with dermatomyositis, but the findings, regardless, suggest the guidelines will lead to overscreening, wrote Andrea D. Maderal, MD, University of Miami Miller School of Medicine in Florida, and Alisa Femia, MD, New York University Grossman School of Medicine, New York City, in an accompanying editorial. Given that the median age in patients with cancer in the study was 58 years — 18 years older than the age cutoff for high-risk criteria — one way to refine the guidelines may be to increase the age for the high-risk category, they suggested.

“While these guidelines led to many ultimately unnecessary screening tests based on currently recommended designations of intermediate-risk and high-risk patients, these guidelines reflect a more conservative approach to screening than was previously performed,” Dr. Maderal and Dr. Femia wrote.

Jeff Gehlhausen, MD, PhD, an assistant professor of dermatology at Yale School of Medicine, New Haven, Connecticut, said he is not concerned about overscreening in patients, however, and is “very enthusiastic” about the findings.

“Patients are very anxious for good reason,” given the typical cancer prevalence of 25% in this population, he said in an interview. “I think therein lies the challenge — with that risk, what is ‘enough’ screening?” Yet this “incredibly impressive” study “provides real insights into the applicability of the IMACS screenings to our dermatomyositis management,” including relevance to his own patients. “Their findings are instructive for how to better evaluate these patients in a more mindful fashion,” he said, and they are particularly welcome, given how widely variable practice has historically been before the guidelines were issued.

“This question has been an outstanding one for decades, and nearly every doctor has a different answer,” Dr. Gehlhausen said. “The introduction of the guidelines alone are now much more actionable with this study, and that’s why it’s such an important one for our community.”

Benedict Wu, DO, PhD, director of Inpatient Dermatology and an assistant professor at Montefiore Einstein and a member of the Montefiore Einstein Comprehensive Cancer Center in New York City, similarly regarded the findings as reassuring, though he was surprised at the low prevalence of cancer in the patients.

“The most reassuring finding was that the detection of most malignancies was possible by using routine age- and sex-related screening combined with basic cancer screening,” Wu said in an interview. “Basic cancer screening can reduce costs while keeping patients safe.”

He also found it reassuring that all the paraneoplastic dermatomyositis was in intermediate- or high-risk patients, and while he does not see the IMACS guidelines as overestimating cancer risk, he does think “the risk stratification and recommended screening tests could be revised to be less ‘aggressive.’ ” 

The overall low rate of cancer in the group “calls into question the need for stringent and annual cancer screening,” he said. “In this large cohort of patients, the fact that malignancy was detected within 2 years of dermatomyositis diagnosis will help guide us with long-term screening recommendations.”

Despite the study’s small size and single-center design, the demographics of the patients nearly represents exactly what is found in the United States more broadly, Wu noted. He also drew attention to how many patients lacked the myositis antibody profile performed, and he agreed with the authors that more extensive and prospective studies need to be conducted. He also emphasized the need to keep in mind that “the primary goal of dermatomyositis management should focus on controlling/reducing the disease burden.”

The research was funded by the National Institutes of Health and the US Department of Veterans Affairs. The authors had no disclosures. Dr. Maderal reported personal fees from argenx. No disclosures were noted for Dr. Gehlhausen and Dr. Wu.

A version of this article appeared on Medscape.com.

Newly issued guidelines for cancer screening in patients with dermatomyositis had 100% sensitivity in a single institution’s cohort, though most of the cancers found would have been detected with standard cancer screenings recommended for the general population, according to a research letter published in JAMA Dermatology.

“These early results emphasize the continued need to refine risk assessment and cancer screening for patients with dermatomyositis while balancing resource use and outcomes,” concluded Caroline J. Stone and her colleagues at the Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.

dermatology.cdlib.org/CC BY-SA 3.0/wikimedia

Patients with dermatomyositis have approximately a 4.7 times greater risk for cancer than those without it, according to a 2016 meta-analysis. Despite the well-established link between cancer and dermatomyositis, cancer in people with idiopathic inflammatory myopathies is commonly diagnosed at a later stage and is the leading cause of death in people with these conditions.
 

Guidelines First Presented in 2022 and Published in 2023

A wide variability in screening practices eventually led the International Myositis Assessment & Clinical Studies Group (IMACS) to present the first evidence-based and consensus-based guidelines for cancer screening of patients with idiopathic inflammatory myopathies, including those with dermatomyositis, at the 2022 annual meeting of the American College of Rheumatology and publish them in 2023 in Nature Reviews Rheumatology. The guidelines advise low-risk patients to undergo basic cancer screening with routine blood and urine studies, liver function tests, plain chest radiography, and age- and sex-appropriate cancer screening.

Intermediate- and high-risk patients are recommended to undergo enhanced screening that can include mammography, Pap tests, endoscopy/colonoscopy, pelvic and transvaginal ultrasonography, prostate-specific antigen or cancer antigen 125 blood tests, fecal occult blood tests, and CT of the neck, thorax, abdomen, and pelvis.

But because the guidelines are new, little evidence exists regarding their validation in real-world cohorts. Researchers, therefore, assessed the IMACS guidelines in 370 patients, aged 18-80 years, who visited the University of Pennsylvania rheumatology-dermatology specialty clinic between July 2008 and January 2024. All participants had dermatomyositis and at least 3 years of follow-up and were an average 48 years old. The vast majority were women (87%) and White participants (89%).

Most (68.6%) had myositis-specific autoantibody test results, one of the factors included in the guidelines for determining whether the patient should be classified as low, intermediate, or high risk. Other factors for risk stratification included myositis subtype, age at disease onset, and clinical features. About half (49.2%) had classic dermatomyositis, 42.4% had amyopathic dermatomyositis, 3.8% had juvenile dermatomyositis, 3.2% had hypomyopathic dermatomyositis, 0.8% had antisynthetase syndrome, and 0.5% had immune-mediated necrotizing myopathy.

Just over half the patients (54%) were classified as high risk, while 37.3% were classified as intermediate risk and 8.9% as low risk using the guidelines. Among the 18 patients (4.9%) with paraneoplastic dermatomyositis, 15 were classified as high risk and 3 as intermediate risk.

Of the patients diagnosed with cancer, 55% of cases were diagnosed about a year before their dermatomyositis diagnosis. In three patients, symptoms “suggestive of cancer at the time of dermatomyositis diagnosis, including lymphadenopathy and unexplained weight loss,” led to diagnostic testing that found an underlying cancer.

In the eight patients diagnosed with cancer after their dermatomyositis diagnosis, 75% of the cancers were identified during the first year of follow-up and 25% in the second year. Five were identified based on basic cancer screening and three on enhanced screening.

A total of 11 patients (3%) developed intravenous contrast allergies, and no other adverse events were reported to be associated with cancer screening, but the study was not designed to capture other types of adverse screening effects, such as cost, quality of life, or risk from radiation exposure.

The most common neoplasm identified was breast cancer, found in nine (50%) of the patients using mammography. Two patients had lung cancer identified with chest radiography and two had ovarian cancer identified with abdominal radiography and CT. The remaining five patients included one each with bladder cancer, papillary thyroid cancer, renal cell carcinoma, non-Hodgkin lymphoma, and adenocarcinoma with unknown primary.

The sensitivity of the guidelines in detecting cancer related to dermatomyositis was 100%, though the authors noted that the “IMACS risk-stratification scheme may overestimate cancer risk and encourage enhanced screening protocols of unclear benefit.” Most of the cancers found after dermatomyositis diagnosis were detected with routine age- and sex-related screening that already falls under basic cancer screening recommendations for the general population. Nonetheless, 90% of the participants fell into the intermediate- and high-risk groups, warranting a more comprehensive and costly enhanced screening protocol.
 

Will the Guidelines Lead to Overscreening? 

The 4.9% cancer prevalence is considerably lower than the typical 15%-25% prevalence among patients with dermatomyositis, but the findings, regardless, suggest the guidelines will lead to overscreening, wrote Andrea D. Maderal, MD, University of Miami Miller School of Medicine in Florida, and Alisa Femia, MD, New York University Grossman School of Medicine, New York City, in an accompanying editorial. Given that the median age in patients with cancer in the study was 58 years — 18 years older than the age cutoff for high-risk criteria — one way to refine the guidelines may be to increase the age for the high-risk category, they suggested.

“While these guidelines led to many ultimately unnecessary screening tests based on currently recommended designations of intermediate-risk and high-risk patients, these guidelines reflect a more conservative approach to screening than was previously performed,” Dr. Maderal and Dr. Femia wrote.

Jeff Gehlhausen, MD, PhD, an assistant professor of dermatology at Yale School of Medicine, New Haven, Connecticut, said he is not concerned about overscreening in patients, however, and is “very enthusiastic” about the findings.

“Patients are very anxious for good reason,” given the typical cancer prevalence of 25% in this population, he said in an interview. “I think therein lies the challenge — with that risk, what is ‘enough’ screening?” Yet this “incredibly impressive” study “provides real insights into the applicability of the IMACS screenings to our dermatomyositis management,” including relevance to his own patients. “Their findings are instructive for how to better evaluate these patients in a more mindful fashion,” he said, and they are particularly welcome, given how widely variable practice has historically been before the guidelines were issued.

“This question has been an outstanding one for decades, and nearly every doctor has a different answer,” Dr. Gehlhausen said. “The introduction of the guidelines alone are now much more actionable with this study, and that’s why it’s such an important one for our community.”

Benedict Wu, DO, PhD, director of Inpatient Dermatology and an assistant professor at Montefiore Einstein and a member of the Montefiore Einstein Comprehensive Cancer Center in New York City, similarly regarded the findings as reassuring, though he was surprised at the low prevalence of cancer in the patients.

“The most reassuring finding was that the detection of most malignancies was possible by using routine age- and sex-related screening combined with basic cancer screening,” Wu said in an interview. “Basic cancer screening can reduce costs while keeping patients safe.”

He also found it reassuring that all the paraneoplastic dermatomyositis was in intermediate- or high-risk patients, and while he does not see the IMACS guidelines as overestimating cancer risk, he does think “the risk stratification and recommended screening tests could be revised to be less ‘aggressive.’ ” 

The overall low rate of cancer in the group “calls into question the need for stringent and annual cancer screening,” he said. “In this large cohort of patients, the fact that malignancy was detected within 2 years of dermatomyositis diagnosis will help guide us with long-term screening recommendations.”

Despite the study’s small size and single-center design, the demographics of the patients nearly represents exactly what is found in the United States more broadly, Wu noted. He also drew attention to how many patients lacked the myositis antibody profile performed, and he agreed with the authors that more extensive and prospective studies need to be conducted. He also emphasized the need to keep in mind that “the primary goal of dermatomyositis management should focus on controlling/reducing the disease burden.”

The research was funded by the National Institutes of Health and the US Department of Veterans Affairs. The authors had no disclosures. Dr. Maderal reported personal fees from argenx. No disclosures were noted for Dr. Gehlhausen and Dr. Wu.

A version of this article appeared on Medscape.com.

TOPLINE:

Home-based phototherapy for plaque and guttate psoriasis is as effective as office-based phototherapy, according to results of the randomized Light Treatment Effectiveness study.

METHODOLOGY:

• The pragmatic, investigator-initiated, open-label, noninferiority, randomized trial compared the effectiveness of 12 weeks of treatment with narrow-band ultraviolet B phototherapy administered at home (n = 393) vs at the doctor’s office (n = 390).
• Overall, 783 patients with plaque or guttate psoriasis (mean age, 48 years; 48% women) were enrolled at 42 academic and private clinical dermatology practices in the United States from March 1, 2019, to December 4, 2023, and were followed up through June 2024. At baseline, the mean Physician Global Assessment (PGA) and the mean Dermatology Life Quality Index (DLQI) scores were 2.7 and 12.2, respectively.
• The two co-primary endpoints were a PGA score ≤ 1 indicating clear or almost clear skin and a DLQI score ≤ 5.

TAKEAWAY:

• At 12 weeks, a PGA score ≤ 1 was achieved in 32.8% of patients using home-based phototherapy and in 25.6% of those who received office-based phototherapy (P < .001).
• At 12 weeks, a DLQI score ≤ 5 was achieved in 52.4% and 33.6% of home- and office-treated patients, respectively (P < .001).
• Similar benefits were seen across all Fitzpatrick skin types.
• A higher percentage of patients were adherent to home-based (51.4%) vs office-based (15.9%) phototherapy (P < .001).

IN PRACTICE:

“These data support the use of home phototherapy as a first-line treatment option for psoriasis,” and “efforts are needed to make home and office phototherapy more available to patients,” said the study’s lead author.

SOURCE:

Joel M. Gelfand, MD, director of the Psoriasis and Phototherapy Treatment Center at the University of Pennsylvania, Philadelphia, presented the findings at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis meeting during the annual meeting of the European Academy of Dermatology and Venereology, with simultaneous publication in JAMA Dermatology.

LIMITATIONS:

This was an open-label trial and because of its pragmatic design, outcome data were missing. The cost of the home-based phototherapy equipment used in the study was $6040.88, which was mostly covered by Medicare, but direct costs to patients may have varied depending on their insurance plan.

DISCLOSURES:

The Patient-Centered Outcomes Research Institute funded the study. Daavlin provided and shipped machines for home-based phototherapy to patients at no cost. Dr. Gelfand disclosed serving as a consultant for AbbVie, Artax, Bristol-Myers Squibb, Boehringer Ingelheim, Celldex, and other companies. The full list of author disclosures can be found in the published study.

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

TOPLINE:

Home-based phototherapy for plaque and guttate psoriasis is as effective as office-based phototherapy, according to results of the randomized Light Treatment Effectiveness study.

METHODOLOGY:

• The pragmatic, investigator-initiated, open-label, noninferiority, randomized trial compared the effectiveness of 12 weeks of treatment with narrow-band ultraviolet B phototherapy administered at home (n = 393) vs at the doctor’s office (n = 390).
• Overall, 783 patients with plaque or guttate psoriasis (mean age, 48 years; 48% women) were enrolled at 42 academic and private clinical dermatology practices in the United States from March 1, 2019, to December 4, 2023, and were followed up through June 2024. At baseline, the mean Physician Global Assessment (PGA) and the mean Dermatology Life Quality Index (DLQI) scores were 2.7 and 12.2, respectively.
• The two co-primary endpoints were a PGA score ≤ 1 indicating clear or almost clear skin and a DLQI score ≤ 5.

TAKEAWAY:

• At 12 weeks, a PGA score ≤ 1 was achieved in 32.8% of patients using home-based phototherapy and in 25.6% of those who received office-based phototherapy (P < .001).
• At 12 weeks, a DLQI score ≤ 5 was achieved in 52.4% and 33.6% of home- and office-treated patients, respectively (P < .001).
• Similar benefits were seen across all Fitzpatrick skin types.
• A higher percentage of patients were adherent to home-based (51.4%) vs office-based (15.9%) phototherapy (P < .001).

IN PRACTICE:

“These data support the use of home phototherapy as a first-line treatment option for psoriasis,” and “efforts are needed to make home and office phototherapy more available to patients,” said the study’s lead author.

SOURCE:

Joel M. Gelfand, MD, director of the Psoriasis and Phototherapy Treatment Center at the University of Pennsylvania, Philadelphia, presented the findings at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis meeting during the annual meeting of the European Academy of Dermatology and Venereology, with simultaneous publication in JAMA Dermatology.

LIMITATIONS:

This was an open-label trial and because of its pragmatic design, outcome data were missing. The cost of the home-based phototherapy equipment used in the study was $6040.88, which was mostly covered by Medicare, but direct costs to patients may have varied depending on their insurance plan.

DISCLOSURES:

The Patient-Centered Outcomes Research Institute funded the study. Daavlin provided and shipped machines for home-based phototherapy to patients at no cost. Dr. Gelfand disclosed serving as a consultant for AbbVie, Artax, Bristol-Myers Squibb, Boehringer Ingelheim, Celldex, and other companies. The full list of author disclosures can be found in the published study.

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

TOPLINE:

Home-based phototherapy for plaque and guttate psoriasis is as effective as office-based phototherapy, according to results of the randomized Light Treatment Effectiveness study.

METHODOLOGY:

• The pragmatic, investigator-initiated, open-label, noninferiority, randomized trial compared the effectiveness of 12 weeks of treatment with narrow-band ultraviolet B phototherapy administered at home (n = 393) vs at the doctor’s office (n = 390).
• Overall, 783 patients with plaque or guttate psoriasis (mean age, 48 years; 48% women) were enrolled at 42 academic and private clinical dermatology practices in the United States from March 1, 2019, to December 4, 2023, and were followed up through June 2024. At baseline, the mean Physician Global Assessment (PGA) and the mean Dermatology Life Quality Index (DLQI) scores were 2.7 and 12.2, respectively.
• The two co-primary endpoints were a PGA score ≤ 1 indicating clear or almost clear skin and a DLQI score ≤ 5.

TAKEAWAY:

• At 12 weeks, a PGA score ≤ 1 was achieved in 32.8% of patients using home-based phototherapy and in 25.6% of those who received office-based phototherapy (P < .001).
• At 12 weeks, a DLQI score ≤ 5 was achieved in 52.4% and 33.6% of home- and office-treated patients, respectively (P < .001).
• Similar benefits were seen across all Fitzpatrick skin types.
• A higher percentage of patients were adherent to home-based (51.4%) vs office-based (15.9%) phototherapy (P < .001).

IN PRACTICE:

“These data support the use of home phototherapy as a first-line treatment option for psoriasis,” and “efforts are needed to make home and office phototherapy more available to patients,” said the study’s lead author.

SOURCE:

Joel M. Gelfand, MD, director of the Psoriasis and Phototherapy Treatment Center at the University of Pennsylvania, Philadelphia, presented the findings at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis meeting during the annual meeting of the European Academy of Dermatology and Venereology, with simultaneous publication in JAMA Dermatology.

LIMITATIONS:

This was an open-label trial and because of its pragmatic design, outcome data were missing. The cost of the home-based phototherapy equipment used in the study was $6040.88, which was mostly covered by Medicare, but direct costs to patients may have varied depending on their insurance plan.

DISCLOSURES:

The Patient-Centered Outcomes Research Institute funded the study. Daavlin provided and shipped machines for home-based phototherapy to patients at no cost. Dr. Gelfand disclosed serving as a consultant for AbbVie, Artax, Bristol-Myers Squibb, Boehringer Ingelheim, Celldex, and other companies. The full list of author disclosures can be found in the published study.

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

DUBLIN – As healthcare systems across Europe deal with an increasing prevalence of cognitive impairment, family doctors are emerging as key players in assessing and supporting patients’ decision-making capacities. 

This was a central theme at the 29th WONCA Europe Conference, where the European Young Family Doctors Movement (EYFDM) presented insights from a project conducted across Europe, involving young general practitioners who participated in workshops held in multiple countries.

“Family doctors are the linchpin in these decisions,” said Alina Zidaru, MD, from the Irish College of Physicians, Dublin. “They understand the patient’s history, build long-term relationships, and are best positioned to ensure that decisions reflect the patient’s values, not just what the law or the family might say.”

Dr. Zidaru and her colleague, Nick Mamo, MD, member of EYFDM in Glasgow, Scotland, emphasized the central role family doctors play in ensuring that patient rights and preferences are respected, regardless of their cognitive state. They are often the first to identify cognitive impairments and must carefully navigate the legal and ethical landscape of decision-making support.

“Often, we focus too much on avoiding harm and overlook the principle of autonomy,” said Dr. Mamo. “But it’s essential to give patients the right to make their own decisions, even when those decisions might seem unwise to us.”
 

The Case of Jay

Dr. Zidaru said: “We’ve conducted workshops in Brussels, Vienna, and Sydney, focusing on how to build habits that support patients. We presented real-life cases, like Jay, a 43-year-old man with trisomy and a moderate intellectual disability who must decide whether to undergo surgery for a hernia. The most significant challenge was ensuring continuity of care and respecting his autonomy, despite cognitive limitations.”

Jay’s case illustrates the complex ethical dilemmas faced by family doctors when balancing autonomy with patient safety. In many cases, cognitive impairments raise concerns about whether a patient can make decisions independently. 

During the session, the audience was asked to share their thoughts on the case and to indicate whether they would allow Jay to make his own decision, and if they felt confident in assessing his cognitive capacity. The responses revealed a range of mixed feelings. 
 

Legal and Cultural Variations Across Europe

The session also explored how different European countries approach decision-making for cognitively impaired individuals. A clear divide exists between nations that give family members automatic decision-making rights and those that require legal appointments. 

In the United Kingdom, the Mental Capacity Act 2005 presumes capacity unless proven otherwise. Family doctors can assess patients’ decision-making abilities using any validated tool they find suitable. They should also aim to ensure that decisions are made in the patient’s best interests if they lack capacity. Family members only have legal authority if appointed through formal means, such as a lasting power of attorney.

In Spain and Italy, functional assessments are performed when patients retain decision-making authority in areas where they demonstrate competence. Legal guardianship can be appointed by the courts, sometimes limited to specific areas, but it is intended to support rather than replace the patient’s autonomy. 

In France and Portugal, guardianship may be implemented in specific domains, but the patient’s ability to participate in decisions is always prioritized. 

In Turkey, according to Turkish general practitioners in the audience, the courts and close family members often share the decision-making responsibility.

Dr. Zidaru added that Ireland’s Assisted Decision-Making (Capacity) Act 2015 introduced significant changes to how cognitive impairment is managed there. “Ireland adopted a standardized functional test of capacity, used by any doctor. A person can still make decisions as long as they understand, retain, and weigh the information needed to make that choice. If their capacity diminishes, a decision-making assistant, co–decision-maker, or representative can be appointed, but the patient’s will and preferences always come first.”
 

Family Doctors, a Growing Responsibility

“It’s not just about the legal framework: it’s about cultural awareness and early communication,” added Dr. Mamo. “We have to ask ourselves: Do patients have the right to make bad decisions? And how do we, as family doctors, respect that while still ensuring their safety?”

The session concluded with a discussion on how the role of family doctors in decision-making for cognitively impaired patients will evolve as populations age and the incidence of conditions like dementia increases. The workload is rising, and the need for clear, consistent guidelines is critical.

“Family doctors will continue to play a central role in managing these challenges,” Dr. Zidaru emphasized. “But we need more resources, more education, and more support to ensure we can respect patient autonomy without compromising their well-being.”

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

DUBLIN – As healthcare systems across Europe deal with an increasing prevalence of cognitive impairment, family doctors are emerging as key players in assessing and supporting patients’ decision-making capacities. 

This was a central theme at the 29th WONCA Europe Conference, where the European Young Family Doctors Movement (EYFDM) presented insights from a project conducted across Europe, involving young general practitioners who participated in workshops held in multiple countries.

“Family doctors are the linchpin in these decisions,” said Alina Zidaru, MD, from the Irish College of Physicians, Dublin. “They understand the patient’s history, build long-term relationships, and are best positioned to ensure that decisions reflect the patient’s values, not just what the law or the family might say.”

Dr. Zidaru and her colleague, Nick Mamo, MD, member of EYFDM in Glasgow, Scotland, emphasized the central role family doctors play in ensuring that patient rights and preferences are respected, regardless of their cognitive state. They are often the first to identify cognitive impairments and must carefully navigate the legal and ethical landscape of decision-making support.

“Often, we focus too much on avoiding harm and overlook the principle of autonomy,” said Dr. Mamo. “But it’s essential to give patients the right to make their own decisions, even when those decisions might seem unwise to us.”
 

The Case of Jay

Dr. Zidaru said: “We’ve conducted workshops in Brussels, Vienna, and Sydney, focusing on how to build habits that support patients. We presented real-life cases, like Jay, a 43-year-old man with trisomy and a moderate intellectual disability who must decide whether to undergo surgery for a hernia. The most significant challenge was ensuring continuity of care and respecting his autonomy, despite cognitive limitations.”

Jay’s case illustrates the complex ethical dilemmas faced by family doctors when balancing autonomy with patient safety. In many cases, cognitive impairments raise concerns about whether a patient can make decisions independently. 

During the session, the audience was asked to share their thoughts on the case and to indicate whether they would allow Jay to make his own decision, and if they felt confident in assessing his cognitive capacity. The responses revealed a range of mixed feelings. 
 

Legal and Cultural Variations Across Europe

The session also explored how different European countries approach decision-making for cognitively impaired individuals. A clear divide exists between nations that give family members automatic decision-making rights and those that require legal appointments. 

In the United Kingdom, the Mental Capacity Act 2005 presumes capacity unless proven otherwise. Family doctors can assess patients’ decision-making abilities using any validated tool they find suitable. They should also aim to ensure that decisions are made in the patient’s best interests if they lack capacity. Family members only have legal authority if appointed through formal means, such as a lasting power of attorney.

In Spain and Italy, functional assessments are performed when patients retain decision-making authority in areas where they demonstrate competence. Legal guardianship can be appointed by the courts, sometimes limited to specific areas, but it is intended to support rather than replace the patient’s autonomy. 

In France and Portugal, guardianship may be implemented in specific domains, but the patient’s ability to participate in decisions is always prioritized. 

In Turkey, according to Turkish general practitioners in the audience, the courts and close family members often share the decision-making responsibility.

Dr. Zidaru added that Ireland’s Assisted Decision-Making (Capacity) Act 2015 introduced significant changes to how cognitive impairment is managed there. “Ireland adopted a standardized functional test of capacity, used by any doctor. A person can still make decisions as long as they understand, retain, and weigh the information needed to make that choice. If their capacity diminishes, a decision-making assistant, co–decision-maker, or representative can be appointed, but the patient’s will and preferences always come first.”
 

Family Doctors, a Growing Responsibility

“It’s not just about the legal framework: it’s about cultural awareness and early communication,” added Dr. Mamo. “We have to ask ourselves: Do patients have the right to make bad decisions? And how do we, as family doctors, respect that while still ensuring their safety?”

The session concluded with a discussion on how the role of family doctors in decision-making for cognitively impaired patients will evolve as populations age and the incidence of conditions like dementia increases. The workload is rising, and the need for clear, consistent guidelines is critical.

“Family doctors will continue to play a central role in managing these challenges,” Dr. Zidaru emphasized. “But we need more resources, more education, and more support to ensure we can respect patient autonomy without compromising their well-being.”

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

DUBLIN – As healthcare systems across Europe deal with an increasing prevalence of cognitive impairment, family doctors are emerging as key players in assessing and supporting patients’ decision-making capacities. 

This was a central theme at the 29th WONCA Europe Conference, where the European Young Family Doctors Movement (EYFDM) presented insights from a project conducted across Europe, involving young general practitioners who participated in workshops held in multiple countries.

“Family doctors are the linchpin in these decisions,” said Alina Zidaru, MD, from the Irish College of Physicians, Dublin. “They understand the patient’s history, build long-term relationships, and are best positioned to ensure that decisions reflect the patient’s values, not just what the law or the family might say.”

Dr. Zidaru and her colleague, Nick Mamo, MD, member of EYFDM in Glasgow, Scotland, emphasized the central role family doctors play in ensuring that patient rights and preferences are respected, regardless of their cognitive state. They are often the first to identify cognitive impairments and must carefully navigate the legal and ethical landscape of decision-making support.

“Often, we focus too much on avoiding harm and overlook the principle of autonomy,” said Dr. Mamo. “But it’s essential to give patients the right to make their own decisions, even when those decisions might seem unwise to us.”
 

The Case of Jay

Dr. Zidaru said: “We’ve conducted workshops in Brussels, Vienna, and Sydney, focusing on how to build habits that support patients. We presented real-life cases, like Jay, a 43-year-old man with trisomy and a moderate intellectual disability who must decide whether to undergo surgery for a hernia. The most significant challenge was ensuring continuity of care and respecting his autonomy, despite cognitive limitations.”

Jay’s case illustrates the complex ethical dilemmas faced by family doctors when balancing autonomy with patient safety. In many cases, cognitive impairments raise concerns about whether a patient can make decisions independently. 

During the session, the audience was asked to share their thoughts on the case and to indicate whether they would allow Jay to make his own decision, and if they felt confident in assessing his cognitive capacity. The responses revealed a range of mixed feelings. 
 

Legal and Cultural Variations Across Europe

The session also explored how different European countries approach decision-making for cognitively impaired individuals. A clear divide exists between nations that give family members automatic decision-making rights and those that require legal appointments. 

In the United Kingdom, the Mental Capacity Act 2005 presumes capacity unless proven otherwise. Family doctors can assess patients’ decision-making abilities using any validated tool they find suitable. They should also aim to ensure that decisions are made in the patient’s best interests if they lack capacity. Family members only have legal authority if appointed through formal means, such as a lasting power of attorney.

In Spain and Italy, functional assessments are performed when patients retain decision-making authority in areas where they demonstrate competence. Legal guardianship can be appointed by the courts, sometimes limited to specific areas, but it is intended to support rather than replace the patient’s autonomy. 

In France and Portugal, guardianship may be implemented in specific domains, but the patient’s ability to participate in decisions is always prioritized. 

In Turkey, according to Turkish general practitioners in the audience, the courts and close family members often share the decision-making responsibility.

Dr. Zidaru added that Ireland’s Assisted Decision-Making (Capacity) Act 2015 introduced significant changes to how cognitive impairment is managed there. “Ireland adopted a standardized functional test of capacity, used by any doctor. A person can still make decisions as long as they understand, retain, and weigh the information needed to make that choice. If their capacity diminishes, a decision-making assistant, co–decision-maker, or representative can be appointed, but the patient’s will and preferences always come first.”
 

Family Doctors, a Growing Responsibility

“It’s not just about the legal framework: it’s about cultural awareness and early communication,” added Dr. Mamo. “We have to ask ourselves: Do patients have the right to make bad decisions? And how do we, as family doctors, respect that while still ensuring their safety?”

The session concluded with a discussion on how the role of family doctors in decision-making for cognitively impaired patients will evolve as populations age and the incidence of conditions like dementia increases. The workload is rising, and the need for clear, consistent guidelines is critical.

“Family doctors will continue to play a central role in managing these challenges,” Dr. Zidaru emphasized. “But we need more resources, more education, and more support to ensure we can respect patient autonomy without compromising their well-being.”

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

Salaries for millennial physicians are slightly increasing, but clinicians still face pay disparities across location, practice type, and gender.

Medscape Medical News reviewed survey data from more than 1200 practicing doctors under age 40 across 29 specialties over a 4-month period starting in October 2023.

The average annual total compensation (including any bonuses) for young clinicians rose from $326,000 to $338,000, about 4%, between 2022 and 2023. Among millennials, primary care physicians saw a 5% increase. But a large pay gap exists between fields: Specialists under age 40 earned an average of $357,000 in 2023, compared with the average primary care clinician salary of $271,000.

“Procedures are reimbursed too high, while very little value is placed on primary care,” one survey respondent complained.

The type of practice plays a major part in compensation. Millennial doctors in office-based, single-specialty group practices earned an average of $358,000 per year, followed by those in office-based multispecialty group practices at 355,000 per year. Those in outpatient clinics earned $278,000 per year.

“I believe the practice situation is a huge portion of compensation,” said Tiffany Di Pietro, DO, a cardiologist and internal medicine physician in Fort Lauderdale, Florida. “Owning your own private practice is generally more lucrative (if you have good business sense), but it is also quite a bit more time-consuming, whereas employed physicians usually make less but have fewer concerns with staffing and overhead.”

Like in previous years, a gender pay gap equated to men outearning women. Female physicians under age 40 of any kind earned about $302,000 per year, 24% less than their male counterparts, on average.

Millennial doctors in the Midwest brought home the biggest earnings, with an average salary of $343,000 vs $332,000 on the West Coast.

Millennial physicians also reported higher levels of dissatisfaction. In the 2022 report, 46% said they were not paid fairly. That figure rose to 49%. Just 68% of millennial doctors would choose medicine again if they could do things over, down from 76% in the 2021 report.

“Doctors go through multiple years of school and then have to act like we are working at Dunkin’ Donuts — like we’re on an assembly line,” one survey respondent said. “We should not have to be paid per patient seen but valued for 8-9 years of training.”

Despite these complaints, close to 7 out of 10 millennial respondents said pay was not a major factor in what area of medicine they chose, with 29% saying it played no role at all in their decision.

Psychiatrists and anesthesiologists were the happiest with their earnings, with 61% of both specialties reporting that they felt fairly paid. They were followed by dermatologists and emergency medicine doctors, both of whom 60% reported fair earnings.

Many millennial doctors are finding ways to make money outside of their practice, with 18% securing other medical-related work, 15% doing medical moonlighting, and 5% taking on non–medical-related work.

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

Salaries for millennial physicians are slightly increasing, but clinicians still face pay disparities across location, practice type, and gender.

Medscape Medical News reviewed survey data from more than 1200 practicing doctors under age 40 across 29 specialties over a 4-month period starting in October 2023.

The average annual total compensation (including any bonuses) for young clinicians rose from $326,000 to $338,000, about 4%, between 2022 and 2023. Among millennials, primary care physicians saw a 5% increase. But a large pay gap exists between fields: Specialists under age 40 earned an average of $357,000 in 2023, compared with the average primary care clinician salary of $271,000.

“Procedures are reimbursed too high, while very little value is placed on primary care,” one survey respondent complained.

The type of practice plays a major part in compensation. Millennial doctors in office-based, single-specialty group practices earned an average of $358,000 per year, followed by those in office-based multispecialty group practices at 355,000 per year. Those in outpatient clinics earned $278,000 per year.

“I believe the practice situation is a huge portion of compensation,” said Tiffany Di Pietro, DO, a cardiologist and internal medicine physician in Fort Lauderdale, Florida. “Owning your own private practice is generally more lucrative (if you have good business sense), but it is also quite a bit more time-consuming, whereas employed physicians usually make less but have fewer concerns with staffing and overhead.”

Like in previous years, a gender pay gap equated to men outearning women. Female physicians under age 40 of any kind earned about $302,000 per year, 24% less than their male counterparts, on average.

Millennial doctors in the Midwest brought home the biggest earnings, with an average salary of $343,000 vs $332,000 on the West Coast.

Millennial physicians also reported higher levels of dissatisfaction. In the 2022 report, 46% said they were not paid fairly. That figure rose to 49%. Just 68% of millennial doctors would choose medicine again if they could do things over, down from 76% in the 2021 report.

“Doctors go through multiple years of school and then have to act like we are working at Dunkin’ Donuts — like we’re on an assembly line,” one survey respondent said. “We should not have to be paid per patient seen but valued for 8-9 years of training.”

Despite these complaints, close to 7 out of 10 millennial respondents said pay was not a major factor in what area of medicine they chose, with 29% saying it played no role at all in their decision.

Psychiatrists and anesthesiologists were the happiest with their earnings, with 61% of both specialties reporting that they felt fairly paid. They were followed by dermatologists and emergency medicine doctors, both of whom 60% reported fair earnings.

Many millennial doctors are finding ways to make money outside of their practice, with 18% securing other medical-related work, 15% doing medical moonlighting, and 5% taking on non–medical-related work.

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

Salaries for millennial physicians are slightly increasing, but clinicians still face pay disparities across location, practice type, and gender.

Medscape Medical News reviewed survey data from more than 1200 practicing doctors under age 40 across 29 specialties over a 4-month period starting in October 2023.

The average annual total compensation (including any bonuses) for young clinicians rose from $326,000 to $338,000, about 4%, between 2022 and 2023. Among millennials, primary care physicians saw a 5% increase. But a large pay gap exists between fields: Specialists under age 40 earned an average of $357,000 in 2023, compared with the average primary care clinician salary of $271,000.

“Procedures are reimbursed too high, while very little value is placed on primary care,” one survey respondent complained.

The type of practice plays a major part in compensation. Millennial doctors in office-based, single-specialty group practices earned an average of $358,000 per year, followed by those in office-based multispecialty group practices at 355,000 per year. Those in outpatient clinics earned $278,000 per year.

“I believe the practice situation is a huge portion of compensation,” said Tiffany Di Pietro, DO, a cardiologist and internal medicine physician in Fort Lauderdale, Florida. “Owning your own private practice is generally more lucrative (if you have good business sense), but it is also quite a bit more time-consuming, whereas employed physicians usually make less but have fewer concerns with staffing and overhead.”

Like in previous years, a gender pay gap equated to men outearning women. Female physicians under age 40 of any kind earned about $302,000 per year, 24% less than their male counterparts, on average.

Millennial doctors in the Midwest brought home the biggest earnings, with an average salary of $343,000 vs $332,000 on the West Coast.

Millennial physicians also reported higher levels of dissatisfaction. In the 2022 report, 46% said they were not paid fairly. That figure rose to 49%. Just 68% of millennial doctors would choose medicine again if they could do things over, down from 76% in the 2021 report.

“Doctors go through multiple years of school and then have to act like we are working at Dunkin’ Donuts — like we’re on an assembly line,” one survey respondent said. “We should not have to be paid per patient seen but valued for 8-9 years of training.”

Despite these complaints, close to 7 out of 10 millennial respondents said pay was not a major factor in what area of medicine they chose, with 29% saying it played no role at all in their decision.

Psychiatrists and anesthesiologists were the happiest with their earnings, with 61% of both specialties reporting that they felt fairly paid. They were followed by dermatologists and emergency medicine doctors, both of whom 60% reported fair earnings.

Many millennial doctors are finding ways to make money outside of their practice, with 18% securing other medical-related work, 15% doing medical moonlighting, and 5% taking on non–medical-related work.

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

TOPLINE: 

Women with premature ovarian insufficiency (POI) have a 2.6 times higher prevalence of severe autoimmune diseases before diagnosis and a 2- to 3-fold increased risk for these diseases after diagnosis.
 

METHODOLOGY:

• Researchers conducted a population-based registry study including 3972 women diagnosed with spontaneous POI between 1988 and 2017.
• A total of 15,708 female population controls matched by age and municipality of residence were included for comparison.
• Autoimmune disease diagnoses were evaluated from childhood until the end of 2017 using the Hospital Discharge Registry.
• Women with a history of cancer or bilateral oophorectomy were excluded from the study.

TAKEAWAY:

• Women with POI had a 2.6 times higher prevalence of severe autoimmune diseases before diagnosis compared to controls (odds ratio [OR], 2.6; 95% CI, 2.2-3.1).
• The prevalence of specific autoimmune diseases such as polyglandular autoimmune diseases (OR, 25.8; 95% CI, 9.0-74.1) and Addison disease (OR, 22.9; 95% CI, 7.9-66.1) was significantly higher in women with POI.
• The standardized incidence ratios for being diagnosed with a severe autoimmune disease after POI diagnosis was 2.8 (95% CI, 2.3-3.4) during the first 3 years, decreasing to 1.3 (95% CI, 1.1-1.6) after 12 years.
• No significant difference was found in the prevalence of diabetes type 1 and ankylosing spondylitis between women with POI and the reference cohort.

IN PRACTICE:

“The study results strengthen the hypothesis that autoimmune mechanisms play an important role in the pathogenesis of POI. Future studies should focus on the immunological mechanism of POI from preventative and curative perspectives,” wrote the authors of the study.

SOURCE:

The study was led by Susanna M. Savukoski, Oulu University Hospital in Finland. It was published online in Human Reproduction.

LIMITATIONS: 

The study included only autoimmune disorders diagnosed in specialized health care, which may underestimate the overall prevalence of autoimmune disorders in women with POI. Additionally, the study did not account for confounders such as body mass index and smoking, which are associated with the risk for autoimmune disease and POI.

DISCLOSURES:

Ms. Savukoski received grants from the Finnish Menopause Society, the Finnish Medical Foundation, and the Juho Vainio Foundation. 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: 

Women with premature ovarian insufficiency (POI) have a 2.6 times higher prevalence of severe autoimmune diseases before diagnosis and a 2- to 3-fold increased risk for these diseases after diagnosis.
 

METHODOLOGY:

• Researchers conducted a population-based registry study including 3972 women diagnosed with spontaneous POI between 1988 and 2017.
• A total of 15,708 female population controls matched by age and municipality of residence were included for comparison.
• Autoimmune disease diagnoses were evaluated from childhood until the end of 2017 using the Hospital Discharge Registry.
• Women with a history of cancer or bilateral oophorectomy were excluded from the study.

TAKEAWAY:

• Women with POI had a 2.6 times higher prevalence of severe autoimmune diseases before diagnosis compared to controls (odds ratio [OR], 2.6; 95% CI, 2.2-3.1).
• The prevalence of specific autoimmune diseases such as polyglandular autoimmune diseases (OR, 25.8; 95% CI, 9.0-74.1) and Addison disease (OR, 22.9; 95% CI, 7.9-66.1) was significantly higher in women with POI.
• The standardized incidence ratios for being diagnosed with a severe autoimmune disease after POI diagnosis was 2.8 (95% CI, 2.3-3.4) during the first 3 years, decreasing to 1.3 (95% CI, 1.1-1.6) after 12 years.
• No significant difference was found in the prevalence of diabetes type 1 and ankylosing spondylitis between women with POI and the reference cohort.

IN PRACTICE:

“The study results strengthen the hypothesis that autoimmune mechanisms play an important role in the pathogenesis of POI. Future studies should focus on the immunological mechanism of POI from preventative and curative perspectives,” wrote the authors of the study.

SOURCE:

The study was led by Susanna M. Savukoski, Oulu University Hospital in Finland. It was published online in Human Reproduction.

LIMITATIONS: 

The study included only autoimmune disorders diagnosed in specialized health care, which may underestimate the overall prevalence of autoimmune disorders in women with POI. Additionally, the study did not account for confounders such as body mass index and smoking, which are associated with the risk for autoimmune disease and POI.

DISCLOSURES:

Ms. Savukoski received grants from the Finnish Menopause Society, the Finnish Medical Foundation, and the Juho Vainio Foundation. 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: 

Women with premature ovarian insufficiency (POI) have a 2.6 times higher prevalence of severe autoimmune diseases before diagnosis and a 2- to 3-fold increased risk for these diseases after diagnosis.
 

METHODOLOGY:

• Researchers conducted a population-based registry study including 3972 women diagnosed with spontaneous POI between 1988 and 2017.
• A total of 15,708 female population controls matched by age and municipality of residence were included for comparison.
• Autoimmune disease diagnoses were evaluated from childhood until the end of 2017 using the Hospital Discharge Registry.
• Women with a history of cancer or bilateral oophorectomy were excluded from the study.

TAKEAWAY:

• Women with POI had a 2.6 times higher prevalence of severe autoimmune diseases before diagnosis compared to controls (odds ratio [OR], 2.6; 95% CI, 2.2-3.1).
• The prevalence of specific autoimmune diseases such as polyglandular autoimmune diseases (OR, 25.8; 95% CI, 9.0-74.1) and Addison disease (OR, 22.9; 95% CI, 7.9-66.1) was significantly higher in women with POI.
• The standardized incidence ratios for being diagnosed with a severe autoimmune disease after POI diagnosis was 2.8 (95% CI, 2.3-3.4) during the first 3 years, decreasing to 1.3 (95% CI, 1.1-1.6) after 12 years.
• No significant difference was found in the prevalence of diabetes type 1 and ankylosing spondylitis between women with POI and the reference cohort.

IN PRACTICE:

“The study results strengthen the hypothesis that autoimmune mechanisms play an important role in the pathogenesis of POI. Future studies should focus on the immunological mechanism of POI from preventative and curative perspectives,” wrote the authors of the study.

SOURCE:

The study was led by Susanna M. Savukoski, Oulu University Hospital in Finland. It was published online in Human Reproduction.

LIMITATIONS: 

The study included only autoimmune disorders diagnosed in specialized health care, which may underestimate the overall prevalence of autoimmune disorders in women with POI. Additionally, the study did not account for confounders such as body mass index and smoking, which are associated with the risk for autoimmune disease and POI.

DISCLOSURES:

Ms. Savukoski received grants from the Finnish Menopause Society, the Finnish Medical Foundation, and the Juho Vainio Foundation. 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.