Patient & Survivor Care

SAN DIEGO – Children and young adults with low-risk relapsed or refractory classic Hodgkin lymphoma may be able to skip autologous stem cell transplant.

Patients who received second-line chemoimmunotherapy with nivolumab-brentuximab vedotin, with or without bendamustine, and proceeded to involved-site radiation appeared to have similar survival outcomes to those who received the chemoimmunotherapy combination plus the current second-line standard of care, which includes high-dose therapy and autologous stem cell transplant.

Among 28 patients with low-risk relapsed or refractory Hodgkin lymphoma followed for a median of 32 months, 3-year event-free survival without autologous stem cell transplant was 86.9% and 3-year progression-free survival was 95%, reported Brad Hoppe, MD, MPH, from the Mayo Clinic in Jacksonville, Fla. In contrast, 1-year progression-free survival was 91% among the 44 standard-risk patients who received high-dose therapy and autologous stem cell transplant, according to results of a trial the investigators published online in Blood in late 2022.

The latest results from the phase 2 CheckMate 744 trial were reported at the annual meeting of the American Society of Radiation Oncology.

“The findings suggest that children, adolescents, and young adults with low-risk relapsed classic Hodgkin lymphoma can be salvaged with low-toxicity chemoimmunotherapy and may not require high-dose therapy and transplant for a cure,” Dr. Hoppe said in an oral abstract session.

Andrea Ng, MD, MPH, a radiation oncologist who specializes in treating patients with Hodgkin lymphoma and other hematologic malignancies, said that, while the number of patients in the study was small and the follow-up too short, this option is “certainly something that’s very promising for the future.”

“The use of transplant in relapsed patients, which we have been doing for decades, is based on two very old, small, randomized studies,” said Dr. Ng, from the Dana-Farber Cancer Institute in Boston, who moderated the session.

“So, do we really need to transplant everybody? In the back of our minds, we think that we may be overtreating some patients,” she said.

Several small, retrospective studies exploring treatment with conventional chemotherapy with or without radiation therapy and without transplant in patients with relapsed or refractory Hodgkin lymphoma have demonstrated only modest results.

The CheckMate 744 trial, however, was designed to examine a risk-adapted and response-adapted approach to treating children, adolescents, and young adults with relapsed or refractory classic Hodgkin lymphoma within the setting of modern immunotherapy and targeted therapy. This approach was developed jointly by investigators with the Children’s Oncology Group and Euronet.

In the nonrandomized trial, patients were stratified into low-risk or standard-risk disease categories based on an algorithm that included factors at the time of initial diagnosis and relapse.

Patients were considered low-risk for relapse in three scenarios: (1) if they had initial stage IA or IIA disease that relapsed at least 1 year after the end of therapy; (2) if they had initial stage IA or IIA disease that relapsed between 3 and 12 months from the end of therapy but had received no more than three cycles of chemotherapy and no radiation therapy; or (3) if they had initial stage IB, IIB, or IIIA disease that relapsed more than 12 months after the end of first-line therapy.

To be included in the low-risk category, patients also had to be free of B symptoms or extranodal disease, free of relapse in prior radiation therapy fields, and have no more than four sites of lymphoma. 

Low-risk patients were treated with a combination of nivolumab and brentuximab vedotin, which could be followed by additional brentuximab vedotin and bendamustine for those with a suboptimal response. Patients who achieved complete molecular remission after induction went on to consolidation therapy with involved-site radiation at a total dose of 30 Gy.

Patients considered standard-risk for relapse received the same nivolumab-brentuximab vedotin combination, with or without bendamustine, and then went on to high-dose therapy and autologous stem cell transplant.

In other results for the previously mentioned study published in Blood, the 44 standard-risk patients who received high-dose therapy and autologous stem cell transplant had an objective response rate of 95% – 86% of patients achieved complete molecular remission, and 9% achieved partial molecular remission.

At ASTRO, Dr. Hoppe reported results for the 28 patients with low-risk disease. One patient discontinued nivolumab/brentuximab vedotin after two cycles because of skin toxicity and was lost to follow-up. Of the remaining 27 patients, 21 had complete molecular remission after four cycles of the combination, and these patients went on to an additional two cycles of the combination, with 19 of 21 receiving involved-site radiation consolidation. 

Six patients who had either a partial molecular remission or no response were given two additional cycles of brentuximab vedotin plus bendamustine. Of this group, three went on to complete molecular remission and received involved-site radiation consolidation on protocol. The remaining three patients who did not experience complete molecular remission received involved-site radiation off protocol.

The rate of complete molecular remission after four cycles of induction was 82.1%, and the rate of partial molecular remission was 14.3%, for an objective response rate of 96.4%. The respective response rates with the addition of two cycles of brentuximab vedotin and bendamustine were 92.9% and 7.1%, for an objective response rate of 100%, Dr. Hoppe reported.

Overall, at a median follow-up of 32 months, the 3-year event-free survival rate without transplant was 86.9%, and the 3-year progression-free survival rate was 95%.

Treatment-related adverse events of any grade occurred in 22 patients (78.6%) after induction, with 7 of those events (25%) being grade 3 or 4 in severity. Grade 3 or 4 events consisted of skin and subcutaneous tissue disorders in 3 patients, elevated liver function tests in 3 patients, and blood and lymphatic system disorders in 1 patient.

There were no new toxicities detected within 100 days of treatment.

“The results that Dr. Hoppe showed us are really, really good,” Dr. Ng said. And “the volume of treatment is pretty tiny, so I think we can safely say that long-term toxicities are very, very minimal.”

The study was supported by Bristol-Myers Squibb in collaboration with Seagen, Euronet-Paediatric Hodgkin Lymphoma, and the Children’s Oncology Group. Dr. Hoppe reported serving on a scientific advisory committee for Merck. Dr. Ng reported having no relevant conflicts of interest.

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

SAN DIEGO – Children and young adults with low-risk relapsed or refractory classic Hodgkin lymphoma may be able to skip autologous stem cell transplant.

Patients who received second-line chemoimmunotherapy with nivolumab-brentuximab vedotin, with or without bendamustine, and proceeded to involved-site radiation appeared to have similar survival outcomes to those who received the chemoimmunotherapy combination plus the current second-line standard of care, which includes high-dose therapy and autologous stem cell transplant.

Among 28 patients with low-risk relapsed or refractory Hodgkin lymphoma followed for a median of 32 months, 3-year event-free survival without autologous stem cell transplant was 86.9% and 3-year progression-free survival was 95%, reported Brad Hoppe, MD, MPH, from the Mayo Clinic in Jacksonville, Fla. In contrast, 1-year progression-free survival was 91% among the 44 standard-risk patients who received high-dose therapy and autologous stem cell transplant, according to results of a trial the investigators published online in Blood in late 2022.

The latest results from the phase 2 CheckMate 744 trial were reported at the annual meeting of the American Society of Radiation Oncology.

“The findings suggest that children, adolescents, and young adults with low-risk relapsed classic Hodgkin lymphoma can be salvaged with low-toxicity chemoimmunotherapy and may not require high-dose therapy and transplant for a cure,” Dr. Hoppe said in an oral abstract session.

Andrea Ng, MD, MPH, a radiation oncologist who specializes in treating patients with Hodgkin lymphoma and other hematologic malignancies, said that, while the number of patients in the study was small and the follow-up too short, this option is “certainly something that’s very promising for the future.”

“The use of transplant in relapsed patients, which we have been doing for decades, is based on two very old, small, randomized studies,” said Dr. Ng, from the Dana-Farber Cancer Institute in Boston, who moderated the session.

“So, do we really need to transplant everybody? In the back of our minds, we think that we may be overtreating some patients,” she said.

Several small, retrospective studies exploring treatment with conventional chemotherapy with or without radiation therapy and without transplant in patients with relapsed or refractory Hodgkin lymphoma have demonstrated only modest results.

The CheckMate 744 trial, however, was designed to examine a risk-adapted and response-adapted approach to treating children, adolescents, and young adults with relapsed or refractory classic Hodgkin lymphoma within the setting of modern immunotherapy and targeted therapy. This approach was developed jointly by investigators with the Children’s Oncology Group and Euronet.

In the nonrandomized trial, patients were stratified into low-risk or standard-risk disease categories based on an algorithm that included factors at the time of initial diagnosis and relapse.

Patients were considered low-risk for relapse in three scenarios: (1) if they had initial stage IA or IIA disease that relapsed at least 1 year after the end of therapy; (2) if they had initial stage IA or IIA disease that relapsed between 3 and 12 months from the end of therapy but had received no more than three cycles of chemotherapy and no radiation therapy; or (3) if they had initial stage IB, IIB, or IIIA disease that relapsed more than 12 months after the end of first-line therapy.

To be included in the low-risk category, patients also had to be free of B symptoms or extranodal disease, free of relapse in prior radiation therapy fields, and have no more than four sites of lymphoma. 

Low-risk patients were treated with a combination of nivolumab and brentuximab vedotin, which could be followed by additional brentuximab vedotin and bendamustine for those with a suboptimal response. Patients who achieved complete molecular remission after induction went on to consolidation therapy with involved-site radiation at a total dose of 30 Gy.

Patients considered standard-risk for relapse received the same nivolumab-brentuximab vedotin combination, with or without bendamustine, and then went on to high-dose therapy and autologous stem cell transplant.

In other results for the previously mentioned study published in Blood, the 44 standard-risk patients who received high-dose therapy and autologous stem cell transplant had an objective response rate of 95% – 86% of patients achieved complete molecular remission, and 9% achieved partial molecular remission.

At ASTRO, Dr. Hoppe reported results for the 28 patients with low-risk disease. One patient discontinued nivolumab/brentuximab vedotin after two cycles because of skin toxicity and was lost to follow-up. Of the remaining 27 patients, 21 had complete molecular remission after four cycles of the combination, and these patients went on to an additional two cycles of the combination, with 19 of 21 receiving involved-site radiation consolidation. 

Six patients who had either a partial molecular remission or no response were given two additional cycles of brentuximab vedotin plus bendamustine. Of this group, three went on to complete molecular remission and received involved-site radiation consolidation on protocol. The remaining three patients who did not experience complete molecular remission received involved-site radiation off protocol.

The rate of complete molecular remission after four cycles of induction was 82.1%, and the rate of partial molecular remission was 14.3%, for an objective response rate of 96.4%. The respective response rates with the addition of two cycles of brentuximab vedotin and bendamustine were 92.9% and 7.1%, for an objective response rate of 100%, Dr. Hoppe reported.

Overall, at a median follow-up of 32 months, the 3-year event-free survival rate without transplant was 86.9%, and the 3-year progression-free survival rate was 95%.

Treatment-related adverse events of any grade occurred in 22 patients (78.6%) after induction, with 7 of those events (25%) being grade 3 or 4 in severity. Grade 3 or 4 events consisted of skin and subcutaneous tissue disorders in 3 patients, elevated liver function tests in 3 patients, and blood and lymphatic system disorders in 1 patient.

There were no new toxicities detected within 100 days of treatment.

“The results that Dr. Hoppe showed us are really, really good,” Dr. Ng said. And “the volume of treatment is pretty tiny, so I think we can safely say that long-term toxicities are very, very minimal.”

The study was supported by Bristol-Myers Squibb in collaboration with Seagen, Euronet-Paediatric Hodgkin Lymphoma, and the Children’s Oncology Group. Dr. Hoppe reported serving on a scientific advisory committee for Merck. Dr. Ng reported having no relevant conflicts of interest.

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

SAN DIEGO – Children and young adults with low-risk relapsed or refractory classic Hodgkin lymphoma may be able to skip autologous stem cell transplant.

Patients who received second-line chemoimmunotherapy with nivolumab-brentuximab vedotin, with or without bendamustine, and proceeded to involved-site radiation appeared to have similar survival outcomes to those who received the chemoimmunotherapy combination plus the current second-line standard of care, which includes high-dose therapy and autologous stem cell transplant.

Among 28 patients with low-risk relapsed or refractory Hodgkin lymphoma followed for a median of 32 months, 3-year event-free survival without autologous stem cell transplant was 86.9% and 3-year progression-free survival was 95%, reported Brad Hoppe, MD, MPH, from the Mayo Clinic in Jacksonville, Fla. In contrast, 1-year progression-free survival was 91% among the 44 standard-risk patients who received high-dose therapy and autologous stem cell transplant, according to results of a trial the investigators published online in Blood in late 2022.

The latest results from the phase 2 CheckMate 744 trial were reported at the annual meeting of the American Society of Radiation Oncology.

“The findings suggest that children, adolescents, and young adults with low-risk relapsed classic Hodgkin lymphoma can be salvaged with low-toxicity chemoimmunotherapy and may not require high-dose therapy and transplant for a cure,” Dr. Hoppe said in an oral abstract session.

Andrea Ng, MD, MPH, a radiation oncologist who specializes in treating patients with Hodgkin lymphoma and other hematologic malignancies, said that, while the number of patients in the study was small and the follow-up too short, this option is “certainly something that’s very promising for the future.”

“The use of transplant in relapsed patients, which we have been doing for decades, is based on two very old, small, randomized studies,” said Dr. Ng, from the Dana-Farber Cancer Institute in Boston, who moderated the session.

“So, do we really need to transplant everybody? In the back of our minds, we think that we may be overtreating some patients,” she said.

Several small, retrospective studies exploring treatment with conventional chemotherapy with or without radiation therapy and without transplant in patients with relapsed or refractory Hodgkin lymphoma have demonstrated only modest results.

The CheckMate 744 trial, however, was designed to examine a risk-adapted and response-adapted approach to treating children, adolescents, and young adults with relapsed or refractory classic Hodgkin lymphoma within the setting of modern immunotherapy and targeted therapy. This approach was developed jointly by investigators with the Children’s Oncology Group and Euronet.

In the nonrandomized trial, patients were stratified into low-risk or standard-risk disease categories based on an algorithm that included factors at the time of initial diagnosis and relapse.

Patients were considered low-risk for relapse in three scenarios: (1) if they had initial stage IA or IIA disease that relapsed at least 1 year after the end of therapy; (2) if they had initial stage IA or IIA disease that relapsed between 3 and 12 months from the end of therapy but had received no more than three cycles of chemotherapy and no radiation therapy; or (3) if they had initial stage IB, IIB, or IIIA disease that relapsed more than 12 months after the end of first-line therapy.

To be included in the low-risk category, patients also had to be free of B symptoms or extranodal disease, free of relapse in prior radiation therapy fields, and have no more than four sites of lymphoma. 

Low-risk patients were treated with a combination of nivolumab and brentuximab vedotin, which could be followed by additional brentuximab vedotin and bendamustine for those with a suboptimal response. Patients who achieved complete molecular remission after induction went on to consolidation therapy with involved-site radiation at a total dose of 30 Gy.

Patients considered standard-risk for relapse received the same nivolumab-brentuximab vedotin combination, with or without bendamustine, and then went on to high-dose therapy and autologous stem cell transplant.

In other results for the previously mentioned study published in Blood, the 44 standard-risk patients who received high-dose therapy and autologous stem cell transplant had an objective response rate of 95% – 86% of patients achieved complete molecular remission, and 9% achieved partial molecular remission.

At ASTRO, Dr. Hoppe reported results for the 28 patients with low-risk disease. One patient discontinued nivolumab/brentuximab vedotin after two cycles because of skin toxicity and was lost to follow-up. Of the remaining 27 patients, 21 had complete molecular remission after four cycles of the combination, and these patients went on to an additional two cycles of the combination, with 19 of 21 receiving involved-site radiation consolidation. 

Six patients who had either a partial molecular remission or no response were given two additional cycles of brentuximab vedotin plus bendamustine. Of this group, three went on to complete molecular remission and received involved-site radiation consolidation on protocol. The remaining three patients who did not experience complete molecular remission received involved-site radiation off protocol.

The rate of complete molecular remission after four cycles of induction was 82.1%, and the rate of partial molecular remission was 14.3%, for an objective response rate of 96.4%. The respective response rates with the addition of two cycles of brentuximab vedotin and bendamustine were 92.9% and 7.1%, for an objective response rate of 100%, Dr. Hoppe reported.

Overall, at a median follow-up of 32 months, the 3-year event-free survival rate without transplant was 86.9%, and the 3-year progression-free survival rate was 95%.

Treatment-related adverse events of any grade occurred in 22 patients (78.6%) after induction, with 7 of those events (25%) being grade 3 or 4 in severity. Grade 3 or 4 events consisted of skin and subcutaneous tissue disorders in 3 patients, elevated liver function tests in 3 patients, and blood and lymphatic system disorders in 1 patient.

There were no new toxicities detected within 100 days of treatment.

“The results that Dr. Hoppe showed us are really, really good,” Dr. Ng said. And “the volume of treatment is pretty tiny, so I think we can safely say that long-term toxicities are very, very minimal.”

The study was supported by Bristol-Myers Squibb in collaboration with Seagen, Euronet-Paediatric Hodgkin Lymphoma, and the Children’s Oncology Group. Dr. Hoppe reported serving on a scientific advisory committee for Merck. Dr. Ng reported having no relevant conflicts of interest.

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

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.
 

Patients with active cancer and newly diagnosed isolated distal deep vein thrombosis (DVT) who received 12 months of edoxaban (Savaysa) had fewer thrombotic events at 1 year than those who received 3 months of treatment, without significantly increased bleeding, in the ONCO-DVT trial.

However, lead author Yugo Yamashita, MD, of Kyoto University noted that caution is needed when determining anticoagulation strategies in individual patients with distal DVT, especially those with high risk for bleeding.

Dr. Yamashita presented the results at the annual congress of the European Society of Cardiology, and the trial was simultaneously published in the journal Circulation.

“This is the first and only randomized trial to show the superiority of longer duration over shorter duration of anticoagulation therapy for reducing thrombotic events in cancer patients with isolated distal DVT,” he said in a press briefing.  

The results provide support for 12 months of edoxaban in patients with active cancer and isolated distal DVD, he said in an email.

However, “considering the risk of bleeding associated with anticoagulation therapy, physicians should make the decision of anticoagulation strategies for these patients based on risk-benefit balance of anticoagulation therapy in individual patients,” he stressed.

The take-home message for clinicians is that, “if you find minor DVT in cancer patients, please be careful, because their thrombotic risk was not low” in this trial, Dr. Yamashita said.  

The study was conducted in Japan, so whether or not the results are generalizable to other populations is not clear. “Subgroup analysis based on body weight did not show any signal of different effect,” he noted, which suggests that the main results could be applied to other populations, including the U.S. population. However, “generalizability of the current results should be carried out carefully.”  
 

Caution needed when translating findings into clinical practice

The assigned discussant, Teresa Lopez-Fernandez, MD, from La Paz University Hospital, Madrid, who was co-chairperson of 2022 ESC guidelines on cardio-oncology, noted that the optimal anticoagulation therapy strategy is unclear in patients with cancer and isolated distal DVT.

“2022 ESC guidelines on cardio-oncology and [European Society for Medical Oncology] guidelines from this year,” she said, “are both in agreement that we need to prolong anticoagulation [therapy to prevent venous thromboembolism (VTE)] when active cancer exists, and particularly in patients with metastatic cancer. The problem is that none of this text refers specifically to distal DVT.”

The ONCO-DVT trial sheds light on this, but there are a few points to consider when interpreting the findings.

Major bleeding was slightly increased in the 12-month vs 3-month edoxaban groups, although this was not statistically significant, she noted. Moreover, 75% of the patients were treated with low-dose edoxaban, mainly due to their low weight. Also, bleeding risk probably differs in different cancer types.

“These are important things that we need to keep in mind when we try to transfer this data to [inform] our clinical practice,” Dr. Lopez-Fernandez said.

She drew attention to a recent study based on RIETE registry data that suggests that “isolated distal DVT is a big problem for patients with cancer in comparison with noncancer patients, where it seems it’s a low-risk problem.”

The main takeaways from ONCO-DVT, Dr. Lopez-Fernandez said, are that it confirms that cancer-associated isolated distal DVT is a marker of poor prognosis, and it supports the need for extended anticoagulation in patients with active, ongoing cancer and isolated distal DVT.

However, “we need to be cautious to try to really understand what the bleeding risks of these patients are,” she said, “particularly because it is not always easy to transfer the results from an Asian population to other populations.”

There is also a need for further studies with other doses, with other novel oral anticoagulants, and in patients at high risk for bleeding, in clinical practice.

Dr. Yamashita said that the study suggests that there is a potential benefit of prolonged duration of anticoagulant therapy for some patients with isolated distal DVT, but not all patients should receive this dosing strategy, because some patients may be at high risk for bleeding or VTE recurrence. A subanalysis of data from ONCO-DVT study should shed further light on this.

“We need to individualize our risk stratification,” Dr. Lopez-Fernandez said, adding that notably, “a lot of patients in the 12-month group did not continue with the 12-month treatment,” which may have affected bleeding results. Dr. Yamashita agreed.
 

Study design and findings

From April 2019 to June 2022, the researchers enrolled and randomly assigned 604 patients with active cancer who had newly diagnosed isolated distal DVT, confirmed by ultrasonography, and were scheduled for DVT treatment with anticoagulation therapy, at 60 centers.

Active cancer was defined as a cancer diagnosis or cancer treatment (surgery, chemotherapy, radiotherapy, etc.) within 6 months of randomization, or current recurrence, local invasion, distant metastases, or hematopoietic malignancy without complete remission.

The most common reasons for ultrasonography were elevated D-dimer levels (62%) and suspected DVT because of symptoms (20%).

The patients had a mean age of 70.8 years and 28% were men. The most common cancer sites were ovaries (14%), uterus (13%), lung (11%), colon (9%), and pancreas (8%), followed by stomach, blood, and breast (each 5%).  

The patients were randomly assigned 1:1 to receive 12 months or 3 months of oral edoxaban at a dose of 60 mg once daily or 30 mg once daily in patients with body weight of 60 kg or less, creatinine clearance of 30-50 mL/minute, or concomitant treatment with a potent P-glycoprotein inhibitor.

After excluding 3 patients who withdrew consent, 601 patients were included in the intention-to-treat population: 296 patients in the 12-month edoxaban group and 305 patients in the 3-month edoxaban group.

About 70% of patients had a body weight of 60 kg or less and about 22% had a creatinine clearance less than 50 mL/min. About three quarters received the lower dose of edoxaban.

In the 12-month edoxaban group, 223 patients completed the 1-year follow-up (66 patients had died and 7 were lost to follow-up). In the 3-month edoxaban group, 224 patients completed the 1-year follow-up (77 had died and 4 were lost to follow-up).

In the 12-month edoxaban group, 41% of the patients had discontinued treatment by 12 months. In the 3-month edoxaban group, 41% of patients had discontinued treatment by 3 months.

The primary endpoint – a symptomatic recurrent VTE event or VTE-related death – occurred in 3 of the 222 patients (1.2%) in the 12-month edoxaban group and in 22 of the 210 (8.5%) in the 3-month edoxaban group (odds ratio,0.13; 95% confidence interval, 0.03-0.44, P < .001). There were no VTE-related deaths.

The major secondary endpoint – major bleeding, according to International Society on Thrombosis and Hemostasis criteria – occurred in 28 of the 210 patients (10.2%) in the 12-month edoxaban group and in 22 of the 217 (7.6%) in the 3-month edoxaban group (OR, 1.34; 95% CI, 0.75-2.41, P = NS).

The researchers acknowledged that study limitations include an open-label design, a lower-than-expected primary endpoint rate, and less than high adherence to edoxaban, as well as the need for caution when generalizing the results to other populations.

The study was funded by Daiichi Sankyo. Dr. Yamashita disclosed receiving lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo, and grant support from Bayer Healthcare and Daiichi Sankyo. Dr. Lopez-Fernandez disclosed receiving speaker fees from Phillips, Janssen, Daiichi Sankyo, Myocardial Solutions, AstraZeneca, Pfizer, Beigene, and Bayer not related to this study.

A version of this article appeared on Medscape.com.

Patients with active cancer and newly diagnosed isolated distal deep vein thrombosis (DVT) who received 12 months of edoxaban (Savaysa) had fewer thrombotic events at 1 year than those who received 3 months of treatment, without significantly increased bleeding, in the ONCO-DVT trial.

However, lead author Yugo Yamashita, MD, of Kyoto University noted that caution is needed when determining anticoagulation strategies in individual patients with distal DVT, especially those with high risk for bleeding.

Dr. Yamashita presented the results at the annual congress of the European Society of Cardiology, and the trial was simultaneously published in the journal Circulation.

“This is the first and only randomized trial to show the superiority of longer duration over shorter duration of anticoagulation therapy for reducing thrombotic events in cancer patients with isolated distal DVT,” he said in a press briefing.  

The results provide support for 12 months of edoxaban in patients with active cancer and isolated distal DVD, he said in an email.

However, “considering the risk of bleeding associated with anticoagulation therapy, physicians should make the decision of anticoagulation strategies for these patients based on risk-benefit balance of anticoagulation therapy in individual patients,” he stressed.

The take-home message for clinicians is that, “if you find minor DVT in cancer patients, please be careful, because their thrombotic risk was not low” in this trial, Dr. Yamashita said.  

The study was conducted in Japan, so whether or not the results are generalizable to other populations is not clear. “Subgroup analysis based on body weight did not show any signal of different effect,” he noted, which suggests that the main results could be applied to other populations, including the U.S. population. However, “generalizability of the current results should be carried out carefully.”  
 

Caution needed when translating findings into clinical practice

The assigned discussant, Teresa Lopez-Fernandez, MD, from La Paz University Hospital, Madrid, who was co-chairperson of 2022 ESC guidelines on cardio-oncology, noted that the optimal anticoagulation therapy strategy is unclear in patients with cancer and isolated distal DVT.

“2022 ESC guidelines on cardio-oncology and [European Society for Medical Oncology] guidelines from this year,” she said, “are both in agreement that we need to prolong anticoagulation [therapy to prevent venous thromboembolism (VTE)] when active cancer exists, and particularly in patients with metastatic cancer. The problem is that none of this text refers specifically to distal DVT.”

The ONCO-DVT trial sheds light on this, but there are a few points to consider when interpreting the findings.

Major bleeding was slightly increased in the 12-month vs 3-month edoxaban groups, although this was not statistically significant, she noted. Moreover, 75% of the patients were treated with low-dose edoxaban, mainly due to their low weight. Also, bleeding risk probably differs in different cancer types.

“These are important things that we need to keep in mind when we try to transfer this data to [inform] our clinical practice,” Dr. Lopez-Fernandez said.

She drew attention to a recent study based on RIETE registry data that suggests that “isolated distal DVT is a big problem for patients with cancer in comparison with noncancer patients, where it seems it’s a low-risk problem.”

The main takeaways from ONCO-DVT, Dr. Lopez-Fernandez said, are that it confirms that cancer-associated isolated distal DVT is a marker of poor prognosis, and it supports the need for extended anticoagulation in patients with active, ongoing cancer and isolated distal DVT.

However, “we need to be cautious to try to really understand what the bleeding risks of these patients are,” she said, “particularly because it is not always easy to transfer the results from an Asian population to other populations.”

There is also a need for further studies with other doses, with other novel oral anticoagulants, and in patients at high risk for bleeding, in clinical practice.

Dr. Yamashita said that the study suggests that there is a potential benefit of prolonged duration of anticoagulant therapy for some patients with isolated distal DVT, but not all patients should receive this dosing strategy, because some patients may be at high risk for bleeding or VTE recurrence. A subanalysis of data from ONCO-DVT study should shed further light on this.

“We need to individualize our risk stratification,” Dr. Lopez-Fernandez said, adding that notably, “a lot of patients in the 12-month group did not continue with the 12-month treatment,” which may have affected bleeding results. Dr. Yamashita agreed.
 

Study design and findings

From April 2019 to June 2022, the researchers enrolled and randomly assigned 604 patients with active cancer who had newly diagnosed isolated distal DVT, confirmed by ultrasonography, and were scheduled for DVT treatment with anticoagulation therapy, at 60 centers.

Active cancer was defined as a cancer diagnosis or cancer treatment (surgery, chemotherapy, radiotherapy, etc.) within 6 months of randomization, or current recurrence, local invasion, distant metastases, or hematopoietic malignancy without complete remission.

The most common reasons for ultrasonography were elevated D-dimer levels (62%) and suspected DVT because of symptoms (20%).

The patients had a mean age of 70.8 years and 28% were men. The most common cancer sites were ovaries (14%), uterus (13%), lung (11%), colon (9%), and pancreas (8%), followed by stomach, blood, and breast (each 5%).  

The patients were randomly assigned 1:1 to receive 12 months or 3 months of oral edoxaban at a dose of 60 mg once daily or 30 mg once daily in patients with body weight of 60 kg or less, creatinine clearance of 30-50 mL/minute, or concomitant treatment with a potent P-glycoprotein inhibitor.

After excluding 3 patients who withdrew consent, 601 patients were included in the intention-to-treat population: 296 patients in the 12-month edoxaban group and 305 patients in the 3-month edoxaban group.

About 70% of patients had a body weight of 60 kg or less and about 22% had a creatinine clearance less than 50 mL/min. About three quarters received the lower dose of edoxaban.

In the 12-month edoxaban group, 223 patients completed the 1-year follow-up (66 patients had died and 7 were lost to follow-up). In the 3-month edoxaban group, 224 patients completed the 1-year follow-up (77 had died and 4 were lost to follow-up).

In the 12-month edoxaban group, 41% of the patients had discontinued treatment by 12 months. In the 3-month edoxaban group, 41% of patients had discontinued treatment by 3 months.

The primary endpoint – a symptomatic recurrent VTE event or VTE-related death – occurred in 3 of the 222 patients (1.2%) in the 12-month edoxaban group and in 22 of the 210 (8.5%) in the 3-month edoxaban group (odds ratio,0.13; 95% confidence interval, 0.03-0.44, P < .001). There were no VTE-related deaths.

The major secondary endpoint – major bleeding, according to International Society on Thrombosis and Hemostasis criteria – occurred in 28 of the 210 patients (10.2%) in the 12-month edoxaban group and in 22 of the 217 (7.6%) in the 3-month edoxaban group (OR, 1.34; 95% CI, 0.75-2.41, P = NS).

The researchers acknowledged that study limitations include an open-label design, a lower-than-expected primary endpoint rate, and less than high adherence to edoxaban, as well as the need for caution when generalizing the results to other populations.

The study was funded by Daiichi Sankyo. Dr. Yamashita disclosed receiving lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo, and grant support from Bayer Healthcare and Daiichi Sankyo. Dr. Lopez-Fernandez disclosed receiving speaker fees from Phillips, Janssen, Daiichi Sankyo, Myocardial Solutions, AstraZeneca, Pfizer, Beigene, and Bayer not related to this study.

A version of this article appeared on Medscape.com.

Patients with active cancer and newly diagnosed isolated distal deep vein thrombosis (DVT) who received 12 months of edoxaban (Savaysa) had fewer thrombotic events at 1 year than those who received 3 months of treatment, without significantly increased bleeding, in the ONCO-DVT trial.

However, lead author Yugo Yamashita, MD, of Kyoto University noted that caution is needed when determining anticoagulation strategies in individual patients with distal DVT, especially those with high risk for bleeding.

Dr. Yamashita presented the results at the annual congress of the European Society of Cardiology, and the trial was simultaneously published in the journal Circulation.

“This is the first and only randomized trial to show the superiority of longer duration over shorter duration of anticoagulation therapy for reducing thrombotic events in cancer patients with isolated distal DVT,” he said in a press briefing.  

The results provide support for 12 months of edoxaban in patients with active cancer and isolated distal DVD, he said in an email.

However, “considering the risk of bleeding associated with anticoagulation therapy, physicians should make the decision of anticoagulation strategies for these patients based on risk-benefit balance of anticoagulation therapy in individual patients,” he stressed.

The take-home message for clinicians is that, “if you find minor DVT in cancer patients, please be careful, because their thrombotic risk was not low” in this trial, Dr. Yamashita said.  

The study was conducted in Japan, so whether or not the results are generalizable to other populations is not clear. “Subgroup analysis based on body weight did not show any signal of different effect,” he noted, which suggests that the main results could be applied to other populations, including the U.S. population. However, “generalizability of the current results should be carried out carefully.”  
 

Caution needed when translating findings into clinical practice

The assigned discussant, Teresa Lopez-Fernandez, MD, from La Paz University Hospital, Madrid, who was co-chairperson of 2022 ESC guidelines on cardio-oncology, noted that the optimal anticoagulation therapy strategy is unclear in patients with cancer and isolated distal DVT.

“2022 ESC guidelines on cardio-oncology and [European Society for Medical Oncology] guidelines from this year,” she said, “are both in agreement that we need to prolong anticoagulation [therapy to prevent venous thromboembolism (VTE)] when active cancer exists, and particularly in patients with metastatic cancer. The problem is that none of this text refers specifically to distal DVT.”

The ONCO-DVT trial sheds light on this, but there are a few points to consider when interpreting the findings.

Major bleeding was slightly increased in the 12-month vs 3-month edoxaban groups, although this was not statistically significant, she noted. Moreover, 75% of the patients were treated with low-dose edoxaban, mainly due to their low weight. Also, bleeding risk probably differs in different cancer types.

“These are important things that we need to keep in mind when we try to transfer this data to [inform] our clinical practice,” Dr. Lopez-Fernandez said.

She drew attention to a recent study based on RIETE registry data that suggests that “isolated distal DVT is a big problem for patients with cancer in comparison with noncancer patients, where it seems it’s a low-risk problem.”

The main takeaways from ONCO-DVT, Dr. Lopez-Fernandez said, are that it confirms that cancer-associated isolated distal DVT is a marker of poor prognosis, and it supports the need for extended anticoagulation in patients with active, ongoing cancer and isolated distal DVT.

However, “we need to be cautious to try to really understand what the bleeding risks of these patients are,” she said, “particularly because it is not always easy to transfer the results from an Asian population to other populations.”

There is also a need for further studies with other doses, with other novel oral anticoagulants, and in patients at high risk for bleeding, in clinical practice.

Dr. Yamashita said that the study suggests that there is a potential benefit of prolonged duration of anticoagulant therapy for some patients with isolated distal DVT, but not all patients should receive this dosing strategy, because some patients may be at high risk for bleeding or VTE recurrence. A subanalysis of data from ONCO-DVT study should shed further light on this.

“We need to individualize our risk stratification,” Dr. Lopez-Fernandez said, adding that notably, “a lot of patients in the 12-month group did not continue with the 12-month treatment,” which may have affected bleeding results. Dr. Yamashita agreed.
 

Study design and findings

From April 2019 to June 2022, the researchers enrolled and randomly assigned 604 patients with active cancer who had newly diagnosed isolated distal DVT, confirmed by ultrasonography, and were scheduled for DVT treatment with anticoagulation therapy, at 60 centers.

Active cancer was defined as a cancer diagnosis or cancer treatment (surgery, chemotherapy, radiotherapy, etc.) within 6 months of randomization, or current recurrence, local invasion, distant metastases, or hematopoietic malignancy without complete remission.

The most common reasons for ultrasonography were elevated D-dimer levels (62%) and suspected DVT because of symptoms (20%).

The patients had a mean age of 70.8 years and 28% were men. The most common cancer sites were ovaries (14%), uterus (13%), lung (11%), colon (9%), and pancreas (8%), followed by stomach, blood, and breast (each 5%).  

The patients were randomly assigned 1:1 to receive 12 months or 3 months of oral edoxaban at a dose of 60 mg once daily or 30 mg once daily in patients with body weight of 60 kg or less, creatinine clearance of 30-50 mL/minute, or concomitant treatment with a potent P-glycoprotein inhibitor.

After excluding 3 patients who withdrew consent, 601 patients were included in the intention-to-treat population: 296 patients in the 12-month edoxaban group and 305 patients in the 3-month edoxaban group.

About 70% of patients had a body weight of 60 kg or less and about 22% had a creatinine clearance less than 50 mL/min. About three quarters received the lower dose of edoxaban.

In the 12-month edoxaban group, 223 patients completed the 1-year follow-up (66 patients had died and 7 were lost to follow-up). In the 3-month edoxaban group, 224 patients completed the 1-year follow-up (77 had died and 4 were lost to follow-up).

In the 12-month edoxaban group, 41% of the patients had discontinued treatment by 12 months. In the 3-month edoxaban group, 41% of patients had discontinued treatment by 3 months.

The primary endpoint – a symptomatic recurrent VTE event or VTE-related death – occurred in 3 of the 222 patients (1.2%) in the 12-month edoxaban group and in 22 of the 210 (8.5%) in the 3-month edoxaban group (odds ratio,0.13; 95% confidence interval, 0.03-0.44, P < .001). There were no VTE-related deaths.

The major secondary endpoint – major bleeding, according to International Society on Thrombosis and Hemostasis criteria – occurred in 28 of the 210 patients (10.2%) in the 12-month edoxaban group and in 22 of the 217 (7.6%) in the 3-month edoxaban group (OR, 1.34; 95% CI, 0.75-2.41, P = NS).

The researchers acknowledged that study limitations include an open-label design, a lower-than-expected primary endpoint rate, and less than high adherence to edoxaban, as well as the need for caution when generalizing the results to other populations.

The study was funded by Daiichi Sankyo. Dr. Yamashita disclosed receiving lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo, and grant support from Bayer Healthcare and Daiichi Sankyo. Dr. Lopez-Fernandez disclosed receiving speaker fees from Phillips, Janssen, Daiichi Sankyo, Myocardial Solutions, AstraZeneca, Pfizer, Beigene, and Bayer not related to this study.

A version of this article appeared on Medscape.com.

An innovative care model involving an expanded role for advanced practice radiation therapists (APRTs) has improved the quality and efficiency of care and reduced work-related distress among cancer care team members in the radiation oncology department of Mount Sinai Health System in New York.

At a time when clinician burnout is rampant, a novel approach that brings value to both patients and health systems – and helps advance the careers of highly educated and skilled practitioners – represents a welcome step forward, according to Samantha Skubish, MS, RT, chief technical director of radiation oncology and Mount Sinai.

In the new care model, APRTs work alongside radiation oncologists and support “the care of resource-intensive patient populations,” according to the Association of Community Cancer Centers, which recently recognized the Mount Sinai Health System program as a 2023 ACCC Innovator Award winner.

The new and improved “model for continuity of care” with the APRT role has “helped improve the patient experience and create a more streamlined, efficient process while also alleviating some of the burden on our physicians,” Ms. Skubish said in the ACCC press release. She explained that APRTs possess the skills, knowledge, and judgment to provide an elevated level of care, as evidenced by decades of international research.

A 2022 systematic review of APRT-based care models outside the United States explored how the models have worked. Overall, the research shows that such models improve quality, efficiency, wellness, and administrative outcomes, according to investigators.

At Mount Sinai, the first health system to develop the APRT role in the United States, research to demonstrate the benefits of APRT model continues. In 2021, an APRT working group was established to “garner a network of individuals across the country focused on the work to prove the advanced practice radiation therapy model in the U.S.,” according to Danielle McDonagh, MS, RT, Mount Sinai’s clinical coordinator of radiation sciences education and research.

A paper published in May by Ms. McDonagh and colleagues underscored the potential for “positive change and impact” of the APRT care model in radiation oncology.

“We’re all in this current and longstanding crisis of clinician shortages,” Kimberly Smith, MPA, explained in a video introducing the Mount Sinai program.

“If you look at your therapists’ skill set and allow them to work at the top of their license, you can provide a cost-saving solution that lends itself to value-based care,” said Ms. Smith, vice president of radiation oncology services at Mount Sinai.

Indeed, Sheryl Green, MBBCh, professor and medical director of radiation oncology at Mount Sinai, noted that “the APRT has allowed us to really improve the quality of care that we deliver, primarily in the aspects of optimizing and personalizing the patient experience.”

Ms. Skubish and Ms. Smith will share details of the new care model at the ACCC’s upcoming National Oncology Conference.

An innovative care model involving an expanded role for advanced practice radiation therapists (APRTs) has improved the quality and efficiency of care and reduced work-related distress among cancer care team members in the radiation oncology department of Mount Sinai Health System in New York.

At a time when clinician burnout is rampant, a novel approach that brings value to both patients and health systems – and helps advance the careers of highly educated and skilled practitioners – represents a welcome step forward, according to Samantha Skubish, MS, RT, chief technical director of radiation oncology and Mount Sinai.

In the new care model, APRTs work alongside radiation oncologists and support “the care of resource-intensive patient populations,” according to the Association of Community Cancer Centers, which recently recognized the Mount Sinai Health System program as a 2023 ACCC Innovator Award winner.

The new and improved “model for continuity of care” with the APRT role has “helped improve the patient experience and create a more streamlined, efficient process while also alleviating some of the burden on our physicians,” Ms. Skubish said in the ACCC press release. She explained that APRTs possess the skills, knowledge, and judgment to provide an elevated level of care, as evidenced by decades of international research.

A 2022 systematic review of APRT-based care models outside the United States explored how the models have worked. Overall, the research shows that such models improve quality, efficiency, wellness, and administrative outcomes, according to investigators.

At Mount Sinai, the first health system to develop the APRT role in the United States, research to demonstrate the benefits of APRT model continues. In 2021, an APRT working group was established to “garner a network of individuals across the country focused on the work to prove the advanced practice radiation therapy model in the U.S.,” according to Danielle McDonagh, MS, RT, Mount Sinai’s clinical coordinator of radiation sciences education and research.

A paper published in May by Ms. McDonagh and colleagues underscored the potential for “positive change and impact” of the APRT care model in radiation oncology.

“We’re all in this current and longstanding crisis of clinician shortages,” Kimberly Smith, MPA, explained in a video introducing the Mount Sinai program.

“If you look at your therapists’ skill set and allow them to work at the top of their license, you can provide a cost-saving solution that lends itself to value-based care,” said Ms. Smith, vice president of radiation oncology services at Mount Sinai.

Indeed, Sheryl Green, MBBCh, professor and medical director of radiation oncology at Mount Sinai, noted that “the APRT has allowed us to really improve the quality of care that we deliver, primarily in the aspects of optimizing and personalizing the patient experience.”

Ms. Skubish and Ms. Smith will share details of the new care model at the ACCC’s upcoming National Oncology Conference.

An innovative care model involving an expanded role for advanced practice radiation therapists (APRTs) has improved the quality and efficiency of care and reduced work-related distress among cancer care team members in the radiation oncology department of Mount Sinai Health System in New York.

At a time when clinician burnout is rampant, a novel approach that brings value to both patients and health systems – and helps advance the careers of highly educated and skilled practitioners – represents a welcome step forward, according to Samantha Skubish, MS, RT, chief technical director of radiation oncology and Mount Sinai.

In the new care model, APRTs work alongside radiation oncologists and support “the care of resource-intensive patient populations,” according to the Association of Community Cancer Centers, which recently recognized the Mount Sinai Health System program as a 2023 ACCC Innovator Award winner.

The new and improved “model for continuity of care” with the APRT role has “helped improve the patient experience and create a more streamlined, efficient process while also alleviating some of the burden on our physicians,” Ms. Skubish said in the ACCC press release. She explained that APRTs possess the skills, knowledge, and judgment to provide an elevated level of care, as evidenced by decades of international research.

A 2022 systematic review of APRT-based care models outside the United States explored how the models have worked. Overall, the research shows that such models improve quality, efficiency, wellness, and administrative outcomes, according to investigators.

At Mount Sinai, the first health system to develop the APRT role in the United States, research to demonstrate the benefits of APRT model continues. In 2021, an APRT working group was established to “garner a network of individuals across the country focused on the work to prove the advanced practice radiation therapy model in the U.S.,” according to Danielle McDonagh, MS, RT, Mount Sinai’s clinical coordinator of radiation sciences education and research.

A paper published in May by Ms. McDonagh and colleagues underscored the potential for “positive change and impact” of the APRT care model in radiation oncology.

“We’re all in this current and longstanding crisis of clinician shortages,” Kimberly Smith, MPA, explained in a video introducing the Mount Sinai program.

“If you look at your therapists’ skill set and allow them to work at the top of their license, you can provide a cost-saving solution that lends itself to value-based care,” said Ms. Smith, vice president of radiation oncology services at Mount Sinai.

Indeed, Sheryl Green, MBBCh, professor and medical director of radiation oncology at Mount Sinai, noted that “the APRT has allowed us to really improve the quality of care that we deliver, primarily in the aspects of optimizing and personalizing the patient experience.”

Ms. Skubish and Ms. Smith will share details of the new care model at the ACCC’s upcoming National Oncology Conference.

TOPLINE:

When patients deal directly with their insurance companies for answers about copayments and other issues, they are more likely to experience delays in cancer care and to be nonadherent.

METHODOLOGY:

• Navigating the complexities of insurance coverage is difficult for cancer patients, and the clinical impact of managing these intricacies remains unclear.
• To understand the issue, investigators surveyed 510 insured cancer patients in the United States about how often they estimate out-of-pocket costs for medications, doctors’ visits, and lab tests and scans, as well as how often they ask their insurance company to help them understand their coverage and how often they appeal coverage decisions.
• The team then correlated the answers with how often patients reported postponing or skipping doctors’ appointments and lab tests and how often they delayed filling prescriptions or skipped doses.
• Breast, colorectal, lung, and prostate cancer were the most common diagnoses among respondents.

TAKEAWAY:

• Overall, 55% of participants said they “never” or “rarely” engaged in any insurance-related cost tasks. The most frequently performed administrative tasks included finding out the cost before filling a prescription (28%) or before undergoing lab tests or scans (20%), as well as estimating the cost before agreeing to a treatment (20%), asking an insurance company for help understanding coverage (18%), or appealing a denial (17%).
• After adjusting for age, race/ethnicity, education, and monthly out-of-pocket costs, participants who engaged in any cost task were 18% more likely to experience treatment delays or forgo care.
• Every additional cost task or increase in frequency of a cost task was associated with 32% higher frequency of treatment delay or nonadherence.
• Age, race, and monthly out-of-pocket costs were more strongly associated with treatment delays/nonadherence than cost-task burden. Younger patients and Black patients were more likely than others to experience cost-related delays/nonadherence.

IN PRACTICE:

• “Reductions to administrative burden on patients, whether through patient-level education interventions, the adaptation of hospital-based navigation programs, or policy-focused changes to insurance systems, will be crucial” for helping patients with cancer to overcome administrative burdens and improve access to care, the authors said.

SOURCE:

• The study, led by Meredith Doherty, PhD, of the University of Pennsylvania, Philadelphia, was published in Cancer Epidemiology, Biomarkers and Prevention.

LIMITATIONS:

The survey was voluntary, which raises the possibility of self-selection bias. Recall bias may also have occurred, particularly among patients farther out from diagnosis and treatment. The investigators did not include uninsured patients and did not stratify patients by insurance type, and they did not measure or account for health care literacy.

DISCLOSURES:

The study was funded by the American Cancer Society. The investigators have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

When patients deal directly with their insurance companies for answers about copayments and other issues, they are more likely to experience delays in cancer care and to be nonadherent.

METHODOLOGY:

• Navigating the complexities of insurance coverage is difficult for cancer patients, and the clinical impact of managing these intricacies remains unclear.
• To understand the issue, investigators surveyed 510 insured cancer patients in the United States about how often they estimate out-of-pocket costs for medications, doctors’ visits, and lab tests and scans, as well as how often they ask their insurance company to help them understand their coverage and how often they appeal coverage decisions.
• The team then correlated the answers with how often patients reported postponing or skipping doctors’ appointments and lab tests and how often they delayed filling prescriptions or skipped doses.
• Breast, colorectal, lung, and prostate cancer were the most common diagnoses among respondents.

TAKEAWAY:

• Overall, 55% of participants said they “never” or “rarely” engaged in any insurance-related cost tasks. The most frequently performed administrative tasks included finding out the cost before filling a prescription (28%) or before undergoing lab tests or scans (20%), as well as estimating the cost before agreeing to a treatment (20%), asking an insurance company for help understanding coverage (18%), or appealing a denial (17%).
• After adjusting for age, race/ethnicity, education, and monthly out-of-pocket costs, participants who engaged in any cost task were 18% more likely to experience treatment delays or forgo care.
• Every additional cost task or increase in frequency of a cost task was associated with 32% higher frequency of treatment delay or nonadherence.
• Age, race, and monthly out-of-pocket costs were more strongly associated with treatment delays/nonadherence than cost-task burden. Younger patients and Black patients were more likely than others to experience cost-related delays/nonadherence.

IN PRACTICE:

• “Reductions to administrative burden on patients, whether through patient-level education interventions, the adaptation of hospital-based navigation programs, or policy-focused changes to insurance systems, will be crucial” for helping patients with cancer to overcome administrative burdens and improve access to care, the authors said.

SOURCE:

• The study, led by Meredith Doherty, PhD, of the University of Pennsylvania, Philadelphia, was published in Cancer Epidemiology, Biomarkers and Prevention.

LIMITATIONS:

The survey was voluntary, which raises the possibility of self-selection bias. Recall bias may also have occurred, particularly among patients farther out from diagnosis and treatment. The investigators did not include uninsured patients and did not stratify patients by insurance type, and they did not measure or account for health care literacy.

DISCLOSURES:

The study was funded by the American Cancer Society. The investigators have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

When patients deal directly with their insurance companies for answers about copayments and other issues, they are more likely to experience delays in cancer care and to be nonadherent.

METHODOLOGY:

• Navigating the complexities of insurance coverage is difficult for cancer patients, and the clinical impact of managing these intricacies remains unclear.
• To understand the issue, investigators surveyed 510 insured cancer patients in the United States about how often they estimate out-of-pocket costs for medications, doctors’ visits, and lab tests and scans, as well as how often they ask their insurance company to help them understand their coverage and how often they appeal coverage decisions.
• The team then correlated the answers with how often patients reported postponing or skipping doctors’ appointments and lab tests and how often they delayed filling prescriptions or skipped doses.
• Breast, colorectal, lung, and prostate cancer were the most common diagnoses among respondents.

TAKEAWAY:

• Overall, 55% of participants said they “never” or “rarely” engaged in any insurance-related cost tasks. The most frequently performed administrative tasks included finding out the cost before filling a prescription (28%) or before undergoing lab tests or scans (20%), as well as estimating the cost before agreeing to a treatment (20%), asking an insurance company for help understanding coverage (18%), or appealing a denial (17%).
• After adjusting for age, race/ethnicity, education, and monthly out-of-pocket costs, participants who engaged in any cost task were 18% more likely to experience treatment delays or forgo care.
• Every additional cost task or increase in frequency of a cost task was associated with 32% higher frequency of treatment delay or nonadherence.
• Age, race, and monthly out-of-pocket costs were more strongly associated with treatment delays/nonadherence than cost-task burden. Younger patients and Black patients were more likely than others to experience cost-related delays/nonadherence.

IN PRACTICE:

• “Reductions to administrative burden on patients, whether through patient-level education interventions, the adaptation of hospital-based navigation programs, or policy-focused changes to insurance systems, will be crucial” for helping patients with cancer to overcome administrative burdens and improve access to care, the authors said.

SOURCE:

• The study, led by Meredith Doherty, PhD, of the University of Pennsylvania, Philadelphia, was published in Cancer Epidemiology, Biomarkers and Prevention.

LIMITATIONS:

The survey was voluntary, which raises the possibility of self-selection bias. Recall bias may also have occurred, particularly among patients farther out from diagnosis and treatment. The investigators did not include uninsured patients and did not stratify patients by insurance type, and they did not measure or account for health care literacy.

DISCLOSURES:

The study was funded by the American Cancer Society. The investigators have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Sentinel lymph node biopsy (SLNB) is the standard of care for axillary node staging in early breast cancer, but previous studies have shown that removal of axillary lymph nodes has no therapeutic effect.

The finding raises a question: Is SLNB even necessary when preoperative axillary imaging is negative?

A new randomized trial addresses the question and brings much “welcome clarity” to the issue, Seema Khan, MD, a surgical oncologist and breast cancer researcher at Northwestern University, Chicago, said in an editorial to the trial, both of which were published in JAMA Oncology.

In short, European investigators found that it’s safe to skip SLNBs in women with breast cancers no larger than 2 cm if preoperative ultrasounds of the axilla show no evidence of nodal disease.

At a median of follow-up of 5.7 years, distant disease-free survival and other outcomes were essentially equivalent between 708 women randomized to SLNB followed by full axillary dissection if nodes are positive and 697 other women randomized to observation without SLNB.

Adjuvant therapies were not significantly different between the two groups largely because adjuvant decisions were driven by tumor characteristics, not axillary studies.

The results support “the argument that sentinel node positivity is not, in and of itself, a critical parameter that determines therapeutic plans and outcomes in patients with stage I breast cancer. This is a major accomplishment of the SOUND [Sentinel Node vs. Observation After Axillary Ultra-Sound] trial, which will be strengthened when longer-term data become available” at 10-year follow up, Dr. Khan said.

Investigators led by Oreste Davide Gentilini, MD, a breast cancer surgeon at San Raffaele Scientific and Research Hospital, Milan, estimated that, of the 2.3 million breast cancers diagnosed globally each year, the study suggests “that approximately 500,000 patients might be able to take advantage of the total omission of axillary surgery,” sparing women lymphedema and other serious side effects and saving health care systems substantial dollars.
 

A case-by-case decision

The study included women of all ages, with a median age of 60 years.

Subjects had a single tumor 0.8-1.5 cm across with negative preoperative axillary ultrasonography. Almost 90% had estrogen receptor ERBB2 (formerly HER2) positive tumors. Almost all of the subjects had radiotherapy, and about 20% of women in each arm also had chemotherapy.

The trial was conducted in 18 sites, most in Italy with other sites in Switzerland, Spain, and Chile.

Overall, 13.7% of women in the SLNB group turned out to have positive axillary nodes, with 0.6% having four or more positive nodes.

However, it didn’t seem to make a difference in the overall study results.

Five-year distant disease-free survival was 97.7% in the SLNB group and 98% in the observation arm (P for noninferiority = .02).

Secondary outcomes were also essentially identical, including local/regional relapse (1.7% with SLNB versus 1.6% without); distant metastases (1.8% vs. 2%), and death from breast cancer (1% vs. 0.6%). The cumulative incidence of axillary lymph node recurrences in the observation arm was just 0.4%.

“These findings suggest that patients with BC of a diameter equal to or smaller than 2 cm and a negative result on preoperative axillary lymph node ultrasonography can be safely spared any axillary surgery whenever the lack of pathological information does not affect the postoperative treatment plan,” Dr. Gentilini and associates concluded.

The team cautioned that decision to forgo SLNB must be made on a case-by-case basis in a multidisciplinary setting because there are still situations where nodal pathology is relevant, for instance when deciding to add chemotherapy to endocrine treatments in premenopausal women with endocrine-responsive disease.

Only about 20% of the subjects were under 50 years old and the team didn’t break down their results by age, which makes it difficult to apply their results to the situation.

The work was funded by the European Institute of Oncology. Dr. Khan didn’t have any disclosures. Dr. Gentilini reported personal fees from AstraZeneca, Bayer, BD, Eli Lilly, and MSD. Two other investigators also reported personal fees from those and/or other companies.

Sentinel lymph node biopsy (SLNB) is the standard of care for axillary node staging in early breast cancer, but previous studies have shown that removal of axillary lymph nodes has no therapeutic effect.

The finding raises a question: Is SLNB even necessary when preoperative axillary imaging is negative?

A new randomized trial addresses the question and brings much “welcome clarity” to the issue, Seema Khan, MD, a surgical oncologist and breast cancer researcher at Northwestern University, Chicago, said in an editorial to the trial, both of which were published in JAMA Oncology.

In short, European investigators found that it’s safe to skip SLNBs in women with breast cancers no larger than 2 cm if preoperative ultrasounds of the axilla show no evidence of nodal disease.

At a median of follow-up of 5.7 years, distant disease-free survival and other outcomes were essentially equivalent between 708 women randomized to SLNB followed by full axillary dissection if nodes are positive and 697 other women randomized to observation without SLNB.

Adjuvant therapies were not significantly different between the two groups largely because adjuvant decisions were driven by tumor characteristics, not axillary studies.

The results support “the argument that sentinel node positivity is not, in and of itself, a critical parameter that determines therapeutic plans and outcomes in patients with stage I breast cancer. This is a major accomplishment of the SOUND [Sentinel Node vs. Observation After Axillary Ultra-Sound] trial, which will be strengthened when longer-term data become available” at 10-year follow up, Dr. Khan said.

Investigators led by Oreste Davide Gentilini, MD, a breast cancer surgeon at San Raffaele Scientific and Research Hospital, Milan, estimated that, of the 2.3 million breast cancers diagnosed globally each year, the study suggests “that approximately 500,000 patients might be able to take advantage of the total omission of axillary surgery,” sparing women lymphedema and other serious side effects and saving health care systems substantial dollars.
 

A case-by-case decision

The study included women of all ages, with a median age of 60 years.

Subjects had a single tumor 0.8-1.5 cm across with negative preoperative axillary ultrasonography. Almost 90% had estrogen receptor ERBB2 (formerly HER2) positive tumors. Almost all of the subjects had radiotherapy, and about 20% of women in each arm also had chemotherapy.

The trial was conducted in 18 sites, most in Italy with other sites in Switzerland, Spain, and Chile.

Overall, 13.7% of women in the SLNB group turned out to have positive axillary nodes, with 0.6% having four or more positive nodes.

However, it didn’t seem to make a difference in the overall study results.

Five-year distant disease-free survival was 97.7% in the SLNB group and 98% in the observation arm (P for noninferiority = .02).

Secondary outcomes were also essentially identical, including local/regional relapse (1.7% with SLNB versus 1.6% without); distant metastases (1.8% vs. 2%), and death from breast cancer (1% vs. 0.6%). The cumulative incidence of axillary lymph node recurrences in the observation arm was just 0.4%.

“These findings suggest that patients with BC of a diameter equal to or smaller than 2 cm and a negative result on preoperative axillary lymph node ultrasonography can be safely spared any axillary surgery whenever the lack of pathological information does not affect the postoperative treatment plan,” Dr. Gentilini and associates concluded.

The team cautioned that decision to forgo SLNB must be made on a case-by-case basis in a multidisciplinary setting because there are still situations where nodal pathology is relevant, for instance when deciding to add chemotherapy to endocrine treatments in premenopausal women with endocrine-responsive disease.

Only about 20% of the subjects were under 50 years old and the team didn’t break down their results by age, which makes it difficult to apply their results to the situation.

The work was funded by the European Institute of Oncology. Dr. Khan didn’t have any disclosures. Dr. Gentilini reported personal fees from AstraZeneca, Bayer, BD, Eli Lilly, and MSD. Two other investigators also reported personal fees from those and/or other companies.

Sentinel lymph node biopsy (SLNB) is the standard of care for axillary node staging in early breast cancer, but previous studies have shown that removal of axillary lymph nodes has no therapeutic effect.

The finding raises a question: Is SLNB even necessary when preoperative axillary imaging is negative?

A new randomized trial addresses the question and brings much “welcome clarity” to the issue, Seema Khan, MD, a surgical oncologist and breast cancer researcher at Northwestern University, Chicago, said in an editorial to the trial, both of which were published in JAMA Oncology.

In short, European investigators found that it’s safe to skip SLNBs in women with breast cancers no larger than 2 cm if preoperative ultrasounds of the axilla show no evidence of nodal disease.

At a median of follow-up of 5.7 years, distant disease-free survival and other outcomes were essentially equivalent between 708 women randomized to SLNB followed by full axillary dissection if nodes are positive and 697 other women randomized to observation without SLNB.

Adjuvant therapies were not significantly different between the two groups largely because adjuvant decisions were driven by tumor characteristics, not axillary studies.

The results support “the argument that sentinel node positivity is not, in and of itself, a critical parameter that determines therapeutic plans and outcomes in patients with stage I breast cancer. This is a major accomplishment of the SOUND [Sentinel Node vs. Observation After Axillary Ultra-Sound] trial, which will be strengthened when longer-term data become available” at 10-year follow up, Dr. Khan said.

Investigators led by Oreste Davide Gentilini, MD, a breast cancer surgeon at San Raffaele Scientific and Research Hospital, Milan, estimated that, of the 2.3 million breast cancers diagnosed globally each year, the study suggests “that approximately 500,000 patients might be able to take advantage of the total omission of axillary surgery,” sparing women lymphedema and other serious side effects and saving health care systems substantial dollars.
 

A case-by-case decision

The study included women of all ages, with a median age of 60 years.

Subjects had a single tumor 0.8-1.5 cm across with negative preoperative axillary ultrasonography. Almost 90% had estrogen receptor ERBB2 (formerly HER2) positive tumors. Almost all of the subjects had radiotherapy, and about 20% of women in each arm also had chemotherapy.

The trial was conducted in 18 sites, most in Italy with other sites in Switzerland, Spain, and Chile.

Overall, 13.7% of women in the SLNB group turned out to have positive axillary nodes, with 0.6% having four or more positive nodes.

However, it didn’t seem to make a difference in the overall study results.

Five-year distant disease-free survival was 97.7% in the SLNB group and 98% in the observation arm (P for noninferiority = .02).

Secondary outcomes were also essentially identical, including local/regional relapse (1.7% with SLNB versus 1.6% without); distant metastases (1.8% vs. 2%), and death from breast cancer (1% vs. 0.6%). The cumulative incidence of axillary lymph node recurrences in the observation arm was just 0.4%.

“These findings suggest that patients with BC of a diameter equal to or smaller than 2 cm and a negative result on preoperative axillary lymph node ultrasonography can be safely spared any axillary surgery whenever the lack of pathological information does not affect the postoperative treatment plan,” Dr. Gentilini and associates concluded.

The team cautioned that decision to forgo SLNB must be made on a case-by-case basis in a multidisciplinary setting because there are still situations where nodal pathology is relevant, for instance when deciding to add chemotherapy to endocrine treatments in premenopausal women with endocrine-responsive disease.

Only about 20% of the subjects were under 50 years old and the team didn’t break down their results by age, which makes it difficult to apply their results to the situation.

The work was funded by the European Institute of Oncology. Dr. Khan didn’t have any disclosures. Dr. Gentilini reported personal fees from AstraZeneca, Bayer, BD, Eli Lilly, and MSD. Two other investigators also reported personal fees from those and/or other companies.

TOPLINE:

Women with node-negative breast cancers 2 cm or smaller and negative preoperative axillary ultrasound results may be safely spared sentinel lymph node (SLN) biopsy, new research suggests.

METHODOLOGY:

• SLN biopsy is standard for axillary staging in early breast cancer, but whether this biopsy is necessary and whether imaging could replace it remain uncertain.
• In the prospective SOUND trial, researchers randomized 1,405 women with node-negative breast cancers up to 2 cm and negative preoperative axillary ultrasound 1:1 to SLN biopsy or no axillary surgery.
• The primary outcome was 5-year distant disease-free survival (DFS), analyzed as intention-to-treat in 708 women randomized to SLN biopsy and 697 to no axillary surgery.
• Most patients (87.8%) had ER-positive ERBB2-negative disease, were postmenopausal (78%), and had T1 tumors (95%). In the biopsy group, 13.7% of patients had positive axillary nodes.
• Secondary end points were the cumulative incidence of distant recurrences and axillary recurrences, disease-free survival (DFS), and overall survival.

TAKEAWAY:

• Overall, omitting SLN biopsy did not appear to affect outcomes, with patients demonstrating similar 5-year locoregional relapse rates with and without SLN biopsy (1.7% vs. 1.6%), 5-year distant metastases (1.8% with vs. 2.0% without), and 5-year distant DFS (97.7% with vs. 98.0% without).
• Five-year overall survival was also similar between the two groups: 98.2% among those who received SLN biopsy and 98.4% among those who did not.
• Overall, 21 (3.0%) deaths were observed in the SLNB group and 18 (2.6%) deaths in the no axillary surgery group.
• The authors reported no significant differences in adjuvant treatment recommendations between the two groups.

IN PRACTICE:

“The results of this trial support the safety of omitting axillary surgery in older postmenopausal women with ER-positive ERBB2-negative [breast cancer] who met the SOUND eligibility criteria,” the study authors concluded.

In an accompanying editorial, Seema A. Khan, MD, agreed that the outcome data support “the argument that sentinel node positivity is not, in and of itself, a critical parameter that determines therapeutic plans and outcomes in patients with stage I breast cancer.”

SOURCE:

The study, led by Oreste Davide Gentilini, MD, San Raffaele Scientific and Research Hospital, Milan, was published online in JAMA Oncology, with an editorial by Seema Khan, MD, Northwestern University, Chicago.

LIMITATIONS:

The study enrolled patients who could be considered low risk for recurrence in the short-term (median tumor size of 1.1 cm and 87.8% of patients had hormone-receptor positive, ERBB2-negative disease). The authors noted that differences in outcomes might appear over a longer follow-up period.

DISCLOSURES:

The SOUND trial was funded by the European Institute of Oncology Foundation. Some authors report personal fees from pharmaceutical companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Women with node-negative breast cancers 2 cm or smaller and negative preoperative axillary ultrasound results may be safely spared sentinel lymph node (SLN) biopsy, new research suggests.

METHODOLOGY:

• SLN biopsy is standard for axillary staging in early breast cancer, but whether this biopsy is necessary and whether imaging could replace it remain uncertain.
• In the prospective SOUND trial, researchers randomized 1,405 women with node-negative breast cancers up to 2 cm and negative preoperative axillary ultrasound 1:1 to SLN biopsy or no axillary surgery.
• The primary outcome was 5-year distant disease-free survival (DFS), analyzed as intention-to-treat in 708 women randomized to SLN biopsy and 697 to no axillary surgery.
• Most patients (87.8%) had ER-positive ERBB2-negative disease, were postmenopausal (78%), and had T1 tumors (95%). In the biopsy group, 13.7% of patients had positive axillary nodes.
• Secondary end points were the cumulative incidence of distant recurrences and axillary recurrences, disease-free survival (DFS), and overall survival.

TAKEAWAY:

• Overall, omitting SLN biopsy did not appear to affect outcomes, with patients demonstrating similar 5-year locoregional relapse rates with and without SLN biopsy (1.7% vs. 1.6%), 5-year distant metastases (1.8% with vs. 2.0% without), and 5-year distant DFS (97.7% with vs. 98.0% without).
• Five-year overall survival was also similar between the two groups: 98.2% among those who received SLN biopsy and 98.4% among those who did not.
• Overall, 21 (3.0%) deaths were observed in the SLNB group and 18 (2.6%) deaths in the no axillary surgery group.
• The authors reported no significant differences in adjuvant treatment recommendations between the two groups.

IN PRACTICE:

“The results of this trial support the safety of omitting axillary surgery in older postmenopausal women with ER-positive ERBB2-negative [breast cancer] who met the SOUND eligibility criteria,” the study authors concluded.

In an accompanying editorial, Seema A. Khan, MD, agreed that the outcome data support “the argument that sentinel node positivity is not, in and of itself, a critical parameter that determines therapeutic plans and outcomes in patients with stage I breast cancer.”

SOURCE:

The study, led by Oreste Davide Gentilini, MD, San Raffaele Scientific and Research Hospital, Milan, was published online in JAMA Oncology, with an editorial by Seema Khan, MD, Northwestern University, Chicago.

LIMITATIONS:

The study enrolled patients who could be considered low risk for recurrence in the short-term (median tumor size of 1.1 cm and 87.8% of patients had hormone-receptor positive, ERBB2-negative disease). The authors noted that differences in outcomes might appear over a longer follow-up period.

DISCLOSURES:

The SOUND trial was funded by the European Institute of Oncology Foundation. Some authors report personal fees from pharmaceutical companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Women with node-negative breast cancers 2 cm or smaller and negative preoperative axillary ultrasound results may be safely spared sentinel lymph node (SLN) biopsy, new research suggests.

METHODOLOGY:

• SLN biopsy is standard for axillary staging in early breast cancer, but whether this biopsy is necessary and whether imaging could replace it remain uncertain.
• In the prospective SOUND trial, researchers randomized 1,405 women with node-negative breast cancers up to 2 cm and negative preoperative axillary ultrasound 1:1 to SLN biopsy or no axillary surgery.
• The primary outcome was 5-year distant disease-free survival (DFS), analyzed as intention-to-treat in 708 women randomized to SLN biopsy and 697 to no axillary surgery.
• Most patients (87.8%) had ER-positive ERBB2-negative disease, were postmenopausal (78%), and had T1 tumors (95%). In the biopsy group, 13.7% of patients had positive axillary nodes.
• Secondary end points were the cumulative incidence of distant recurrences and axillary recurrences, disease-free survival (DFS), and overall survival.

TAKEAWAY:

• Overall, omitting SLN biopsy did not appear to affect outcomes, with patients demonstrating similar 5-year locoregional relapse rates with and without SLN biopsy (1.7% vs. 1.6%), 5-year distant metastases (1.8% with vs. 2.0% without), and 5-year distant DFS (97.7% with vs. 98.0% without).
• Five-year overall survival was also similar between the two groups: 98.2% among those who received SLN biopsy and 98.4% among those who did not.
• Overall, 21 (3.0%) deaths were observed in the SLNB group and 18 (2.6%) deaths in the no axillary surgery group.
• The authors reported no significant differences in adjuvant treatment recommendations between the two groups.

IN PRACTICE:

“The results of this trial support the safety of omitting axillary surgery in older postmenopausal women with ER-positive ERBB2-negative [breast cancer] who met the SOUND eligibility criteria,” the study authors concluded.

In an accompanying editorial, Seema A. Khan, MD, agreed that the outcome data support “the argument that sentinel node positivity is not, in and of itself, a critical parameter that determines therapeutic plans and outcomes in patients with stage I breast cancer.”

SOURCE:

The study, led by Oreste Davide Gentilini, MD, San Raffaele Scientific and Research Hospital, Milan, was published online in JAMA Oncology, with an editorial by Seema Khan, MD, Northwestern University, Chicago.

LIMITATIONS:

The study enrolled patients who could be considered low risk for recurrence in the short-term (median tumor size of 1.1 cm and 87.8% of patients had hormone-receptor positive, ERBB2-negative disease). The authors noted that differences in outcomes might appear over a longer follow-up period.

DISCLOSURES:

The SOUND trial was funded by the European Institute of Oncology Foundation. Some authors report personal fees from pharmaceutical companies.

A version of this article appeared on Medscape.com.

Patients with breast cancer often stay on endocrine therapy for 5-10 years.

For many, however, long-term use is a challenge. Studies show about half of breast cancer patients don’t take their hormone therapy as prescribed, and as many as 40% discontinue treatment early.

Stopping adjuvant endocrine therapy prematurely can have major consequences. These patients are more likely to experience cancer recurrence and to die earlier, research shows.

“Given that suboptimal adjuvant endocrine therapy adherence is common and is associated with breast cancer recurrence and mortality, there is a vital need for effective interventions to promote adherence,” Joanna J. Arch, PhD, from the University of Colorado Boulder, and colleagues write in a recent meta-analysis.

Experts discuss why it’s so challenging for patients to adhere to adjuvant endocrine therapy as well as which strategies may help boost long-term use and which likely will not.
 

The adherence problem

To improve adherence to adjuvant endocrine therapy, clinicians first need to understand the barriers patients face.

Studies indicate that a host of issues play into long-term adherence. Medication side effects, such as insomnia, fatigue, anxiety, depression, joint pain, and hot flashes, can deter patients from continuing endocrine therapy.

Tamoxifen, in particular, is known for its severe adverse events. Research suggests it may even increase patients’ risk for endometrial cancer and other uterine diseases.

Recent approvals of aromatase inhibitors – such as anastrozole, exemestane, and letrozole – have provided patients a tamoxifen alterative, but these agents come with their own issues, which include bone loss and vaginal dryness.

Common and severe side effects that affect adherence “should absolutely be addressed sooner, more frequently, and by any provider, not just the medical oncologist,” said Anna Weiss, MD, a breast cancer surgeon with the Wilmot Cancer Center, University of Rochester Medical Center, N.Y.

Other barriers to long-term use include the burden of managing comorbidities and drug costs as well as patients’ uncertainty about the value of long-term cancer therapy.

The issues that take center stage for individual patients may also vary by age. For older patients, comorbidities, cognitive function, and lack of social support may be key barriers to adherence, while for younger patients, fertility and sexual health issues are more pressing.

Clinicians should especially not underestimate the effects of hormonal suppression on adherence, explained Dr. Weiss, who recently published practice pearls on managing side effects of adjunctive endocrine therapy. “I do believe that we have been ignoring the sexual wellness aspect of breast cancer survivorship care for too long,” she said.
 

An array of fixes needed

Given the array of potential obstacles to endocrine therapy adherence, improving long-term use may be equally complex.

In a recent meta-analysis, Dr. Arch and colleagues combed the literature for studies exploring a host of strategies to improve endocrine therapy adherence. The team focused on 25 studies involving 367,873 women with breast cancer who were prescribed tamoxifen or an aromatase inhibitor.

The studies assessed a variety of interventions – disease management and exercise programs to lower side effects, medication reminders via phone or letter to limit missed doses, online educational materials to highlight the importance of adherence, as well as medication changes to reduce drug costs.

Overall, these interventions were of modest benefit in improving adherence. The findings indicate that “a variety of approaches” can be effective, Dr. Arch said.

But, she noted, aside from cost-cutting strategies, “no single approach stood out as more effective than others,” and some studies found minimal or inconsistent benefits to specific interventions.

One analysis, for instance, explored a text message intervention that involved sending patients several texts per week reminding them to take their medication, exercise more, or monitor their side effects. Overall, participants who received text messages missed fewer endocrine therapy doses, compared with those who didn’t – 7.1% versus 17.0% – and for about two-thirds of participants, the text messages motivated lifestyle changes.

Another study included in the meta-analysis, however, found that “twice-weekly text reminders did not improve adherence to aromatase inhibitors.”

Studies in which patients received educational materials about the importance of adherence or how to manage side effects found that effectiveness varied as well. Other analyses indicated that integrating relaxation techniques or other cognitive-behavioral approaches into patient care may have small beneficial effects on adherence.

Dr. Arch’s meta-analysis did, however, find a consistent benefit for cost-cutting interventions. Three large studies reported that medication adherence improved following policy changes that were focused on reducing costs of adjuvant endocrine therapy, either through legislation limiting out-of-pocket costs for oral drugs or by switching to generic formulations.

Xuanzi Qin, PhD, first author on one of the studies, explained that after generic aromatase inhibitor options became available, patients who switched to these options had lower out-of-pocket costs and higher rates of drug adherence.

The take-home message of the study is that “clinicians should know the out-of-pocket costs of the drugs and discuss the costs with patients,” Dr. Qin, of the University of Maryland School of Public Health, College Park, told this news organization.

Dr. Arch pointed out that although the meta-analysis found a consistent benefit to cost-cutting strategies, that does not necessarily translate to a strong benefit.

And overall, the body of research indicates that “we need to develop and test new strategies and hone existing ones,” Dr. Arch said, “so that we can boost adherence even more and help more women benefit fully from these life-extending medications.”

However, Dr. Weiss explained, seemingly small measures may still make important clinical differences for individual patients, even if studies don’t show a statistically significant impact overall on endocrine therapy adherence.

For Dr. Weiss, “even getting one patient to continue their endocrine therapy is a win in my book.”

Dr. Arch reported a consulting or advisory role with AbbVie/Genentech and Bristol-Meyers Squibb and research funding from NCCN/Astrazeneca. Dr. Weiss reports being on the advisory board for Merck and Myriad. Dr. Qin has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Patients with breast cancer often stay on endocrine therapy for 5-10 years.

For many, however, long-term use is a challenge. Studies show about half of breast cancer patients don’t take their hormone therapy as prescribed, and as many as 40% discontinue treatment early.

Stopping adjuvant endocrine therapy prematurely can have major consequences. These patients are more likely to experience cancer recurrence and to die earlier, research shows.

“Given that suboptimal adjuvant endocrine therapy adherence is common and is associated with breast cancer recurrence and mortality, there is a vital need for effective interventions to promote adherence,” Joanna J. Arch, PhD, from the University of Colorado Boulder, and colleagues write in a recent meta-analysis.

Experts discuss why it’s so challenging for patients to adhere to adjuvant endocrine therapy as well as which strategies may help boost long-term use and which likely will not.
 

The adherence problem

To improve adherence to adjuvant endocrine therapy, clinicians first need to understand the barriers patients face.

Studies indicate that a host of issues play into long-term adherence. Medication side effects, such as insomnia, fatigue, anxiety, depression, joint pain, and hot flashes, can deter patients from continuing endocrine therapy.

Tamoxifen, in particular, is known for its severe adverse events. Research suggests it may even increase patients’ risk for endometrial cancer and other uterine diseases.

Recent approvals of aromatase inhibitors – such as anastrozole, exemestane, and letrozole – have provided patients a tamoxifen alterative, but these agents come with their own issues, which include bone loss and vaginal dryness.

Common and severe side effects that affect adherence “should absolutely be addressed sooner, more frequently, and by any provider, not just the medical oncologist,” said Anna Weiss, MD, a breast cancer surgeon with the Wilmot Cancer Center, University of Rochester Medical Center, N.Y.

Other barriers to long-term use include the burden of managing comorbidities and drug costs as well as patients’ uncertainty about the value of long-term cancer therapy.

The issues that take center stage for individual patients may also vary by age. For older patients, comorbidities, cognitive function, and lack of social support may be key barriers to adherence, while for younger patients, fertility and sexual health issues are more pressing.

Clinicians should especially not underestimate the effects of hormonal suppression on adherence, explained Dr. Weiss, who recently published practice pearls on managing side effects of adjunctive endocrine therapy. “I do believe that we have been ignoring the sexual wellness aspect of breast cancer survivorship care for too long,” she said.
 

An array of fixes needed

Given the array of potential obstacles to endocrine therapy adherence, improving long-term use may be equally complex.

In a recent meta-analysis, Dr. Arch and colleagues combed the literature for studies exploring a host of strategies to improve endocrine therapy adherence. The team focused on 25 studies involving 367,873 women with breast cancer who were prescribed tamoxifen or an aromatase inhibitor.

The studies assessed a variety of interventions – disease management and exercise programs to lower side effects, medication reminders via phone or letter to limit missed doses, online educational materials to highlight the importance of adherence, as well as medication changes to reduce drug costs.

Overall, these interventions were of modest benefit in improving adherence. The findings indicate that “a variety of approaches” can be effective, Dr. Arch said.

But, she noted, aside from cost-cutting strategies, “no single approach stood out as more effective than others,” and some studies found minimal or inconsistent benefits to specific interventions.

One analysis, for instance, explored a text message intervention that involved sending patients several texts per week reminding them to take their medication, exercise more, or monitor their side effects. Overall, participants who received text messages missed fewer endocrine therapy doses, compared with those who didn’t – 7.1% versus 17.0% – and for about two-thirds of participants, the text messages motivated lifestyle changes.

Another study included in the meta-analysis, however, found that “twice-weekly text reminders did not improve adherence to aromatase inhibitors.”

Studies in which patients received educational materials about the importance of adherence or how to manage side effects found that effectiveness varied as well. Other analyses indicated that integrating relaxation techniques or other cognitive-behavioral approaches into patient care may have small beneficial effects on adherence.

Dr. Arch’s meta-analysis did, however, find a consistent benefit for cost-cutting interventions. Three large studies reported that medication adherence improved following policy changes that were focused on reducing costs of adjuvant endocrine therapy, either through legislation limiting out-of-pocket costs for oral drugs or by switching to generic formulations.

Xuanzi Qin, PhD, first author on one of the studies, explained that after generic aromatase inhibitor options became available, patients who switched to these options had lower out-of-pocket costs and higher rates of drug adherence.

The take-home message of the study is that “clinicians should know the out-of-pocket costs of the drugs and discuss the costs with patients,” Dr. Qin, of the University of Maryland School of Public Health, College Park, told this news organization.

Dr. Arch pointed out that although the meta-analysis found a consistent benefit to cost-cutting strategies, that does not necessarily translate to a strong benefit.

And overall, the body of research indicates that “we need to develop and test new strategies and hone existing ones,” Dr. Arch said, “so that we can boost adherence even more and help more women benefit fully from these life-extending medications.”

However, Dr. Weiss explained, seemingly small measures may still make important clinical differences for individual patients, even if studies don’t show a statistically significant impact overall on endocrine therapy adherence.

For Dr. Weiss, “even getting one patient to continue their endocrine therapy is a win in my book.”

Dr. Arch reported a consulting or advisory role with AbbVie/Genentech and Bristol-Meyers Squibb and research funding from NCCN/Astrazeneca. Dr. Weiss reports being on the advisory board for Merck and Myriad. Dr. Qin has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Patients with breast cancer often stay on endocrine therapy for 5-10 years.

For many, however, long-term use is a challenge. Studies show about half of breast cancer patients don’t take their hormone therapy as prescribed, and as many as 40% discontinue treatment early.

Stopping adjuvant endocrine therapy prematurely can have major consequences. These patients are more likely to experience cancer recurrence and to die earlier, research shows.

“Given that suboptimal adjuvant endocrine therapy adherence is common and is associated with breast cancer recurrence and mortality, there is a vital need for effective interventions to promote adherence,” Joanna J. Arch, PhD, from the University of Colorado Boulder, and colleagues write in a recent meta-analysis.

Experts discuss why it’s so challenging for patients to adhere to adjuvant endocrine therapy as well as which strategies may help boost long-term use and which likely will not.
 

The adherence problem

To improve adherence to adjuvant endocrine therapy, clinicians first need to understand the barriers patients face.

Studies indicate that a host of issues play into long-term adherence. Medication side effects, such as insomnia, fatigue, anxiety, depression, joint pain, and hot flashes, can deter patients from continuing endocrine therapy.

Tamoxifen, in particular, is known for its severe adverse events. Research suggests it may even increase patients’ risk for endometrial cancer and other uterine diseases.

Recent approvals of aromatase inhibitors – such as anastrozole, exemestane, and letrozole – have provided patients a tamoxifen alterative, but these agents come with their own issues, which include bone loss and vaginal dryness.

Common and severe side effects that affect adherence “should absolutely be addressed sooner, more frequently, and by any provider, not just the medical oncologist,” said Anna Weiss, MD, a breast cancer surgeon with the Wilmot Cancer Center, University of Rochester Medical Center, N.Y.

Other barriers to long-term use include the burden of managing comorbidities and drug costs as well as patients’ uncertainty about the value of long-term cancer therapy.

The issues that take center stage for individual patients may also vary by age. For older patients, comorbidities, cognitive function, and lack of social support may be key barriers to adherence, while for younger patients, fertility and sexual health issues are more pressing.

Clinicians should especially not underestimate the effects of hormonal suppression on adherence, explained Dr. Weiss, who recently published practice pearls on managing side effects of adjunctive endocrine therapy. “I do believe that we have been ignoring the sexual wellness aspect of breast cancer survivorship care for too long,” she said.
 

An array of fixes needed

Given the array of potential obstacles to endocrine therapy adherence, improving long-term use may be equally complex.

In a recent meta-analysis, Dr. Arch and colleagues combed the literature for studies exploring a host of strategies to improve endocrine therapy adherence. The team focused on 25 studies involving 367,873 women with breast cancer who were prescribed tamoxifen or an aromatase inhibitor.

The studies assessed a variety of interventions – disease management and exercise programs to lower side effects, medication reminders via phone or letter to limit missed doses, online educational materials to highlight the importance of adherence, as well as medication changes to reduce drug costs.

Overall, these interventions were of modest benefit in improving adherence. The findings indicate that “a variety of approaches” can be effective, Dr. Arch said.

But, she noted, aside from cost-cutting strategies, “no single approach stood out as more effective than others,” and some studies found minimal or inconsistent benefits to specific interventions.

One analysis, for instance, explored a text message intervention that involved sending patients several texts per week reminding them to take their medication, exercise more, or monitor their side effects. Overall, participants who received text messages missed fewer endocrine therapy doses, compared with those who didn’t – 7.1% versus 17.0% – and for about two-thirds of participants, the text messages motivated lifestyle changes.

Another study included in the meta-analysis, however, found that “twice-weekly text reminders did not improve adherence to aromatase inhibitors.”

Studies in which patients received educational materials about the importance of adherence or how to manage side effects found that effectiveness varied as well. Other analyses indicated that integrating relaxation techniques or other cognitive-behavioral approaches into patient care may have small beneficial effects on adherence.

Dr. Arch’s meta-analysis did, however, find a consistent benefit for cost-cutting interventions. Three large studies reported that medication adherence improved following policy changes that were focused on reducing costs of adjuvant endocrine therapy, either through legislation limiting out-of-pocket costs for oral drugs or by switching to generic formulations.

Xuanzi Qin, PhD, first author on one of the studies, explained that after generic aromatase inhibitor options became available, patients who switched to these options had lower out-of-pocket costs and higher rates of drug adherence.

The take-home message of the study is that “clinicians should know the out-of-pocket costs of the drugs and discuss the costs with patients,” Dr. Qin, of the University of Maryland School of Public Health, College Park, told this news organization.

Dr. Arch pointed out that although the meta-analysis found a consistent benefit to cost-cutting strategies, that does not necessarily translate to a strong benefit.

And overall, the body of research indicates that “we need to develop and test new strategies and hone existing ones,” Dr. Arch said, “so that we can boost adherence even more and help more women benefit fully from these life-extending medications.”

However, Dr. Weiss explained, seemingly small measures may still make important clinical differences for individual patients, even if studies don’t show a statistically significant impact overall on endocrine therapy adherence.

For Dr. Weiss, “even getting one patient to continue their endocrine therapy is a win in my book.”

Dr. Arch reported a consulting or advisory role with AbbVie/Genentech and Bristol-Meyers Squibb and research funding from NCCN/Astrazeneca. Dr. Weiss reports being on the advisory board for Merck and Myriad. Dr. Qin has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

The risk of developing breast cancer in individuals with pathogenic cancer syndrome variants may be less elevated in those without a first-degree family history, according to findings from a large population-based cohort study.

Similar results were seen for patients with Lynch syndrome.

The findings suggest that a first-degree family history confers much of the risk that is associated with pathogenic variants associated with hereditary breast, ovarian, and colorectal cancers. Furthermore, to avoid overtreatment in those without a first-degree family history who undergo genetic testing, that history should be considered when discussing potential follow-up care, the investigators argue.

“This difference in penetrance in carrier individuals, if replicated in larger studies, could be sufficient to justify stratifying just individuals with a family history into high-risk groups currently eligible for specialist clinical care,” Leigh Jackson, PhD, of the University of Exeter College of Medicine and Health, Royal Devon and Exeter Hospital, England, and his colleagues noted.

To assess how population penetrance of familial cancer syndromes varies based on family history, researchers analyzed exome sequences and clinical data collected between March 2006 and June 25, 2021, from 454,712 UK Biobank participants with either breast or colorectal cancer, a self-reported family history of breast or colorectal cancer, and a pathogenic/likely pathogenic variant in the major genes associated with hereditary breast cancer or Lynch syndrome.

After researchers controlled for sex, death, recruitment center, screening, and prophylactic surgery, those with a pathogenic BRCA1 (n = 230) or BRCA2 (n = 611) variant had an increased risk of breast cancer, and the risk was higher in those with a first-degree family history (relative hazard, 10.3 and 7.8, respectively), than in those without a first-degree family history (relative hazard, 7.2 and 4.7), the investigators reported.

Penetrance to age 60 years was also higher in those with vs. without a first-degree family history (44.7% and 24.1% vs 22.8% and 17.9%, respectively).

Similarly, patients with Lynch syndrome and a pathogenic MLH1, MSH2, or MSH6 variant (n = 89, 71, and 421, respectively) had an increased risk of colorectal cancer, and that risk was higher in those with vs. without a family history (relative hazard, 35.6, 48.0, and 9.9 vs. 13.0, 15.4, and 7.2). Penetrance to age 60 was higher for those with a pathogenic MLH1 and MSH2 variant with vs. without a family history (30.9% and 38% vs. 20.5% and 8.3%).

The study results were published online in eClinicalMedicine, part of The Lancet Discovery Science.

“The findings of this study suggest that any universal policy of returning pathogenic cancer predisposing genetic variants found incidentally or through direct-to-consumer genetic testing of asymptomatic individuals should consider family history and other factors when counseling patients on the risks and benefits of follow-up care,” the investigators recommended. “It will be very difficult to counsel individuals as to their particular risk profile without further pedigree construction or investigations.

“If penetrance estimates from affected families are used, there is a danger of overmanagement of asymptomatic individuals with no family history of disease. These ‘patients-in-waiting’ may be exposed to unnecessary surveillance or more invasive prophylactic procedures,” they added.

This study was supported by an MRC grant. The authors reported having no competing interests.

The risk of developing breast cancer in individuals with pathogenic cancer syndrome variants may be less elevated in those without a first-degree family history, according to findings from a large population-based cohort study.

Similar results were seen for patients with Lynch syndrome.

The findings suggest that a first-degree family history confers much of the risk that is associated with pathogenic variants associated with hereditary breast, ovarian, and colorectal cancers. Furthermore, to avoid overtreatment in those without a first-degree family history who undergo genetic testing, that history should be considered when discussing potential follow-up care, the investigators argue.

“This difference in penetrance in carrier individuals, if replicated in larger studies, could be sufficient to justify stratifying just individuals with a family history into high-risk groups currently eligible for specialist clinical care,” Leigh Jackson, PhD, of the University of Exeter College of Medicine and Health, Royal Devon and Exeter Hospital, England, and his colleagues noted.

To assess how population penetrance of familial cancer syndromes varies based on family history, researchers analyzed exome sequences and clinical data collected between March 2006 and June 25, 2021, from 454,712 UK Biobank participants with either breast or colorectal cancer, a self-reported family history of breast or colorectal cancer, and a pathogenic/likely pathogenic variant in the major genes associated with hereditary breast cancer or Lynch syndrome.

After researchers controlled for sex, death, recruitment center, screening, and prophylactic surgery, those with a pathogenic BRCA1 (n = 230) or BRCA2 (n = 611) variant had an increased risk of breast cancer, and the risk was higher in those with a first-degree family history (relative hazard, 10.3 and 7.8, respectively), than in those without a first-degree family history (relative hazard, 7.2 and 4.7), the investigators reported.

Penetrance to age 60 years was also higher in those with vs. without a first-degree family history (44.7% and 24.1% vs 22.8% and 17.9%, respectively).

Similarly, patients with Lynch syndrome and a pathogenic MLH1, MSH2, or MSH6 variant (n = 89, 71, and 421, respectively) had an increased risk of colorectal cancer, and that risk was higher in those with vs. without a family history (relative hazard, 35.6, 48.0, and 9.9 vs. 13.0, 15.4, and 7.2). Penetrance to age 60 was higher for those with a pathogenic MLH1 and MSH2 variant with vs. without a family history (30.9% and 38% vs. 20.5% and 8.3%).

The study results were published online in eClinicalMedicine, part of The Lancet Discovery Science.

“The findings of this study suggest that any universal policy of returning pathogenic cancer predisposing genetic variants found incidentally or through direct-to-consumer genetic testing of asymptomatic individuals should consider family history and other factors when counseling patients on the risks and benefits of follow-up care,” the investigators recommended. “It will be very difficult to counsel individuals as to their particular risk profile without further pedigree construction or investigations.

“If penetrance estimates from affected families are used, there is a danger of overmanagement of asymptomatic individuals with no family history of disease. These ‘patients-in-waiting’ may be exposed to unnecessary surveillance or more invasive prophylactic procedures,” they added.

This study was supported by an MRC grant. The authors reported having no competing interests.

The risk of developing breast cancer in individuals with pathogenic cancer syndrome variants may be less elevated in those without a first-degree family history, according to findings from a large population-based cohort study.

Similar results were seen for patients with Lynch syndrome.

The findings suggest that a first-degree family history confers much of the risk that is associated with pathogenic variants associated with hereditary breast, ovarian, and colorectal cancers. Furthermore, to avoid overtreatment in those without a first-degree family history who undergo genetic testing, that history should be considered when discussing potential follow-up care, the investigators argue.

“This difference in penetrance in carrier individuals, if replicated in larger studies, could be sufficient to justify stratifying just individuals with a family history into high-risk groups currently eligible for specialist clinical care,” Leigh Jackson, PhD, of the University of Exeter College of Medicine and Health, Royal Devon and Exeter Hospital, England, and his colleagues noted.

To assess how population penetrance of familial cancer syndromes varies based on family history, researchers analyzed exome sequences and clinical data collected between March 2006 and June 25, 2021, from 454,712 UK Biobank participants with either breast or colorectal cancer, a self-reported family history of breast or colorectal cancer, and a pathogenic/likely pathogenic variant in the major genes associated with hereditary breast cancer or Lynch syndrome.

After researchers controlled for sex, death, recruitment center, screening, and prophylactic surgery, those with a pathogenic BRCA1 (n = 230) or BRCA2 (n = 611) variant had an increased risk of breast cancer, and the risk was higher in those with a first-degree family history (relative hazard, 10.3 and 7.8, respectively), than in those without a first-degree family history (relative hazard, 7.2 and 4.7), the investigators reported.

Penetrance to age 60 years was also higher in those with vs. without a first-degree family history (44.7% and 24.1% vs 22.8% and 17.9%, respectively).

Similarly, patients with Lynch syndrome and a pathogenic MLH1, MSH2, or MSH6 variant (n = 89, 71, and 421, respectively) had an increased risk of colorectal cancer, and that risk was higher in those with vs. without a family history (relative hazard, 35.6, 48.0, and 9.9 vs. 13.0, 15.4, and 7.2). Penetrance to age 60 was higher for those with a pathogenic MLH1 and MSH2 variant with vs. without a family history (30.9% and 38% vs. 20.5% and 8.3%).

The study results were published online in eClinicalMedicine, part of The Lancet Discovery Science.

“The findings of this study suggest that any universal policy of returning pathogenic cancer predisposing genetic variants found incidentally or through direct-to-consumer genetic testing of asymptomatic individuals should consider family history and other factors when counseling patients on the risks and benefits of follow-up care,” the investigators recommended. “It will be very difficult to counsel individuals as to their particular risk profile without further pedigree construction or investigations.

“If penetrance estimates from affected families are used, there is a danger of overmanagement of asymptomatic individuals with no family history of disease. These ‘patients-in-waiting’ may be exposed to unnecessary surveillance or more invasive prophylactic procedures,” they added.

This study was supported by an MRC grant. The authors reported having no competing interests.

Currently, more than 3.8 million breast cancer survivors reside in the United States, reflecting high prevalence as well as cure rates for this common malignancy.

When over-the-counter measures including vaginal lubricants and moisturizers are not adequate, vaginal estrogen may be a highly effective treatment for genitourinary syndrome of menopause (GSM), a common condition associated with hypoestrogenism that impairs sexual function and quality of life.

Use of vaginal formulations does not result in systemic levels of estrogen above the normal postmenopausal range. Nonetheless, the U.S. Food and Drug Administration lists a history of breast cancer as a contraindication to the use of all systemic as well as vaginal estrogens.

In premenopausal women, chemotherapy for breast cancer often results in early menopause. Aromatase inhibitors, although effective in preventing recurrent disease in menopausal women, exacerbate GSM. These factors result in a high prevalence of GSM in breast cancer survivors.

Because the safety of vaginal estrogen in the setting of breast cancer is uncertain, investigators at Johns Hopkins conducted a cohort study using claims-based data from more than 200 million U.S. patients that identified women with GSM who had previously been diagnosed with breast cancer. Among some 42,000 women diagnosed with GSM after breast cancer, 5% had three or more prescriptions and were considered vaginal estrogen users.

No significant differences were noted in recurrence-free survival between the vaginal estrogen group and the no estrogen group. At 5 and 10 years of follow-up, use of vaginal estrogen was not associated with higher all-cause mortality. Among women with estrogen receptor–positive tumors, risk for breast cancer recurrence was similar between estrogen users and nonusers.

However, concomitant use of vaginal estrogen and aromatase inhibitors was associated with a higher risk for breast cancer recurrence than was use of vaginal estrogen alone.

Although this important study’s findings have the limitations characteristic of observational studies, its large size and careful analyses suggest that in selected well-counseled breast cancer survivors, off-label use of vaginal estrogen may safely improve their sexual function and quality of life.

Dr. Kaunitz is associate chairman, department of obstetrics and gynecology, University of Florida College of Medicine, Jacksonville. This transcript has been edited for clarity. A version of this article first appeared on Medscape.com.

Currently, more than 3.8 million breast cancer survivors reside in the United States, reflecting high prevalence as well as cure rates for this common malignancy.

When over-the-counter measures including vaginal lubricants and moisturizers are not adequate, vaginal estrogen may be a highly effective treatment for genitourinary syndrome of menopause (GSM), a common condition associated with hypoestrogenism that impairs sexual function and quality of life.

Use of vaginal formulations does not result in systemic levels of estrogen above the normal postmenopausal range. Nonetheless, the U.S. Food and Drug Administration lists a history of breast cancer as a contraindication to the use of all systemic as well as vaginal estrogens.

In premenopausal women, chemotherapy for breast cancer often results in early menopause. Aromatase inhibitors, although effective in preventing recurrent disease in menopausal women, exacerbate GSM. These factors result in a high prevalence of GSM in breast cancer survivors.

Because the safety of vaginal estrogen in the setting of breast cancer is uncertain, investigators at Johns Hopkins conducted a cohort study using claims-based data from more than 200 million U.S. patients that identified women with GSM who had previously been diagnosed with breast cancer. Among some 42,000 women diagnosed with GSM after breast cancer, 5% had three or more prescriptions and were considered vaginal estrogen users.

No significant differences were noted in recurrence-free survival between the vaginal estrogen group and the no estrogen group. At 5 and 10 years of follow-up, use of vaginal estrogen was not associated with higher all-cause mortality. Among women with estrogen receptor–positive tumors, risk for breast cancer recurrence was similar between estrogen users and nonusers.

However, concomitant use of vaginal estrogen and aromatase inhibitors was associated with a higher risk for breast cancer recurrence than was use of vaginal estrogen alone.

Although this important study’s findings have the limitations characteristic of observational studies, its large size and careful analyses suggest that in selected well-counseled breast cancer survivors, off-label use of vaginal estrogen may safely improve their sexual function and quality of life.

Dr. Kaunitz is associate chairman, department of obstetrics and gynecology, University of Florida College of Medicine, Jacksonville. This transcript has been edited for clarity. A version of this article first appeared on Medscape.com.

Currently, more than 3.8 million breast cancer survivors reside in the United States, reflecting high prevalence as well as cure rates for this common malignancy.

When over-the-counter measures including vaginal lubricants and moisturizers are not adequate, vaginal estrogen may be a highly effective treatment for genitourinary syndrome of menopause (GSM), a common condition associated with hypoestrogenism that impairs sexual function and quality of life.

Use of vaginal formulations does not result in systemic levels of estrogen above the normal postmenopausal range. Nonetheless, the U.S. Food and Drug Administration lists a history of breast cancer as a contraindication to the use of all systemic as well as vaginal estrogens.

In premenopausal women, chemotherapy for breast cancer often results in early menopause. Aromatase inhibitors, although effective in preventing recurrent disease in menopausal women, exacerbate GSM. These factors result in a high prevalence of GSM in breast cancer survivors.

Because the safety of vaginal estrogen in the setting of breast cancer is uncertain, investigators at Johns Hopkins conducted a cohort study using claims-based data from more than 200 million U.S. patients that identified women with GSM who had previously been diagnosed with breast cancer. Among some 42,000 women diagnosed with GSM after breast cancer, 5% had three or more prescriptions and were considered vaginal estrogen users.

No significant differences were noted in recurrence-free survival between the vaginal estrogen group and the no estrogen group. At 5 and 10 years of follow-up, use of vaginal estrogen was not associated with higher all-cause mortality. Among women with estrogen receptor–positive tumors, risk for breast cancer recurrence was similar between estrogen users and nonusers.

However, concomitant use of vaginal estrogen and aromatase inhibitors was associated with a higher risk for breast cancer recurrence than was use of vaginal estrogen alone.

Although this important study’s findings have the limitations characteristic of observational studies, its large size and careful analyses suggest that in selected well-counseled breast cancer survivors, off-label use of vaginal estrogen may safely improve their sexual function and quality of life.

Dr. Kaunitz is associate chairman, department of obstetrics and gynecology, University of Florida College of Medicine, Jacksonville. This transcript has been edited for clarity. A version of this article first appeared on Medscape.com.