Randy Dotinga

SAN DIEGO – Patients with limited-stage small cell lung cancer (LS-SCLC) had improved overall survival and progression-free survival when they received higher-dose thoracic radiotherapy instead of the standard treatment, according to a new multicenter, open-label, randomized phase III trial.

Among 224 patients in China, aged 18-70, those randomly assigned to receive volumetric-modulated arc radiotherapy of high-dose, hypofractionated thoracic radiotherapy of 54 Gy in 30 fractions had a much higher median overall survival (62.4 months) than those who received the standard dose of 45 Gy in 30 fractions (43.1 months, P = .001), reported Jiayi Yu, PhD, of Beijing University Cancer Hospital and Institute and colleagues at the annual meeting of the American Society for Radiation Oncology.

Median progression-free survival was also higher in the 54 Gy group (30.5 months vs. 16.7 months in the 45 Gy group, P = .044).

Kristin Higgins, MD, of Winship Cancer Institute of Emory University, Atlanta, provided perspective at the ASTRO session following Dr. Yu’s presentation. She noted that the study population is quite different than that of LS-SCLC patients in the United States, where patients are often older and more likely to have a history of smoking.

“We need more technical details to understand how to deliver this regimen in clinical practice, and it may not be applicable for all patients,” she said. Still, she added that “a key takeaway here is that optimizing the radiotherapy component of treatment is very important.”

Both groups received chemotherapy. “Higher-dose thoracic radiation therapy concurrently with chemotherapy is an alternative therapeutic option,” Dr. Yu said at an ASTRO presentation.

As Dr. Yu noted, twice-daily thoracic radiotherapy of 45 Gy in 30 fractions and concurrent chemotherapy has been the standard treatment for LS-SCLC for the last 20 years. Trials failed to show benefits for once-daily 66-Gy (33 fractions) or 70-Gy treatment (35 fractions), but a phase 2 trial published in 2023 did indicate that twice-daily treatment of 60 Gy (40 fractions) improved survival without boosting side effects.

For the new study, researchers tracked 224 patients from 2017 to 2021 who were previously untreated or had received specific chemotherapy treatments and had ECOG performance status scores of 0 or 1; 108 patients were randomly assigned to the 54-Gy arm and 116 to the 45-Gy arm. All were recruited at 16 public hospitals in China.

The median age in the two groups were 60 in the 54-Gy arm and 62 in the 45-Gy arm; the percentages of women were similar (45.4% and 45.7%, respectively). Most were current or former smokers (62.0% and 61.2%, respectively).

The researchers closed the trial in April 2021 because of the survival benefit in the 54-Gy arm, and patients were tracked through January 2023 for a median 45 months.

Nearly three-quarters of patients in the 54-Gy arm survived to 2 years (77.7%) vs. 53.4% in the 45-Gy arm, a 41% reduction in risk of death. Adverse events were similar between the groups, with 1 reported treatment-related death (myocardial infarction), in the 54-Gy group.

In an interview, Kenneth Rosenzweig, MD, chairman of the department of radiation oncology at Icahn School of Medicine at Mount Sinai, New York, praised the study. It’s “no surprise” that higher radiation doses are well-tolerated since “our ability to shield normal tissue has improved” over the years, said Dr. Rosenzweig, who served as a moderator of the ASTRO session where the research was presented.

However, he cautioned that hypofractionation is still “intense” and may not be appropriate for certain patients. And he added that some clinics may not be set up to provide twice-daily treatments.

Information about study funding was not provided. The study authors have no disclosures. Dr. Higgins discloses relationships with AstraZeneca and Regeneron (advisory board), Jazz (funded research), and Janssen and Picture Health (consulting). Dr. Rosenzweig has no disclosures.

SAN DIEGO – Patients with limited-stage small cell lung cancer (LS-SCLC) had improved overall survival and progression-free survival when they received higher-dose thoracic radiotherapy instead of the standard treatment, according to a new multicenter, open-label, randomized phase III trial.

Among 224 patients in China, aged 18-70, those randomly assigned to receive volumetric-modulated arc radiotherapy of high-dose, hypofractionated thoracic radiotherapy of 54 Gy in 30 fractions had a much higher median overall survival (62.4 months) than those who received the standard dose of 45 Gy in 30 fractions (43.1 months, P = .001), reported Jiayi Yu, PhD, of Beijing University Cancer Hospital and Institute and colleagues at the annual meeting of the American Society for Radiation Oncology.

Median progression-free survival was also higher in the 54 Gy group (30.5 months vs. 16.7 months in the 45 Gy group, P = .044).

Kristin Higgins, MD, of Winship Cancer Institute of Emory University, Atlanta, provided perspective at the ASTRO session following Dr. Yu’s presentation. She noted that the study population is quite different than that of LS-SCLC patients in the United States, where patients are often older and more likely to have a history of smoking.

“We need more technical details to understand how to deliver this regimen in clinical practice, and it may not be applicable for all patients,” she said. Still, she added that “a key takeaway here is that optimizing the radiotherapy component of treatment is very important.”

Both groups received chemotherapy. “Higher-dose thoracic radiation therapy concurrently with chemotherapy is an alternative therapeutic option,” Dr. Yu said at an ASTRO presentation.

As Dr. Yu noted, twice-daily thoracic radiotherapy of 45 Gy in 30 fractions and concurrent chemotherapy has been the standard treatment for LS-SCLC for the last 20 years. Trials failed to show benefits for once-daily 66-Gy (33 fractions) or 70-Gy treatment (35 fractions), but a phase 2 trial published in 2023 did indicate that twice-daily treatment of 60 Gy (40 fractions) improved survival without boosting side effects.

For the new study, researchers tracked 224 patients from 2017 to 2021 who were previously untreated or had received specific chemotherapy treatments and had ECOG performance status scores of 0 or 1; 108 patients were randomly assigned to the 54-Gy arm and 116 to the 45-Gy arm. All were recruited at 16 public hospitals in China.

The median age in the two groups were 60 in the 54-Gy arm and 62 in the 45-Gy arm; the percentages of women were similar (45.4% and 45.7%, respectively). Most were current or former smokers (62.0% and 61.2%, respectively).

The researchers closed the trial in April 2021 because of the survival benefit in the 54-Gy arm, and patients were tracked through January 2023 for a median 45 months.

Nearly three-quarters of patients in the 54-Gy arm survived to 2 years (77.7%) vs. 53.4% in the 45-Gy arm, a 41% reduction in risk of death. Adverse events were similar between the groups, with 1 reported treatment-related death (myocardial infarction), in the 54-Gy group.

In an interview, Kenneth Rosenzweig, MD, chairman of the department of radiation oncology at Icahn School of Medicine at Mount Sinai, New York, praised the study. It’s “no surprise” that higher radiation doses are well-tolerated since “our ability to shield normal tissue has improved” over the years, said Dr. Rosenzweig, who served as a moderator of the ASTRO session where the research was presented.

However, he cautioned that hypofractionation is still “intense” and may not be appropriate for certain patients. And he added that some clinics may not be set up to provide twice-daily treatments.

Information about study funding was not provided. The study authors have no disclosures. Dr. Higgins discloses relationships with AstraZeneca and Regeneron (advisory board), Jazz (funded research), and Janssen and Picture Health (consulting). Dr. Rosenzweig has no disclosures.

SAN DIEGO – Patients with limited-stage small cell lung cancer (LS-SCLC) had improved overall survival and progression-free survival when they received higher-dose thoracic radiotherapy instead of the standard treatment, according to a new multicenter, open-label, randomized phase III trial.

Among 224 patients in China, aged 18-70, those randomly assigned to receive volumetric-modulated arc radiotherapy of high-dose, hypofractionated thoracic radiotherapy of 54 Gy in 30 fractions had a much higher median overall survival (62.4 months) than those who received the standard dose of 45 Gy in 30 fractions (43.1 months, P = .001), reported Jiayi Yu, PhD, of Beijing University Cancer Hospital and Institute and colleagues at the annual meeting of the American Society for Radiation Oncology.

Median progression-free survival was also higher in the 54 Gy group (30.5 months vs. 16.7 months in the 45 Gy group, P = .044).

Kristin Higgins, MD, of Winship Cancer Institute of Emory University, Atlanta, provided perspective at the ASTRO session following Dr. Yu’s presentation. She noted that the study population is quite different than that of LS-SCLC patients in the United States, where patients are often older and more likely to have a history of smoking.

“We need more technical details to understand how to deliver this regimen in clinical practice, and it may not be applicable for all patients,” she said. Still, she added that “a key takeaway here is that optimizing the radiotherapy component of treatment is very important.”

Both groups received chemotherapy. “Higher-dose thoracic radiation therapy concurrently with chemotherapy is an alternative therapeutic option,” Dr. Yu said at an ASTRO presentation.

As Dr. Yu noted, twice-daily thoracic radiotherapy of 45 Gy in 30 fractions and concurrent chemotherapy has been the standard treatment for LS-SCLC for the last 20 years. Trials failed to show benefits for once-daily 66-Gy (33 fractions) or 70-Gy treatment (35 fractions), but a phase 2 trial published in 2023 did indicate that twice-daily treatment of 60 Gy (40 fractions) improved survival without boosting side effects.

For the new study, researchers tracked 224 patients from 2017 to 2021 who were previously untreated or had received specific chemotherapy treatments and had ECOG performance status scores of 0 or 1; 108 patients were randomly assigned to the 54-Gy arm and 116 to the 45-Gy arm. All were recruited at 16 public hospitals in China.

The median age in the two groups were 60 in the 54-Gy arm and 62 in the 45-Gy arm; the percentages of women were similar (45.4% and 45.7%, respectively). Most were current or former smokers (62.0% and 61.2%, respectively).

The researchers closed the trial in April 2021 because of the survival benefit in the 54-Gy arm, and patients were tracked through January 2023 for a median 45 months.

Nearly three-quarters of patients in the 54-Gy arm survived to 2 years (77.7%) vs. 53.4% in the 45-Gy arm, a 41% reduction in risk of death. Adverse events were similar between the groups, with 1 reported treatment-related death (myocardial infarction), in the 54-Gy group.

In an interview, Kenneth Rosenzweig, MD, chairman of the department of radiation oncology at Icahn School of Medicine at Mount Sinai, New York, praised the study. It’s “no surprise” that higher radiation doses are well-tolerated since “our ability to shield normal tissue has improved” over the years, said Dr. Rosenzweig, who served as a moderator of the ASTRO session where the research was presented.

However, he cautioned that hypofractionation is still “intense” and may not be appropriate for certain patients. And he added that some clinics may not be set up to provide twice-daily treatments.

Information about study funding was not provided. The study authors have no disclosures. Dr. Higgins discloses relationships with AstraZeneca and Regeneron (advisory board), Jazz (funded research), and Janssen and Picture Health (consulting). Dr. Rosenzweig has no disclosures.

SAN DIEGO – Women with breast cancer who underwent postmastectomy breast reconstruction benefited from shorter bursts of higher-dose radiation, compared with the standard therapy, according to a new prospective, randomized study.

Side effects and physical well-being scores were similar among 400 women who received the two treatment regimens, and outcomes were similar or slightly better in the higher-dose group, reported Rinaa Punglia, MD, MPH, an associate professor of radiation oncology at Dana-Farber Brigham Cancer Center in Boston and colleagues at the annual meeting of the American Society for Radiation Oncology. In a press statement, Dr. Punglia noted that the outcomes weren’t as impressive as researchers had hoped, but it’s positive that higher doses didn’t cause more side effects.

The use of the higher-dose approach, known as hypofractionation, “resulted in fewer treatment breaks and less financial toxicity” vs. conventional fractionation, Dr. Punglia said at a news briefing. The findings of the FABREC study “support the use of hypofractionated postmastectomy radiation for patients with basic reconstruction.”

According to Dr. Punglia, “postmastectomy radiation therapy is indicated for almost one-third of mastectomy patients and improves the lives of patients who are at an elevated risk for recurrence.” However, “the addition of radiation therapy greatly increases the risk of reconstruction complications.”

The typical radiation treatment period is 5-6 weeks in these patients, a major hardship for patients that can take them away from their families for extended periods of time. The researchers sought to understand whether another approach – hypofractionation over 3-4 weeks – is a better option. The strategy is widely used after breast-conserving surgery, she said, and has been linked to similar cancer outcomes, improved quality of life, and improved breast appearance.

From 2018 to 2021, the researchers recruited 400 patients with stage 0-III breast cancer who were treated with mastectomy and immediately underwent implant-based reconstruction (median age = 47.0, 23-79). None had tumors growing into the chest wall or skin.

The patients, spread nationwide across 16 institutions, were randomized to receive conventional fractionation (n = 201, 25 fractions, 5 days a week for 5 weeks of 200 cGy) or hypofractionation (n=199, 16 fractions, 5 days a week, for about 3 weeks of 266 cGy).

The researchers tracked 385 patients over a median follow-up of 40.4 months. There was no statistically significant difference in distant recurrence (12 in conventional fractionation arm, 11 in hypofractionation arm), death (2 in each arm), local recurrence (1 in each arm), or toxicity in the chest wall area (20 in conventional fractionation arm, 19 in hypofractionation arm). Changes in physical well-being scores, the primary endpoint, were similar after controlling for age.

“We found that younger patients randomized to hypofractionation were less bothered by side effects of treatment at 6 months relative to their counterparts who received conventional fractionation,” Dr. Punglia said.

Treatment breaks were more common in the conventional fractionation arm (7.7%, mean = 3.3 days) vs. the hypofractionation arm (2.7%, mean = 2.8 days, P = .03).

Among 51 patients who took unpaid time off work, those who underwent hypofractionation took fewer mean days off (73.7 days vs. 125.8 days for conventional fractionation, P = .046).

The study is the first of its kind to compare conventional fractionation to hypofractionation in this population in a randomized, phase III study, Dr. Punglia said.

At the news briefing, an independent expert – Lori Pierce, MD, a professor of radiation oncology at the University of Michigan – said the new study is a “game changer.”

The findings about the benefits of hypofractionation “will potentially impact thousands of women,” said Dr. Pierce, former president of the American Society of Clinical Oncology. The shorter course of radiation is more convenient for patients, she said, and reduces hardship.

“Without a doubt, these results should be discussed with all patients who have had mastectomy and implant-based reconstruction,” she said.

In an interview, Bruce G. Haffty, MD, MS, professor and chair of Radiation Oncology at Rutgers Cancer Institute of New Jersey, said the study adds to existing data suggesting that shorter courses of therapy “are probably OK.” The new findings “give people a little more confidence that [short courses are] safe in terms of well-being and toxicity.”

However, the follow-up in the trial is relatively short, he said, and longer-term research will be needed to change the standard of care in these patients. “It’ll be an evolving story over the next 5-10 years,” he said.

The study was funded by the Patient-Centered Outcomes Research Institute. Dr. Punglia has no disclosures; disclosures for other authors were not provided. Disclosure information for Dr. Pierce was not provided. Dr. Haffty is an investigator in a similar study called RT CHARM.

SAN DIEGO – Women with breast cancer who underwent postmastectomy breast reconstruction benefited from shorter bursts of higher-dose radiation, compared with the standard therapy, according to a new prospective, randomized study.

Side effects and physical well-being scores were similar among 400 women who received the two treatment regimens, and outcomes were similar or slightly better in the higher-dose group, reported Rinaa Punglia, MD, MPH, an associate professor of radiation oncology at Dana-Farber Brigham Cancer Center in Boston and colleagues at the annual meeting of the American Society for Radiation Oncology. In a press statement, Dr. Punglia noted that the outcomes weren’t as impressive as researchers had hoped, but it’s positive that higher doses didn’t cause more side effects.

The use of the higher-dose approach, known as hypofractionation, “resulted in fewer treatment breaks and less financial toxicity” vs. conventional fractionation, Dr. Punglia said at a news briefing. The findings of the FABREC study “support the use of hypofractionated postmastectomy radiation for patients with basic reconstruction.”

According to Dr. Punglia, “postmastectomy radiation therapy is indicated for almost one-third of mastectomy patients and improves the lives of patients who are at an elevated risk for recurrence.” However, “the addition of radiation therapy greatly increases the risk of reconstruction complications.”

The typical radiation treatment period is 5-6 weeks in these patients, a major hardship for patients that can take them away from their families for extended periods of time. The researchers sought to understand whether another approach – hypofractionation over 3-4 weeks – is a better option. The strategy is widely used after breast-conserving surgery, she said, and has been linked to similar cancer outcomes, improved quality of life, and improved breast appearance.

From 2018 to 2021, the researchers recruited 400 patients with stage 0-III breast cancer who were treated with mastectomy and immediately underwent implant-based reconstruction (median age = 47.0, 23-79). None had tumors growing into the chest wall or skin.

The patients, spread nationwide across 16 institutions, were randomized to receive conventional fractionation (n = 201, 25 fractions, 5 days a week for 5 weeks of 200 cGy) or hypofractionation (n=199, 16 fractions, 5 days a week, for about 3 weeks of 266 cGy).

The researchers tracked 385 patients over a median follow-up of 40.4 months. There was no statistically significant difference in distant recurrence (12 in conventional fractionation arm, 11 in hypofractionation arm), death (2 in each arm), local recurrence (1 in each arm), or toxicity in the chest wall area (20 in conventional fractionation arm, 19 in hypofractionation arm). Changes in physical well-being scores, the primary endpoint, were similar after controlling for age.

“We found that younger patients randomized to hypofractionation were less bothered by side effects of treatment at 6 months relative to their counterparts who received conventional fractionation,” Dr. Punglia said.

Treatment breaks were more common in the conventional fractionation arm (7.7%, mean = 3.3 days) vs. the hypofractionation arm (2.7%, mean = 2.8 days, P = .03).

Among 51 patients who took unpaid time off work, those who underwent hypofractionation took fewer mean days off (73.7 days vs. 125.8 days for conventional fractionation, P = .046).

The study is the first of its kind to compare conventional fractionation to hypofractionation in this population in a randomized, phase III study, Dr. Punglia said.

At the news briefing, an independent expert – Lori Pierce, MD, a professor of radiation oncology at the University of Michigan – said the new study is a “game changer.”

The findings about the benefits of hypofractionation “will potentially impact thousands of women,” said Dr. Pierce, former president of the American Society of Clinical Oncology. The shorter course of radiation is more convenient for patients, she said, and reduces hardship.

“Without a doubt, these results should be discussed with all patients who have had mastectomy and implant-based reconstruction,” she said.

In an interview, Bruce G. Haffty, MD, MS, professor and chair of Radiation Oncology at Rutgers Cancer Institute of New Jersey, said the study adds to existing data suggesting that shorter courses of therapy “are probably OK.” The new findings “give people a little more confidence that [short courses are] safe in terms of well-being and toxicity.”

However, the follow-up in the trial is relatively short, he said, and longer-term research will be needed to change the standard of care in these patients. “It’ll be an evolving story over the next 5-10 years,” he said.

The study was funded by the Patient-Centered Outcomes Research Institute. Dr. Punglia has no disclosures; disclosures for other authors were not provided. Disclosure information for Dr. Pierce was not provided. Dr. Haffty is an investigator in a similar study called RT CHARM.

SAN DIEGO – Women with breast cancer who underwent postmastectomy breast reconstruction benefited from shorter bursts of higher-dose radiation, compared with the standard therapy, according to a new prospective, randomized study.

Side effects and physical well-being scores were similar among 400 women who received the two treatment regimens, and outcomes were similar or slightly better in the higher-dose group, reported Rinaa Punglia, MD, MPH, an associate professor of radiation oncology at Dana-Farber Brigham Cancer Center in Boston and colleagues at the annual meeting of the American Society for Radiation Oncology. In a press statement, Dr. Punglia noted that the outcomes weren’t as impressive as researchers had hoped, but it’s positive that higher doses didn’t cause more side effects.

The use of the higher-dose approach, known as hypofractionation, “resulted in fewer treatment breaks and less financial toxicity” vs. conventional fractionation, Dr. Punglia said at a news briefing. The findings of the FABREC study “support the use of hypofractionated postmastectomy radiation for patients with basic reconstruction.”

According to Dr. Punglia, “postmastectomy radiation therapy is indicated for almost one-third of mastectomy patients and improves the lives of patients who are at an elevated risk for recurrence.” However, “the addition of radiation therapy greatly increases the risk of reconstruction complications.”

The typical radiation treatment period is 5-6 weeks in these patients, a major hardship for patients that can take them away from their families for extended periods of time. The researchers sought to understand whether another approach – hypofractionation over 3-4 weeks – is a better option. The strategy is widely used after breast-conserving surgery, she said, and has been linked to similar cancer outcomes, improved quality of life, and improved breast appearance.

From 2018 to 2021, the researchers recruited 400 patients with stage 0-III breast cancer who were treated with mastectomy and immediately underwent implant-based reconstruction (median age = 47.0, 23-79). None had tumors growing into the chest wall or skin.

The patients, spread nationwide across 16 institutions, were randomized to receive conventional fractionation (n = 201, 25 fractions, 5 days a week for 5 weeks of 200 cGy) or hypofractionation (n=199, 16 fractions, 5 days a week, for about 3 weeks of 266 cGy).

The researchers tracked 385 patients over a median follow-up of 40.4 months. There was no statistically significant difference in distant recurrence (12 in conventional fractionation arm, 11 in hypofractionation arm), death (2 in each arm), local recurrence (1 in each arm), or toxicity in the chest wall area (20 in conventional fractionation arm, 19 in hypofractionation arm). Changes in physical well-being scores, the primary endpoint, were similar after controlling for age.

“We found that younger patients randomized to hypofractionation were less bothered by side effects of treatment at 6 months relative to their counterparts who received conventional fractionation,” Dr. Punglia said.

Treatment breaks were more common in the conventional fractionation arm (7.7%, mean = 3.3 days) vs. the hypofractionation arm (2.7%, mean = 2.8 days, P = .03).

Among 51 patients who took unpaid time off work, those who underwent hypofractionation took fewer mean days off (73.7 days vs. 125.8 days for conventional fractionation, P = .046).

The study is the first of its kind to compare conventional fractionation to hypofractionation in this population in a randomized, phase III study, Dr. Punglia said.

At the news briefing, an independent expert – Lori Pierce, MD, a professor of radiation oncology at the University of Michigan – said the new study is a “game changer.”

The findings about the benefits of hypofractionation “will potentially impact thousands of women,” said Dr. Pierce, former president of the American Society of Clinical Oncology. The shorter course of radiation is more convenient for patients, she said, and reduces hardship.

“Without a doubt, these results should be discussed with all patients who have had mastectomy and implant-based reconstruction,” she said.

In an interview, Bruce G. Haffty, MD, MS, professor and chair of Radiation Oncology at Rutgers Cancer Institute of New Jersey, said the study adds to existing data suggesting that shorter courses of therapy “are probably OK.” The new findings “give people a little more confidence that [short courses are] safe in terms of well-being and toxicity.”

However, the follow-up in the trial is relatively short, he said, and longer-term research will be needed to change the standard of care in these patients. “It’ll be an evolving story over the next 5-10 years,” he said.

The study was funded by the Patient-Centered Outcomes Research Institute. Dr. Punglia has no disclosures; disclosures for other authors were not provided. Disclosure information for Dr. Pierce was not provided. Dr. Haffty is an investigator in a similar study called RT CHARM.

SAN DIEGO – Stereotactic ablative body radiotherapy (SABR) appeared to delay the need for changes in systemic therapy in postmenopausal patients with oligoprogressive luminal ER-positive, HER2-negative breast cancer, according to a new phase 2 study.

In the AVATAR trial, patients with one to five metastatic lesions who’d been treated with cyclin-dependent kinase (CDK) 4/6 inhibitors and aromatase inhibitors for at least 6 months underwent SABR. Of those, 47% had event-free survival of more than 6 months, an unexpectedly high figure, reported radiation oncologist Steven David, MBBS, of Peter MacCallum Cancer Center, Melbourne, and colleagues at the annual meeting of the American Society for Radiation Oncology.

“We found surprisingly that SABR delayed a change in therapy by 10 months, which is great for patients. Also, one in three patients had a second round of SABR,” said Dr. David in an interview. “This trial provides the first prospective evidence to delay a change in therapy in this population, and this strategy is ready to go now.”

According to Dr. David, oligoprogressive luminal, ER-positive, HER2-negative, advanced breast cancer cannot be cured. However, patients can live more than 10 years in some cases, and an early treatment – CDK 4/6 inhibitors and aromatase inhibitors – is well tolerated. “Patients can lead a normal life and avoid chemo” as long as those medications keep working.

The goal of the study was to determine if SABR is helpful in these patients. The treatment, which produces highly focused radiation, “has very few side effects and does a great job in eliminating progressing metastases,” Dr. David said.

For the study, researchers recruited 32 subjects at 13 Australian sites. Participants could not have had leptomeningeal disease, previous chemotherapy for metastatic disease, or prior radiotherapy to an oligoprogressing lesion. Most metastases were to bone (n = 44, 71%), node (systemic, n = 8; 13%) and lung (n = 4; 6%).

The patients were treated with SABR, most commonly 24 Gy (n = 25; 43%) and 20 Gy (n = 10; 17%); half had one lesion treated (50%), and 25% had two lesions treated.

The median follow-up was 15.8 months. The median event-free survival was 5.2 months (95% confidence interval, 3.1-9.4 months), with events defined as progression within 6 months or in at least three lesions. Fifteen patients (47%) reached event-free survival of 6 or more months.

Elysia Donovan, MD, MSc, a radiation oncologist at McMaster University, Hamilton, Ont., said in an interview that the new study is thoughtfully designed, although it’s not definitive. “At this point we still do not know the optimal treatment regimen for oligoprogressive breast cancer. The findings of this trial are promising and exciting. However, further randomized trials are required before routine implementation in clinical practice. For now, patients should be considered in a case by case basis with multidisciplinary discussion to determine the optimal systemic therapy regimen at oligoprogression and whether SABR may provide benefit.”

Median modified progression-free survival was 10.4 months, and median progression-free survival was 5.2 months; 31% of patients received SABR for further oligoprogression, and 46% patients remained on CDK4/6 inhibitors and aromatase inhibitors for 12 months. Overall survival was 100%.

A total of 14 patients had grade 1 adverse events, 2 had grade 2 events, and none had grade 3 or higher events; 47% had no treatment-related toxicity.

The strategy “potentially has a place in other cancer types and other breast cancer types,” Dr. David said.

In an interview, Katarzyna Jerzak, MD, MSc, a medical oncologist with Sunnybrook Odette Cancer Center in Toronto, said the findings are promising, although the study is small and the patients are similar. Toxicity was limited, and a 12-month delay in a switch to therapy – reached by 46% – “is very meaningful for patients.” She added that “the positive results should serve as motivation to investigate the strategy further.”

Dr. David said a larger trial called AVATAR 2 is funded and in the works. It will have more patients and more breast cancer subtypes.

The study was funded by the Donald Ratcliffe and Phyllis McLeod Trust. Dr. David disclosed grant/research funding from Roche Genentech, and other authors reported various disclosures including relationships with AstraZeneca, Pfizer, Gilead, and others. Dr. Jerzak disclosed speaker/advisor board/consultant relationships with Amgen, AstraZeneca, Apobiologix, Eli Lilly, Esai, Genomic Health, Gilead, Knight Therapeutics, Merck, Myriad Genetics, Pfizer, Roche, Seagen, and Novartis and research funding from AstraZeneca, Eli Lilly, and Seagen. Dr. Donovan disclosed a Bright Foundation grant for a prospective trial of SABR for oligoprogressive breast cancer.

SAN DIEGO – Stereotactic ablative body radiotherapy (SABR) appeared to delay the need for changes in systemic therapy in postmenopausal patients with oligoprogressive luminal ER-positive, HER2-negative breast cancer, according to a new phase 2 study.

In the AVATAR trial, patients with one to five metastatic lesions who’d been treated with cyclin-dependent kinase (CDK) 4/6 inhibitors and aromatase inhibitors for at least 6 months underwent SABR. Of those, 47% had event-free survival of more than 6 months, an unexpectedly high figure, reported radiation oncologist Steven David, MBBS, of Peter MacCallum Cancer Center, Melbourne, and colleagues at the annual meeting of the American Society for Radiation Oncology.

“We found surprisingly that SABR delayed a change in therapy by 10 months, which is great for patients. Also, one in three patients had a second round of SABR,” said Dr. David in an interview. “This trial provides the first prospective evidence to delay a change in therapy in this population, and this strategy is ready to go now.”

According to Dr. David, oligoprogressive luminal, ER-positive, HER2-negative, advanced breast cancer cannot be cured. However, patients can live more than 10 years in some cases, and an early treatment – CDK 4/6 inhibitors and aromatase inhibitors – is well tolerated. “Patients can lead a normal life and avoid chemo” as long as those medications keep working.

The goal of the study was to determine if SABR is helpful in these patients. The treatment, which produces highly focused radiation, “has very few side effects and does a great job in eliminating progressing metastases,” Dr. David said.

For the study, researchers recruited 32 subjects at 13 Australian sites. Participants could not have had leptomeningeal disease, previous chemotherapy for metastatic disease, or prior radiotherapy to an oligoprogressing lesion. Most metastases were to bone (n = 44, 71%), node (systemic, n = 8; 13%) and lung (n = 4; 6%).

The patients were treated with SABR, most commonly 24 Gy (n = 25; 43%) and 20 Gy (n = 10; 17%); half had one lesion treated (50%), and 25% had two lesions treated.

The median follow-up was 15.8 months. The median event-free survival was 5.2 months (95% confidence interval, 3.1-9.4 months), with events defined as progression within 6 months or in at least three lesions. Fifteen patients (47%) reached event-free survival of 6 or more months.

Elysia Donovan, MD, MSc, a radiation oncologist at McMaster University, Hamilton, Ont., said in an interview that the new study is thoughtfully designed, although it’s not definitive. “At this point we still do not know the optimal treatment regimen for oligoprogressive breast cancer. The findings of this trial are promising and exciting. However, further randomized trials are required before routine implementation in clinical practice. For now, patients should be considered in a case by case basis with multidisciplinary discussion to determine the optimal systemic therapy regimen at oligoprogression and whether SABR may provide benefit.”

Median modified progression-free survival was 10.4 months, and median progression-free survival was 5.2 months; 31% of patients received SABR for further oligoprogression, and 46% patients remained on CDK4/6 inhibitors and aromatase inhibitors for 12 months. Overall survival was 100%.

A total of 14 patients had grade 1 adverse events, 2 had grade 2 events, and none had grade 3 or higher events; 47% had no treatment-related toxicity.

The strategy “potentially has a place in other cancer types and other breast cancer types,” Dr. David said.

In an interview, Katarzyna Jerzak, MD, MSc, a medical oncologist with Sunnybrook Odette Cancer Center in Toronto, said the findings are promising, although the study is small and the patients are similar. Toxicity was limited, and a 12-month delay in a switch to therapy – reached by 46% – “is very meaningful for patients.” She added that “the positive results should serve as motivation to investigate the strategy further.”

Dr. David said a larger trial called AVATAR 2 is funded and in the works. It will have more patients and more breast cancer subtypes.

The study was funded by the Donald Ratcliffe and Phyllis McLeod Trust. Dr. David disclosed grant/research funding from Roche Genentech, and other authors reported various disclosures including relationships with AstraZeneca, Pfizer, Gilead, and others. Dr. Jerzak disclosed speaker/advisor board/consultant relationships with Amgen, AstraZeneca, Apobiologix, Eli Lilly, Esai, Genomic Health, Gilead, Knight Therapeutics, Merck, Myriad Genetics, Pfizer, Roche, Seagen, and Novartis and research funding from AstraZeneca, Eli Lilly, and Seagen. Dr. Donovan disclosed a Bright Foundation grant for a prospective trial of SABR for oligoprogressive breast cancer.

SAN DIEGO – Stereotactic ablative body radiotherapy (SABR) appeared to delay the need for changes in systemic therapy in postmenopausal patients with oligoprogressive luminal ER-positive, HER2-negative breast cancer, according to a new phase 2 study.

In the AVATAR trial, patients with one to five metastatic lesions who’d been treated with cyclin-dependent kinase (CDK) 4/6 inhibitors and aromatase inhibitors for at least 6 months underwent SABR. Of those, 47% had event-free survival of more than 6 months, an unexpectedly high figure, reported radiation oncologist Steven David, MBBS, of Peter MacCallum Cancer Center, Melbourne, and colleagues at the annual meeting of the American Society for Radiation Oncology.

“We found surprisingly that SABR delayed a change in therapy by 10 months, which is great for patients. Also, one in three patients had a second round of SABR,” said Dr. David in an interview. “This trial provides the first prospective evidence to delay a change in therapy in this population, and this strategy is ready to go now.”

According to Dr. David, oligoprogressive luminal, ER-positive, HER2-negative, advanced breast cancer cannot be cured. However, patients can live more than 10 years in some cases, and an early treatment – CDK 4/6 inhibitors and aromatase inhibitors – is well tolerated. “Patients can lead a normal life and avoid chemo” as long as those medications keep working.

The goal of the study was to determine if SABR is helpful in these patients. The treatment, which produces highly focused radiation, “has very few side effects and does a great job in eliminating progressing metastases,” Dr. David said.

For the study, researchers recruited 32 subjects at 13 Australian sites. Participants could not have had leptomeningeal disease, previous chemotherapy for metastatic disease, or prior radiotherapy to an oligoprogressing lesion. Most metastases were to bone (n = 44, 71%), node (systemic, n = 8; 13%) and lung (n = 4; 6%).

The patients were treated with SABR, most commonly 24 Gy (n = 25; 43%) and 20 Gy (n = 10; 17%); half had one lesion treated (50%), and 25% had two lesions treated.

The median follow-up was 15.8 months. The median event-free survival was 5.2 months (95% confidence interval, 3.1-9.4 months), with events defined as progression within 6 months or in at least three lesions. Fifteen patients (47%) reached event-free survival of 6 or more months.

Elysia Donovan, MD, MSc, a radiation oncologist at McMaster University, Hamilton, Ont., said in an interview that the new study is thoughtfully designed, although it’s not definitive. “At this point we still do not know the optimal treatment regimen for oligoprogressive breast cancer. The findings of this trial are promising and exciting. However, further randomized trials are required before routine implementation in clinical practice. For now, patients should be considered in a case by case basis with multidisciplinary discussion to determine the optimal systemic therapy regimen at oligoprogression and whether SABR may provide benefit.”

Median modified progression-free survival was 10.4 months, and median progression-free survival was 5.2 months; 31% of patients received SABR for further oligoprogression, and 46% patients remained on CDK4/6 inhibitors and aromatase inhibitors for 12 months. Overall survival was 100%.

A total of 14 patients had grade 1 adverse events, 2 had grade 2 events, and none had grade 3 or higher events; 47% had no treatment-related toxicity.

The strategy “potentially has a place in other cancer types and other breast cancer types,” Dr. David said.

In an interview, Katarzyna Jerzak, MD, MSc, a medical oncologist with Sunnybrook Odette Cancer Center in Toronto, said the findings are promising, although the study is small and the patients are similar. Toxicity was limited, and a 12-month delay in a switch to therapy – reached by 46% – “is very meaningful for patients.” She added that “the positive results should serve as motivation to investigate the strategy further.”

Dr. David said a larger trial called AVATAR 2 is funded and in the works. It will have more patients and more breast cancer subtypes.

The study was funded by the Donald Ratcliffe and Phyllis McLeod Trust. Dr. David disclosed grant/research funding from Roche Genentech, and other authors reported various disclosures including relationships with AstraZeneca, Pfizer, Gilead, and others. Dr. Jerzak disclosed speaker/advisor board/consultant relationships with Amgen, AstraZeneca, Apobiologix, Eli Lilly, Esai, Genomic Health, Gilead, Knight Therapeutics, Merck, Myriad Genetics, Pfizer, Roche, Seagen, and Novartis and research funding from AstraZeneca, Eli Lilly, and Seagen. Dr. Donovan disclosed a Bright Foundation grant for a prospective trial of SABR for oligoprogressive breast cancer.

SAN DIEGO – Engaging in sexual intercourse and vaginal dilation appears to lower the risk of stenosis, the narrowing/shortening of the vaginal canal, after chemoradiation treatment for cervical cancer, a new 5-year prospective study reports.

Findings from the EMBRACE study were presented at the annual American Society for Radiation Oncology (ASTRO) meeting and included 882 women with locally advanced cervical cancer. Of those, 565 women reported regular vaginal dilation and/or sexual intercourse during at least three of their follow-up assessments. Patients who reported both dilation and intercourse had the lowest risk of developing vaginal stenosis of grade ≥ 2 (18%) at 5 years.

The other 317 women were described in the study as having no penetration (13%) or infrequent penetration (23%) and were more likely to experience stenosis of grade ≥ 2 (36% and 37% respectively (P ≤ 0.001)), reported psycho-oncologist, clinical psychologist Kathrin Kirchheiner, PhD, MSc, of the Medical University of Vienna, and colleagues at ASTRO 2023.

While noting that the observational study cannot determine cause and effect, “these long-term data support clinical recommendations worldwide,” said Dr. Kirchheiner at an ASTRO news briefing.

According to Dr. Kirchheiner, external beam radiotherapy, chemotherapy, and internal brachytherapy are the standard of care for locally advanced cervical cancer that cannot be removed by surgery.

Studies have shown that the treatment can cause vaginal shortening and narrowing due to the formation of scar tissue, she said. As a result, there can be “permanent changes in the vaginal tissue that lead to a loss of elasticity. This can often cause problems during the gynecological follow-up examination and pain during sexual intercourse.”

In an earlier reported 2-year analysis of the EMBRACE study (median follow-up of 15 months), the study authors reported that 89% of 588 patients developed grade ≥ 1 vaginal stenosis following their treatment, with 29% at grade ≥ 2 and 3.6% at grade ≥ 3.

The use of medical dilators is commonly recommended after cervical cancer treatment to stretch the vaginal canal. Women are instructed to increase the dilator size over time. But research suggests that adherence may be low.

For the observational, multi-institution study, researchers tracked 1,416 cervical cancer patients from 2008 to 2015 for a median follow-up of 5 years. The new analysis focuses on 882 patients with at least three follow-up assessments, with a median age of 49. Researchers reported that patients who didn’t engage in intercourse or use dilators were most likely to experience vaginal stenosis (37%) vs. those who did both (18%), those who just had intercourse (23%), and those who only used dilators (28%) (P ≤ 0.001).

The findings were confirmed in a multivariable analysis with adjustments for tumor infiltration, age, treatment parameters, and hormonal replacement therapy, the researchers reported.

Regular sexual activity, vaginal dilation, or both were linked to higher risk of mild vaginal dryness at grade ≥ 1 (72% vs. 67% in the no/infrequent penetration group, P = 0.028) and vaginal bleeding at grade ≥ 1 (61% vs. 34% in the no/infrequent penetration group, P ≤ 0.001). There was no link to higher rates of vaginal mucositis.

Dr. Kirchheiner noted that these symptoms can be treated with lubricants, moisturizer, and hormonal replacement therapy.

As for limitations, Dr. Kirchheiner, in a press release provided by ASTRO, noted that “we cannot and should not randomize patients in a clinical trial into groups with and without regular dilation.” She also noted that future research should explore why sexual intercourse had slightly better results than use of dilators, a finding that could be related to blood flow during sexual arousal.

In comments at the news briefing, Akila Viswanathan, MD, MPH, MSc, director of Radiation Oncology and Molecular Radiation Sciences at Johns Hopkins Medicine, Baltimore, praised the new study and noted that quality of life after cervical cancer treatment is “very understudied.”

Vaginal side effects in particular are underreported because physicians often fail to ask about them and patients “are hesitant to accurately describe what they’re feeling,” she said.

The interventions of providing medical dilators and encouraging sexual activity are “very low cost,” Dr. Viswanathan said. But she noted that women – especially older women – may “find the concepts of using a dilator very difficult to understand.”

The study offers the “best evidence to date” supporting vaginal dilation, said Yale University, New Haven, Conn., radiation oncologist Shari Damast, MD, in an interview. It has “a large dataset, longitudinal design, lengthy follow-up, and uses validated tools of measurement. It gives us strong confidence in the efficacy of vaginal dilators.”

In an interview, Deborah Watkins Bruner, RN, PhD, senior vice president for research at Emory University, Atlanta, also praised the research. But she noted that it’s not clear how often vaginal dilation/sexual intercourse should be performed in order to reduce stenosis. “In addition, it is clear that vaginal dilation only is not enough to treat the myriad of symptoms that survivors must deal with,” she said.

Dr. Bruner urged colleagues “to routinely assess symptoms at each visit and offer treatments which should include hormone replacement therapy, vaginal dilation, and appropriate referral for anxiety, depression, or marital problems.”

The study was funded by Elekta and Varian Medical System via the Medical University of Vienna. The study authors, Dr. Bruner, and Dr. Damast have no disclosures. Disclosure information for Dr. Viswanathan was not available.
 

SAN DIEGO – Engaging in sexual intercourse and vaginal dilation appears to lower the risk of stenosis, the narrowing/shortening of the vaginal canal, after chemoradiation treatment for cervical cancer, a new 5-year prospective study reports.

Findings from the EMBRACE study were presented at the annual American Society for Radiation Oncology (ASTRO) meeting and included 882 women with locally advanced cervical cancer. Of those, 565 women reported regular vaginal dilation and/or sexual intercourse during at least three of their follow-up assessments. Patients who reported both dilation and intercourse had the lowest risk of developing vaginal stenosis of grade ≥ 2 (18%) at 5 years.

The other 317 women were described in the study as having no penetration (13%) or infrequent penetration (23%) and were more likely to experience stenosis of grade ≥ 2 (36% and 37% respectively (P ≤ 0.001)), reported psycho-oncologist, clinical psychologist Kathrin Kirchheiner, PhD, MSc, of the Medical University of Vienna, and colleagues at ASTRO 2023.

While noting that the observational study cannot determine cause and effect, “these long-term data support clinical recommendations worldwide,” said Dr. Kirchheiner at an ASTRO news briefing.

According to Dr. Kirchheiner, external beam radiotherapy, chemotherapy, and internal brachytherapy are the standard of care for locally advanced cervical cancer that cannot be removed by surgery.

Studies have shown that the treatment can cause vaginal shortening and narrowing due to the formation of scar tissue, she said. As a result, there can be “permanent changes in the vaginal tissue that lead to a loss of elasticity. This can often cause problems during the gynecological follow-up examination and pain during sexual intercourse.”

In an earlier reported 2-year analysis of the EMBRACE study (median follow-up of 15 months), the study authors reported that 89% of 588 patients developed grade ≥ 1 vaginal stenosis following their treatment, with 29% at grade ≥ 2 and 3.6% at grade ≥ 3.

The use of medical dilators is commonly recommended after cervical cancer treatment to stretch the vaginal canal. Women are instructed to increase the dilator size over time. But research suggests that adherence may be low.

For the observational, multi-institution study, researchers tracked 1,416 cervical cancer patients from 2008 to 2015 for a median follow-up of 5 years. The new analysis focuses on 882 patients with at least three follow-up assessments, with a median age of 49. Researchers reported that patients who didn’t engage in intercourse or use dilators were most likely to experience vaginal stenosis (37%) vs. those who did both (18%), those who just had intercourse (23%), and those who only used dilators (28%) (P ≤ 0.001).

The findings were confirmed in a multivariable analysis with adjustments for tumor infiltration, age, treatment parameters, and hormonal replacement therapy, the researchers reported.

Regular sexual activity, vaginal dilation, or both were linked to higher risk of mild vaginal dryness at grade ≥ 1 (72% vs. 67% in the no/infrequent penetration group, P = 0.028) and vaginal bleeding at grade ≥ 1 (61% vs. 34% in the no/infrequent penetration group, P ≤ 0.001). There was no link to higher rates of vaginal mucositis.

Dr. Kirchheiner noted that these symptoms can be treated with lubricants, moisturizer, and hormonal replacement therapy.

As for limitations, Dr. Kirchheiner, in a press release provided by ASTRO, noted that “we cannot and should not randomize patients in a clinical trial into groups with and without regular dilation.” She also noted that future research should explore why sexual intercourse had slightly better results than use of dilators, a finding that could be related to blood flow during sexual arousal.

In comments at the news briefing, Akila Viswanathan, MD, MPH, MSc, director of Radiation Oncology and Molecular Radiation Sciences at Johns Hopkins Medicine, Baltimore, praised the new study and noted that quality of life after cervical cancer treatment is “very understudied.”

Vaginal side effects in particular are underreported because physicians often fail to ask about them and patients “are hesitant to accurately describe what they’re feeling,” she said.

The interventions of providing medical dilators and encouraging sexual activity are “very low cost,” Dr. Viswanathan said. But she noted that women – especially older women – may “find the concepts of using a dilator very difficult to understand.”

The study offers the “best evidence to date” supporting vaginal dilation, said Yale University, New Haven, Conn., radiation oncologist Shari Damast, MD, in an interview. It has “a large dataset, longitudinal design, lengthy follow-up, and uses validated tools of measurement. It gives us strong confidence in the efficacy of vaginal dilators.”

In an interview, Deborah Watkins Bruner, RN, PhD, senior vice president for research at Emory University, Atlanta, also praised the research. But she noted that it’s not clear how often vaginal dilation/sexual intercourse should be performed in order to reduce stenosis. “In addition, it is clear that vaginal dilation only is not enough to treat the myriad of symptoms that survivors must deal with,” she said.

Dr. Bruner urged colleagues “to routinely assess symptoms at each visit and offer treatments which should include hormone replacement therapy, vaginal dilation, and appropriate referral for anxiety, depression, or marital problems.”

The study was funded by Elekta and Varian Medical System via the Medical University of Vienna. The study authors, Dr. Bruner, and Dr. Damast have no disclosures. Disclosure information for Dr. Viswanathan was not available.
 

SAN DIEGO – Engaging in sexual intercourse and vaginal dilation appears to lower the risk of stenosis, the narrowing/shortening of the vaginal canal, after chemoradiation treatment for cervical cancer, a new 5-year prospective study reports.

Findings from the EMBRACE study were presented at the annual American Society for Radiation Oncology (ASTRO) meeting and included 882 women with locally advanced cervical cancer. Of those, 565 women reported regular vaginal dilation and/or sexual intercourse during at least three of their follow-up assessments. Patients who reported both dilation and intercourse had the lowest risk of developing vaginal stenosis of grade ≥ 2 (18%) at 5 years.

The other 317 women were described in the study as having no penetration (13%) or infrequent penetration (23%) and were more likely to experience stenosis of grade ≥ 2 (36% and 37% respectively (P ≤ 0.001)), reported psycho-oncologist, clinical psychologist Kathrin Kirchheiner, PhD, MSc, of the Medical University of Vienna, and colleagues at ASTRO 2023.

While noting that the observational study cannot determine cause and effect, “these long-term data support clinical recommendations worldwide,” said Dr. Kirchheiner at an ASTRO news briefing.

According to Dr. Kirchheiner, external beam radiotherapy, chemotherapy, and internal brachytherapy are the standard of care for locally advanced cervical cancer that cannot be removed by surgery.

Studies have shown that the treatment can cause vaginal shortening and narrowing due to the formation of scar tissue, she said. As a result, there can be “permanent changes in the vaginal tissue that lead to a loss of elasticity. This can often cause problems during the gynecological follow-up examination and pain during sexual intercourse.”

In an earlier reported 2-year analysis of the EMBRACE study (median follow-up of 15 months), the study authors reported that 89% of 588 patients developed grade ≥ 1 vaginal stenosis following their treatment, with 29% at grade ≥ 2 and 3.6% at grade ≥ 3.

The use of medical dilators is commonly recommended after cervical cancer treatment to stretch the vaginal canal. Women are instructed to increase the dilator size over time. But research suggests that adherence may be low.

For the observational, multi-institution study, researchers tracked 1,416 cervical cancer patients from 2008 to 2015 for a median follow-up of 5 years. The new analysis focuses on 882 patients with at least three follow-up assessments, with a median age of 49. Researchers reported that patients who didn’t engage in intercourse or use dilators were most likely to experience vaginal stenosis (37%) vs. those who did both (18%), those who just had intercourse (23%), and those who only used dilators (28%) (P ≤ 0.001).

The findings were confirmed in a multivariable analysis with adjustments for tumor infiltration, age, treatment parameters, and hormonal replacement therapy, the researchers reported.

Regular sexual activity, vaginal dilation, or both were linked to higher risk of mild vaginal dryness at grade ≥ 1 (72% vs. 67% in the no/infrequent penetration group, P = 0.028) and vaginal bleeding at grade ≥ 1 (61% vs. 34% in the no/infrequent penetration group, P ≤ 0.001). There was no link to higher rates of vaginal mucositis.

Dr. Kirchheiner noted that these symptoms can be treated with lubricants, moisturizer, and hormonal replacement therapy.

As for limitations, Dr. Kirchheiner, in a press release provided by ASTRO, noted that “we cannot and should not randomize patients in a clinical trial into groups with and without regular dilation.” She also noted that future research should explore why sexual intercourse had slightly better results than use of dilators, a finding that could be related to blood flow during sexual arousal.

In comments at the news briefing, Akila Viswanathan, MD, MPH, MSc, director of Radiation Oncology and Molecular Radiation Sciences at Johns Hopkins Medicine, Baltimore, praised the new study and noted that quality of life after cervical cancer treatment is “very understudied.”

Vaginal side effects in particular are underreported because physicians often fail to ask about them and patients “are hesitant to accurately describe what they’re feeling,” she said.

The interventions of providing medical dilators and encouraging sexual activity are “very low cost,” Dr. Viswanathan said. But she noted that women – especially older women – may “find the concepts of using a dilator very difficult to understand.”

The study offers the “best evidence to date” supporting vaginal dilation, said Yale University, New Haven, Conn., radiation oncologist Shari Damast, MD, in an interview. It has “a large dataset, longitudinal design, lengthy follow-up, and uses validated tools of measurement. It gives us strong confidence in the efficacy of vaginal dilators.”

In an interview, Deborah Watkins Bruner, RN, PhD, senior vice president for research at Emory University, Atlanta, also praised the research. But she noted that it’s not clear how often vaginal dilation/sexual intercourse should be performed in order to reduce stenosis. “In addition, it is clear that vaginal dilation only is not enough to treat the myriad of symptoms that survivors must deal with,” she said.

Dr. Bruner urged colleagues “to routinely assess symptoms at each visit and offer treatments which should include hormone replacement therapy, vaginal dilation, and appropriate referral for anxiety, depression, or marital problems.”

The study was funded by Elekta and Varian Medical System via the Medical University of Vienna. The study authors, Dr. Bruner, and Dr. Damast have no disclosures. Disclosure information for Dr. Viswanathan was not available.
 

CHICAGO – The US Department of Veterans Affairs (VA) top medical officer told the Association of VA Hematology/Oncology (AVAHO) oncology members that they are at the forefront of the agency’s push to expand care for veterans who may have been injured by exposure to hazardous materials on the job.

“All of you are playing a critical role in implementing the PACT Act, the signature legislative achievement of the Biden administration,” said Shereef Elnahal, MD, MBA, the VA Under Secretary for Health, in a keynote address at the 2023 annual meeting of AVAHO. “But more importantly, if we do our jobs right, it could be the largest expansion of veterans’ benefits in the history of this country. That requires us to have the capacity to deliver care to so many more individuals.”

The VA has provided more than 4.1 million free toxic exposure screenings to veterans since President Biden signed the PACT Act (The Sergeant First Class Heath Robinson Honoring our Promise to Address Comprehensive Toxics Act) in August 2022. The legislation prioritizes claims for cancer, terminal illnesses, and homelessness, and the White House says it has allowed the Veterans Health Administration and the Veterans Benefits Administration to grow at the fastest rates in 2 decades. 

“Almost every type of solid tumor is now considered a presumptive condition associated with burden of exposure to veterans deployed anywhere in Central Command, either in the Persian Gulf War or the post-9/11 conflicts,” said Under Secretary Elnahal, who was confirmed in his job by the Senate in July 2022. 

Implementing the PACT Act “requires all of us to make investments and further strengthen our system’s care for oncology,” he said. It is also crucial, to reduce “leakage into the community,” referring to veterans who leave the VA for private care. “I know for a fact that the care that veterans get when they have oncology services available in our direct-care system within VA is better. That's not a contention. That is proven by different peer-reviewed studies over the years. And I think that comparison is only intensifying when it comes to how much better evidence-based care our veterans receive at the hands of all of you across the country.”

Elnahal highlighted the development of a “2-way” cancer registry that will allow the National Institute and the VA to exchange cancer diagnosis and treatment data with state registries. “This will give the VA access to critical data in a complete way—to what veterans have experienced, especially veterans who are getting parts of their care in one place and parts of their care in a different place.”

On the data front, he also noted that “the PACT Act also requires us to research the future and determine the next set of presumptive conditions that are related to the hazards of serving our country. It requires that we have robust data sets to be able to gain those insights.”
More globally, Elnahal said the VA can play a crucial role in the Cancer Moonshot Program: “We can win the race, and VA can contribute asymmetrically to that race, to make cancer a chronic condition.”

He highlighted efforts within the VA to battle cancer such as programs to reduce disparities, boost cancer screening, treat rural veterans via a national teleoncology service, and implement the Close to Me program to bring infusion services to veterans in isolated regions.

But Elnahal’s presentation was not entirely rosy. He warned that 40% of veterans are being served outside the VA. “That's sort of a rule-of-thumb threshold when you start looking more like a payer than a provider.”

He also noted that while the VA hired 54,000 people in just the past year—6.2% growth—it takes a long time to bring workers on board. “That’s why I'm holding every single leader in our system accountable for reducing onboarding times by at least a month,” he said. The AVAHO audience enthusiastically applauded.

CHICAGO – The US Department of Veterans Affairs (VA) top medical officer told the Association of VA Hematology/Oncology (AVAHO) oncology members that they are at the forefront of the agency’s push to expand care for veterans who may have been injured by exposure to hazardous materials on the job.

“All of you are playing a critical role in implementing the PACT Act, the signature legislative achievement of the Biden administration,” said Shereef Elnahal, MD, MBA, the VA Under Secretary for Health, in a keynote address at the 2023 annual meeting of AVAHO. “But more importantly, if we do our jobs right, it could be the largest expansion of veterans’ benefits in the history of this country. That requires us to have the capacity to deliver care to so many more individuals.”

The VA has provided more than 4.1 million free toxic exposure screenings to veterans since President Biden signed the PACT Act (The Sergeant First Class Heath Robinson Honoring our Promise to Address Comprehensive Toxics Act) in August 2022. The legislation prioritizes claims for cancer, terminal illnesses, and homelessness, and the White House says it has allowed the Veterans Health Administration and the Veterans Benefits Administration to grow at the fastest rates in 2 decades. 

“Almost every type of solid tumor is now considered a presumptive condition associated with burden of exposure to veterans deployed anywhere in Central Command, either in the Persian Gulf War or the post-9/11 conflicts,” said Under Secretary Elnahal, who was confirmed in his job by the Senate in July 2022. 

Implementing the PACT Act “requires all of us to make investments and further strengthen our system’s care for oncology,” he said. It is also crucial, to reduce “leakage into the community,” referring to veterans who leave the VA for private care. “I know for a fact that the care that veterans get when they have oncology services available in our direct-care system within VA is better. That's not a contention. That is proven by different peer-reviewed studies over the years. And I think that comparison is only intensifying when it comes to how much better evidence-based care our veterans receive at the hands of all of you across the country.”

Elnahal highlighted the development of a “2-way” cancer registry that will allow the National Institute and the VA to exchange cancer diagnosis and treatment data with state registries. “This will give the VA access to critical data in a complete way—to what veterans have experienced, especially veterans who are getting parts of their care in one place and parts of their care in a different place.”

On the data front, he also noted that “the PACT Act also requires us to research the future and determine the next set of presumptive conditions that are related to the hazards of serving our country. It requires that we have robust data sets to be able to gain those insights.”
More globally, Elnahal said the VA can play a crucial role in the Cancer Moonshot Program: “We can win the race, and VA can contribute asymmetrically to that race, to make cancer a chronic condition.”

He highlighted efforts within the VA to battle cancer such as programs to reduce disparities, boost cancer screening, treat rural veterans via a national teleoncology service, and implement the Close to Me program to bring infusion services to veterans in isolated regions.

But Elnahal’s presentation was not entirely rosy. He warned that 40% of veterans are being served outside the VA. “That's sort of a rule-of-thumb threshold when you start looking more like a payer than a provider.”

He also noted that while the VA hired 54,000 people in just the past year—6.2% growth—it takes a long time to bring workers on board. “That’s why I'm holding every single leader in our system accountable for reducing onboarding times by at least a month,” he said. The AVAHO audience enthusiastically applauded.

CHICAGO – The US Department of Veterans Affairs (VA) top medical officer told the Association of VA Hematology/Oncology (AVAHO) oncology members that they are at the forefront of the agency’s push to expand care for veterans who may have been injured by exposure to hazardous materials on the job.

“All of you are playing a critical role in implementing the PACT Act, the signature legislative achievement of the Biden administration,” said Shereef Elnahal, MD, MBA, the VA Under Secretary for Health, in a keynote address at the 2023 annual meeting of AVAHO. “But more importantly, if we do our jobs right, it could be the largest expansion of veterans’ benefits in the history of this country. That requires us to have the capacity to deliver care to so many more individuals.”

The VA has provided more than 4.1 million free toxic exposure screenings to veterans since President Biden signed the PACT Act (The Sergeant First Class Heath Robinson Honoring our Promise to Address Comprehensive Toxics Act) in August 2022. The legislation prioritizes claims for cancer, terminal illnesses, and homelessness, and the White House says it has allowed the Veterans Health Administration and the Veterans Benefits Administration to grow at the fastest rates in 2 decades. 

“Almost every type of solid tumor is now considered a presumptive condition associated with burden of exposure to veterans deployed anywhere in Central Command, either in the Persian Gulf War or the post-9/11 conflicts,” said Under Secretary Elnahal, who was confirmed in his job by the Senate in July 2022. 

Implementing the PACT Act “requires all of us to make investments and further strengthen our system’s care for oncology,” he said. It is also crucial, to reduce “leakage into the community,” referring to veterans who leave the VA for private care. “I know for a fact that the care that veterans get when they have oncology services available in our direct-care system within VA is better. That's not a contention. That is proven by different peer-reviewed studies over the years. And I think that comparison is only intensifying when it comes to how much better evidence-based care our veterans receive at the hands of all of you across the country.”

Elnahal highlighted the development of a “2-way” cancer registry that will allow the National Institute and the VA to exchange cancer diagnosis and treatment data with state registries. “This will give the VA access to critical data in a complete way—to what veterans have experienced, especially veterans who are getting parts of their care in one place and parts of their care in a different place.”

On the data front, he also noted that “the PACT Act also requires us to research the future and determine the next set of presumptive conditions that are related to the hazards of serving our country. It requires that we have robust data sets to be able to gain those insights.”
More globally, Elnahal said the VA can play a crucial role in the Cancer Moonshot Program: “We can win the race, and VA can contribute asymmetrically to that race, to make cancer a chronic condition.”

He highlighted efforts within the VA to battle cancer such as programs to reduce disparities, boost cancer screening, treat rural veterans via a national teleoncology service, and implement the Close to Me program to bring infusion services to veterans in isolated regions.

But Elnahal’s presentation was not entirely rosy. He warned that 40% of veterans are being served outside the VA. “That's sort of a rule-of-thumb threshold when you start looking more like a payer than a provider.”

He also noted that while the VA hired 54,000 people in just the past year—6.2% growth—it takes a long time to bring workers on board. “That’s why I'm holding every single leader in our system accountable for reducing onboarding times by at least a month,” he said. The AVAHO audience enthusiastically applauded.

Transgender patients in the United States and Canada told researchers that they often face voyeuristic and stigmatizing treatment in medical clinics and they fear they’re getting substandard care.

“Transgender people feel that their care worsens when clinicians learn that they are transgender, and thus they often have to choose between stigma if clinicians learn that they are transgender and potentially ineffective clinical problem-solving if they do not,” said Yale Cancer Center instructor of medicine Ash B. Alpert, MD, MFA, lead author of the study, which was published in Annals of Family Medicine. For the qualitative study, researchers held seven online focus groups with 30 transgender adults (median age, 31; age range, 20-67; 40% people of color; and 47% with incomes of more than $40,000 a year). All but one were from the United States.

According to the study, the participants said clinicians often ask “irrelevant” questions, sometimes with intentions that appear voyeuristic. “I saw a pulmonologist earlier in the year and one of his first questions was, ‘When are you getting genital surgery?’ and I was like, ‘I’m here for my lungs,’ ” said a White, nonbinary participant. A White male participant said “As soon as I walk in, no matter what I’m there for, the first [order] of business is for them to determine my gender or sex assigned at birth ... and ... once they ... know they’re ... much more at ease.”

Participants also described how medical encounters went awry once clinicians realized they were transgender. “It wasn’t until after I told the doctor that I was on hormones for transition that I started being ‘he’d.’ ” Before that, it was “she,” said a Black transgender woman.

One participant, a Black person who declined to identify by gender, said “I don’t feel comfortable sharing medical records with physicians anyway because it’s a guarantee that I’m not gonna get services. So I lost [my medical records] and they’re good wherever they are now, far away from me.”

Ten participants were clinicians. “Many seemed concerned that transgender people are being put in distressing and difficult situations in medical settings and also seemed dubious that health care for transgender people would improve without a complete overhaul,” Dr. Alpert said.

In an interview, Boston University assistant professor of medicine C. Streed Jr., MD, MPH, who studies gender and health, praised the study. He said it plays an early role in revealing the problems faced by transgender people in the health system.

“We do not fully know the experience of transgender persons accessing care in various contexts, especially in specialty care such as oncology, pulmonology, nephrology, etc.” Dr. Streed said. “We do not know how they identify specialists who are welcoming, compassionate, and competent in care for transgender persons.”

The results aren’t surprising, Dr. Streed said, “given the lack of training in medical school, residency, and fellowship specific to the unique needs of transgender persons.”
 

How can clinicians improve interactions with transgender people?

What can clinicians do to help transgender patients feel comfortable? Dr. Alpert suggested they “ask [only] for medically relevant information and to explain to patients why it is medically relevant.”

“This is important because transgender people are often weighing the risks and benefits of disclosing information that could be used to stigmatize them,” Dr. Alpert said.

What if a clinician wants to create a personal connection with a patient by asking questions about their life? “If you as a clinician think it’s important to ask for nonmedical information to get to know a patient, explicitly clarify that your questions are optional and not medically relevant,” Dr. Alpert said. “That way patients have the ability to consent or not to questions that likely will not directly benefit their care.”

Dr. Streed offered a similar perspective. “Clinicians should only be asking questions of patients that will affect the care the patient is seeking and for which the clinician is trained to provide,” he said. “Having a transgender patient is not an opportunity for a clinician to satisfy their curiosity when it is not related to the care the patient is seeking or needs.”

More specifically, Dr. Streed offered an example: Clinicians should not be asking about a patient’s genitals if they are seeking care related to their asthma diagnosis.

Dr. Streed referred clinicians to resources from the American Medical Association and the Human Rights Campaign for guidelines on caring for transgender patients.

The study was funded by Conquer Cancer. The study authors and Dr. Streed have no relevant disclosures.
 

Transgender patients in the United States and Canada told researchers that they often face voyeuristic and stigmatizing treatment in medical clinics and they fear they’re getting substandard care.

“Transgender people feel that their care worsens when clinicians learn that they are transgender, and thus they often have to choose between stigma if clinicians learn that they are transgender and potentially ineffective clinical problem-solving if they do not,” said Yale Cancer Center instructor of medicine Ash B. Alpert, MD, MFA, lead author of the study, which was published in Annals of Family Medicine. For the qualitative study, researchers held seven online focus groups with 30 transgender adults (median age, 31; age range, 20-67; 40% people of color; and 47% with incomes of more than $40,000 a year). All but one were from the United States.

According to the study, the participants said clinicians often ask “irrelevant” questions, sometimes with intentions that appear voyeuristic. “I saw a pulmonologist earlier in the year and one of his first questions was, ‘When are you getting genital surgery?’ and I was like, ‘I’m here for my lungs,’ ” said a White, nonbinary participant. A White male participant said “As soon as I walk in, no matter what I’m there for, the first [order] of business is for them to determine my gender or sex assigned at birth ... and ... once they ... know they’re ... much more at ease.”

Participants also described how medical encounters went awry once clinicians realized they were transgender. “It wasn’t until after I told the doctor that I was on hormones for transition that I started being ‘he’d.’ ” Before that, it was “she,” said a Black transgender woman.

One participant, a Black person who declined to identify by gender, said “I don’t feel comfortable sharing medical records with physicians anyway because it’s a guarantee that I’m not gonna get services. So I lost [my medical records] and they’re good wherever they are now, far away from me.”

Ten participants were clinicians. “Many seemed concerned that transgender people are being put in distressing and difficult situations in medical settings and also seemed dubious that health care for transgender people would improve without a complete overhaul,” Dr. Alpert said.

In an interview, Boston University assistant professor of medicine C. Streed Jr., MD, MPH, who studies gender and health, praised the study. He said it plays an early role in revealing the problems faced by transgender people in the health system.

“We do not fully know the experience of transgender persons accessing care in various contexts, especially in specialty care such as oncology, pulmonology, nephrology, etc.” Dr. Streed said. “We do not know how they identify specialists who are welcoming, compassionate, and competent in care for transgender persons.”

The results aren’t surprising, Dr. Streed said, “given the lack of training in medical school, residency, and fellowship specific to the unique needs of transgender persons.”
 

How can clinicians improve interactions with transgender people?

What can clinicians do to help transgender patients feel comfortable? Dr. Alpert suggested they “ask [only] for medically relevant information and to explain to patients why it is medically relevant.”

“This is important because transgender people are often weighing the risks and benefits of disclosing information that could be used to stigmatize them,” Dr. Alpert said.

What if a clinician wants to create a personal connection with a patient by asking questions about their life? “If you as a clinician think it’s important to ask for nonmedical information to get to know a patient, explicitly clarify that your questions are optional and not medically relevant,” Dr. Alpert said. “That way patients have the ability to consent or not to questions that likely will not directly benefit their care.”

Dr. Streed offered a similar perspective. “Clinicians should only be asking questions of patients that will affect the care the patient is seeking and for which the clinician is trained to provide,” he said. “Having a transgender patient is not an opportunity for a clinician to satisfy their curiosity when it is not related to the care the patient is seeking or needs.”

More specifically, Dr. Streed offered an example: Clinicians should not be asking about a patient’s genitals if they are seeking care related to their asthma diagnosis.

Dr. Streed referred clinicians to resources from the American Medical Association and the Human Rights Campaign for guidelines on caring for transgender patients.

The study was funded by Conquer Cancer. The study authors and Dr. Streed have no relevant disclosures.
 

Transgender patients in the United States and Canada told researchers that they often face voyeuristic and stigmatizing treatment in medical clinics and they fear they’re getting substandard care.

“Transgender people feel that their care worsens when clinicians learn that they are transgender, and thus they often have to choose between stigma if clinicians learn that they are transgender and potentially ineffective clinical problem-solving if they do not,” said Yale Cancer Center instructor of medicine Ash B. Alpert, MD, MFA, lead author of the study, which was published in Annals of Family Medicine. For the qualitative study, researchers held seven online focus groups with 30 transgender adults (median age, 31; age range, 20-67; 40% people of color; and 47% with incomes of more than $40,000 a year). All but one were from the United States.

According to the study, the participants said clinicians often ask “irrelevant” questions, sometimes with intentions that appear voyeuristic. “I saw a pulmonologist earlier in the year and one of his first questions was, ‘When are you getting genital surgery?’ and I was like, ‘I’m here for my lungs,’ ” said a White, nonbinary participant. A White male participant said “As soon as I walk in, no matter what I’m there for, the first [order] of business is for them to determine my gender or sex assigned at birth ... and ... once they ... know they’re ... much more at ease.”

Participants also described how medical encounters went awry once clinicians realized they were transgender. “It wasn’t until after I told the doctor that I was on hormones for transition that I started being ‘he’d.’ ” Before that, it was “she,” said a Black transgender woman.

One participant, a Black person who declined to identify by gender, said “I don’t feel comfortable sharing medical records with physicians anyway because it’s a guarantee that I’m not gonna get services. So I lost [my medical records] and they’re good wherever they are now, far away from me.”

Ten participants were clinicians. “Many seemed concerned that transgender people are being put in distressing and difficult situations in medical settings and also seemed dubious that health care for transgender people would improve without a complete overhaul,” Dr. Alpert said.

In an interview, Boston University assistant professor of medicine C. Streed Jr., MD, MPH, who studies gender and health, praised the study. He said it plays an early role in revealing the problems faced by transgender people in the health system.

“We do not fully know the experience of transgender persons accessing care in various contexts, especially in specialty care such as oncology, pulmonology, nephrology, etc.” Dr. Streed said. “We do not know how they identify specialists who are welcoming, compassionate, and competent in care for transgender persons.”

The results aren’t surprising, Dr. Streed said, “given the lack of training in medical school, residency, and fellowship specific to the unique needs of transgender persons.”
 

How can clinicians improve interactions with transgender people?

What can clinicians do to help transgender patients feel comfortable? Dr. Alpert suggested they “ask [only] for medically relevant information and to explain to patients why it is medically relevant.”

“This is important because transgender people are often weighing the risks and benefits of disclosing information that could be used to stigmatize them,” Dr. Alpert said.

What if a clinician wants to create a personal connection with a patient by asking questions about their life? “If you as a clinician think it’s important to ask for nonmedical information to get to know a patient, explicitly clarify that your questions are optional and not medically relevant,” Dr. Alpert said. “That way patients have the ability to consent or not to questions that likely will not directly benefit their care.”

Dr. Streed offered a similar perspective. “Clinicians should only be asking questions of patients that will affect the care the patient is seeking and for which the clinician is trained to provide,” he said. “Having a transgender patient is not an opportunity for a clinician to satisfy their curiosity when it is not related to the care the patient is seeking or needs.”

More specifically, Dr. Streed offered an example: Clinicians should not be asking about a patient’s genitals if they are seeking care related to their asthma diagnosis.

Dr. Streed referred clinicians to resources from the American Medical Association and the Human Rights Campaign for guidelines on caring for transgender patients.

The study was funded by Conquer Cancer. The study authors and Dr. Streed have no relevant disclosures.
 

A Miami-area nurse practitioner has been convicted of defrauding Medicare by submitting fraudulent claims for more than $200 million worth of unnecessary genetic testing and medical equipment, federal prosecutors announced.

Elizabeth Hernandez, 45, of Homestead, Fla., could face as many as 75 years in prison when she’s sentenced on December 14.

Ms. Hernandez overbilled Medicare by more than $200 million, according to prosecutors who say she ordered more cancer genetic tests for Medicare beneficiaries in 2020 than any other clinician in the nation. She “personally pocketed approximately $1.6 million in the scheme, which she used to purchase expensive cars, jewelry, home renovations, and travel,” prosecutors said.

After a 6-day trial, Ms. Hernandez was convicted last week of a single count of conspiracy to commit health care fraud and wire fraud, four counts of health care fraud and three counts of making false statements relating to health care matters. She was acquitted of two counts of health care fraud.

The case is part of an ongoing effort by federal prosecutors to target schemes alleged to have defrauded Medicare of billions of dollars in reimbursement for genetic testing and other health services.

Prosecutors alleged that Ms. Hernandez took advantage of the flexible telemedicine rules allowed during the COVID-19 pandemic, and she and another nurse “essentially robo-signed” the orders.

As part of the scheme, telemarketing companies would contact Medicare beneficiaries to convince them to request orthotic braces and genetic tests, and then send prefilled orders for these products to Ms. Hernandez, who signed them, attesting that she had examined or treated the patients, prosecutors said in a statement.

According to prosecutors, Ms. Hernandez billed Medicare as if she had performed complex in-person evaluations of patients. The time she attested she spent on these supposed office visits often accounted for more than 24 hours in a day. Prosecutors said Ms. Hernandez never examined the patients for whom she ordered $14 million in medical equipment, and that she lied when she certified that she’d personally examined them and determined the supplies were necessary.

Prosecutors also alleged that Ms. Hernandez ordered $119 million worth of unnecessary genetic tests for patients she wasn’t treating. The tests include “cancer genetic” (CGx) tests, which look for mutations that may raise the risk of certain diseases, and pharmacogenetic (PGx) tests, which can provide information about how patients will respond to medications.

According to prosecutors, Medicare only rarely covers CGx tests, doing so primarily when a patient has cancer and the patient’s physician orders such tests to improve treatment.

Ms. Hernandez also allegedly submitted claims for $1.3 million worth of telemedicine consultations that were not performed.

Prosecutors later put the total amount of fraudulent claims at more than $200 million.

Federal prosecutors also alleged that several companies that claimed to be in the telemedicine business gave bribes and kickbacks to Ms. Hernandez.

In recent years, federal officials have increasingly targeted schemes to defraud Medicare through fake claims for genetic testing. In 2020, for instance, prosecutors charged 345 defendants, including more than 100 doctors, nurses, and other licensed medical professionals, with submitting more than $6 billion in fraudulent claims for genetic testing and other services.

Last December, a Georgia man was convicted in a scheme alleged to have cost Medicare $463 million. He was accused of having “conspired with patient brokers, telemedicine companies, and call centers to target Medicare beneficiaries with telemarketing calls falsely stating that Medicare covered expensive cancer genetic tests,” according to a statement from federal prosecutors.

In a 2021 report, the inspector general of the U.S. Department of Health & Human Services warned that a sharp rise in Medicare payments for genetic tests could be a sign of fraud even as federal guidance related to coverage for genetic testing has been inconsistent. The payments quadrupled to $1.41 billion from 2016 to 2019.

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

A Miami-area nurse practitioner has been convicted of defrauding Medicare by submitting fraudulent claims for more than $200 million worth of unnecessary genetic testing and medical equipment, federal prosecutors announced.

Elizabeth Hernandez, 45, of Homestead, Fla., could face as many as 75 years in prison when she’s sentenced on December 14.

Ms. Hernandez overbilled Medicare by more than $200 million, according to prosecutors who say she ordered more cancer genetic tests for Medicare beneficiaries in 2020 than any other clinician in the nation. She “personally pocketed approximately $1.6 million in the scheme, which she used to purchase expensive cars, jewelry, home renovations, and travel,” prosecutors said.

After a 6-day trial, Ms. Hernandez was convicted last week of a single count of conspiracy to commit health care fraud and wire fraud, four counts of health care fraud and three counts of making false statements relating to health care matters. She was acquitted of two counts of health care fraud.

The case is part of an ongoing effort by federal prosecutors to target schemes alleged to have defrauded Medicare of billions of dollars in reimbursement for genetic testing and other health services.

Prosecutors alleged that Ms. Hernandez took advantage of the flexible telemedicine rules allowed during the COVID-19 pandemic, and she and another nurse “essentially robo-signed” the orders.

As part of the scheme, telemarketing companies would contact Medicare beneficiaries to convince them to request orthotic braces and genetic tests, and then send prefilled orders for these products to Ms. Hernandez, who signed them, attesting that she had examined or treated the patients, prosecutors said in a statement.

According to prosecutors, Ms. Hernandez billed Medicare as if she had performed complex in-person evaluations of patients. The time she attested she spent on these supposed office visits often accounted for more than 24 hours in a day. Prosecutors said Ms. Hernandez never examined the patients for whom she ordered $14 million in medical equipment, and that she lied when she certified that she’d personally examined them and determined the supplies were necessary.

Prosecutors also alleged that Ms. Hernandez ordered $119 million worth of unnecessary genetic tests for patients she wasn’t treating. The tests include “cancer genetic” (CGx) tests, which look for mutations that may raise the risk of certain diseases, and pharmacogenetic (PGx) tests, which can provide information about how patients will respond to medications.

According to prosecutors, Medicare only rarely covers CGx tests, doing so primarily when a patient has cancer and the patient’s physician orders such tests to improve treatment.

Ms. Hernandez also allegedly submitted claims for $1.3 million worth of telemedicine consultations that were not performed.

Prosecutors later put the total amount of fraudulent claims at more than $200 million.

Federal prosecutors also alleged that several companies that claimed to be in the telemedicine business gave bribes and kickbacks to Ms. Hernandez.

In recent years, federal officials have increasingly targeted schemes to defraud Medicare through fake claims for genetic testing. In 2020, for instance, prosecutors charged 345 defendants, including more than 100 doctors, nurses, and other licensed medical professionals, with submitting more than $6 billion in fraudulent claims for genetic testing and other services.

Last December, a Georgia man was convicted in a scheme alleged to have cost Medicare $463 million. He was accused of having “conspired with patient brokers, telemedicine companies, and call centers to target Medicare beneficiaries with telemarketing calls falsely stating that Medicare covered expensive cancer genetic tests,” according to a statement from federal prosecutors.

In a 2021 report, the inspector general of the U.S. Department of Health & Human Services warned that a sharp rise in Medicare payments for genetic tests could be a sign of fraud even as federal guidance related to coverage for genetic testing has been inconsistent. The payments quadrupled to $1.41 billion from 2016 to 2019.

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

A Miami-area nurse practitioner has been convicted of defrauding Medicare by submitting fraudulent claims for more than $200 million worth of unnecessary genetic testing and medical equipment, federal prosecutors announced.

Elizabeth Hernandez, 45, of Homestead, Fla., could face as many as 75 years in prison when she’s sentenced on December 14.

Ms. Hernandez overbilled Medicare by more than $200 million, according to prosecutors who say she ordered more cancer genetic tests for Medicare beneficiaries in 2020 than any other clinician in the nation. She “personally pocketed approximately $1.6 million in the scheme, which she used to purchase expensive cars, jewelry, home renovations, and travel,” prosecutors said.

After a 6-day trial, Ms. Hernandez was convicted last week of a single count of conspiracy to commit health care fraud and wire fraud, four counts of health care fraud and three counts of making false statements relating to health care matters. She was acquitted of two counts of health care fraud.

The case is part of an ongoing effort by federal prosecutors to target schemes alleged to have defrauded Medicare of billions of dollars in reimbursement for genetic testing and other health services.

Prosecutors alleged that Ms. Hernandez took advantage of the flexible telemedicine rules allowed during the COVID-19 pandemic, and she and another nurse “essentially robo-signed” the orders.

As part of the scheme, telemarketing companies would contact Medicare beneficiaries to convince them to request orthotic braces and genetic tests, and then send prefilled orders for these products to Ms. Hernandez, who signed them, attesting that she had examined or treated the patients, prosecutors said in a statement.

According to prosecutors, Ms. Hernandez billed Medicare as if she had performed complex in-person evaluations of patients. The time she attested she spent on these supposed office visits often accounted for more than 24 hours in a day. Prosecutors said Ms. Hernandez never examined the patients for whom she ordered $14 million in medical equipment, and that she lied when she certified that she’d personally examined them and determined the supplies were necessary.

Prosecutors also alleged that Ms. Hernandez ordered $119 million worth of unnecessary genetic tests for patients she wasn’t treating. The tests include “cancer genetic” (CGx) tests, which look for mutations that may raise the risk of certain diseases, and pharmacogenetic (PGx) tests, which can provide information about how patients will respond to medications.

According to prosecutors, Medicare only rarely covers CGx tests, doing so primarily when a patient has cancer and the patient’s physician orders such tests to improve treatment.

Ms. Hernandez also allegedly submitted claims for $1.3 million worth of telemedicine consultations that were not performed.

Prosecutors later put the total amount of fraudulent claims at more than $200 million.

Federal prosecutors also alleged that several companies that claimed to be in the telemedicine business gave bribes and kickbacks to Ms. Hernandez.

In recent years, federal officials have increasingly targeted schemes to defraud Medicare through fake claims for genetic testing. In 2020, for instance, prosecutors charged 345 defendants, including more than 100 doctors, nurses, and other licensed medical professionals, with submitting more than $6 billion in fraudulent claims for genetic testing and other services.

Last December, a Georgia man was convicted in a scheme alleged to have cost Medicare $463 million. He was accused of having “conspired with patient brokers, telemedicine companies, and call centers to target Medicare beneficiaries with telemarketing calls falsely stating that Medicare covered expensive cancer genetic tests,” according to a statement from federal prosecutors.

In a 2021 report, the inspector general of the U.S. Department of Health & Human Services warned that a sharp rise in Medicare payments for genetic tests could be a sign of fraud even as federal guidance related to coverage for genetic testing has been inconsistent. The payments quadrupled to $1.41 billion from 2016 to 2019.

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

At a glance, “health literacy” sounds like it has something specifically to do with the ability to read. Mary Laudon Thomas, MS, CNS, AOCN, a former president of Association of VA Hematology/Oncology, knows better.

“It’s not the same as reading level, and it’s not the same as educational level,” Thomas told Federal Practitioner. “Even educated people can think men can’t get breast cancer or misunderstand how to properly take their medications.”

Instead, health literacy is a broader topic: Do patients understand what’s going on when they get medical care? Can they use the information they get to make informed decisions about their health? Low health literacy is associated with lower use of preventative care of poorer adherence, poorer ability to navigate the health system and contributes to social inequities. In cancer care, low health literacy is associated with lower levels of screening, longer lag times in symptom identification, impairments in risk perception, fewer questions, lower perceived quality of life, and less follow-up.

Thomas and colleagues explored strategies to improve health literacy in cancer care during a half-day session on September 28th, kicking off the AVAHO 2023 annual meeting in Chicago. 

There are countless examples of patients who fail to understand aspects of their care, said Thomas, a retired clinical nurse specialist in hematology at California’s VA Palo Alto Health Care System who now serves as cochair of the AVAHO education committee. A patient may not realize that high blood pressure and hypertension are the same thing, for instance, or not understand that they need to go to the radiology department for a computed tomography.

“That’s our problem,” Thomas said. “We’re so fluent in our medical-speak that we forget we’re speaking a foreign language to other people.”

The goal of the AVAHO 2023 workshop is to “help people develop awareness of the scope of the problem and give them tools they can use to simplify how they speak to patients, teach patients and inform patients,” Thomas said.

In the first segment of the program, Angela Kumar, MPH, national program manager for Veterans Health Education and Information, discussed the VA organizational approach to health literacy. She noted that building a health-literate care organization aligns with the VA goal to be a high reliability organization. Veterans who have questions and concerns will need additional information throughout their cancer journey. The role for VA clinicians is to help answer veterans’ questions. “Rather than assume patients know what we are talking about, we have to make sure they understand,” Kumar explained. Institutional support will lead to better health outcomes and patient satisfaction throughout the system. VA is in the process of creating a patient centered learning program, Kumar noted. The program will be open to veterans, their families, caregivers, and provide training for VA health care professionals.

In the workshop’s 2 other sessions Janet Papadakos, PhD, MEd, a scientist at the University of Toronto’s Institute for Education Research, discussed the impact of health literacy on cancer treatment and outcomes and Fatemeh Youssefi, PhD, RN, OCN, director at large and committee member of the Oncology Nursing Society, discussed the roles of health literacy and patient education in empowering patients. Both speakers noted that patients with cancer are undergoing intense emotional stress, which can significantly impact their ability to understanding their treatment. Importantly, Papadakos explained, people can change and improve their health literacy, so clinicians have an opportunity to help influence and improve comprehension for their patient, by taking basic steps shown to improve health literacy.

“We know that in general, people with low health literacy report worse health, and they also have historically have poor outcomes,” Thomas said. Indeed, a 2021 systematic review of 66 papers found that “lower health literacy was associated with greater difficulties understanding and processing cancer related information, poorer quality of life and poorer experience of care.” Just 12% of US adults have proficient health literacy and one-third of adults have difficulty with common health tasks.

Papadakos and Youssefi provided some guidance for better communication with patients. Teach back, for example, is a tool to ensure patients understand topics when discussed. The key, Papadakos explained, is that it is not a test of the patient but rather a test of how well the information was communicated. Youssefi and Papadakos also emphasized the importance of using plain language. Clear and precise words that avoid technical terms avoid miscommunication and confusion. Finally, they urged clinicians to never assume health literacy and to approach all patients using clear language to ensure that they understand and can provide back the content covered.

Thomas said 3 more virtual sessions about health literacy will be offered over the coming year. Organizers will develop the specific topics after engaging in a discussion with attendees at the end of the AVAHO session. Meanwhile, advocates are developing a section of the AVAHO website that will be devoted to health literacy.

The workshop received support from Genentech.

At a glance, “health literacy” sounds like it has something specifically to do with the ability to read. Mary Laudon Thomas, MS, CNS, AOCN, a former president of Association of VA Hematology/Oncology, knows better.

“It’s not the same as reading level, and it’s not the same as educational level,” Thomas told Federal Practitioner. “Even educated people can think men can’t get breast cancer or misunderstand how to properly take their medications.”

Instead, health literacy is a broader topic: Do patients understand what’s going on when they get medical care? Can they use the information they get to make informed decisions about their health? Low health literacy is associated with lower use of preventative care of poorer adherence, poorer ability to navigate the health system and contributes to social inequities. In cancer care, low health literacy is associated with lower levels of screening, longer lag times in symptom identification, impairments in risk perception, fewer questions, lower perceived quality of life, and less follow-up.

Thomas and colleagues explored strategies to improve health literacy in cancer care during a half-day session on September 28th, kicking off the AVAHO 2023 annual meeting in Chicago. 

There are countless examples of patients who fail to understand aspects of their care, said Thomas, a retired clinical nurse specialist in hematology at California’s VA Palo Alto Health Care System who now serves as cochair of the AVAHO education committee. A patient may not realize that high blood pressure and hypertension are the same thing, for instance, or not understand that they need to go to the radiology department for a computed tomography.

“That’s our problem,” Thomas said. “We’re so fluent in our medical-speak that we forget we’re speaking a foreign language to other people.”

The goal of the AVAHO 2023 workshop is to “help people develop awareness of the scope of the problem and give them tools they can use to simplify how they speak to patients, teach patients and inform patients,” Thomas said.

In the first segment of the program, Angela Kumar, MPH, national program manager for Veterans Health Education and Information, discussed the VA organizational approach to health literacy. She noted that building a health-literate care organization aligns with the VA goal to be a high reliability organization. Veterans who have questions and concerns will need additional information throughout their cancer journey. The role for VA clinicians is to help answer veterans’ questions. “Rather than assume patients know what we are talking about, we have to make sure they understand,” Kumar explained. Institutional support will lead to better health outcomes and patient satisfaction throughout the system. VA is in the process of creating a patient centered learning program, Kumar noted. The program will be open to veterans, their families, caregivers, and provide training for VA health care professionals.

In the workshop’s 2 other sessions Janet Papadakos, PhD, MEd, a scientist at the University of Toronto’s Institute for Education Research, discussed the impact of health literacy on cancer treatment and outcomes and Fatemeh Youssefi, PhD, RN, OCN, director at large and committee member of the Oncology Nursing Society, discussed the roles of health literacy and patient education in empowering patients. Both speakers noted that patients with cancer are undergoing intense emotional stress, which can significantly impact their ability to understanding their treatment. Importantly, Papadakos explained, people can change and improve their health literacy, so clinicians have an opportunity to help influence and improve comprehension for their patient, by taking basic steps shown to improve health literacy.

“We know that in general, people with low health literacy report worse health, and they also have historically have poor outcomes,” Thomas said. Indeed, a 2021 systematic review of 66 papers found that “lower health literacy was associated with greater difficulties understanding and processing cancer related information, poorer quality of life and poorer experience of care.” Just 12% of US adults have proficient health literacy and one-third of adults have difficulty with common health tasks.

Papadakos and Youssefi provided some guidance for better communication with patients. Teach back, for example, is a tool to ensure patients understand topics when discussed. The key, Papadakos explained, is that it is not a test of the patient but rather a test of how well the information was communicated. Youssefi and Papadakos also emphasized the importance of using plain language. Clear and precise words that avoid technical terms avoid miscommunication and confusion. Finally, they urged clinicians to never assume health literacy and to approach all patients using clear language to ensure that they understand and can provide back the content covered.

Thomas said 3 more virtual sessions about health literacy will be offered over the coming year. Organizers will develop the specific topics after engaging in a discussion with attendees at the end of the AVAHO session. Meanwhile, advocates are developing a section of the AVAHO website that will be devoted to health literacy.

The workshop received support from Genentech.

At a glance, “health literacy” sounds like it has something specifically to do with the ability to read. Mary Laudon Thomas, MS, CNS, AOCN, a former president of Association of VA Hematology/Oncology, knows better.

“It’s not the same as reading level, and it’s not the same as educational level,” Thomas told Federal Practitioner. “Even educated people can think men can’t get breast cancer or misunderstand how to properly take their medications.”

Instead, health literacy is a broader topic: Do patients understand what’s going on when they get medical care? Can they use the information they get to make informed decisions about their health? Low health literacy is associated with lower use of preventative care of poorer adherence, poorer ability to navigate the health system and contributes to social inequities. In cancer care, low health literacy is associated with lower levels of screening, longer lag times in symptom identification, impairments in risk perception, fewer questions, lower perceived quality of life, and less follow-up.

Thomas and colleagues explored strategies to improve health literacy in cancer care during a half-day session on September 28th, kicking off the AVAHO 2023 annual meeting in Chicago. 

There are countless examples of patients who fail to understand aspects of their care, said Thomas, a retired clinical nurse specialist in hematology at California’s VA Palo Alto Health Care System who now serves as cochair of the AVAHO education committee. A patient may not realize that high blood pressure and hypertension are the same thing, for instance, or not understand that they need to go to the radiology department for a computed tomography.

“That’s our problem,” Thomas said. “We’re so fluent in our medical-speak that we forget we’re speaking a foreign language to other people.”

The goal of the AVAHO 2023 workshop is to “help people develop awareness of the scope of the problem and give them tools they can use to simplify how they speak to patients, teach patients and inform patients,” Thomas said.

In the first segment of the program, Angela Kumar, MPH, national program manager for Veterans Health Education and Information, discussed the VA organizational approach to health literacy. She noted that building a health-literate care organization aligns with the VA goal to be a high reliability organization. Veterans who have questions and concerns will need additional information throughout their cancer journey. The role for VA clinicians is to help answer veterans’ questions. “Rather than assume patients know what we are talking about, we have to make sure they understand,” Kumar explained. Institutional support will lead to better health outcomes and patient satisfaction throughout the system. VA is in the process of creating a patient centered learning program, Kumar noted. The program will be open to veterans, their families, caregivers, and provide training for VA health care professionals.

In the workshop’s 2 other sessions Janet Papadakos, PhD, MEd, a scientist at the University of Toronto’s Institute for Education Research, discussed the impact of health literacy on cancer treatment and outcomes and Fatemeh Youssefi, PhD, RN, OCN, director at large and committee member of the Oncology Nursing Society, discussed the roles of health literacy and patient education in empowering patients. Both speakers noted that patients with cancer are undergoing intense emotional stress, which can significantly impact their ability to understanding their treatment. Importantly, Papadakos explained, people can change and improve their health literacy, so clinicians have an opportunity to help influence and improve comprehension for their patient, by taking basic steps shown to improve health literacy.

“We know that in general, people with low health literacy report worse health, and they also have historically have poor outcomes,” Thomas said. Indeed, a 2021 systematic review of 66 papers found that “lower health literacy was associated with greater difficulties understanding and processing cancer related information, poorer quality of life and poorer experience of care.” Just 12% of US adults have proficient health literacy and one-third of adults have difficulty with common health tasks.

Papadakos and Youssefi provided some guidance for better communication with patients. Teach back, for example, is a tool to ensure patients understand topics when discussed. The key, Papadakos explained, is that it is not a test of the patient but rather a test of how well the information was communicated. Youssefi and Papadakos also emphasized the importance of using plain language. Clear and precise words that avoid technical terms avoid miscommunication and confusion. Finally, they urged clinicians to never assume health literacy and to approach all patients using clear language to ensure that they understand and can provide back the content covered.

Thomas said 3 more virtual sessions about health literacy will be offered over the coming year. Organizers will develop the specific topics after engaging in a discussion with attendees at the end of the AVAHO session. Meanwhile, advocates are developing a section of the AVAHO website that will be devoted to health literacy.

The workshop received support from Genentech.

For patients with acute myeloid leukemia (AML), especially those who are older or have relapsed/refractory disease, standard chemotherapy treatments often fail to change their poor clinical trajectories. These days, however, a new era of targeted therapy is improving prognoses somewhat – and raising hopes that even bigger advancements are on the horizon.

“We went almost 3 decades with nothing, then all of a sudden we’ve had nine approvals in 5 or 6 years,” said Harvard Medical School, Boston, leukemia specialist Amir Fathi, MD, in an interview. “We’ve had a lot of advancement and a number of good options emerge.”

However, Dr. Fathi and other hematologists cautioned that the treatment landscape is becoming more complex to navigate. And they noted that prognoses for many older patients with AML remain grim. The expensive new treatments may only extend their lifespans by a matter of months, although some are surviving for years.

As the specialists explained, there are a variety of reasons why AML is especially difficult to treat.

“AML is one of the fastest growing human cancers, with tumor cell doubling times measured in mere hours in some patients. Therefore patients can present critically ill with white blood cell counts in the [hundreds of thousands of white blood cells per microliter instead of the normal range of 4,000-11,000]," said leukemia specialist Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y. “Because blood cells are found in every organ of the body, the sheer volume of rapidly growing cancer cells can overwhelm multiple organ systems in a very short amount of time. These rapid growing cells and the fact that the median age of diagnosis with AML is 67-70 years old makes this a clinically challenging cancer to treat. Chemotherapy strong enough to kill cancer cells run the risk of also harming the patient as well.”

Also, older patients often have comorbidities, and they face risks of infection from both the disease and its treatments, said AML specialist Nicole R. Grieselhuber, MD, PhD, of the Ohio State University, Columbus, in an interview.

Enter targeted therapy, which “has allowed individuals who previously were not candidates for cytotoxic chemotherapy because of their age or possible toxicities to receive effective therapy for AML,” Dr. Wang said. “Therapy directed at specific biological features of AML cells such as mutations (FLT3, IDH1, IDH2) or surface proteins (CD33) can augment the efficacy of conventional chemotherapy or in some cases (i.e., FLT3 inhibitors) be more effective than chemotherapy in controlling AML.”

Targeted therapy drugs “are expected to more selectively kill cancer cells and spare normal counterparts,” she added.

The FDA has approved nine targeted therapy drugs for AML in the last few years.

Retinoic acid and arsenic trioxide therapy for acute promyelocytic leukemia “has transformed this AML subtype into one of the most curable AML diseases,” Dr. Wang said. A 2017 long-term analysis of the drug combination found that complete remission was reached in 96% of 54 high-risk patients and 133 low-risk patients; the 5-year survival rate was 88%. (Some patients also received gemtuzumab ozogamicin, a CD33 antibody-drug conjugate.)

According to Dr. Wang, three FLT3 inhibitors have been approved for AML with the FLT3 mutation: midostaurin and quizartinib in the frontline setting in conjunction with intensive chemotherapy and gilteritinib for relapsed/refractory FLT3-mutant AML.

A 2017 study linked midostaurin plus chemotherapy to longer survival (hazard ratio for death = 0.78; P = .009), versus placebo plus chemotherapy, in patients aged 18-59. This year, a phase 3 randomized trial of quizartinib versus placebo linked the drug to longer survival median overall (31.9 months versus 15.1 months; P = .032) In a 2019 trial, patients who took gilteritinib had longer median overall survival (9.3 months versus 5.6 months; HR for death = 0.64; P < .001).

The success of these treatments “has led FLT3 mutant AML to be reclassified from a poor risk AML subtype to intermediate risk AML,” Dr. Wang said.

A 2022 report about FLT3 inhibitors cautioned, however, that “several drug resistance mechanisms have been identified” and added that “the benefit of FLT3 inhibitor maintenance therapy, either post chemotherapy or post transplant, remains controversial, although several studies are ongoing.”

Gemtuzumab ozogamicin is a monoclonal antibody connected to a chemotherapy drug, according to the American Cancer Society. “The addition of gemtuzumab ozogamicin to intensive chemotherapy has enhanced outcomes of favorable and intermediate risk disease,” Dr. Wang said.

Ivosidenib, olutasidenib, and enasidenib target the IDH1 or IDH2 genes in ADL. “These drugs seem to work by helping the leukemia cells mature (differentiate) into more normal cells,” according to the American Cancer Society. “Because of this, they are sometimes referred to as differentiation agents.”

In older adults, a combination treatment with venetoclax, a BCL-2 inhibitor, and a hypomethylating agent has become standard, Ohio State’s Dr. Grieselhuber said. The treatment is FDA approved.

There are caveats to targeted therapy in AML. The treatments can be enormously expensive, “and even patients with insurance are often shocked by the copay,” Dr. Grieselhuber said. It helps to work with pharmacists, social workers, or nurse navigators to help patients afford the treatments, she said.

Side effects vary by therapy and can include QT elongation and differentiation syndrome.

Most challenging of all, many AML patients still face shortened lifespans even if new treatments are available for them.

“Typically for older patients with AML, the lifespan of patients with therapy was 5-7 months and without therapy was 2-3 months,” Dr. Wang said. “Now, with regimens specifically designed for elderly and/or unfit subjects, many individuals are now routinely living more than a year: 14-18 months to 3-4 years.”

But “the vast majority of AML patients will still die of their disease with overall 5-year outcomes still less than 30% in all age categories,” she said. In addition, “fewer than 50% of AML patients are eligible for treatment with FDA-approved targeted therapies, as their disease biology does not express the mutation or protein needed for efficacy.”

Still, she said, “this represents a vast improvement.” And, she added, “in younger individuals, the combination of chemotherapy followed by allogeneic transplant has now permitted more of these individuals to be cured of their disease.” Dr. Grieselhuber noted that transplants are now considered appropriate even for patients in their 60s or early 70s, and they can be combined with targeted therapy.

Dr. Grieselhuber urged colleagues to keep in mind that quality-of-life preferences will play a role in some patient choices. For example, a elderly patient may reject burdensome infusion therapy and choose a pill instead, even if it has less efficacy. “There’s really no one-size-fits-all,” she said.

And, she added, it can be difficult to make choices about treatment because of the lack of randomized, head-to-head data regarding new therapies.

What’s on the horizon? Dr. Wang highlighted a novel class of targeted therapies called menin inhibitors for patients with NPM1-mutated AML, which she said accounts for one-third of patients with the disease. A treatment targeting disease in the 5%-10% patients with the KMT2A gene is also in the works, she said.

For now, Dr. Wang said it’s essential for clinicians “to perform timely comprehensive molecular and genomic tests on all AML patients at diagnosis and relapse to determine which individuals would benefit from targeted therapy versus cytotoxic chemotherapy. And participation in clinical trials at every stage of AML therapy can help accelerate clinical development of new agents for this disease.”

Dr. Fathi discloses relationships with Daiichi Sankyo, Pfizer, Rigel, Autolus, Amgen, Servier, Takeda, Orum, Menarini, Remix, AbbVie, Astellas, BMS, Ibsen, Gilead, Genentech, and AstraZeneca. Dr. Wang discloses ties with AbbVie, Astellas, BMS, CTI Biopharma, Daiichi Sankyo, Gilead, GSK, Johnson & Johnson, Kite, Kura, Novartis, Pfizer, Rigel, Sellas, and Sumitomo Pharma. Dr. Grieselhuber has no disclosures.

For patients with acute myeloid leukemia (AML), especially those who are older or have relapsed/refractory disease, standard chemotherapy treatments often fail to change their poor clinical trajectories. These days, however, a new era of targeted therapy is improving prognoses somewhat – and raising hopes that even bigger advancements are on the horizon.

“We went almost 3 decades with nothing, then all of a sudden we’ve had nine approvals in 5 or 6 years,” said Harvard Medical School, Boston, leukemia specialist Amir Fathi, MD, in an interview. “We’ve had a lot of advancement and a number of good options emerge.”

However, Dr. Fathi and other hematologists cautioned that the treatment landscape is becoming more complex to navigate. And they noted that prognoses for many older patients with AML remain grim. The expensive new treatments may only extend their lifespans by a matter of months, although some are surviving for years.

As the specialists explained, there are a variety of reasons why AML is especially difficult to treat.

“AML is one of the fastest growing human cancers, with tumor cell doubling times measured in mere hours in some patients. Therefore patients can present critically ill with white blood cell counts in the [hundreds of thousands of white blood cells per microliter instead of the normal range of 4,000-11,000]," said leukemia specialist Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y. “Because blood cells are found in every organ of the body, the sheer volume of rapidly growing cancer cells can overwhelm multiple organ systems in a very short amount of time. These rapid growing cells and the fact that the median age of diagnosis with AML is 67-70 years old makes this a clinically challenging cancer to treat. Chemotherapy strong enough to kill cancer cells run the risk of also harming the patient as well.”

Also, older patients often have comorbidities, and they face risks of infection from both the disease and its treatments, said AML specialist Nicole R. Grieselhuber, MD, PhD, of the Ohio State University, Columbus, in an interview.

Enter targeted therapy, which “has allowed individuals who previously were not candidates for cytotoxic chemotherapy because of their age or possible toxicities to receive effective therapy for AML,” Dr. Wang said. “Therapy directed at specific biological features of AML cells such as mutations (FLT3, IDH1, IDH2) or surface proteins (CD33) can augment the efficacy of conventional chemotherapy or in some cases (i.e., FLT3 inhibitors) be more effective than chemotherapy in controlling AML.”

Targeted therapy drugs “are expected to more selectively kill cancer cells and spare normal counterparts,” she added.

The FDA has approved nine targeted therapy drugs for AML in the last few years.

Retinoic acid and arsenic trioxide therapy for acute promyelocytic leukemia “has transformed this AML subtype into one of the most curable AML diseases,” Dr. Wang said. A 2017 long-term analysis of the drug combination found that complete remission was reached in 96% of 54 high-risk patients and 133 low-risk patients; the 5-year survival rate was 88%. (Some patients also received gemtuzumab ozogamicin, a CD33 antibody-drug conjugate.)

According to Dr. Wang, three FLT3 inhibitors have been approved for AML with the FLT3 mutation: midostaurin and quizartinib in the frontline setting in conjunction with intensive chemotherapy and gilteritinib for relapsed/refractory FLT3-mutant AML.

A 2017 study linked midostaurin plus chemotherapy to longer survival (hazard ratio for death = 0.78; P = .009), versus placebo plus chemotherapy, in patients aged 18-59. This year, a phase 3 randomized trial of quizartinib versus placebo linked the drug to longer survival median overall (31.9 months versus 15.1 months; P = .032) In a 2019 trial, patients who took gilteritinib had longer median overall survival (9.3 months versus 5.6 months; HR for death = 0.64; P < .001).

The success of these treatments “has led FLT3 mutant AML to be reclassified from a poor risk AML subtype to intermediate risk AML,” Dr. Wang said.

A 2022 report about FLT3 inhibitors cautioned, however, that “several drug resistance mechanisms have been identified” and added that “the benefit of FLT3 inhibitor maintenance therapy, either post chemotherapy or post transplant, remains controversial, although several studies are ongoing.”

Gemtuzumab ozogamicin is a monoclonal antibody connected to a chemotherapy drug, according to the American Cancer Society. “The addition of gemtuzumab ozogamicin to intensive chemotherapy has enhanced outcomes of favorable and intermediate risk disease,” Dr. Wang said.

Ivosidenib, olutasidenib, and enasidenib target the IDH1 or IDH2 genes in ADL. “These drugs seem to work by helping the leukemia cells mature (differentiate) into more normal cells,” according to the American Cancer Society. “Because of this, they are sometimes referred to as differentiation agents.”

In older adults, a combination treatment with venetoclax, a BCL-2 inhibitor, and a hypomethylating agent has become standard, Ohio State’s Dr. Grieselhuber said. The treatment is FDA approved.

There are caveats to targeted therapy in AML. The treatments can be enormously expensive, “and even patients with insurance are often shocked by the copay,” Dr. Grieselhuber said. It helps to work with pharmacists, social workers, or nurse navigators to help patients afford the treatments, she said.

Side effects vary by therapy and can include QT elongation and differentiation syndrome.

Most challenging of all, many AML patients still face shortened lifespans even if new treatments are available for them.

“Typically for older patients with AML, the lifespan of patients with therapy was 5-7 months and without therapy was 2-3 months,” Dr. Wang said. “Now, with regimens specifically designed for elderly and/or unfit subjects, many individuals are now routinely living more than a year: 14-18 months to 3-4 years.”

But “the vast majority of AML patients will still die of their disease with overall 5-year outcomes still less than 30% in all age categories,” she said. In addition, “fewer than 50% of AML patients are eligible for treatment with FDA-approved targeted therapies, as their disease biology does not express the mutation or protein needed for efficacy.”

Still, she said, “this represents a vast improvement.” And, she added, “in younger individuals, the combination of chemotherapy followed by allogeneic transplant has now permitted more of these individuals to be cured of their disease.” Dr. Grieselhuber noted that transplants are now considered appropriate even for patients in their 60s or early 70s, and they can be combined with targeted therapy.

Dr. Grieselhuber urged colleagues to keep in mind that quality-of-life preferences will play a role in some patient choices. For example, a elderly patient may reject burdensome infusion therapy and choose a pill instead, even if it has less efficacy. “There’s really no one-size-fits-all,” she said.

And, she added, it can be difficult to make choices about treatment because of the lack of randomized, head-to-head data regarding new therapies.

What’s on the horizon? Dr. Wang highlighted a novel class of targeted therapies called menin inhibitors for patients with NPM1-mutated AML, which she said accounts for one-third of patients with the disease. A treatment targeting disease in the 5%-10% patients with the KMT2A gene is also in the works, she said.

For now, Dr. Wang said it’s essential for clinicians “to perform timely comprehensive molecular and genomic tests on all AML patients at diagnosis and relapse to determine which individuals would benefit from targeted therapy versus cytotoxic chemotherapy. And participation in clinical trials at every stage of AML therapy can help accelerate clinical development of new agents for this disease.”

Dr. Fathi discloses relationships with Daiichi Sankyo, Pfizer, Rigel, Autolus, Amgen, Servier, Takeda, Orum, Menarini, Remix, AbbVie, Astellas, BMS, Ibsen, Gilead, Genentech, and AstraZeneca. Dr. Wang discloses ties with AbbVie, Astellas, BMS, CTI Biopharma, Daiichi Sankyo, Gilead, GSK, Johnson & Johnson, Kite, Kura, Novartis, Pfizer, Rigel, Sellas, and Sumitomo Pharma. Dr. Grieselhuber has no disclosures.

For patients with acute myeloid leukemia (AML), especially those who are older or have relapsed/refractory disease, standard chemotherapy treatments often fail to change their poor clinical trajectories. These days, however, a new era of targeted therapy is improving prognoses somewhat – and raising hopes that even bigger advancements are on the horizon.

“We went almost 3 decades with nothing, then all of a sudden we’ve had nine approvals in 5 or 6 years,” said Harvard Medical School, Boston, leukemia specialist Amir Fathi, MD, in an interview. “We’ve had a lot of advancement and a number of good options emerge.”

However, Dr. Fathi and other hematologists cautioned that the treatment landscape is becoming more complex to navigate. And they noted that prognoses for many older patients with AML remain grim. The expensive new treatments may only extend their lifespans by a matter of months, although some are surviving for years.

As the specialists explained, there are a variety of reasons why AML is especially difficult to treat.

“AML is one of the fastest growing human cancers, with tumor cell doubling times measured in mere hours in some patients. Therefore patients can present critically ill with white blood cell counts in the [hundreds of thousands of white blood cells per microliter instead of the normal range of 4,000-11,000]," said leukemia specialist Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y. “Because blood cells are found in every organ of the body, the sheer volume of rapidly growing cancer cells can overwhelm multiple organ systems in a very short amount of time. These rapid growing cells and the fact that the median age of diagnosis with AML is 67-70 years old makes this a clinically challenging cancer to treat. Chemotherapy strong enough to kill cancer cells run the risk of also harming the patient as well.”

Also, older patients often have comorbidities, and they face risks of infection from both the disease and its treatments, said AML specialist Nicole R. Grieselhuber, MD, PhD, of the Ohio State University, Columbus, in an interview.

Enter targeted therapy, which “has allowed individuals who previously were not candidates for cytotoxic chemotherapy because of their age or possible toxicities to receive effective therapy for AML,” Dr. Wang said. “Therapy directed at specific biological features of AML cells such as mutations (FLT3, IDH1, IDH2) or surface proteins (CD33) can augment the efficacy of conventional chemotherapy or in some cases (i.e., FLT3 inhibitors) be more effective than chemotherapy in controlling AML.”

Targeted therapy drugs “are expected to more selectively kill cancer cells and spare normal counterparts,” she added.

The FDA has approved nine targeted therapy drugs for AML in the last few years.

Retinoic acid and arsenic trioxide therapy for acute promyelocytic leukemia “has transformed this AML subtype into one of the most curable AML diseases,” Dr. Wang said. A 2017 long-term analysis of the drug combination found that complete remission was reached in 96% of 54 high-risk patients and 133 low-risk patients; the 5-year survival rate was 88%. (Some patients also received gemtuzumab ozogamicin, a CD33 antibody-drug conjugate.)

According to Dr. Wang, three FLT3 inhibitors have been approved for AML with the FLT3 mutation: midostaurin and quizartinib in the frontline setting in conjunction with intensive chemotherapy and gilteritinib for relapsed/refractory FLT3-mutant AML.

A 2017 study linked midostaurin plus chemotherapy to longer survival (hazard ratio for death = 0.78; P = .009), versus placebo plus chemotherapy, in patients aged 18-59. This year, a phase 3 randomized trial of quizartinib versus placebo linked the drug to longer survival median overall (31.9 months versus 15.1 months; P = .032) In a 2019 trial, patients who took gilteritinib had longer median overall survival (9.3 months versus 5.6 months; HR for death = 0.64; P < .001).

The success of these treatments “has led FLT3 mutant AML to be reclassified from a poor risk AML subtype to intermediate risk AML,” Dr. Wang said.

A 2022 report about FLT3 inhibitors cautioned, however, that “several drug resistance mechanisms have been identified” and added that “the benefit of FLT3 inhibitor maintenance therapy, either post chemotherapy or post transplant, remains controversial, although several studies are ongoing.”

Gemtuzumab ozogamicin is a monoclonal antibody connected to a chemotherapy drug, according to the American Cancer Society. “The addition of gemtuzumab ozogamicin to intensive chemotherapy has enhanced outcomes of favorable and intermediate risk disease,” Dr. Wang said.

Ivosidenib, olutasidenib, and enasidenib target the IDH1 or IDH2 genes in ADL. “These drugs seem to work by helping the leukemia cells mature (differentiate) into more normal cells,” according to the American Cancer Society. “Because of this, they are sometimes referred to as differentiation agents.”

In older adults, a combination treatment with venetoclax, a BCL-2 inhibitor, and a hypomethylating agent has become standard, Ohio State’s Dr. Grieselhuber said. The treatment is FDA approved.

There are caveats to targeted therapy in AML. The treatments can be enormously expensive, “and even patients with insurance are often shocked by the copay,” Dr. Grieselhuber said. It helps to work with pharmacists, social workers, or nurse navigators to help patients afford the treatments, she said.

Side effects vary by therapy and can include QT elongation and differentiation syndrome.

Most challenging of all, many AML patients still face shortened lifespans even if new treatments are available for them.

“Typically for older patients with AML, the lifespan of patients with therapy was 5-7 months and without therapy was 2-3 months,” Dr. Wang said. “Now, with regimens specifically designed for elderly and/or unfit subjects, many individuals are now routinely living more than a year: 14-18 months to 3-4 years.”

But “the vast majority of AML patients will still die of their disease with overall 5-year outcomes still less than 30% in all age categories,” she said. In addition, “fewer than 50% of AML patients are eligible for treatment with FDA-approved targeted therapies, as their disease biology does not express the mutation or protein needed for efficacy.”

Still, she said, “this represents a vast improvement.” And, she added, “in younger individuals, the combination of chemotherapy followed by allogeneic transplant has now permitted more of these individuals to be cured of their disease.” Dr. Grieselhuber noted that transplants are now considered appropriate even for patients in their 60s or early 70s, and they can be combined with targeted therapy.

Dr. Grieselhuber urged colleagues to keep in mind that quality-of-life preferences will play a role in some patient choices. For example, a elderly patient may reject burdensome infusion therapy and choose a pill instead, even if it has less efficacy. “There’s really no one-size-fits-all,” she said.

And, she added, it can be difficult to make choices about treatment because of the lack of randomized, head-to-head data regarding new therapies.

What’s on the horizon? Dr. Wang highlighted a novel class of targeted therapies called menin inhibitors for patients with NPM1-mutated AML, which she said accounts for one-third of patients with the disease. A treatment targeting disease in the 5%-10% patients with the KMT2A gene is also in the works, she said.

For now, Dr. Wang said it’s essential for clinicians “to perform timely comprehensive molecular and genomic tests on all AML patients at diagnosis and relapse to determine which individuals would benefit from targeted therapy versus cytotoxic chemotherapy. And participation in clinical trials at every stage of AML therapy can help accelerate clinical development of new agents for this disease.”

Dr. Fathi discloses relationships with Daiichi Sankyo, Pfizer, Rigel, Autolus, Amgen, Servier, Takeda, Orum, Menarini, Remix, AbbVie, Astellas, BMS, Ibsen, Gilead, Genentech, and AstraZeneca. Dr. Wang discloses ties with AbbVie, Astellas, BMS, CTI Biopharma, Daiichi Sankyo, Gilead, GSK, Johnson & Johnson, Kite, Kura, Novartis, Pfizer, Rigel, Sellas, and Sumitomo Pharma. Dr. Grieselhuber has no disclosures.

In a new salvo in the dispute over the wisdom of early “bridging” treatment with glucocorticoids in rheumatoid arthritis, Dutch researchers suggested in a new meta-analysis that the American College of Rheumatology guideline is too cautious.

The report, published in Annals of the Rheumatic Diseases, examined three randomized trials of bridging versus nonbridging. The findings “emphasize the benefits of bridging therapy and shows that bridgers are not using more glucocorticoids after their intended bridging period, compared with nonbridgers, during a 2-year follow-up,” study coauthor Sytske Anne Bergstra, PhD, a postdoctoral researcher at Leiden (the Netherlands) University Medical Center, said in an interview.

However, an American researcher who helped create the 2021 ACR guideline is unmoved by the new report. “This publication didn’t do anything to assuage my concerns,” Joel Kremer, MD, founder and president of the Corrona Research Foundation and professor of medicine emeritus at Albany (N.Y.) Medical College, said in an interview.

At issue is whether patients with early RA should be temporarily treated with glucocorticoids in order to provide rapid relief. The ACR’s 2021 guideline on the treatment of RA says short-term glucocorticoids should not be “systematically prescribed” but notes that they are still “frequently necessary to alleviate symptoms” before disease-modifying therapies are given. The guideline adds that “these recommendations were made in recognition of the frequent difficulty tapering glucocorticoids, leading to undesirable prolonged use and the increasing evidence of the negative impact of glucocorticoids on long-term patient outcomes, including risk for infection, osteoporosis, and cardiovascular disease, in RA and other rheumatic diseases.”

For its part, the European Alliance of Associations for Rheumatology’s 2022 recommendations state that short-term glucocorticoids “should be considered when initiating or changing [disease-modifying antirheumatic drugs], in different dose regimens and routes of administration, but should be tapered and discontinued as rapidly as clinically feasible.”

Members of the Dutch team behind the new meta-analysis have been supporters of “bridging” therapy. For the new report, they analyzed three studies, including one led by a member of the team. Each study had at least one arm that randomized patients with RA to glucocorticoid bridging. Patients also took disease-modifying antirheumatic drugs (DMARDs).

There were 252 patients in study arms that started with bridging (mean age, 52 years; 68% female) and 373 other patients (mean age, 53 years; 67% female).

The researchers found that glucocorticoid use was higher in the bridgers at 12 months (odds ratio, 3.27; 95% confidence interval, 1.06-10.08), but the excess risk at 18 months (OR, 1.60; 95% CI, 0.46-5.60) and 24 months (OR, 1.70; 95% CI, 0.58-4.97) dipped below statistical significance. Also, they reported that “bridgers improved more rapidly (P < .001) in the first 6 months and the bridgers required significantly fewer changes in DMARDs (incidence rate ratio, 0.59; 95% CI, 0.38-0.94).”

“Based on our results, combined with two earlier publications [here and here], we show that most patients included in clinical trials with protocolized tapering schedules are able to stop glucocorticoids after bridging,” Dr. Bergstra said. “We also confirm the well-known short-term clinical effects and show that patients using glucocorticoid bridging require fewer DMARD changes. For a re-evaluation of the ACR guideline, this evidence should be combined with the extensive evidence showing short- as well as long-term clinical benefits of glucocorticoid bridging but also with evidence on potential side effects at different doses.”

She added that “implementing predefined tapering protocols may help clinicians and patients to stop glucocorticoids after bridging.” As for limitations, “patients included in these trials may differ from patients in clinical practice. We cannot be sure whether these results can be generalized to the full patient population.”

Mitchel L. Zoler/MDedge News

Dr. Kremer, a coauthor of the ACR guideline, pointed out that the patients who took glucocorticoids early were much more likely to be on them at 12 months.

By definition, “bridging” is temporary, he said, a brief period to help patients tolerate RA until DMARDs kick in. But in the studies, many of the patients clearly took the drugs for extended periods of time. In those cases, “it not a bridge,” and the risk is that “you’re treating people with a lifelong disease with doses of glucocorticoids that have been shown in multiple studies to be dangerous.”

He added that, while the excess likelihood of these patients staying on the drugs at 18 or 24 months wasn’t deemed to be statistically significant in the meta-analysis, the confidence intervals were unusually wide. That raises questions about whether some of the patients actually stay on the drugs.

Dr. Kremer said it can still be appropriate to give glucocorticoids to patients in distress, although it’s crucial in those cases to take the patients off them as soon as possible. It’s best, though, to not prescribe them at all. “If you can avoid it,” he said, “definitely avoid it.”

The study was conducted without outside funding. Dr. Bergstra reported receiving grant funding from Pfizer, and some of the other study authors reported various relationships with industry. Dr. Kremer had no relevant disclosures.

In a new salvo in the dispute over the wisdom of early “bridging” treatment with glucocorticoids in rheumatoid arthritis, Dutch researchers suggested in a new meta-analysis that the American College of Rheumatology guideline is too cautious.

The report, published in Annals of the Rheumatic Diseases, examined three randomized trials of bridging versus nonbridging. The findings “emphasize the benefits of bridging therapy and shows that bridgers are not using more glucocorticoids after their intended bridging period, compared with nonbridgers, during a 2-year follow-up,” study coauthor Sytske Anne Bergstra, PhD, a postdoctoral researcher at Leiden (the Netherlands) University Medical Center, said in an interview.

However, an American researcher who helped create the 2021 ACR guideline is unmoved by the new report. “This publication didn’t do anything to assuage my concerns,” Joel Kremer, MD, founder and president of the Corrona Research Foundation and professor of medicine emeritus at Albany (N.Y.) Medical College, said in an interview.

At issue is whether patients with early RA should be temporarily treated with glucocorticoids in order to provide rapid relief. The ACR’s 2021 guideline on the treatment of RA says short-term glucocorticoids should not be “systematically prescribed” but notes that they are still “frequently necessary to alleviate symptoms” before disease-modifying therapies are given. The guideline adds that “these recommendations were made in recognition of the frequent difficulty tapering glucocorticoids, leading to undesirable prolonged use and the increasing evidence of the negative impact of glucocorticoids on long-term patient outcomes, including risk for infection, osteoporosis, and cardiovascular disease, in RA and other rheumatic diseases.”

For its part, the European Alliance of Associations for Rheumatology’s 2022 recommendations state that short-term glucocorticoids “should be considered when initiating or changing [disease-modifying antirheumatic drugs], in different dose regimens and routes of administration, but should be tapered and discontinued as rapidly as clinically feasible.”

Members of the Dutch team behind the new meta-analysis have been supporters of “bridging” therapy. For the new report, they analyzed three studies, including one led by a member of the team. Each study had at least one arm that randomized patients with RA to glucocorticoid bridging. Patients also took disease-modifying antirheumatic drugs (DMARDs).

There were 252 patients in study arms that started with bridging (mean age, 52 years; 68% female) and 373 other patients (mean age, 53 years; 67% female).

The researchers found that glucocorticoid use was higher in the bridgers at 12 months (odds ratio, 3.27; 95% confidence interval, 1.06-10.08), but the excess risk at 18 months (OR, 1.60; 95% CI, 0.46-5.60) and 24 months (OR, 1.70; 95% CI, 0.58-4.97) dipped below statistical significance. Also, they reported that “bridgers improved more rapidly (P < .001) in the first 6 months and the bridgers required significantly fewer changes in DMARDs (incidence rate ratio, 0.59; 95% CI, 0.38-0.94).”

“Based on our results, combined with two earlier publications [here and here], we show that most patients included in clinical trials with protocolized tapering schedules are able to stop glucocorticoids after bridging,” Dr. Bergstra said. “We also confirm the well-known short-term clinical effects and show that patients using glucocorticoid bridging require fewer DMARD changes. For a re-evaluation of the ACR guideline, this evidence should be combined with the extensive evidence showing short- as well as long-term clinical benefits of glucocorticoid bridging but also with evidence on potential side effects at different doses.”

She added that “implementing predefined tapering protocols may help clinicians and patients to stop glucocorticoids after bridging.” As for limitations, “patients included in these trials may differ from patients in clinical practice. We cannot be sure whether these results can be generalized to the full patient population.”

Mitchel L. Zoler/MDedge News

Dr. Kremer, a coauthor of the ACR guideline, pointed out that the patients who took glucocorticoids early were much more likely to be on them at 12 months.

By definition, “bridging” is temporary, he said, a brief period to help patients tolerate RA until DMARDs kick in. But in the studies, many of the patients clearly took the drugs for extended periods of time. In those cases, “it not a bridge,” and the risk is that “you’re treating people with a lifelong disease with doses of glucocorticoids that have been shown in multiple studies to be dangerous.”

He added that, while the excess likelihood of these patients staying on the drugs at 18 or 24 months wasn’t deemed to be statistically significant in the meta-analysis, the confidence intervals were unusually wide. That raises questions about whether some of the patients actually stay on the drugs.

Dr. Kremer said it can still be appropriate to give glucocorticoids to patients in distress, although it’s crucial in those cases to take the patients off them as soon as possible. It’s best, though, to not prescribe them at all. “If you can avoid it,” he said, “definitely avoid it.”

The study was conducted without outside funding. Dr. Bergstra reported receiving grant funding from Pfizer, and some of the other study authors reported various relationships with industry. Dr. Kremer had no relevant disclosures.

In a new salvo in the dispute over the wisdom of early “bridging” treatment with glucocorticoids in rheumatoid arthritis, Dutch researchers suggested in a new meta-analysis that the American College of Rheumatology guideline is too cautious.

The report, published in Annals of the Rheumatic Diseases, examined three randomized trials of bridging versus nonbridging. The findings “emphasize the benefits of bridging therapy and shows that bridgers are not using more glucocorticoids after their intended bridging period, compared with nonbridgers, during a 2-year follow-up,” study coauthor Sytske Anne Bergstra, PhD, a postdoctoral researcher at Leiden (the Netherlands) University Medical Center, said in an interview.

However, an American researcher who helped create the 2021 ACR guideline is unmoved by the new report. “This publication didn’t do anything to assuage my concerns,” Joel Kremer, MD, founder and president of the Corrona Research Foundation and professor of medicine emeritus at Albany (N.Y.) Medical College, said in an interview.

At issue is whether patients with early RA should be temporarily treated with glucocorticoids in order to provide rapid relief. The ACR’s 2021 guideline on the treatment of RA says short-term glucocorticoids should not be “systematically prescribed” but notes that they are still “frequently necessary to alleviate symptoms” before disease-modifying therapies are given. The guideline adds that “these recommendations were made in recognition of the frequent difficulty tapering glucocorticoids, leading to undesirable prolonged use and the increasing evidence of the negative impact of glucocorticoids on long-term patient outcomes, including risk for infection, osteoporosis, and cardiovascular disease, in RA and other rheumatic diseases.”

For its part, the European Alliance of Associations for Rheumatology’s 2022 recommendations state that short-term glucocorticoids “should be considered when initiating or changing [disease-modifying antirheumatic drugs], in different dose regimens and routes of administration, but should be tapered and discontinued as rapidly as clinically feasible.”

Members of the Dutch team behind the new meta-analysis have been supporters of “bridging” therapy. For the new report, they analyzed three studies, including one led by a member of the team. Each study had at least one arm that randomized patients with RA to glucocorticoid bridging. Patients also took disease-modifying antirheumatic drugs (DMARDs).

There were 252 patients in study arms that started with bridging (mean age, 52 years; 68% female) and 373 other patients (mean age, 53 years; 67% female).

The researchers found that glucocorticoid use was higher in the bridgers at 12 months (odds ratio, 3.27; 95% confidence interval, 1.06-10.08), but the excess risk at 18 months (OR, 1.60; 95% CI, 0.46-5.60) and 24 months (OR, 1.70; 95% CI, 0.58-4.97) dipped below statistical significance. Also, they reported that “bridgers improved more rapidly (P < .001) in the first 6 months and the bridgers required significantly fewer changes in DMARDs (incidence rate ratio, 0.59; 95% CI, 0.38-0.94).”

“Based on our results, combined with two earlier publications [here and here], we show that most patients included in clinical trials with protocolized tapering schedules are able to stop glucocorticoids after bridging,” Dr. Bergstra said. “We also confirm the well-known short-term clinical effects and show that patients using glucocorticoid bridging require fewer DMARD changes. For a re-evaluation of the ACR guideline, this evidence should be combined with the extensive evidence showing short- as well as long-term clinical benefits of glucocorticoid bridging but also with evidence on potential side effects at different doses.”

She added that “implementing predefined tapering protocols may help clinicians and patients to stop glucocorticoids after bridging.” As for limitations, “patients included in these trials may differ from patients in clinical practice. We cannot be sure whether these results can be generalized to the full patient population.”

Mitchel L. Zoler/MDedge News

Dr. Kremer, a coauthor of the ACR guideline, pointed out that the patients who took glucocorticoids early were much more likely to be on them at 12 months.

By definition, “bridging” is temporary, he said, a brief period to help patients tolerate RA until DMARDs kick in. But in the studies, many of the patients clearly took the drugs for extended periods of time. In those cases, “it not a bridge,” and the risk is that “you’re treating people with a lifelong disease with doses of glucocorticoids that have been shown in multiple studies to be dangerous.”

He added that, while the excess likelihood of these patients staying on the drugs at 18 or 24 months wasn’t deemed to be statistically significant in the meta-analysis, the confidence intervals were unusually wide. That raises questions about whether some of the patients actually stay on the drugs.

Dr. Kremer said it can still be appropriate to give glucocorticoids to patients in distress, although it’s crucial in those cases to take the patients off them as soon as possible. It’s best, though, to not prescribe them at all. “If you can avoid it,” he said, “definitely avoid it.”

The study was conducted without outside funding. Dr. Bergstra reported receiving grant funding from Pfizer, and some of the other study authors reported various relationships with industry. Dr. Kremer had no relevant disclosures.