Conference Coverage

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.
 

CARLSBAD, CALIF. – Spironolactone may be an effective and safe treatment option for women with hidradenitis suppurativa (HS), regardless of whether they report having menstrual HS flares or have been diagnosed with polycystic ovary syndrome (PCOS).

Those are the key findings from a single-center retrospective study that Jennifer L. Hsiao, MD, and colleagues presented during a poster session at the annual symposium of the California Society of Dermatology & Dermatologic Surgery.

In an interview after the meeting, Dr. Hsiao, a dermatologist who directs the hidradenitis suppurativa clinic at the University of Southern California, Los Angeles, said that hormones are thought to play a role in HS pathogenesis given the typical HS symptom onset around puberty and fluctuations in disease activity with menses (typically premenstrual flares) and pregnancy. “Spironolactone, an anti-androgenic agent, is used to treat HS in women; however, there is a paucity of data on the efficacy of spironolactone for HS and whether certain patient characteristics may influence treatment response,” she told this news organization. “This study is unique in that we contribute to existing literature regarding spironolactone efficacy in HS and we also investigate whether the presence of menstrual HS flares or polycystic ovarian syndrome influences the likelihood of response to spironolactone.”

Wikimedia Commons/Creative Commons Attribution-Share Alike 4.0 International

For the analysis, Dr. Hsiao and colleagues retrospectively reviewed the medical records of 53 adult women with HS who were prescribed spironolactone and who received care at USC’s HS clinic between January 2015 and December 2021. They collected data on demographics, comorbidities, HS medications, treatment response at 3 and 6 months, as well as adverse events. They also evaluated physician-assessed response to treatment when available.

The mean age of patients was 31 years, 37% were White, 30.4% were Black, 21.7% were Hispanic, 6.5% were Asian, and the remainder were biracial. The mean age at HS diagnosis was 25.1 years and the three most common comorbidities were acne (50.9%), obesity (45.3%), and anemia (37.7%). As for menstrual history, 56.6% had perimenstrual HS flares and 37.7% had irregular menstrual cycles. The top three classes of concomitant medications were antibiotics (58.5%), oral contraceptives (50.9%), and other birth control methods (18.9%).

The mean spironolactone dose was 104 mg/day; 84.1% of the women experienced improvement of HS 3 months after starting the drug, while 81.8% had improvement of their HS 6 months after starting the drug. The researchers also found that 56.6% of women had documented perimenstrual HS flares and 7.5% had PCOS.

“Spironolactone is often thought of as a helpful medication to consider if a patient reports having HS flares around menses or features of PCOS,” Dr. Hsiao said. However, she added, “our study found that there was no statistically significant difference in the response to spironolactone based on the presence of premenstrual flares or concomitant PCOS.” She said that spironolactone may be used as an adjunct therapeutic option in patients with more severe disease in addition to other medical and surgical therapies for HS. “Combining different treatment options that target different pathophysiologic factors is usually required to achieve adequate disease control in HS,” she said.

Dr. Hsiao acknowledged certain limitations of the study, including its single-center design and small sample size. “A confounding variable is that some patients were on other medications in addition to spironolactone, which may have influenced treatment outcomes,” she noted. “Larger prospective studies are needed to identify optimal dosing for spironolactone therapy in HS as well as predictors of treatment response.”

Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, who was asked to comment on the study, said that with only one FDA-approved systemic medication for the management of HS (adalimumab), “we off-label bandits must be creative to curtail the incredibly painful impact this chronic, destructive inflammatory disease can have on our patients.”

“The evidence supporting our approaches, whether it be antibiotics, immunomodulators, or in this case, antihormonal therapies, is limited, so more data is always welcome,” said Dr. Friedman, who was not involved with the study. “One very interesting point raised by the authors, one I share with my trainees frequently from my own experience, is that regardless of menstrual cycle abnormalities, spironolactone can be impactful. This is important to remember, in that overt signs of hormonal influences is not a requisite for the use or effectiveness of antihormonal therapy.”

Dr. Hsiao disclosed that she is a member of board of directors for the Hidradenitis Suppurativa Foundation. She has also served as a consultant for AbbVie, Aclaris, Boehringer Ingelheim, Novartis, UCB, as a speaker for AbbVie, and as an investigator for Amgen, Boehringer Ingelheim, and Incyte. Dr. Friedman reported having no relevant financial disclosures.

CARLSBAD, CALIF. – Spironolactone may be an effective and safe treatment option for women with hidradenitis suppurativa (HS), regardless of whether they report having menstrual HS flares or have been diagnosed with polycystic ovary syndrome (PCOS).

Those are the key findings from a single-center retrospective study that Jennifer L. Hsiao, MD, and colleagues presented during a poster session at the annual symposium of the California Society of Dermatology & Dermatologic Surgery.

In an interview after the meeting, Dr. Hsiao, a dermatologist who directs the hidradenitis suppurativa clinic at the University of Southern California, Los Angeles, said that hormones are thought to play a role in HS pathogenesis given the typical HS symptom onset around puberty and fluctuations in disease activity with menses (typically premenstrual flares) and pregnancy. “Spironolactone, an anti-androgenic agent, is used to treat HS in women; however, there is a paucity of data on the efficacy of spironolactone for HS and whether certain patient characteristics may influence treatment response,” she told this news organization. “This study is unique in that we contribute to existing literature regarding spironolactone efficacy in HS and we also investigate whether the presence of menstrual HS flares or polycystic ovarian syndrome influences the likelihood of response to spironolactone.”

Wikimedia Commons/Creative Commons Attribution-Share Alike 4.0 International

For the analysis, Dr. Hsiao and colleagues retrospectively reviewed the medical records of 53 adult women with HS who were prescribed spironolactone and who received care at USC’s HS clinic between January 2015 and December 2021. They collected data on demographics, comorbidities, HS medications, treatment response at 3 and 6 months, as well as adverse events. They also evaluated physician-assessed response to treatment when available.

The mean age of patients was 31 years, 37% were White, 30.4% were Black, 21.7% were Hispanic, 6.5% were Asian, and the remainder were biracial. The mean age at HS diagnosis was 25.1 years and the three most common comorbidities were acne (50.9%), obesity (45.3%), and anemia (37.7%). As for menstrual history, 56.6% had perimenstrual HS flares and 37.7% had irregular menstrual cycles. The top three classes of concomitant medications were antibiotics (58.5%), oral contraceptives (50.9%), and other birth control methods (18.9%).

The mean spironolactone dose was 104 mg/day; 84.1% of the women experienced improvement of HS 3 months after starting the drug, while 81.8% had improvement of their HS 6 months after starting the drug. The researchers also found that 56.6% of women had documented perimenstrual HS flares and 7.5% had PCOS.

“Spironolactone is often thought of as a helpful medication to consider if a patient reports having HS flares around menses or features of PCOS,” Dr. Hsiao said. However, she added, “our study found that there was no statistically significant difference in the response to spironolactone based on the presence of premenstrual flares or concomitant PCOS.” She said that spironolactone may be used as an adjunct therapeutic option in patients with more severe disease in addition to other medical and surgical therapies for HS. “Combining different treatment options that target different pathophysiologic factors is usually required to achieve adequate disease control in HS,” she said.

Dr. Hsiao acknowledged certain limitations of the study, including its single-center design and small sample size. “A confounding variable is that some patients were on other medications in addition to spironolactone, which may have influenced treatment outcomes,” she noted. “Larger prospective studies are needed to identify optimal dosing for spironolactone therapy in HS as well as predictors of treatment response.”

Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, who was asked to comment on the study, said that with only one FDA-approved systemic medication for the management of HS (adalimumab), “we off-label bandits must be creative to curtail the incredibly painful impact this chronic, destructive inflammatory disease can have on our patients.”

“The evidence supporting our approaches, whether it be antibiotics, immunomodulators, or in this case, antihormonal therapies, is limited, so more data is always welcome,” said Dr. Friedman, who was not involved with the study. “One very interesting point raised by the authors, one I share with my trainees frequently from my own experience, is that regardless of menstrual cycle abnormalities, spironolactone can be impactful. This is important to remember, in that overt signs of hormonal influences is not a requisite for the use or effectiveness of antihormonal therapy.”

Dr. Hsiao disclosed that she is a member of board of directors for the Hidradenitis Suppurativa Foundation. She has also served as a consultant for AbbVie, Aclaris, Boehringer Ingelheim, Novartis, UCB, as a speaker for AbbVie, and as an investigator for Amgen, Boehringer Ingelheim, and Incyte. Dr. Friedman reported having no relevant financial disclosures.

CARLSBAD, CALIF. – Spironolactone may be an effective and safe treatment option for women with hidradenitis suppurativa (HS), regardless of whether they report having menstrual HS flares or have been diagnosed with polycystic ovary syndrome (PCOS).

Those are the key findings from a single-center retrospective study that Jennifer L. Hsiao, MD, and colleagues presented during a poster session at the annual symposium of the California Society of Dermatology & Dermatologic Surgery.

In an interview after the meeting, Dr. Hsiao, a dermatologist who directs the hidradenitis suppurativa clinic at the University of Southern California, Los Angeles, said that hormones are thought to play a role in HS pathogenesis given the typical HS symptom onset around puberty and fluctuations in disease activity with menses (typically premenstrual flares) and pregnancy. “Spironolactone, an anti-androgenic agent, is used to treat HS in women; however, there is a paucity of data on the efficacy of spironolactone for HS and whether certain patient characteristics may influence treatment response,” she told this news organization. “This study is unique in that we contribute to existing literature regarding spironolactone efficacy in HS and we also investigate whether the presence of menstrual HS flares or polycystic ovarian syndrome influences the likelihood of response to spironolactone.”

Wikimedia Commons/Creative Commons Attribution-Share Alike 4.0 International

For the analysis, Dr. Hsiao and colleagues retrospectively reviewed the medical records of 53 adult women with HS who were prescribed spironolactone and who received care at USC’s HS clinic between January 2015 and December 2021. They collected data on demographics, comorbidities, HS medications, treatment response at 3 and 6 months, as well as adverse events. They also evaluated physician-assessed response to treatment when available.

The mean age of patients was 31 years, 37% were White, 30.4% were Black, 21.7% were Hispanic, 6.5% were Asian, and the remainder were biracial. The mean age at HS diagnosis was 25.1 years and the three most common comorbidities were acne (50.9%), obesity (45.3%), and anemia (37.7%). As for menstrual history, 56.6% had perimenstrual HS flares and 37.7% had irregular menstrual cycles. The top three classes of concomitant medications were antibiotics (58.5%), oral contraceptives (50.9%), and other birth control methods (18.9%).

The mean spironolactone dose was 104 mg/day; 84.1% of the women experienced improvement of HS 3 months after starting the drug, while 81.8% had improvement of their HS 6 months after starting the drug. The researchers also found that 56.6% of women had documented perimenstrual HS flares and 7.5% had PCOS.

“Spironolactone is often thought of as a helpful medication to consider if a patient reports having HS flares around menses or features of PCOS,” Dr. Hsiao said. However, she added, “our study found that there was no statistically significant difference in the response to spironolactone based on the presence of premenstrual flares or concomitant PCOS.” She said that spironolactone may be used as an adjunct therapeutic option in patients with more severe disease in addition to other medical and surgical therapies for HS. “Combining different treatment options that target different pathophysiologic factors is usually required to achieve adequate disease control in HS,” she said.

Dr. Hsiao acknowledged certain limitations of the study, including its single-center design and small sample size. “A confounding variable is that some patients were on other medications in addition to spironolactone, which may have influenced treatment outcomes,” she noted. “Larger prospective studies are needed to identify optimal dosing for spironolactone therapy in HS as well as predictors of treatment response.”

Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, who was asked to comment on the study, said that with only one FDA-approved systemic medication for the management of HS (adalimumab), “we off-label bandits must be creative to curtail the incredibly painful impact this chronic, destructive inflammatory disease can have on our patients.”

“The evidence supporting our approaches, whether it be antibiotics, immunomodulators, or in this case, antihormonal therapies, is limited, so more data is always welcome,” said Dr. Friedman, who was not involved with the study. “One very interesting point raised by the authors, one I share with my trainees frequently from my own experience, is that regardless of menstrual cycle abnormalities, spironolactone can be impactful. This is important to remember, in that overt signs of hormonal influences is not a requisite for the use or effectiveness of antihormonal therapy.”

Dr. Hsiao disclosed that she is a member of board of directors for the Hidradenitis Suppurativa Foundation. She has also served as a consultant for AbbVie, Aclaris, Boehringer Ingelheim, Novartis, UCB, as a speaker for AbbVie, and as an investigator for Amgen, Boehringer Ingelheim, and Incyte. Dr. Friedman reported having no relevant financial disclosures.

PHILADELPHIA – Cognitive behavioral therapy (CBT) was effective in addressing peri- and postmenopausal women’s sexual concerns, according to a small study presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society). Four CBT sessions specifically focused on sexual concerns resulted in decreased sexual distress and concern, reduced depressive and menopausal symptoms, and increased sexual desire and functioning, as well as improved body image and relationship satisfaction.

An estimated 68%-87% of perimenopausal and postmenopausal women report sexual concerns, Sheryl Green, PhD, CPsych, an associate professor of psychiatry and behavioral neurosciences at McMaster University and a psychologist at St. Joseph’s Healthcare’s Women’s Health Concerns Clinic, both in Hamilton, Ont., told attendees at the meeting.

“Sexual concerns over the menopausal transition are not just physical, but they’re also psychological and emotional,” Dr. Green said. “Three common challenges include decreased sexual desire, a reduction in physical arousal and ability to achieve an orgasm, and sexual pain and discomfort during intercourse.”

The reasons for these concerns are multifactorial, she said. Decreased sexual desire can stem from stress, medical problems, their relationship with their partner, or other causes. A woman’s difficulty with reduced physical arousal or ability to have an orgasm can result from changes in hormone levels and vaginal changes, such as vaginal atrophy, which can also contribute to the sexual pain or discomfort reported by 17%-45% of postmenopausal women.

Two pharmacologic treatments exist for sexual concerns: oral flibanserin (Addyi) and injectable bremelanotide (Vyleesi). But many women may be unable or unwilling to take medication for their concerns. Previous research from Lori Brotto has found cognitive behavioral therapy and mindfulness interventions to effectively improve sexual functioning in women treated for gynecologic cancer and in women without a history of cancer.

“Sexual function needs to be understood from a bio-psychosocial model, looking at the biologic factors, the psychological factors, the sociocultural factors, and the interpersonal factors,” Sheryl Kingsberg, PhD, a professor of psychiatry and reproductive biology at Case Western Reserve University and a psychologist at University Hospitals in Cleveland, said in an interview.

“They can all overlap, and the clinician can ask a few pointed questions that help identify what the source of the problem is,” said Dr. Kingsberg, who was not involved in this study. She noted that the International Society for the Study of Women’s Sexual Health has an algorithm that can help in determining the source of the problems.

“Sometimes it’s going to be a biologic condition for which pharmacologic options are nice, but even if it is primarily pharmacologic, psychotherapy is always useful,” Dr. Kingsberg said. “Once the problem is there, even if it’s biologically based, then you have all the things in terms of the cognitive distortion, anxiety,” and other issues that a cognitive behavioral approach can help address. “And access is now much wider because of telehealth,” she added.
 

‘Psychology of menopause’

The study led by Dr. Green focused on peri- and postmenopausal women, with an average age of 50, who were experiencing primary sexual concerns based on a score of at least 26 on the Female Sexual Function Index (FSFI). Among the 20 women recruited for the study, 6 had already been prescribed hormone therapy for sexual concerns.

All reported decreased sexual desire, 17 reported decreased sexual arousal, 14 had body image dissatisfaction related to sexual concerns, and 6 reported urogenital problems. Nine of the women were in full remission from major depressive disorder, one had post-traumatic stress syndrome, and one had subclinical generalized anxiety disorder.

After spending 4 weeks on a wait list as self-control group for the study, the 15 women who completed the trial underwent four individual CBT sessions focusing on sexual concerns. The first session focused on psychoeducation and thought monitoring, and the second focused on cognitive distortions, cognitive strategies, and unhelpful beliefs or expectations related to sexual concerns. The third session looked at the role of problematic behaviors and behavioral experiments, and the fourth focused on continuation of strategies, long-term goals, and maintaining gains.

The participants completed eight measures at baseline, after the 4 weeks on the wait list, and after the four CBT sessions to assess the following:

• Sexual satisfaction, distress, and desire, using the FSFI, the Female Sexual Distress Scale-Revised (FSDS-R), and the Female Sexual Desire Questionnaire (FSDQ).
• Menopause symptoms, using the Greene Climacteric Scale (GCS).
• Body image, using the Dresden Body Image Questionnaire (DBIQ).
• Relationship satisfaction, using the Couples Satisfaction Index (CSI).
• Depression, using the Beck Depression Inventory-II (BDI-II).
• Anxiety, using the Hamilton Anxiety Rating Scale (HAM-A).

The women did not experience any significant changes while on the wait list except a slight decrease on the FSDQ concern subscale. Following the CBT sessions, however, the women experienced a significant decrease in sexual distress and concern as well as an increase in sexual dyadic desire and sexual functioning (P = .003 for FSFI, P = .002 for FSDS-R, and P = .003 for FSDQ).

Participants also experienced a decrease in depression (P < .0001) and menopausal symptoms (P = .001) and an increase in body-image satisfaction (P = .018) and relationship satisfaction (P = .0011) after the CBT sessions. The researchers assessed participants’ satisfaction with the Client Satisfaction Questionnaire after the CBT sessions and reported some of the qualitative findings.

“The treatment program was able to assist me with recognizing that some of my sexual concerns were normal, emotional as well as physical and hormonal, and provided me the ability to delve more deeply into the psychology of menopause and how to work through symptoms and concerns in more manageable pieces,” one participant wrote. Another found helpful the “homework exercises of recognizing a thought/feeling/emotion surrounding how I feel about myself/body and working through. More positive thought pattern/restructuring a response the most helpful.”

The main complaint about the program was that it was too short, with women wanting more sessions to help continue their progress.
 

Not an ‘either-or’ approach

Dr. Kingsberg said ISSWSH has a variety of sexual medicine practitioners, including providers who can provide CBT for sexual concerns, and the American Association of Sexuality Educators, Counselors and Therapists has a referral directory.

“Keeping in mind the bio-psychosocial model, sometimes psychotherapy is going to be a really effective treatment for sexual concerns,” Dr. Kingsberg said. “Sometimes the pharmacologic option is going to be a really effective treatment for some concerns, and sometimes the combination is going to have a really nice treatment effect. So it’s not a one-size-fits-all, and it doesn’t have to be an either-or.”

The sexual concerns of women still do not get adequately addressed in medical schools and residencies, Dr. Kingsberg said, which is distinctly different from how male sexual concerns are addressed in health care.

“Erectile dysfunction is kind of in the norm, and women are still a little hesitant to bring up their sexual concerns,” Dr. Kingsberg said. “They don’t know if it’s appropriate and they’re hoping that their clinician will ask.”

One way clinicians can do that is with a global question for all their patients: “Most of my patients have sexual questions or concerns; what concerns do you have?”

“They don’t have to go through a checklist of 10 things,” Dr. Kingsberg said. If the patient does not bring anything up, providers can then ask a single follow up question: “Do you have any concerns with desire, arousal, orgasm, or pain?” That question, Dr. Kingsberg said, covers the four main areas of concern.

The study was funded by the Canadian Institute of Health Research. Dr. Green reported no disclosures. Dr. Kingsberg has consulted for or served on the advisory board for Alloy, Astellas, Bayer, Dare Bioscience, Freya, Reunion Neuroscience, Materna Medical, Madorra, Palatin, Pfizer, ReJoy, Sprout, Strategic Science Technologies, and MsMedicine.

PHILADELPHIA – Cognitive behavioral therapy (CBT) was effective in addressing peri- and postmenopausal women’s sexual concerns, according to a small study presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society). Four CBT sessions specifically focused on sexual concerns resulted in decreased sexual distress and concern, reduced depressive and menopausal symptoms, and increased sexual desire and functioning, as well as improved body image and relationship satisfaction.

An estimated 68%-87% of perimenopausal and postmenopausal women report sexual concerns, Sheryl Green, PhD, CPsych, an associate professor of psychiatry and behavioral neurosciences at McMaster University and a psychologist at St. Joseph’s Healthcare’s Women’s Health Concerns Clinic, both in Hamilton, Ont., told attendees at the meeting.

“Sexual concerns over the menopausal transition are not just physical, but they’re also psychological and emotional,” Dr. Green said. “Three common challenges include decreased sexual desire, a reduction in physical arousal and ability to achieve an orgasm, and sexual pain and discomfort during intercourse.”

The reasons for these concerns are multifactorial, she said. Decreased sexual desire can stem from stress, medical problems, their relationship with their partner, or other causes. A woman’s difficulty with reduced physical arousal or ability to have an orgasm can result from changes in hormone levels and vaginal changes, such as vaginal atrophy, which can also contribute to the sexual pain or discomfort reported by 17%-45% of postmenopausal women.

Two pharmacologic treatments exist for sexual concerns: oral flibanserin (Addyi) and injectable bremelanotide (Vyleesi). But many women may be unable or unwilling to take medication for their concerns. Previous research from Lori Brotto has found cognitive behavioral therapy and mindfulness interventions to effectively improve sexual functioning in women treated for gynecologic cancer and in women without a history of cancer.

“Sexual function needs to be understood from a bio-psychosocial model, looking at the biologic factors, the psychological factors, the sociocultural factors, and the interpersonal factors,” Sheryl Kingsberg, PhD, a professor of psychiatry and reproductive biology at Case Western Reserve University and a psychologist at University Hospitals in Cleveland, said in an interview.

“They can all overlap, and the clinician can ask a few pointed questions that help identify what the source of the problem is,” said Dr. Kingsberg, who was not involved in this study. She noted that the International Society for the Study of Women’s Sexual Health has an algorithm that can help in determining the source of the problems.

“Sometimes it’s going to be a biologic condition for which pharmacologic options are nice, but even if it is primarily pharmacologic, psychotherapy is always useful,” Dr. Kingsberg said. “Once the problem is there, even if it’s biologically based, then you have all the things in terms of the cognitive distortion, anxiety,” and other issues that a cognitive behavioral approach can help address. “And access is now much wider because of telehealth,” she added.
 

‘Psychology of menopause’

The study led by Dr. Green focused on peri- and postmenopausal women, with an average age of 50, who were experiencing primary sexual concerns based on a score of at least 26 on the Female Sexual Function Index (FSFI). Among the 20 women recruited for the study, 6 had already been prescribed hormone therapy for sexual concerns.

All reported decreased sexual desire, 17 reported decreased sexual arousal, 14 had body image dissatisfaction related to sexual concerns, and 6 reported urogenital problems. Nine of the women were in full remission from major depressive disorder, one had post-traumatic stress syndrome, and one had subclinical generalized anxiety disorder.

After spending 4 weeks on a wait list as self-control group for the study, the 15 women who completed the trial underwent four individual CBT sessions focusing on sexual concerns. The first session focused on psychoeducation and thought monitoring, and the second focused on cognitive distortions, cognitive strategies, and unhelpful beliefs or expectations related to sexual concerns. The third session looked at the role of problematic behaviors and behavioral experiments, and the fourth focused on continuation of strategies, long-term goals, and maintaining gains.

The participants completed eight measures at baseline, after the 4 weeks on the wait list, and after the four CBT sessions to assess the following:

• Sexual satisfaction, distress, and desire, using the FSFI, the Female Sexual Distress Scale-Revised (FSDS-R), and the Female Sexual Desire Questionnaire (FSDQ).
• Menopause symptoms, using the Greene Climacteric Scale (GCS).
• Body image, using the Dresden Body Image Questionnaire (DBIQ).
• Relationship satisfaction, using the Couples Satisfaction Index (CSI).
• Depression, using the Beck Depression Inventory-II (BDI-II).
• Anxiety, using the Hamilton Anxiety Rating Scale (HAM-A).

The women did not experience any significant changes while on the wait list except a slight decrease on the FSDQ concern subscale. Following the CBT sessions, however, the women experienced a significant decrease in sexual distress and concern as well as an increase in sexual dyadic desire and sexual functioning (P = .003 for FSFI, P = .002 for FSDS-R, and P = .003 for FSDQ).

Participants also experienced a decrease in depression (P < .0001) and menopausal symptoms (P = .001) and an increase in body-image satisfaction (P = .018) and relationship satisfaction (P = .0011) after the CBT sessions. The researchers assessed participants’ satisfaction with the Client Satisfaction Questionnaire after the CBT sessions and reported some of the qualitative findings.

“The treatment program was able to assist me with recognizing that some of my sexual concerns were normal, emotional as well as physical and hormonal, and provided me the ability to delve more deeply into the psychology of menopause and how to work through symptoms and concerns in more manageable pieces,” one participant wrote. Another found helpful the “homework exercises of recognizing a thought/feeling/emotion surrounding how I feel about myself/body and working through. More positive thought pattern/restructuring a response the most helpful.”

The main complaint about the program was that it was too short, with women wanting more sessions to help continue their progress.
 

Not an ‘either-or’ approach

Dr. Kingsberg said ISSWSH has a variety of sexual medicine practitioners, including providers who can provide CBT for sexual concerns, and the American Association of Sexuality Educators, Counselors and Therapists has a referral directory.

“Keeping in mind the bio-psychosocial model, sometimes psychotherapy is going to be a really effective treatment for sexual concerns,” Dr. Kingsberg said. “Sometimes the pharmacologic option is going to be a really effective treatment for some concerns, and sometimes the combination is going to have a really nice treatment effect. So it’s not a one-size-fits-all, and it doesn’t have to be an either-or.”

The sexual concerns of women still do not get adequately addressed in medical schools and residencies, Dr. Kingsberg said, which is distinctly different from how male sexual concerns are addressed in health care.

“Erectile dysfunction is kind of in the norm, and women are still a little hesitant to bring up their sexual concerns,” Dr. Kingsberg said. “They don’t know if it’s appropriate and they’re hoping that their clinician will ask.”

One way clinicians can do that is with a global question for all their patients: “Most of my patients have sexual questions or concerns; what concerns do you have?”

“They don’t have to go through a checklist of 10 things,” Dr. Kingsberg said. If the patient does not bring anything up, providers can then ask a single follow up question: “Do you have any concerns with desire, arousal, orgasm, or pain?” That question, Dr. Kingsberg said, covers the four main areas of concern.

The study was funded by the Canadian Institute of Health Research. Dr. Green reported no disclosures. Dr. Kingsberg has consulted for or served on the advisory board for Alloy, Astellas, Bayer, Dare Bioscience, Freya, Reunion Neuroscience, Materna Medical, Madorra, Palatin, Pfizer, ReJoy, Sprout, Strategic Science Technologies, and MsMedicine.

PHILADELPHIA – Cognitive behavioral therapy (CBT) was effective in addressing peri- and postmenopausal women’s sexual concerns, according to a small study presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society). Four CBT sessions specifically focused on sexual concerns resulted in decreased sexual distress and concern, reduced depressive and menopausal symptoms, and increased sexual desire and functioning, as well as improved body image and relationship satisfaction.

An estimated 68%-87% of perimenopausal and postmenopausal women report sexual concerns, Sheryl Green, PhD, CPsych, an associate professor of psychiatry and behavioral neurosciences at McMaster University and a psychologist at St. Joseph’s Healthcare’s Women’s Health Concerns Clinic, both in Hamilton, Ont., told attendees at the meeting.

“Sexual concerns over the menopausal transition are not just physical, but they’re also psychological and emotional,” Dr. Green said. “Three common challenges include decreased sexual desire, a reduction in physical arousal and ability to achieve an orgasm, and sexual pain and discomfort during intercourse.”

The reasons for these concerns are multifactorial, she said. Decreased sexual desire can stem from stress, medical problems, their relationship with their partner, or other causes. A woman’s difficulty with reduced physical arousal or ability to have an orgasm can result from changes in hormone levels and vaginal changes, such as vaginal atrophy, which can also contribute to the sexual pain or discomfort reported by 17%-45% of postmenopausal women.

Two pharmacologic treatments exist for sexual concerns: oral flibanserin (Addyi) and injectable bremelanotide (Vyleesi). But many women may be unable or unwilling to take medication for their concerns. Previous research from Lori Brotto has found cognitive behavioral therapy and mindfulness interventions to effectively improve sexual functioning in women treated for gynecologic cancer and in women without a history of cancer.

“Sexual function needs to be understood from a bio-psychosocial model, looking at the biologic factors, the psychological factors, the sociocultural factors, and the interpersonal factors,” Sheryl Kingsberg, PhD, a professor of psychiatry and reproductive biology at Case Western Reserve University and a psychologist at University Hospitals in Cleveland, said in an interview.

“They can all overlap, and the clinician can ask a few pointed questions that help identify what the source of the problem is,” said Dr. Kingsberg, who was not involved in this study. She noted that the International Society for the Study of Women’s Sexual Health has an algorithm that can help in determining the source of the problems.

“Sometimes it’s going to be a biologic condition for which pharmacologic options are nice, but even if it is primarily pharmacologic, psychotherapy is always useful,” Dr. Kingsberg said. “Once the problem is there, even if it’s biologically based, then you have all the things in terms of the cognitive distortion, anxiety,” and other issues that a cognitive behavioral approach can help address. “And access is now much wider because of telehealth,” she added.
 

‘Psychology of menopause’

The study led by Dr. Green focused on peri- and postmenopausal women, with an average age of 50, who were experiencing primary sexual concerns based on a score of at least 26 on the Female Sexual Function Index (FSFI). Among the 20 women recruited for the study, 6 had already been prescribed hormone therapy for sexual concerns.

All reported decreased sexual desire, 17 reported decreased sexual arousal, 14 had body image dissatisfaction related to sexual concerns, and 6 reported urogenital problems. Nine of the women were in full remission from major depressive disorder, one had post-traumatic stress syndrome, and one had subclinical generalized anxiety disorder.

After spending 4 weeks on a wait list as self-control group for the study, the 15 women who completed the trial underwent four individual CBT sessions focusing on sexual concerns. The first session focused on psychoeducation and thought monitoring, and the second focused on cognitive distortions, cognitive strategies, and unhelpful beliefs or expectations related to sexual concerns. The third session looked at the role of problematic behaviors and behavioral experiments, and the fourth focused on continuation of strategies, long-term goals, and maintaining gains.

The participants completed eight measures at baseline, after the 4 weeks on the wait list, and after the four CBT sessions to assess the following:

• Sexual satisfaction, distress, and desire, using the FSFI, the Female Sexual Distress Scale-Revised (FSDS-R), and the Female Sexual Desire Questionnaire (FSDQ).
• Menopause symptoms, using the Greene Climacteric Scale (GCS).
• Body image, using the Dresden Body Image Questionnaire (DBIQ).
• Relationship satisfaction, using the Couples Satisfaction Index (CSI).
• Depression, using the Beck Depression Inventory-II (BDI-II).
• Anxiety, using the Hamilton Anxiety Rating Scale (HAM-A).

The women did not experience any significant changes while on the wait list except a slight decrease on the FSDQ concern subscale. Following the CBT sessions, however, the women experienced a significant decrease in sexual distress and concern as well as an increase in sexual dyadic desire and sexual functioning (P = .003 for FSFI, P = .002 for FSDS-R, and P = .003 for FSDQ).

Participants also experienced a decrease in depression (P < .0001) and menopausal symptoms (P = .001) and an increase in body-image satisfaction (P = .018) and relationship satisfaction (P = .0011) after the CBT sessions. The researchers assessed participants’ satisfaction with the Client Satisfaction Questionnaire after the CBT sessions and reported some of the qualitative findings.

“The treatment program was able to assist me with recognizing that some of my sexual concerns were normal, emotional as well as physical and hormonal, and provided me the ability to delve more deeply into the psychology of menopause and how to work through symptoms and concerns in more manageable pieces,” one participant wrote. Another found helpful the “homework exercises of recognizing a thought/feeling/emotion surrounding how I feel about myself/body and working through. More positive thought pattern/restructuring a response the most helpful.”

The main complaint about the program was that it was too short, with women wanting more sessions to help continue their progress.
 

Not an ‘either-or’ approach

Dr. Kingsberg said ISSWSH has a variety of sexual medicine practitioners, including providers who can provide CBT for sexual concerns, and the American Association of Sexuality Educators, Counselors and Therapists has a referral directory.

“Keeping in mind the bio-psychosocial model, sometimes psychotherapy is going to be a really effective treatment for sexual concerns,” Dr. Kingsberg said. “Sometimes the pharmacologic option is going to be a really effective treatment for some concerns, and sometimes the combination is going to have a really nice treatment effect. So it’s not a one-size-fits-all, and it doesn’t have to be an either-or.”

The sexual concerns of women still do not get adequately addressed in medical schools and residencies, Dr. Kingsberg said, which is distinctly different from how male sexual concerns are addressed in health care.

“Erectile dysfunction is kind of in the norm, and women are still a little hesitant to bring up their sexual concerns,” Dr. Kingsberg said. “They don’t know if it’s appropriate and they’re hoping that their clinician will ask.”

One way clinicians can do that is with a global question for all their patients: “Most of my patients have sexual questions or concerns; what concerns do you have?”

“They don’t have to go through a checklist of 10 things,” Dr. Kingsberg said. If the patient does not bring anything up, providers can then ask a single follow up question: “Do you have any concerns with desire, arousal, orgasm, or pain?” That question, Dr. Kingsberg said, covers the four main areas of concern.

The study was funded by the Canadian Institute of Health Research. Dr. Green reported no disclosures. Dr. Kingsberg has consulted for or served on the advisory board for Alloy, Astellas, Bayer, Dare Bioscience, Freya, Reunion Neuroscience, Materna Medical, Madorra, Palatin, Pfizer, ReJoy, Sprout, Strategic Science Technologies, and MsMedicine.

HAMBURG – Initiating metformin treatment at gestational diabetes diagnosis was associated with improved glycemic control and reduced gestational weight gain, according to the results of a randomized, placebo-controlled trial.

Overall, the trial’s primary outcome, a composite of insulin initiation or a fasting glucose level ≥ 5.1 mmol/L (92 mg/dL) at gestation weeks 32 or 38, did not differ between women with gestational diabetes randomly assigned to either placebo or metformin. However, women taking metformin were significantly less likely to require insulin and had significantly lower fasting blood glucose levels at weeks 32 and 38.

“With a composite outcome it’s more difficult to find a positive result ... So, although the primary composite outcome was not positive, the components of the primary outcome that are clinically meaningful were positive,” lead study author Fidelma Dunne, PhD, professor and endocrine consultant at the University of Galway, Ireland, said in an interview.

There were no differences in maternal or neonatal morbidities, but there was a nonsignificant increase in small for gestational age (SGA), a finding that has been seen in some but not all previous studies of metformin use in gestational diabetes.

Dr. Dunne presented the findings on Oct. 3 at the annual meeting of the European Association for the Study of Diabetes. The results were simultaneously published in JAMA.

Current recommendations from the United Kingdom’s National Institute for Health and Care Excellence say metformin is a suitable first-line therapy for gestational diabetes. However, both the American Diabetes Association and the Society of Maternal-Fetal Medicine do not, particularly for pregnancies with hypertension or preeclampsia or in those who are at risk for intrauterine growth restriction.

“Gestational diabetes is now reaching epidemic proportions. And of course, the vast majority of these women are in low- and middle-income countries where insulin might not be available, or the storage may not allow it to be used effectively. If you have a medication that in the majority of women is safe and effective it may actually help a lot of women in [those regions],” Dr. Dunne said.

Moreover, she noted, “women with gestational diabetes are testing their sugar with finger pricks four to seven times per day and we ask them to take insulin one to four times a day. So if you can relieve any of that pain related to treatment of their condition than that is a benefit for the women as well.”

Asked to comment, Katrien Benhalima, MD, PhD, of University Hospital Gasthuisberg, KU Leuven, Belgium, said, “I think it’s an interesting study because they investigated something novel, to initiate immediately metformin or placebo. Normally what we do with gestational diabetes is once we get the diagnosis, we treat them with lifestyle, and if that’s insufficient then we start with medical therapy. So this is a novel approach.”

She also agreed with Dr. Dunne that the lack of significance for the primary outcome “isn’t an issue of power but it is a composite outcome. If you look at the individual outcomes, as can be expected, the women taking metformin had less need for insulin treatment.”

But, Dr. Benhalima said, the study still leaves open the SGA issue. “It wasn’t significant, but it’s still something we are worried about in the sense that we feel we need more data, especially in the long-term for the offspring health ... You really need to follow them for 10 years or longer to see an effect.”

So for now, Dr. Benhalima said that she wouldn’t use metformin as a first-line treatment for gestational diabetes. “Normally if lifestyle isn’t enough we will still start insulin ... Another issue is why would you offer everybody medical treatment when pregnancy outcomes can be met with lifestyle alone?”

Then again, she added, “of course metformin is easier than an injection. Treatment satisfaction is improved, and the cost is less.”
 

Primary outcome didn’t differ, but study findings point toward metformin benefit

The double-blind, placebo-controlled trial was conducted at two sites in Ireland, with 510 individuals (535 gestational diabetes pregnancies) enrolled between June 2017 and September 2022. In addition to usual care, they were randomly assigned 1:1 to either placebo or metformin (maximum 2,500 mg) at the time of gestational diabetes diagnosis and continued until delivery.

The primary outcome, a composite of insulin initiation or a fasting glucose ≥ 5.1 mmol/L at gestation weeks 32 or 38, did not differ significantly between the two groups, with risk ratio 0.89 (P = 0.13).

Insulin initiation occurred in 38.4% of the metformin and 51.1% of the placebo groups (relative risk, 0.75, P = .004). The amount of insulin required at the last assessment prior to delivery did not differ between the two groups (P = .17).

Mean fasting glucose was significantly lower with metformin vs. placebo at gestational week 32 (4.9 vs. 5.0 mmol/L; P = .03) and at gestational week 38 (4.5 vs 4.7 mmol/L; P < .001).

On average, those in the metformin group gained less weight between randomization and delivery (0.8 kg vs. 2.0 kg; P = .003).

Gestational week at delivery didn’t differ between the groups, both 39.1 weeks, nor did preterm births prior to 37 weeks’ gestation (9.2% metformin vs. 6.5% placebo; P = .33) or any other pregnancy-related complications.

More participants in the metformin group said that they would choose the drug compared with placebo (76.2% vs. 67.1%, P = .04).

Mean birth weight was lower in the metformin group compared with placebo, 3,393 g vs. 3,506 g (P = .005), with fewer weighing > 4,000 g (7.6% vs. 14.8%; P = .02) or being large for gestational age, i.e., above the 90th percentile (6.5% vs. 14.9%; P = .003).

Proportions of offspring that were SGA (less than 10th percentile) were 5.7% in the metformin group vs. 2.7% with placebo (P = .13).

There were no other significant differences in neonatal variables.

Dr. Dunne told this news organization that her group has recently received funding for long-term follow-up of the SGA offspring. “As other papers have pointed out, if there’s any hint of SGA that’s really important to follow up. So we’re now beginning our longitudinal follow up of the mother and infants to see if the small number that were SGA will in fact turn out to have an increase in body mass index and weight in their childhood and adolescent years.”

The trial was funded by the Health Review Board (HRB) of Ireland, coordinated by the HRB-Clinical Research Facility Galway, and sponsored by the University of Galway, Ireland. Metformin and matched placebo were provided by Merck Healthcare KGaA, Darmstadt, Germany (operating as EMD Serono in the United States), and blood glucose monitoring strips were provided by Ascensia.

Dr. Dunne reported nonfinancial support from Merck and matched placebo and nonfinancial support from Ascensia during the conduct of the study. Dr. Benhalima receives research funds from Flemish Research Fund, study medication from Novo Nordisk, and devices and unrestricted grants from Medtronic and Dexcom.

A version of this article appeared on Medscape.com.

HAMBURG – Initiating metformin treatment at gestational diabetes diagnosis was associated with improved glycemic control and reduced gestational weight gain, according to the results of a randomized, placebo-controlled trial.

Overall, the trial’s primary outcome, a composite of insulin initiation or a fasting glucose level ≥ 5.1 mmol/L (92 mg/dL) at gestation weeks 32 or 38, did not differ between women with gestational diabetes randomly assigned to either placebo or metformin. However, women taking metformin were significantly less likely to require insulin and had significantly lower fasting blood glucose levels at weeks 32 and 38.

“With a composite outcome it’s more difficult to find a positive result ... So, although the primary composite outcome was not positive, the components of the primary outcome that are clinically meaningful were positive,” lead study author Fidelma Dunne, PhD, professor and endocrine consultant at the University of Galway, Ireland, said in an interview.

There were no differences in maternal or neonatal morbidities, but there was a nonsignificant increase in small for gestational age (SGA), a finding that has been seen in some but not all previous studies of metformin use in gestational diabetes.

Dr. Dunne presented the findings on Oct. 3 at the annual meeting of the European Association for the Study of Diabetes. The results were simultaneously published in JAMA.

Current recommendations from the United Kingdom’s National Institute for Health and Care Excellence say metformin is a suitable first-line therapy for gestational diabetes. However, both the American Diabetes Association and the Society of Maternal-Fetal Medicine do not, particularly for pregnancies with hypertension or preeclampsia or in those who are at risk for intrauterine growth restriction.

“Gestational diabetes is now reaching epidemic proportions. And of course, the vast majority of these women are in low- and middle-income countries where insulin might not be available, or the storage may not allow it to be used effectively. If you have a medication that in the majority of women is safe and effective it may actually help a lot of women in [those regions],” Dr. Dunne said.

Moreover, she noted, “women with gestational diabetes are testing their sugar with finger pricks four to seven times per day and we ask them to take insulin one to four times a day. So if you can relieve any of that pain related to treatment of their condition than that is a benefit for the women as well.”

Asked to comment, Katrien Benhalima, MD, PhD, of University Hospital Gasthuisberg, KU Leuven, Belgium, said, “I think it’s an interesting study because they investigated something novel, to initiate immediately metformin or placebo. Normally what we do with gestational diabetes is once we get the diagnosis, we treat them with lifestyle, and if that’s insufficient then we start with medical therapy. So this is a novel approach.”

She also agreed with Dr. Dunne that the lack of significance for the primary outcome “isn’t an issue of power but it is a composite outcome. If you look at the individual outcomes, as can be expected, the women taking metformin had less need for insulin treatment.”

But, Dr. Benhalima said, the study still leaves open the SGA issue. “It wasn’t significant, but it’s still something we are worried about in the sense that we feel we need more data, especially in the long-term for the offspring health ... You really need to follow them for 10 years or longer to see an effect.”

So for now, Dr. Benhalima said that she wouldn’t use metformin as a first-line treatment for gestational diabetes. “Normally if lifestyle isn’t enough we will still start insulin ... Another issue is why would you offer everybody medical treatment when pregnancy outcomes can be met with lifestyle alone?”

Then again, she added, “of course metformin is easier than an injection. Treatment satisfaction is improved, and the cost is less.”
 

Primary outcome didn’t differ, but study findings point toward metformin benefit

The double-blind, placebo-controlled trial was conducted at two sites in Ireland, with 510 individuals (535 gestational diabetes pregnancies) enrolled between June 2017 and September 2022. In addition to usual care, they were randomly assigned 1:1 to either placebo or metformin (maximum 2,500 mg) at the time of gestational diabetes diagnosis and continued until delivery.

The primary outcome, a composite of insulin initiation or a fasting glucose ≥ 5.1 mmol/L at gestation weeks 32 or 38, did not differ significantly between the two groups, with risk ratio 0.89 (P = 0.13).

Insulin initiation occurred in 38.4% of the metformin and 51.1% of the placebo groups (relative risk, 0.75, P = .004). The amount of insulin required at the last assessment prior to delivery did not differ between the two groups (P = .17).

Mean fasting glucose was significantly lower with metformin vs. placebo at gestational week 32 (4.9 vs. 5.0 mmol/L; P = .03) and at gestational week 38 (4.5 vs 4.7 mmol/L; P < .001).

On average, those in the metformin group gained less weight between randomization and delivery (0.8 kg vs. 2.0 kg; P = .003).

Gestational week at delivery didn’t differ between the groups, both 39.1 weeks, nor did preterm births prior to 37 weeks’ gestation (9.2% metformin vs. 6.5% placebo; P = .33) or any other pregnancy-related complications.

More participants in the metformin group said that they would choose the drug compared with placebo (76.2% vs. 67.1%, P = .04).

Mean birth weight was lower in the metformin group compared with placebo, 3,393 g vs. 3,506 g (P = .005), with fewer weighing > 4,000 g (7.6% vs. 14.8%; P = .02) or being large for gestational age, i.e., above the 90th percentile (6.5% vs. 14.9%; P = .003).

Proportions of offspring that were SGA (less than 10th percentile) were 5.7% in the metformin group vs. 2.7% with placebo (P = .13).

There were no other significant differences in neonatal variables.

Dr. Dunne told this news organization that her group has recently received funding for long-term follow-up of the SGA offspring. “As other papers have pointed out, if there’s any hint of SGA that’s really important to follow up. So we’re now beginning our longitudinal follow up of the mother and infants to see if the small number that were SGA will in fact turn out to have an increase in body mass index and weight in their childhood and adolescent years.”

The trial was funded by the Health Review Board (HRB) of Ireland, coordinated by the HRB-Clinical Research Facility Galway, and sponsored by the University of Galway, Ireland. Metformin and matched placebo were provided by Merck Healthcare KGaA, Darmstadt, Germany (operating as EMD Serono in the United States), and blood glucose monitoring strips were provided by Ascensia.

Dr. Dunne reported nonfinancial support from Merck and matched placebo and nonfinancial support from Ascensia during the conduct of the study. Dr. Benhalima receives research funds from Flemish Research Fund, study medication from Novo Nordisk, and devices and unrestricted grants from Medtronic and Dexcom.

A version of this article appeared on Medscape.com.

HAMBURG – Initiating metformin treatment at gestational diabetes diagnosis was associated with improved glycemic control and reduced gestational weight gain, according to the results of a randomized, placebo-controlled trial.

Overall, the trial’s primary outcome, a composite of insulin initiation or a fasting glucose level ≥ 5.1 mmol/L (92 mg/dL) at gestation weeks 32 or 38, did not differ between women with gestational diabetes randomly assigned to either placebo or metformin. However, women taking metformin were significantly less likely to require insulin and had significantly lower fasting blood glucose levels at weeks 32 and 38.

“With a composite outcome it’s more difficult to find a positive result ... So, although the primary composite outcome was not positive, the components of the primary outcome that are clinically meaningful were positive,” lead study author Fidelma Dunne, PhD, professor and endocrine consultant at the University of Galway, Ireland, said in an interview.

There were no differences in maternal or neonatal morbidities, but there was a nonsignificant increase in small for gestational age (SGA), a finding that has been seen in some but not all previous studies of metformin use in gestational diabetes.

Dr. Dunne presented the findings on Oct. 3 at the annual meeting of the European Association for the Study of Diabetes. The results were simultaneously published in JAMA.

Current recommendations from the United Kingdom’s National Institute for Health and Care Excellence say metformin is a suitable first-line therapy for gestational diabetes. However, both the American Diabetes Association and the Society of Maternal-Fetal Medicine do not, particularly for pregnancies with hypertension or preeclampsia or in those who are at risk for intrauterine growth restriction.

“Gestational diabetes is now reaching epidemic proportions. And of course, the vast majority of these women are in low- and middle-income countries where insulin might not be available, or the storage may not allow it to be used effectively. If you have a medication that in the majority of women is safe and effective it may actually help a lot of women in [those regions],” Dr. Dunne said.

Moreover, she noted, “women with gestational diabetes are testing their sugar with finger pricks four to seven times per day and we ask them to take insulin one to four times a day. So if you can relieve any of that pain related to treatment of their condition than that is a benefit for the women as well.”

Asked to comment, Katrien Benhalima, MD, PhD, of University Hospital Gasthuisberg, KU Leuven, Belgium, said, “I think it’s an interesting study because they investigated something novel, to initiate immediately metformin or placebo. Normally what we do with gestational diabetes is once we get the diagnosis, we treat them with lifestyle, and if that’s insufficient then we start with medical therapy. So this is a novel approach.”

She also agreed with Dr. Dunne that the lack of significance for the primary outcome “isn’t an issue of power but it is a composite outcome. If you look at the individual outcomes, as can be expected, the women taking metformin had less need for insulin treatment.”

But, Dr. Benhalima said, the study still leaves open the SGA issue. “It wasn’t significant, but it’s still something we are worried about in the sense that we feel we need more data, especially in the long-term for the offspring health ... You really need to follow them for 10 years or longer to see an effect.”

So for now, Dr. Benhalima said that she wouldn’t use metformin as a first-line treatment for gestational diabetes. “Normally if lifestyle isn’t enough we will still start insulin ... Another issue is why would you offer everybody medical treatment when pregnancy outcomes can be met with lifestyle alone?”

Then again, she added, “of course metformin is easier than an injection. Treatment satisfaction is improved, and the cost is less.”
 

Primary outcome didn’t differ, but study findings point toward metformin benefit

The double-blind, placebo-controlled trial was conducted at two sites in Ireland, with 510 individuals (535 gestational diabetes pregnancies) enrolled between June 2017 and September 2022. In addition to usual care, they were randomly assigned 1:1 to either placebo or metformin (maximum 2,500 mg) at the time of gestational diabetes diagnosis and continued until delivery.

The primary outcome, a composite of insulin initiation or a fasting glucose ≥ 5.1 mmol/L at gestation weeks 32 or 38, did not differ significantly between the two groups, with risk ratio 0.89 (P = 0.13).

Insulin initiation occurred in 38.4% of the metformin and 51.1% of the placebo groups (relative risk, 0.75, P = .004). The amount of insulin required at the last assessment prior to delivery did not differ between the two groups (P = .17).

Mean fasting glucose was significantly lower with metformin vs. placebo at gestational week 32 (4.9 vs. 5.0 mmol/L; P = .03) and at gestational week 38 (4.5 vs 4.7 mmol/L; P < .001).

On average, those in the metformin group gained less weight between randomization and delivery (0.8 kg vs. 2.0 kg; P = .003).

Gestational week at delivery didn’t differ between the groups, both 39.1 weeks, nor did preterm births prior to 37 weeks’ gestation (9.2% metformin vs. 6.5% placebo; P = .33) or any other pregnancy-related complications.

More participants in the metformin group said that they would choose the drug compared with placebo (76.2% vs. 67.1%, P = .04).

Mean birth weight was lower in the metformin group compared with placebo, 3,393 g vs. 3,506 g (P = .005), with fewer weighing > 4,000 g (7.6% vs. 14.8%; P = .02) or being large for gestational age, i.e., above the 90th percentile (6.5% vs. 14.9%; P = .003).

Proportions of offspring that were SGA (less than 10th percentile) were 5.7% in the metformin group vs. 2.7% with placebo (P = .13).

There were no other significant differences in neonatal variables.

Dr. Dunne told this news organization that her group has recently received funding for long-term follow-up of the SGA offspring. “As other papers have pointed out, if there’s any hint of SGA that’s really important to follow up. So we’re now beginning our longitudinal follow up of the mother and infants to see if the small number that were SGA will in fact turn out to have an increase in body mass index and weight in their childhood and adolescent years.”

The trial was funded by the Health Review Board (HRB) of Ireland, coordinated by the HRB-Clinical Research Facility Galway, and sponsored by the University of Galway, Ireland. Metformin and matched placebo were provided by Merck Healthcare KGaA, Darmstadt, Germany (operating as EMD Serono in the United States), and blood glucose monitoring strips were provided by Ascensia.

Dr. Dunne reported nonfinancial support from Merck and matched placebo and nonfinancial support from Ascensia during the conduct of the study. Dr. Benhalima receives research funds from Flemish Research Fund, study medication from Novo Nordisk, and devices and unrestricted grants from Medtronic and Dexcom.

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.

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.

Nearly half of patients undergoing drug-induced sleep endoscopy (DISE) experienced a sentinel central event after an average of 6 minutes in a study of 103 individuals with obstructive sleep apnea (OSA).

DISE has become the top choice for surgical selection in patients with OSA, but it has a variable effect on surgical outcomes, Julianna G. Rodin, MD, of the University of Pennsylvania, Philadelphia, and colleagues explained.

The University of Pennsylvania sleep surgery team developed a comprehensive DISE platform that includes simultaneous collection of respiratory airflow and effort measurements, airway collapsibility, and videoendoscopy.

“This home sleep study-style setup has allowed us to better characterize the upper airway during DISE, and even helped our team diagnose a patient with Cheyne-Stokes breathing/central sleep apnea,” Dr. Rodin said in an interview.

“With it, we also began to notice relatively frequent central and/or mixed sleep disordered breathing events during DISE after propofol dosing initiation,” she said.

In a study presented at the annual meeting of the American Academy of Otolaryngology–Head and Neck Surgery, Dr. Rodin and colleagues measured both the frequency and timing of sentinel central and/or mixed events (SCent) in adults undergoing DISE to assess the prevalence and impact on DISE.

The researchers also assessed differences in VOTE classification (velum, oropharynx, tongue base, and epiglottis) in sentinel central events, compared with obstructive events. VOTE scores were calculated using a grade of 0 for no obstruction, 1 for partial obstruction, and 2 for total obstruction.

The study population included 103 adults with OSA who underwent DISE with propofol sedation at a single tertiary academic medical center between June 2020 and November 2022. The mean age of the participants was 53.5 years, the mean body mass index (BMI) was 29.7 kg/m², and 67% were male. The average apnea-hypopnea index (AHI) was 30.7 events per hour. The researchers used a polysomnography platform to capture data on nasal airflow, thoraco-abdominal effort belt signals, and videoendoscopy.

A total of 47 patients (46%) had at least one SCent. The average time to the first SCent was just under 6 minutes, and average transition to obstructive pathology in these patients occurred between 7 and 8 minutes. Using the one-sided prediction interval, at least 95% of patients were expected to transition to obstructive pathology within 12-13 minutes, Dr. Rodin said.

In addition, 29 of the 46 patients with SCent (63%) showed significant variability between central/mixed VOTE scores and obstructive VOTE scores.

No statistically significant differences were noted between patients with and without SCent in terms of demographics or AHI.
 

Surprising prevalence of SCents

“We anecdotally noted that SCents seemed to be somewhat common during the initial period of DISE, but were surprised that we saw at least one SCent in almost 50% of our DISE population,” Dr. Rodin said. “We also saw that the majority of these SCents eventually transitioned to obstructive events after approximately 12 minutes, which is often past the average duration of normal DISE exams.”

The high frequency of differing VOTE scores between SCents and obstructive events also was unexpected, she added. Within the changes in VOTE scores as defined in the study, “there was a higher tendency for SCents to have more complete tongue base collapse compared to no or partial collapse in obstructive events, and to transition from anterior-posterior velum to concentric velum collapse during the obstructive event.”

This outcome could potentially affect a patient’s candidacy for hypoglossal nerve stimulator therapy, she explained.

The takeaway from the current study is an increased awareness of the prevalence and timing of SCents in OSA patients, said Dr. Rodin. Clinicians who offer DISE and PAP alternatives also should be mindful of clinical signs of effort, by monitoring the chest and abdomen during DISE in the absence of respiratory effort belts.

The study findings also suggest that clinicians consider extending the minimum DISE duration to 10 minutes to ensure that the majority of SCents have passed, and delay VOTE scoring until patients transition to obstructive events, she added.

As for additional research, Dr. Rodin said: “If we could repeat the study with a standardized protocol of target-controlled infusion (TCI) of propofol, that would further bolster the data.” However, TCI is not approved in the United States.

“Our propofol dosing technique was not standardized across all patients, which in theory could account for more SCents if patients were more sedated,” Dr. Rodin noted. “However, we did not see a difference in average bispectral index levels across all patients.”

Other limitations of the current study included an inability to visualize the entire upper airway to achieve a complete VOTE score for every patient, which could have led to underestimation of the VOTE difference frequency, she added.
 

Data inform team approaches to DISE

As DISE procedures become more widespread, “it is paramount that we understand the risks associated with these procedures to increase safety, improve shared decision-making, and encourage a team-based approach in the operating room with our anesthesia colleagues,” said Daniel M. Zeitler, MD, from the University of Washington and Virgina Mason Medical Center, both in Seattle, who served as a moderator for the session in which the study was presented.

“I was surprised by these data for two reasons,” Dr. Zeitler said in an interview. “We typically don’t wait more than a few minutes between induction of anesthesia and the initiation of the airway procedure. This study calls that practice into question, and the duration of time before the onset of a sentinel event was much longer than I would have expected,” he said.

Second, “I was quite surprised that there were no differences in the demographics or AHI between the two groups; this reminds us that AHI and BMI alone may not be themselves predictive of risk and all patients should be assessed similarly.”

“Otolaryngologists performing DISE need to be aware of these data, communicate them to the involved teams, including anesthesia, nursing, and postanesthesia care units, and remember to delay the manipulation of the airway long enough to minimize the risk of a sentinel event,” Dr. Zeitler said. “Perhaps this also means we need improved intraoperative monitoring for these patients, including respiratory airflow and effort monitoring.”

For further research, “we need to increase the number of patients, perform a multicenter study, and expand the study to a wider range of ages, BMI, and AHI,” he added. A recommended algorithm for these cases in order to standardize the practice would be useful.

The study received no outside funding. Dr. Rodin and Dr. Zeitler reported no relevant financial relationships. Several coauthors disclosed funding and relationships with multiple companies unrelated to the current study.

A version of this article appeared on Medscape.com.

Nearly half of patients undergoing drug-induced sleep endoscopy (DISE) experienced a sentinel central event after an average of 6 minutes in a study of 103 individuals with obstructive sleep apnea (OSA).

DISE has become the top choice for surgical selection in patients with OSA, but it has a variable effect on surgical outcomes, Julianna G. Rodin, MD, of the University of Pennsylvania, Philadelphia, and colleagues explained.

The University of Pennsylvania sleep surgery team developed a comprehensive DISE platform that includes simultaneous collection of respiratory airflow and effort measurements, airway collapsibility, and videoendoscopy.

“This home sleep study-style setup has allowed us to better characterize the upper airway during DISE, and even helped our team diagnose a patient with Cheyne-Stokes breathing/central sleep apnea,” Dr. Rodin said in an interview.

“With it, we also began to notice relatively frequent central and/or mixed sleep disordered breathing events during DISE after propofol dosing initiation,” she said.

In a study presented at the annual meeting of the American Academy of Otolaryngology–Head and Neck Surgery, Dr. Rodin and colleagues measured both the frequency and timing of sentinel central and/or mixed events (SCent) in adults undergoing DISE to assess the prevalence and impact on DISE.

The researchers also assessed differences in VOTE classification (velum, oropharynx, tongue base, and epiglottis) in sentinel central events, compared with obstructive events. VOTE scores were calculated using a grade of 0 for no obstruction, 1 for partial obstruction, and 2 for total obstruction.

The study population included 103 adults with OSA who underwent DISE with propofol sedation at a single tertiary academic medical center between June 2020 and November 2022. The mean age of the participants was 53.5 years, the mean body mass index (BMI) was 29.7 kg/m², and 67% were male. The average apnea-hypopnea index (AHI) was 30.7 events per hour. The researchers used a polysomnography platform to capture data on nasal airflow, thoraco-abdominal effort belt signals, and videoendoscopy.

A total of 47 patients (46%) had at least one SCent. The average time to the first SCent was just under 6 minutes, and average transition to obstructive pathology in these patients occurred between 7 and 8 minutes. Using the one-sided prediction interval, at least 95% of patients were expected to transition to obstructive pathology within 12-13 minutes, Dr. Rodin said.

In addition, 29 of the 46 patients with SCent (63%) showed significant variability between central/mixed VOTE scores and obstructive VOTE scores.

No statistically significant differences were noted between patients with and without SCent in terms of demographics or AHI.
 

Surprising prevalence of SCents

“We anecdotally noted that SCents seemed to be somewhat common during the initial period of DISE, but were surprised that we saw at least one SCent in almost 50% of our DISE population,” Dr. Rodin said. “We also saw that the majority of these SCents eventually transitioned to obstructive events after approximately 12 minutes, which is often past the average duration of normal DISE exams.”

The high frequency of differing VOTE scores between SCents and obstructive events also was unexpected, she added. Within the changes in VOTE scores as defined in the study, “there was a higher tendency for SCents to have more complete tongue base collapse compared to no or partial collapse in obstructive events, and to transition from anterior-posterior velum to concentric velum collapse during the obstructive event.”

This outcome could potentially affect a patient’s candidacy for hypoglossal nerve stimulator therapy, she explained.

The takeaway from the current study is an increased awareness of the prevalence and timing of SCents in OSA patients, said Dr. Rodin. Clinicians who offer DISE and PAP alternatives also should be mindful of clinical signs of effort, by monitoring the chest and abdomen during DISE in the absence of respiratory effort belts.

The study findings also suggest that clinicians consider extending the minimum DISE duration to 10 minutes to ensure that the majority of SCents have passed, and delay VOTE scoring until patients transition to obstructive events, she added.

As for additional research, Dr. Rodin said: “If we could repeat the study with a standardized protocol of target-controlled infusion (TCI) of propofol, that would further bolster the data.” However, TCI is not approved in the United States.

“Our propofol dosing technique was not standardized across all patients, which in theory could account for more SCents if patients were more sedated,” Dr. Rodin noted. “However, we did not see a difference in average bispectral index levels across all patients.”

Other limitations of the current study included an inability to visualize the entire upper airway to achieve a complete VOTE score for every patient, which could have led to underestimation of the VOTE difference frequency, she added.
 

Data inform team approaches to DISE

As DISE procedures become more widespread, “it is paramount that we understand the risks associated with these procedures to increase safety, improve shared decision-making, and encourage a team-based approach in the operating room with our anesthesia colleagues,” said Daniel M. Zeitler, MD, from the University of Washington and Virgina Mason Medical Center, both in Seattle, who served as a moderator for the session in which the study was presented.

“I was surprised by these data for two reasons,” Dr. Zeitler said in an interview. “We typically don’t wait more than a few minutes between induction of anesthesia and the initiation of the airway procedure. This study calls that practice into question, and the duration of time before the onset of a sentinel event was much longer than I would have expected,” he said.

Second, “I was quite surprised that there were no differences in the demographics or AHI between the two groups; this reminds us that AHI and BMI alone may not be themselves predictive of risk and all patients should be assessed similarly.”

“Otolaryngologists performing DISE need to be aware of these data, communicate them to the involved teams, including anesthesia, nursing, and postanesthesia care units, and remember to delay the manipulation of the airway long enough to minimize the risk of a sentinel event,” Dr. Zeitler said. “Perhaps this also means we need improved intraoperative monitoring for these patients, including respiratory airflow and effort monitoring.”

For further research, “we need to increase the number of patients, perform a multicenter study, and expand the study to a wider range of ages, BMI, and AHI,” he added. A recommended algorithm for these cases in order to standardize the practice would be useful.

The study received no outside funding. Dr. Rodin and Dr. Zeitler reported no relevant financial relationships. Several coauthors disclosed funding and relationships with multiple companies unrelated to the current study.

A version of this article appeared on Medscape.com.

Nearly half of patients undergoing drug-induced sleep endoscopy (DISE) experienced a sentinel central event after an average of 6 minutes in a study of 103 individuals with obstructive sleep apnea (OSA).

DISE has become the top choice for surgical selection in patients with OSA, but it has a variable effect on surgical outcomes, Julianna G. Rodin, MD, of the University of Pennsylvania, Philadelphia, and colleagues explained.

The University of Pennsylvania sleep surgery team developed a comprehensive DISE platform that includes simultaneous collection of respiratory airflow and effort measurements, airway collapsibility, and videoendoscopy.

“This home sleep study-style setup has allowed us to better characterize the upper airway during DISE, and even helped our team diagnose a patient with Cheyne-Stokes breathing/central sleep apnea,” Dr. Rodin said in an interview.

“With it, we also began to notice relatively frequent central and/or mixed sleep disordered breathing events during DISE after propofol dosing initiation,” she said.

In a study presented at the annual meeting of the American Academy of Otolaryngology–Head and Neck Surgery, Dr. Rodin and colleagues measured both the frequency and timing of sentinel central and/or mixed events (SCent) in adults undergoing DISE to assess the prevalence and impact on DISE.

The researchers also assessed differences in VOTE classification (velum, oropharynx, tongue base, and epiglottis) in sentinel central events, compared with obstructive events. VOTE scores were calculated using a grade of 0 for no obstruction, 1 for partial obstruction, and 2 for total obstruction.

The study population included 103 adults with OSA who underwent DISE with propofol sedation at a single tertiary academic medical center between June 2020 and November 2022. The mean age of the participants was 53.5 years, the mean body mass index (BMI) was 29.7 kg/m², and 67% were male. The average apnea-hypopnea index (AHI) was 30.7 events per hour. The researchers used a polysomnography platform to capture data on nasal airflow, thoraco-abdominal effort belt signals, and videoendoscopy.

A total of 47 patients (46%) had at least one SCent. The average time to the first SCent was just under 6 minutes, and average transition to obstructive pathology in these patients occurred between 7 and 8 minutes. Using the one-sided prediction interval, at least 95% of patients were expected to transition to obstructive pathology within 12-13 minutes, Dr. Rodin said.

In addition, 29 of the 46 patients with SCent (63%) showed significant variability between central/mixed VOTE scores and obstructive VOTE scores.

No statistically significant differences were noted between patients with and without SCent in terms of demographics or AHI.
 

Surprising prevalence of SCents

“We anecdotally noted that SCents seemed to be somewhat common during the initial period of DISE, but were surprised that we saw at least one SCent in almost 50% of our DISE population,” Dr. Rodin said. “We also saw that the majority of these SCents eventually transitioned to obstructive events after approximately 12 minutes, which is often past the average duration of normal DISE exams.”

The high frequency of differing VOTE scores between SCents and obstructive events also was unexpected, she added. Within the changes in VOTE scores as defined in the study, “there was a higher tendency for SCents to have more complete tongue base collapse compared to no or partial collapse in obstructive events, and to transition from anterior-posterior velum to concentric velum collapse during the obstructive event.”

This outcome could potentially affect a patient’s candidacy for hypoglossal nerve stimulator therapy, she explained.

The takeaway from the current study is an increased awareness of the prevalence and timing of SCents in OSA patients, said Dr. Rodin. Clinicians who offer DISE and PAP alternatives also should be mindful of clinical signs of effort, by monitoring the chest and abdomen during DISE in the absence of respiratory effort belts.

The study findings also suggest that clinicians consider extending the minimum DISE duration to 10 minutes to ensure that the majority of SCents have passed, and delay VOTE scoring until patients transition to obstructive events, she added.

As for additional research, Dr. Rodin said: “If we could repeat the study with a standardized protocol of target-controlled infusion (TCI) of propofol, that would further bolster the data.” However, TCI is not approved in the United States.

“Our propofol dosing technique was not standardized across all patients, which in theory could account for more SCents if patients were more sedated,” Dr. Rodin noted. “However, we did not see a difference in average bispectral index levels across all patients.”

Other limitations of the current study included an inability to visualize the entire upper airway to achieve a complete VOTE score for every patient, which could have led to underestimation of the VOTE difference frequency, she added.
 

Data inform team approaches to DISE

As DISE procedures become more widespread, “it is paramount that we understand the risks associated with these procedures to increase safety, improve shared decision-making, and encourage a team-based approach in the operating room with our anesthesia colleagues,” said Daniel M. Zeitler, MD, from the University of Washington and Virgina Mason Medical Center, both in Seattle, who served as a moderator for the session in which the study was presented.

“I was surprised by these data for two reasons,” Dr. Zeitler said in an interview. “We typically don’t wait more than a few minutes between induction of anesthesia and the initiation of the airway procedure. This study calls that practice into question, and the duration of time before the onset of a sentinel event was much longer than I would have expected,” he said.

Second, “I was quite surprised that there were no differences in the demographics or AHI between the two groups; this reminds us that AHI and BMI alone may not be themselves predictive of risk and all patients should be assessed similarly.”

“Otolaryngologists performing DISE need to be aware of these data, communicate them to the involved teams, including anesthesia, nursing, and postanesthesia care units, and remember to delay the manipulation of the airway long enough to minimize the risk of a sentinel event,” Dr. Zeitler said. “Perhaps this also means we need improved intraoperative monitoring for these patients, including respiratory airflow and effort monitoring.”

For further research, “we need to increase the number of patients, perform a multicenter study, and expand the study to a wider range of ages, BMI, and AHI,” he added. A recommended algorithm for these cases in order to standardize the practice would be useful.

The study received no outside funding. Dr. Rodin and Dr. Zeitler reported no relevant financial relationships. Several coauthors disclosed funding and relationships with multiple companies unrelated to the current study.

A version of this article appeared on Medscape.com.

Use of A1c levels for the diagnosis of type 2 diabetes (T2D) in women younger than 50 years may lead to underdiagnosis, owing to the effects of menstrual blood loss on A1c readings, shows the first study of its kind.

The analysis estimates that an additional 17% of undiagnosed women younger than 50 years could be reclassified as having T2D, and that women under 50 had an A1c distribution that was markedly lower than that of men under 50, by a mean of 1.6 mmol/mol.

In a study that will be presented at this year’s annual meeting of the European Association for the Study of Diabetes (EASD), the researchers wanted to investigate whether a contributing factor to late diagnosis of T2D in women under 50 may be the difference in A1c levels due to hemoglobin replacement linked to menstrual blood loss.

The study was published online in Diabetes Therapy. “If the threshold for diagnosis of diabetes ... was lowered by 2 mmol/mol in women under the age of 50, an additional 17% of these women (approximately equivalent to 35,000 women in England and Wales) would be diagnosed with diabetes ... which may contribute to up to 64% of the difference in mortality rates between men/women with diabetes mellitus aged 16-50 years,” the researchers noted.

They added that A1c levels in women under 50 years were found to be consistently lower than those in men, and with A1c levels in women reaching the equivalent of those in men up to 10 years later, this “may result in delayed diagnosis of diabetes mellitus in premenopausal women.”

Noting that the study was observational, senior author Adrian Heald, MD, consultant endocrinologist, Salford (England) Royal NHS Foundation Trust, said that it “may be the case that prediabetes and type 2 diabetes in women are not being spotted because the set point needs to be slightly lower, but a systematic study sampling from the population of at-risk individuals is needed further to our findings.

“We also need to refer back to use of the glucose tolerance test, because A1c has been used for the past 15 years but it is not the gold standard,” added Dr. Heald. “Clinicians have often wondered if patients might be missed with A1c measurement, or even overdiagnosed.”

Lucy Chambers, PhD, from Diabetes UK, acknowledged that the research was valuable but added: “More research on sex differences in thresholds for a type 2 diagnosis is needed to inform any changes to clinical practice. In the meantime, we encourage clinicians to follow the current guidance of not ruling out type 2 diabetes based on a one-off A1c below the diagnostic threshold.”

But in support of greater understanding around the sex differences in A1c diagnostic thresholds, Dr. Chambers added: “Receiving an accurate and timely diagnosis ensures that women get the treatment and support needed to manage their type 2 diabetes and avoid long-term complications, including heart disease, where sex-based inequalities in care already contribute to poorer outcomes for women.” 
 

Effect of A1c reference range on T2D diagnosis and associated CVD

Compared with men, women with T2D have poorer glycemic control; a higher risk for cardiovascular (CV) complications; reduced life expectancy (5.3 years shorter vs. 4.5 years shorter); and a higher risk factor burden, such as obesity and hypertension at diagnosis.

In addition, T2D is a stronger risk factor for CV disease (CVD) in women than in men, and those aged 35-59 years who receive a diagnosis have the highest relative CV death risk across all age and sex groups.

The researchers pointed out that previous studies have observed differences in A1c relative to menopause, and they too found that “A1c levels rose after the age of 50 in women.”

However, they noted that the implication of differing A1c reference ranges on delayed diabetes diagnosis with worsening CV risk profile had not been previously recognized and that their study “[h]ighlights for the first time that, while 1.6 mmol/mol may appear only a small difference in terms of laboratory measurement, at population level this has implications for significant number of premenopausal women.”

The researchers initially observed the trend in local data in Salford, in the northwest of England. “These ... data highlighted that women seemed to be diagnosed with type 2 diabetes at an older age, so we wanted to examine what the source of that might be,” study author Mike Stedman, BSc, director, Res Consortium, Andover, England, said in an interview.

Dr. Stedman and his colleagues assessed the sex and age differences of A1c in individuals who had not been diagnosed with diabetes (A1c ≤ 48 mmol/mol [≤ 6.5%]). “We looked at data from other labs [in addition to those in Salford, totaling 938,678 people] to see if this was a local phenomenon. They could only provide more recent data, but these also showed a similar pattern,” he added.

Finally, Dr. Stedman, Dr. Heald, and their colleagues estimated the possible national impact by extrapolating findings based on population data from the UK Office of National Statistics and on National Diabetes Audit data for type 2 diabetes prevalence and related excess mortality. This brought them to the conclusion that T2D would be diagnosed in an additional 17% of women if the threshold were lowered by 2 mmol/mol, to 46 mmol/mol, in women under 50 years.
 

Lower A1c in women under 50 may delay T2D diagnosis by up to 10 years

The analysis found that the median A1c increased with age, with values in women younger than 50 years consistently being 1 mmol/mol lower than values in men. In contrast, A1c values in women over 50 years were equivalent to those in men.

However, at age 50 years, compared with men, A1c in women was found to lag by approximately 5 years. Women under 50 had an A1c distribution that was lower than that of men by an average of 1.6 mmol/mol (4.7% of mean; P < .0001), whereas this difference in individuals aged 50 years or older was less pronounced (P < .0001).

The authors wrote that “an undermeasurement of approximately 1.6 mmol/mol A1c in women may delay their diabetes ... diagnosis by up to 10 years.”

Further analysis showed that, at an A1c of 48 mmol/mol, 50% fewer women than men under the age of 50 could be diagnosed with T2D, whereas only 20% fewer women than men aged 50 years or older could be diagnosed with T2D.

Lowering the A1c threshold for diagnosis of T2D from 48 mmol/mol to 46 mmol/mol in women under 50 led to an estimate that an additional 35,345 undiagnosed women in England could be reclassified as having a T2D diagnosis.

The authors pointed out that “gender difference in adverse cardiovascular risk factors are known to be present prior to the development of [type 2] diabetes” and that “once diagnosed, atherosclerotic CVD prevalence is twice as high in patients with diabetes ... compared to those without a diagnosis.”

Dr. Heald added that there is always the possibility that other factors might be at play and that the work posed questions rather than presented answers.

Taking a pragmatic view, the researchers suggested that “one alternative approach may be to offer further assessment using fasting plasma glucose or oral glucose tolerance testing in those with A1c values of 46 or 47 mmol/mol.”

“In anyone with an early diagnosis of type 2 diabetes, in addition to dietary modification and especially if there is cardiovascular risk, then one might start them on metformin due to the cardiovascular benefits as well as the sugar-lowering effects,” said Dr. Heald, adding that “we certainly don’t want women missing out on metformin that could have huge benefits in the longer term.”

Dr. Stedman and Dr. Heald declared no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years; and no other relationships or activities that could appear to have influenced the submitted work. Dr. Chambers has declared no conflicts.

A version of this article appeared on Medscape.com.

Use of A1c levels for the diagnosis of type 2 diabetes (T2D) in women younger than 50 years may lead to underdiagnosis, owing to the effects of menstrual blood loss on A1c readings, shows the first study of its kind.

The analysis estimates that an additional 17% of undiagnosed women younger than 50 years could be reclassified as having T2D, and that women under 50 had an A1c distribution that was markedly lower than that of men under 50, by a mean of 1.6 mmol/mol.

In a study that will be presented at this year’s annual meeting of the European Association for the Study of Diabetes (EASD), the researchers wanted to investigate whether a contributing factor to late diagnosis of T2D in women under 50 may be the difference in A1c levels due to hemoglobin replacement linked to menstrual blood loss.

The study was published online in Diabetes Therapy. “If the threshold for diagnosis of diabetes ... was lowered by 2 mmol/mol in women under the age of 50, an additional 17% of these women (approximately equivalent to 35,000 women in England and Wales) would be diagnosed with diabetes ... which may contribute to up to 64% of the difference in mortality rates between men/women with diabetes mellitus aged 16-50 years,” the researchers noted.

They added that A1c levels in women under 50 years were found to be consistently lower than those in men, and with A1c levels in women reaching the equivalent of those in men up to 10 years later, this “may result in delayed diagnosis of diabetes mellitus in premenopausal women.”

Noting that the study was observational, senior author Adrian Heald, MD, consultant endocrinologist, Salford (England) Royal NHS Foundation Trust, said that it “may be the case that prediabetes and type 2 diabetes in women are not being spotted because the set point needs to be slightly lower, but a systematic study sampling from the population of at-risk individuals is needed further to our findings.

“We also need to refer back to use of the glucose tolerance test, because A1c has been used for the past 15 years but it is not the gold standard,” added Dr. Heald. “Clinicians have often wondered if patients might be missed with A1c measurement, or even overdiagnosed.”

Lucy Chambers, PhD, from Diabetes UK, acknowledged that the research was valuable but added: “More research on sex differences in thresholds for a type 2 diagnosis is needed to inform any changes to clinical practice. In the meantime, we encourage clinicians to follow the current guidance of not ruling out type 2 diabetes based on a one-off A1c below the diagnostic threshold.”

But in support of greater understanding around the sex differences in A1c diagnostic thresholds, Dr. Chambers added: “Receiving an accurate and timely diagnosis ensures that women get the treatment and support needed to manage their type 2 diabetes and avoid long-term complications, including heart disease, where sex-based inequalities in care already contribute to poorer outcomes for women.” 
 

Effect of A1c reference range on T2D diagnosis and associated CVD

Compared with men, women with T2D have poorer glycemic control; a higher risk for cardiovascular (CV) complications; reduced life expectancy (5.3 years shorter vs. 4.5 years shorter); and a higher risk factor burden, such as obesity and hypertension at diagnosis.

In addition, T2D is a stronger risk factor for CV disease (CVD) in women than in men, and those aged 35-59 years who receive a diagnosis have the highest relative CV death risk across all age and sex groups.

The researchers pointed out that previous studies have observed differences in A1c relative to menopause, and they too found that “A1c levels rose after the age of 50 in women.”

However, they noted that the implication of differing A1c reference ranges on delayed diabetes diagnosis with worsening CV risk profile had not been previously recognized and that their study “[h]ighlights for the first time that, while 1.6 mmol/mol may appear only a small difference in terms of laboratory measurement, at population level this has implications for significant number of premenopausal women.”

The researchers initially observed the trend in local data in Salford, in the northwest of England. “These ... data highlighted that women seemed to be diagnosed with type 2 diabetes at an older age, so we wanted to examine what the source of that might be,” study author Mike Stedman, BSc, director, Res Consortium, Andover, England, said in an interview.

Dr. Stedman and his colleagues assessed the sex and age differences of A1c in individuals who had not been diagnosed with diabetes (A1c ≤ 48 mmol/mol [≤ 6.5%]). “We looked at data from other labs [in addition to those in Salford, totaling 938,678 people] to see if this was a local phenomenon. They could only provide more recent data, but these also showed a similar pattern,” he added.

Finally, Dr. Stedman, Dr. Heald, and their colleagues estimated the possible national impact by extrapolating findings based on population data from the UK Office of National Statistics and on National Diabetes Audit data for type 2 diabetes prevalence and related excess mortality. This brought them to the conclusion that T2D would be diagnosed in an additional 17% of women if the threshold were lowered by 2 mmol/mol, to 46 mmol/mol, in women under 50 years.
 

Lower A1c in women under 50 may delay T2D diagnosis by up to 10 years

The analysis found that the median A1c increased with age, with values in women younger than 50 years consistently being 1 mmol/mol lower than values in men. In contrast, A1c values in women over 50 years were equivalent to those in men.

However, at age 50 years, compared with men, A1c in women was found to lag by approximately 5 years. Women under 50 had an A1c distribution that was lower than that of men by an average of 1.6 mmol/mol (4.7% of mean; P < .0001), whereas this difference in individuals aged 50 years or older was less pronounced (P < .0001).

The authors wrote that “an undermeasurement of approximately 1.6 mmol/mol A1c in women may delay their diabetes ... diagnosis by up to 10 years.”

Further analysis showed that, at an A1c of 48 mmol/mol, 50% fewer women than men under the age of 50 could be diagnosed with T2D, whereas only 20% fewer women than men aged 50 years or older could be diagnosed with T2D.

Lowering the A1c threshold for diagnosis of T2D from 48 mmol/mol to 46 mmol/mol in women under 50 led to an estimate that an additional 35,345 undiagnosed women in England could be reclassified as having a T2D diagnosis.

The authors pointed out that “gender difference in adverse cardiovascular risk factors are known to be present prior to the development of [type 2] diabetes” and that “once diagnosed, atherosclerotic CVD prevalence is twice as high in patients with diabetes ... compared to those without a diagnosis.”

Dr. Heald added that there is always the possibility that other factors might be at play and that the work posed questions rather than presented answers.

Taking a pragmatic view, the researchers suggested that “one alternative approach may be to offer further assessment using fasting plasma glucose or oral glucose tolerance testing in those with A1c values of 46 or 47 mmol/mol.”

“In anyone with an early diagnosis of type 2 diabetes, in addition to dietary modification and especially if there is cardiovascular risk, then one might start them on metformin due to the cardiovascular benefits as well as the sugar-lowering effects,” said Dr. Heald, adding that “we certainly don’t want women missing out on metformin that could have huge benefits in the longer term.”

Dr. Stedman and Dr. Heald declared no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years; and no other relationships or activities that could appear to have influenced the submitted work. Dr. Chambers has declared no conflicts.

A version of this article appeared on Medscape.com.

Use of A1c levels for the diagnosis of type 2 diabetes (T2D) in women younger than 50 years may lead to underdiagnosis, owing to the effects of menstrual blood loss on A1c readings, shows the first study of its kind.

The analysis estimates that an additional 17% of undiagnosed women younger than 50 years could be reclassified as having T2D, and that women under 50 had an A1c distribution that was markedly lower than that of men under 50, by a mean of 1.6 mmol/mol.

In a study that will be presented at this year’s annual meeting of the European Association for the Study of Diabetes (EASD), the researchers wanted to investigate whether a contributing factor to late diagnosis of T2D in women under 50 may be the difference in A1c levels due to hemoglobin replacement linked to menstrual blood loss.

The study was published online in Diabetes Therapy. “If the threshold for diagnosis of diabetes ... was lowered by 2 mmol/mol in women under the age of 50, an additional 17% of these women (approximately equivalent to 35,000 women in England and Wales) would be diagnosed with diabetes ... which may contribute to up to 64% of the difference in mortality rates between men/women with diabetes mellitus aged 16-50 years,” the researchers noted.

They added that A1c levels in women under 50 years were found to be consistently lower than those in men, and with A1c levels in women reaching the equivalent of those in men up to 10 years later, this “may result in delayed diagnosis of diabetes mellitus in premenopausal women.”

Noting that the study was observational, senior author Adrian Heald, MD, consultant endocrinologist, Salford (England) Royal NHS Foundation Trust, said that it “may be the case that prediabetes and type 2 diabetes in women are not being spotted because the set point needs to be slightly lower, but a systematic study sampling from the population of at-risk individuals is needed further to our findings.

“We also need to refer back to use of the glucose tolerance test, because A1c has been used for the past 15 years but it is not the gold standard,” added Dr. Heald. “Clinicians have often wondered if patients might be missed with A1c measurement, or even overdiagnosed.”

Lucy Chambers, PhD, from Diabetes UK, acknowledged that the research was valuable but added: “More research on sex differences in thresholds for a type 2 diagnosis is needed to inform any changes to clinical practice. In the meantime, we encourage clinicians to follow the current guidance of not ruling out type 2 diabetes based on a one-off A1c below the diagnostic threshold.”

But in support of greater understanding around the sex differences in A1c diagnostic thresholds, Dr. Chambers added: “Receiving an accurate and timely diagnosis ensures that women get the treatment and support needed to manage their type 2 diabetes and avoid long-term complications, including heart disease, where sex-based inequalities in care already contribute to poorer outcomes for women.” 
 

Effect of A1c reference range on T2D diagnosis and associated CVD

Compared with men, women with T2D have poorer glycemic control; a higher risk for cardiovascular (CV) complications; reduced life expectancy (5.3 years shorter vs. 4.5 years shorter); and a higher risk factor burden, such as obesity and hypertension at diagnosis.

In addition, T2D is a stronger risk factor for CV disease (CVD) in women than in men, and those aged 35-59 years who receive a diagnosis have the highest relative CV death risk across all age and sex groups.

The researchers pointed out that previous studies have observed differences in A1c relative to menopause, and they too found that “A1c levels rose after the age of 50 in women.”

However, they noted that the implication of differing A1c reference ranges on delayed diabetes diagnosis with worsening CV risk profile had not been previously recognized and that their study “[h]ighlights for the first time that, while 1.6 mmol/mol may appear only a small difference in terms of laboratory measurement, at population level this has implications for significant number of premenopausal women.”

The researchers initially observed the trend in local data in Salford, in the northwest of England. “These ... data highlighted that women seemed to be diagnosed with type 2 diabetes at an older age, so we wanted to examine what the source of that might be,” study author Mike Stedman, BSc, director, Res Consortium, Andover, England, said in an interview.

Dr. Stedman and his colleagues assessed the sex and age differences of A1c in individuals who had not been diagnosed with diabetes (A1c ≤ 48 mmol/mol [≤ 6.5%]). “We looked at data from other labs [in addition to those in Salford, totaling 938,678 people] to see if this was a local phenomenon. They could only provide more recent data, but these also showed a similar pattern,” he added.

Finally, Dr. Stedman, Dr. Heald, and their colleagues estimated the possible national impact by extrapolating findings based on population data from the UK Office of National Statistics and on National Diabetes Audit data for type 2 diabetes prevalence and related excess mortality. This brought them to the conclusion that T2D would be diagnosed in an additional 17% of women if the threshold were lowered by 2 mmol/mol, to 46 mmol/mol, in women under 50 years.
 

Lower A1c in women under 50 may delay T2D diagnosis by up to 10 years

The analysis found that the median A1c increased with age, with values in women younger than 50 years consistently being 1 mmol/mol lower than values in men. In contrast, A1c values in women over 50 years were equivalent to those in men.

However, at age 50 years, compared with men, A1c in women was found to lag by approximately 5 years. Women under 50 had an A1c distribution that was lower than that of men by an average of 1.6 mmol/mol (4.7% of mean; P < .0001), whereas this difference in individuals aged 50 years or older was less pronounced (P < .0001).

The authors wrote that “an undermeasurement of approximately 1.6 mmol/mol A1c in women may delay their diabetes ... diagnosis by up to 10 years.”

Further analysis showed that, at an A1c of 48 mmol/mol, 50% fewer women than men under the age of 50 could be diagnosed with T2D, whereas only 20% fewer women than men aged 50 years or older could be diagnosed with T2D.

Lowering the A1c threshold for diagnosis of T2D from 48 mmol/mol to 46 mmol/mol in women under 50 led to an estimate that an additional 35,345 undiagnosed women in England could be reclassified as having a T2D diagnosis.

The authors pointed out that “gender difference in adverse cardiovascular risk factors are known to be present prior to the development of [type 2] diabetes” and that “once diagnosed, atherosclerotic CVD prevalence is twice as high in patients with diabetes ... compared to those without a diagnosis.”

Dr. Heald added that there is always the possibility that other factors might be at play and that the work posed questions rather than presented answers.

Taking a pragmatic view, the researchers suggested that “one alternative approach may be to offer further assessment using fasting plasma glucose or oral glucose tolerance testing in those with A1c values of 46 or 47 mmol/mol.”

“In anyone with an early diagnosis of type 2 diabetes, in addition to dietary modification and especially if there is cardiovascular risk, then one might start them on metformin due to the cardiovascular benefits as well as the sugar-lowering effects,” said Dr. Heald, adding that “we certainly don’t want women missing out on metformin that could have huge benefits in the longer term.”

Dr. Stedman and Dr. Heald declared no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years; and no other relationships or activities that could appear to have influenced the submitted work. Dr. Chambers has declared no conflicts.

A version of this article appeared on Medscape.com.

Postoperative parathyroid hormone (PTH) showed 100% sensitivity in predicting postthyroidectomy hypocalcemia, according to the results of a prospective study of 60 patients.

Postthyroidectomy hypocalcemia remains a major complication in patients who have undergone total thyroidectomy, and early identification can reduce disease burden and improve outcomes, according to Ahmed Sobhy Youssef, MD, of the University of Oklahoma Health Sciences Center, Oklahoma City, and colleagues.

In a presentation at the annual meeting of the American Academy of Otolaryngology-Head and Neck Surgery, Dr. Youssef presented results of the study, which looked at early postoperative parathyroid hormone as a predictor of postthyroidectomy hypocalcemia.

During his fellowship in Oklahoma in the wake of the COVID-19 pandemic, Dr. Youssef observed a wide variation in follow-up for calcium levels after thyroidectomy. “Some surgeons will order PTH and ionized calcium 4 hours after surgery, others would order later, at 6-8 hours,” he said in an interview. However, “all patients would be admitted for 1-2 nights [before being] discharged home, which meant more restrictions on the number of beds allowed for our head and neck cancer service.”

Discussion with his department chair led to a literature review seeking strategies to discharge patients earlier, and Dr. Youssef developed the idea for early PTH testing.

The study population included 60 adults who underwent thyroidectomy for benign or malignant disease at a single center between January 2022 and January 2023. The researchers measured PTH at 1 hour after surgery and compared it to results of a standard postoperative measure at 4 hours after surgery.

The researchers found a significant positive correlation between PTH measured 1 hour after surgery and ionized calcium (Ca) at 4 hours. The sensitivity of the early PTH assay, defined as “measured below 14 pg/ml,” was 100% to detect hypocalcemia, with an area under the curve of 0.797.

“The results were amazing,” said Dr. Youssef. “We found that when we measure PTH as early as 1 hour after total thyroidectomy, while patients are still in recovery, PTH was very sensitive to predict hypocalcemia.” The correlation was strong with measures at 4 hours.

“Our takeaway message is the 1-hour level PTH is very reliable in predicting hypocalcemia,” he added. This measure can serve as a guide for discharging patients the same day, with instructions to return if they develop any symptoms of hypocalcemia.

The use of early PTH also helped to reduce hospital admissions and identified patients who were eligible for same-day discharge with no need for additional replacement medications, Dr. Youssef said.

So far, “we have had no readmissions for thyroidectomy patients since we started to follow this protocol at our institution,” he noted.

The findings were limited by the relatively small sample size, and more research is needed. However, the results suggest that early measurement of PTH at 1 hour after surgery is an accurate predictor of hypocalcemia in total thyroidectomy patients.

“I strongly recommend high thyroidectomy volume institutions apply the same protocol and publish their data about that so we can come up with a consensus/guideline for management of calcium following thyroidectomy,” Dr. Youssef said.
 

More proof of PTH’s predictive power

“The utility of postoperative PTH for predicting symptomatic hypocalcemia is beneficial for guiding postoperative management of patients following total thyroidectomy,” said Larissa Sweeny, MD, of the University of Miami, who served as a moderator for the session in which the study was presented.

“Proper identification of patients that require supplemental medications following surgery reduces administration of medications to patients that do not require supplemental medications,” Dr. Sweeny said in an interview.

In addition, better identification not only ensures that the patients who do require supplemental medications receive them but also reduces postoperative complications and readmissions, she said.

For clinical practice, the current study “reinforces the utility of postoperative PTH lab values for guiding medication administration following total thyroidectomy,” said Dr. Sweeny. “I have been using postoperative PTH lab values following total thyroidectomy to guide my postoperative management of these patients for over 6 years.” 

However, looking ahead to additional research, “Correlation with dosage of supplemental calcium and duration to return of normal PTH would be helpful information,” Dr. Sweeny said.

The study received no outside funding. The researchers and Dr. Sweeny report no relevant financial relationships. 

A version of this article appeared on Medscape.com.

Postoperative parathyroid hormone (PTH) showed 100% sensitivity in predicting postthyroidectomy hypocalcemia, according to the results of a prospective study of 60 patients.

Postthyroidectomy hypocalcemia remains a major complication in patients who have undergone total thyroidectomy, and early identification can reduce disease burden and improve outcomes, according to Ahmed Sobhy Youssef, MD, of the University of Oklahoma Health Sciences Center, Oklahoma City, and colleagues.

In a presentation at the annual meeting of the American Academy of Otolaryngology-Head and Neck Surgery, Dr. Youssef presented results of the study, which looked at early postoperative parathyroid hormone as a predictor of postthyroidectomy hypocalcemia.

During his fellowship in Oklahoma in the wake of the COVID-19 pandemic, Dr. Youssef observed a wide variation in follow-up for calcium levels after thyroidectomy. “Some surgeons will order PTH and ionized calcium 4 hours after surgery, others would order later, at 6-8 hours,” he said in an interview. However, “all patients would be admitted for 1-2 nights [before being] discharged home, which meant more restrictions on the number of beds allowed for our head and neck cancer service.”

Discussion with his department chair led to a literature review seeking strategies to discharge patients earlier, and Dr. Youssef developed the idea for early PTH testing.

The study population included 60 adults who underwent thyroidectomy for benign or malignant disease at a single center between January 2022 and January 2023. The researchers measured PTH at 1 hour after surgery and compared it to results of a standard postoperative measure at 4 hours after surgery.

The researchers found a significant positive correlation between PTH measured 1 hour after surgery and ionized calcium (Ca) at 4 hours. The sensitivity of the early PTH assay, defined as “measured below 14 pg/ml,” was 100% to detect hypocalcemia, with an area under the curve of 0.797.

“The results were amazing,” said Dr. Youssef. “We found that when we measure PTH as early as 1 hour after total thyroidectomy, while patients are still in recovery, PTH was very sensitive to predict hypocalcemia.” The correlation was strong with measures at 4 hours.

“Our takeaway message is the 1-hour level PTH is very reliable in predicting hypocalcemia,” he added. This measure can serve as a guide for discharging patients the same day, with instructions to return if they develop any symptoms of hypocalcemia.

The use of early PTH also helped to reduce hospital admissions and identified patients who were eligible for same-day discharge with no need for additional replacement medications, Dr. Youssef said.

So far, “we have had no readmissions for thyroidectomy patients since we started to follow this protocol at our institution,” he noted.

The findings were limited by the relatively small sample size, and more research is needed. However, the results suggest that early measurement of PTH at 1 hour after surgery is an accurate predictor of hypocalcemia in total thyroidectomy patients.

“I strongly recommend high thyroidectomy volume institutions apply the same protocol and publish their data about that so we can come up with a consensus/guideline for management of calcium following thyroidectomy,” Dr. Youssef said.
 

More proof of PTH’s predictive power

“The utility of postoperative PTH for predicting symptomatic hypocalcemia is beneficial for guiding postoperative management of patients following total thyroidectomy,” said Larissa Sweeny, MD, of the University of Miami, who served as a moderator for the session in which the study was presented.

“Proper identification of patients that require supplemental medications following surgery reduces administration of medications to patients that do not require supplemental medications,” Dr. Sweeny said in an interview.

In addition, better identification not only ensures that the patients who do require supplemental medications receive them but also reduces postoperative complications and readmissions, she said.

For clinical practice, the current study “reinforces the utility of postoperative PTH lab values for guiding medication administration following total thyroidectomy,” said Dr. Sweeny. “I have been using postoperative PTH lab values following total thyroidectomy to guide my postoperative management of these patients for over 6 years.” 

However, looking ahead to additional research, “Correlation with dosage of supplemental calcium and duration to return of normal PTH would be helpful information,” Dr. Sweeny said.

The study received no outside funding. The researchers and Dr. Sweeny report no relevant financial relationships. 

A version of this article appeared on Medscape.com.

Postoperative parathyroid hormone (PTH) showed 100% sensitivity in predicting postthyroidectomy hypocalcemia, according to the results of a prospective study of 60 patients.

Postthyroidectomy hypocalcemia remains a major complication in patients who have undergone total thyroidectomy, and early identification can reduce disease burden and improve outcomes, according to Ahmed Sobhy Youssef, MD, of the University of Oklahoma Health Sciences Center, Oklahoma City, and colleagues.

In a presentation at the annual meeting of the American Academy of Otolaryngology-Head and Neck Surgery, Dr. Youssef presented results of the study, which looked at early postoperative parathyroid hormone as a predictor of postthyroidectomy hypocalcemia.

During his fellowship in Oklahoma in the wake of the COVID-19 pandemic, Dr. Youssef observed a wide variation in follow-up for calcium levels after thyroidectomy. “Some surgeons will order PTH and ionized calcium 4 hours after surgery, others would order later, at 6-8 hours,” he said in an interview. However, “all patients would be admitted for 1-2 nights [before being] discharged home, which meant more restrictions on the number of beds allowed for our head and neck cancer service.”

Discussion with his department chair led to a literature review seeking strategies to discharge patients earlier, and Dr. Youssef developed the idea for early PTH testing.

The study population included 60 adults who underwent thyroidectomy for benign or malignant disease at a single center between January 2022 and January 2023. The researchers measured PTH at 1 hour after surgery and compared it to results of a standard postoperative measure at 4 hours after surgery.

The researchers found a significant positive correlation between PTH measured 1 hour after surgery and ionized calcium (Ca) at 4 hours. The sensitivity of the early PTH assay, defined as “measured below 14 pg/ml,” was 100% to detect hypocalcemia, with an area under the curve of 0.797.

“The results were amazing,” said Dr. Youssef. “We found that when we measure PTH as early as 1 hour after total thyroidectomy, while patients are still in recovery, PTH was very sensitive to predict hypocalcemia.” The correlation was strong with measures at 4 hours.

“Our takeaway message is the 1-hour level PTH is very reliable in predicting hypocalcemia,” he added. This measure can serve as a guide for discharging patients the same day, with instructions to return if they develop any symptoms of hypocalcemia.

The use of early PTH also helped to reduce hospital admissions and identified patients who were eligible for same-day discharge with no need for additional replacement medications, Dr. Youssef said.

So far, “we have had no readmissions for thyroidectomy patients since we started to follow this protocol at our institution,” he noted.

The findings were limited by the relatively small sample size, and more research is needed. However, the results suggest that early measurement of PTH at 1 hour after surgery is an accurate predictor of hypocalcemia in total thyroidectomy patients.

“I strongly recommend high thyroidectomy volume institutions apply the same protocol and publish their data about that so we can come up with a consensus/guideline for management of calcium following thyroidectomy,” Dr. Youssef said.
 

More proof of PTH’s predictive power

“The utility of postoperative PTH for predicting symptomatic hypocalcemia is beneficial for guiding postoperative management of patients following total thyroidectomy,” said Larissa Sweeny, MD, of the University of Miami, who served as a moderator for the session in which the study was presented.

“Proper identification of patients that require supplemental medications following surgery reduces administration of medications to patients that do not require supplemental medications,” Dr. Sweeny said in an interview.

In addition, better identification not only ensures that the patients who do require supplemental medications receive them but also reduces postoperative complications and readmissions, she said.

For clinical practice, the current study “reinforces the utility of postoperative PTH lab values for guiding medication administration following total thyroidectomy,” said Dr. Sweeny. “I have been using postoperative PTH lab values following total thyroidectomy to guide my postoperative management of these patients for over 6 years.” 

However, looking ahead to additional research, “Correlation with dosage of supplemental calcium and duration to return of normal PTH would be helpful information,” Dr. Sweeny said.

The study received no outside funding. The researchers and Dr. Sweeny report no relevant financial relationships. 

A version of this article appeared on Medscape.com.

TOPLINE:

Among women with genitourinary syndrome of menopause, 12 weeks of treatment with vaginal suppositories containing hyaluronic acid (HLA) reduces vulvovaginal symptoms, according to trial results presented at the annual Menopause Meeting. HLA may be a promising nonhormonal therapy for this condition, the researchers said.

METHODOLOGY:

• Investigators randomly assigned 49 women to receive treatment with a vaginal suppository containing 5 mg of HLA or standard-of-care treatment with vaginal estrogen cream (0.01%).
• The trial was conducted between September 2021 and August 2022.

TAKEAWAY:

• Patients in both treatment arms experienced improvements on the Vulvovaginal Symptom Questionnaire (VSQ), the study’s primary outcome.
• The VSQ assesses vulvovaginal symptoms associated with menopause such as itching, burning, and dryness, as well as the emotional toll of symptoms and their effect on sexual activity.
• Change in VSQ score did not significantly differ between the treatment groups. The measure improved from 5.2 to 1.7 in the group that received estrogen, and from 5.8 to 2.5 in those who received HLA (P = .81).
• No treatment-related severe adverse events were reported.

IN PRACTICE:

“Women often need to decide between different therapies for genitourinary syndrome of menopause,” study author Benjamin Brucker, MD, of New York University said in an interview. “Now we can help counsel them about this formulation of HLA.”

SOURCE:

Poster P-1 was presented at the 2023 meeting of the Menopause Society, held Sept. 27-30 in Philadelphia.

DISCLOSURES:

The study was funded by Bonafide Health, a company that sells supplements to treat menopause symptoms, including vaginal suppositories containing HLA.

A version of this article appeared on Medscape.com.

TOPLINE:

Among women with genitourinary syndrome of menopause, 12 weeks of treatment with vaginal suppositories containing hyaluronic acid (HLA) reduces vulvovaginal symptoms, according to trial results presented at the annual Menopause Meeting. HLA may be a promising nonhormonal therapy for this condition, the researchers said.

METHODOLOGY:

• Investigators randomly assigned 49 women to receive treatment with a vaginal suppository containing 5 mg of HLA or standard-of-care treatment with vaginal estrogen cream (0.01%).
• The trial was conducted between September 2021 and August 2022.

TAKEAWAY:

• Patients in both treatment arms experienced improvements on the Vulvovaginal Symptom Questionnaire (VSQ), the study’s primary outcome.
• The VSQ assesses vulvovaginal symptoms associated with menopause such as itching, burning, and dryness, as well as the emotional toll of symptoms and their effect on sexual activity.
• Change in VSQ score did not significantly differ between the treatment groups. The measure improved from 5.2 to 1.7 in the group that received estrogen, and from 5.8 to 2.5 in those who received HLA (P = .81).
• No treatment-related severe adverse events were reported.

IN PRACTICE:

“Women often need to decide between different therapies for genitourinary syndrome of menopause,” study author Benjamin Brucker, MD, of New York University said in an interview. “Now we can help counsel them about this formulation of HLA.”

SOURCE:

Poster P-1 was presented at the 2023 meeting of the Menopause Society, held Sept. 27-30 in Philadelphia.

DISCLOSURES:

The study was funded by Bonafide Health, a company that sells supplements to treat menopause symptoms, including vaginal suppositories containing HLA.

A version of this article appeared on Medscape.com.

TOPLINE:

Among women with genitourinary syndrome of menopause, 12 weeks of treatment with vaginal suppositories containing hyaluronic acid (HLA) reduces vulvovaginal symptoms, according to trial results presented at the annual Menopause Meeting. HLA may be a promising nonhormonal therapy for this condition, the researchers said.

METHODOLOGY:

• Investigators randomly assigned 49 women to receive treatment with a vaginal suppository containing 5 mg of HLA or standard-of-care treatment with vaginal estrogen cream (0.01%).
• The trial was conducted between September 2021 and August 2022.

TAKEAWAY:

• Patients in both treatment arms experienced improvements on the Vulvovaginal Symptom Questionnaire (VSQ), the study’s primary outcome.
• The VSQ assesses vulvovaginal symptoms associated with menopause such as itching, burning, and dryness, as well as the emotional toll of symptoms and their effect on sexual activity.
• Change in VSQ score did not significantly differ between the treatment groups. The measure improved from 5.2 to 1.7 in the group that received estrogen, and from 5.8 to 2.5 in those who received HLA (P = .81).
• No treatment-related severe adverse events were reported.

IN PRACTICE:

“Women often need to decide between different therapies for genitourinary syndrome of menopause,” study author Benjamin Brucker, MD, of New York University said in an interview. “Now we can help counsel them about this formulation of HLA.”

SOURCE:

Poster P-1 was presented at the 2023 meeting of the Menopause Society, held Sept. 27-30 in Philadelphia.

DISCLOSURES:

The study was funded by Bonafide Health, a company that sells supplements to treat menopause symptoms, including vaginal suppositories containing HLA.

A version of this article appeared on Medscape.com.

WASHINGTON – Adding the PD-1 inhibitor pembrolizumab to the established combination of dabrafenib and trametinib (DT) significantly improves survival outcomes in BRAF V600E-mutated anaplastic thyroid cancer - particularly when administered in a neoadjuvant fashion, prior to surgery. Overall survival rates in the study exceeded 5 years.

“The very long median overall survival in the study’s neoadjuvant group is quite remarkable for a group of patients who used to have a very poor prognosis,” senior author Maria E. Cabanillas, MD, associate professor in the department of endocrine neoplasia and hormonal disorders at the University of Texas MD Anderson Cancer Center in Houston, said in an interview.

“This median overall survival definitely exceeds any other treatments thus far in BRAF-mutated anaplastic thyroid cancer.”

The research was presented at the annual meeting of the American Thyroid Association.

Anaplastic thyroid cancer, though rare, is the most aggressive form of thyroid cancer. It accounts for just 1% of the cancers but causes about 50% of thyroid cancer mortality.

The historical median overall survival is 5-6 months.

With research in recent years showing that as many as 40% of anaplastic thyroid cancers harbor BRAF V600E mutations, the door has opened for potential benefits with the combination of the BRAF inhibitor dabrafenib with the MEK-inhibitor drug trametinib.

The treatment combination was shown in research that included the phase 2 ROAR trial to yield important responses. It was approved by the Food and Drug Administration in 2018 for locally advanced or metastatic BRAF V600E-mutant anaplastic thyroid cancer, as well as other cancers.

However, a key caveat of DT is that patients eventually develop resistance mutations, leading to disease progression.

To overcome the problem, Dr. Cabanillas and her team found two key strategies that show promise – the addition of immunotherapy, such as pembrolizumab to DT, and the use of a neoadjuvant approach, with surgery performed after an initial response to the triplet therapy.
 

Triple therapy showed highly favorable results

In a study presented at the 2022 ATA annual meeting, researchers reported on the triple therapy of BRAF/MEK inhibitors vemurafenib and cobimetinib plus immunotherapy with atezolizumab. Results were highly favorable, with an overall response rate of 72% and an impressive 2-year survival of 67%.

However, a major limitation was that the study lacked a control arm. In the current study, the addition of pembrolizumab to DT was compared with DT alone. The investigators also sought to determine the survival benefits of a neoadjuvant strategy.

For the study, first author Sarah Hamidi, MD, also of the MD Anderson Cancer Center, and her colleagues identified 94 patients with BRAF-mutated anaplastic thyroid cancer who were treated either with first‐line DT or DT plus pembrolizumab between 2014 and 2023, either outside of a trial or in a reported clinical trial.

The study compared three treatment regimens – DT alone (n = 23), DT with pembrolizumab added before or after disease progression (n = 48), and DT with neoadjuvant pembrolizumab added prior to or after surgery (n = 23).

There were no significant differences in baseline characteristics between the groups. Metastatic disease was present at the start of treatment among 87.0% of the DT group, 79.2% of the pembrolizumab group prior to or after disease progression, and 65.2% of the neoadjuvant pembrolizumab group.

The median follow-up of the three groups was 102 months, 28 months, and 42 months, respectively. The median overall survival was 9 months with DT alone, vs. 17 months with DT plus pembrolizumab before or after progression and 63 months with neoadjuvant pembrolizumab plus DT (P < .001).

The 12- and 24-month survival rates with DT alone were 33.7% and 28.9%, respectively; for DT plus pembrolizumab before or after progression, the rates were 60.2% and 36.5%; and for neoadjuvant pembrolizumab plus DT, the rates were 80.7% and 74.5%.

In an analysis that did not include the neoadjuvant group, median progression-free survival was significantly longer with DT plus pembrolizumab as an initial treatment (11.0 months) compared with DT alone (4.0 months; P  =  .049).

A subanalysis that evaluated the timing of the addition of pembrolizumab to DT before or after disease progression showed no significant differences between the two in median overall survival (17 months vs. 16 months; P = .554).

“This is valuable information, especially for centers where pembrolizumab cannot be easily obtained as a first-line therapy for anaplastic thyroid cancer,” Dr. Hamidi said in presenting the findings.

She noted, however, that the results should be interpreted with caution, given the small number of patients who received pembrolizumab before progression (n = 34) and especially after progression (n = 14).

In terms of safety, there were no grade 5 adverse events (AEs); 32.4% of patients experienced immune‐related AEs, most frequently, colitis and hepatitis.
 

Therapies “improve survival”

Overall, the results are important, Dr. Cabanillas said.

The results are “very exciting when you think about the fact that 10 years ago, patients with anaplastic thyroid cancer had a median overall survival measured in months, and now we see that those with a BRAF mutation have a real chance at survival when managed appropriately from the start,” she told this news organization.

She noted that a key caveat is the study’s retrospective nature. Other important considerations are that pembrolizumab adds toxicity as well as cost, and it is largely used off label in anaplastic thyroid cancer.

Nevertheless, “it does feel like there needs to be a call to action in the guidelines for this disease so that it includes neoadjuvant DT or DT plus pembrolizumab as the primary treatment of patients with BRAF-mutated anaplastic thyroid cancer because the initial treatment is critical here,” Dr. Cabanillas said.

She added that a phase 2 trial with neoadjuvant DT plus pembrolizumab is ongoing. Enrollment is expected to be completed soon.

Commenting on the findings, Sarimar Agosto Salgado, MD, of the department of head and neck – endocrine oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla., who was a comoderator of the session, said the results are encouraging.

“These findings are promising because they open the landscape of options of therapies that we can provide these patients,” she said in an interview.

“Anaplastic thyroid cancer has been a disease with a very short survival despite aggressive therapies, but we are seeing that not only have these therapies been able to improve survival but also patients’ quality of life.”

Particularly encouraging is how quickly the therapies can work, Dr. Salgado added.

“Many times when patients present to the clinic, the rapid response to these systemic therapies can even [allow them to avoid] having a tracheostomy, and we’re also seeing that some of these patients are able to go from unresectable disease to resectable disease, and then by having the main tumor out, their survival improves.

“So, this is definitely a big ray of hope for these patients.”

Dr. Cabanillas has received research funding from Merck. Dr. Hamidi has disclosed no relevant financial relationships. Dr. Salgado has relationships with Lilly and Exelixis.
 

A version of this article appeared on Medscape.com.

WASHINGTON – Adding the PD-1 inhibitor pembrolizumab to the established combination of dabrafenib and trametinib (DT) significantly improves survival outcomes in BRAF V600E-mutated anaplastic thyroid cancer - particularly when administered in a neoadjuvant fashion, prior to surgery. Overall survival rates in the study exceeded 5 years.

“The very long median overall survival in the study’s neoadjuvant group is quite remarkable for a group of patients who used to have a very poor prognosis,” senior author Maria E. Cabanillas, MD, associate professor in the department of endocrine neoplasia and hormonal disorders at the University of Texas MD Anderson Cancer Center in Houston, said in an interview.

“This median overall survival definitely exceeds any other treatments thus far in BRAF-mutated anaplastic thyroid cancer.”

The research was presented at the annual meeting of the American Thyroid Association.

Anaplastic thyroid cancer, though rare, is the most aggressive form of thyroid cancer. It accounts for just 1% of the cancers but causes about 50% of thyroid cancer mortality.

The historical median overall survival is 5-6 months.

With research in recent years showing that as many as 40% of anaplastic thyroid cancers harbor BRAF V600E mutations, the door has opened for potential benefits with the combination of the BRAF inhibitor dabrafenib with the MEK-inhibitor drug trametinib.

The treatment combination was shown in research that included the phase 2 ROAR trial to yield important responses. It was approved by the Food and Drug Administration in 2018 for locally advanced or metastatic BRAF V600E-mutant anaplastic thyroid cancer, as well as other cancers.

However, a key caveat of DT is that patients eventually develop resistance mutations, leading to disease progression.

To overcome the problem, Dr. Cabanillas and her team found two key strategies that show promise – the addition of immunotherapy, such as pembrolizumab to DT, and the use of a neoadjuvant approach, with surgery performed after an initial response to the triplet therapy.
 

Triple therapy showed highly favorable results

In a study presented at the 2022 ATA annual meeting, researchers reported on the triple therapy of BRAF/MEK inhibitors vemurafenib and cobimetinib plus immunotherapy with atezolizumab. Results were highly favorable, with an overall response rate of 72% and an impressive 2-year survival of 67%.

However, a major limitation was that the study lacked a control arm. In the current study, the addition of pembrolizumab to DT was compared with DT alone. The investigators also sought to determine the survival benefits of a neoadjuvant strategy.

For the study, first author Sarah Hamidi, MD, also of the MD Anderson Cancer Center, and her colleagues identified 94 patients with BRAF-mutated anaplastic thyroid cancer who were treated either with first‐line DT or DT plus pembrolizumab between 2014 and 2023, either outside of a trial or in a reported clinical trial.

The study compared three treatment regimens – DT alone (n = 23), DT with pembrolizumab added before or after disease progression (n = 48), and DT with neoadjuvant pembrolizumab added prior to or after surgery (n = 23).

There were no significant differences in baseline characteristics between the groups. Metastatic disease was present at the start of treatment among 87.0% of the DT group, 79.2% of the pembrolizumab group prior to or after disease progression, and 65.2% of the neoadjuvant pembrolizumab group.

The median follow-up of the three groups was 102 months, 28 months, and 42 months, respectively. The median overall survival was 9 months with DT alone, vs. 17 months with DT plus pembrolizumab before or after progression and 63 months with neoadjuvant pembrolizumab plus DT (P < .001).

The 12- and 24-month survival rates with DT alone were 33.7% and 28.9%, respectively; for DT plus pembrolizumab before or after progression, the rates were 60.2% and 36.5%; and for neoadjuvant pembrolizumab plus DT, the rates were 80.7% and 74.5%.

In an analysis that did not include the neoadjuvant group, median progression-free survival was significantly longer with DT plus pembrolizumab as an initial treatment (11.0 months) compared with DT alone (4.0 months; P  =  .049).

A subanalysis that evaluated the timing of the addition of pembrolizumab to DT before or after disease progression showed no significant differences between the two in median overall survival (17 months vs. 16 months; P = .554).

“This is valuable information, especially for centers where pembrolizumab cannot be easily obtained as a first-line therapy for anaplastic thyroid cancer,” Dr. Hamidi said in presenting the findings.

She noted, however, that the results should be interpreted with caution, given the small number of patients who received pembrolizumab before progression (n = 34) and especially after progression (n = 14).

In terms of safety, there were no grade 5 adverse events (AEs); 32.4% of patients experienced immune‐related AEs, most frequently, colitis and hepatitis.
 

Therapies “improve survival”

Overall, the results are important, Dr. Cabanillas said.

The results are “very exciting when you think about the fact that 10 years ago, patients with anaplastic thyroid cancer had a median overall survival measured in months, and now we see that those with a BRAF mutation have a real chance at survival when managed appropriately from the start,” she told this news organization.

She noted that a key caveat is the study’s retrospective nature. Other important considerations are that pembrolizumab adds toxicity as well as cost, and it is largely used off label in anaplastic thyroid cancer.

Nevertheless, “it does feel like there needs to be a call to action in the guidelines for this disease so that it includes neoadjuvant DT or DT plus pembrolizumab as the primary treatment of patients with BRAF-mutated anaplastic thyroid cancer because the initial treatment is critical here,” Dr. Cabanillas said.

She added that a phase 2 trial with neoadjuvant DT plus pembrolizumab is ongoing. Enrollment is expected to be completed soon.

Commenting on the findings, Sarimar Agosto Salgado, MD, of the department of head and neck – endocrine oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla., who was a comoderator of the session, said the results are encouraging.

“These findings are promising because they open the landscape of options of therapies that we can provide these patients,” she said in an interview.

“Anaplastic thyroid cancer has been a disease with a very short survival despite aggressive therapies, but we are seeing that not only have these therapies been able to improve survival but also patients’ quality of life.”

Particularly encouraging is how quickly the therapies can work, Dr. Salgado added.

“Many times when patients present to the clinic, the rapid response to these systemic therapies can even [allow them to avoid] having a tracheostomy, and we’re also seeing that some of these patients are able to go from unresectable disease to resectable disease, and then by having the main tumor out, their survival improves.

“So, this is definitely a big ray of hope for these patients.”

Dr. Cabanillas has received research funding from Merck. Dr. Hamidi has disclosed no relevant financial relationships. Dr. Salgado has relationships with Lilly and Exelixis.
 

A version of this article appeared on Medscape.com.

WASHINGTON – Adding the PD-1 inhibitor pembrolizumab to the established combination of dabrafenib and trametinib (DT) significantly improves survival outcomes in BRAF V600E-mutated anaplastic thyroid cancer - particularly when administered in a neoadjuvant fashion, prior to surgery. Overall survival rates in the study exceeded 5 years.

“The very long median overall survival in the study’s neoadjuvant group is quite remarkable for a group of patients who used to have a very poor prognosis,” senior author Maria E. Cabanillas, MD, associate professor in the department of endocrine neoplasia and hormonal disorders at the University of Texas MD Anderson Cancer Center in Houston, said in an interview.

“This median overall survival definitely exceeds any other treatments thus far in BRAF-mutated anaplastic thyroid cancer.”

The research was presented at the annual meeting of the American Thyroid Association.

Anaplastic thyroid cancer, though rare, is the most aggressive form of thyroid cancer. It accounts for just 1% of the cancers but causes about 50% of thyroid cancer mortality.

The historical median overall survival is 5-6 months.

With research in recent years showing that as many as 40% of anaplastic thyroid cancers harbor BRAF V600E mutations, the door has opened for potential benefits with the combination of the BRAF inhibitor dabrafenib with the MEK-inhibitor drug trametinib.

The treatment combination was shown in research that included the phase 2 ROAR trial to yield important responses. It was approved by the Food and Drug Administration in 2018 for locally advanced or metastatic BRAF V600E-mutant anaplastic thyroid cancer, as well as other cancers.

However, a key caveat of DT is that patients eventually develop resistance mutations, leading to disease progression.

To overcome the problem, Dr. Cabanillas and her team found two key strategies that show promise – the addition of immunotherapy, such as pembrolizumab to DT, and the use of a neoadjuvant approach, with surgery performed after an initial response to the triplet therapy.
 

Triple therapy showed highly favorable results

In a study presented at the 2022 ATA annual meeting, researchers reported on the triple therapy of BRAF/MEK inhibitors vemurafenib and cobimetinib plus immunotherapy with atezolizumab. Results were highly favorable, with an overall response rate of 72% and an impressive 2-year survival of 67%.

However, a major limitation was that the study lacked a control arm. In the current study, the addition of pembrolizumab to DT was compared with DT alone. The investigators also sought to determine the survival benefits of a neoadjuvant strategy.

For the study, first author Sarah Hamidi, MD, also of the MD Anderson Cancer Center, and her colleagues identified 94 patients with BRAF-mutated anaplastic thyroid cancer who were treated either with first‐line DT or DT plus pembrolizumab between 2014 and 2023, either outside of a trial or in a reported clinical trial.

The study compared three treatment regimens – DT alone (n = 23), DT with pembrolizumab added before or after disease progression (n = 48), and DT with neoadjuvant pembrolizumab added prior to or after surgery (n = 23).

There were no significant differences in baseline characteristics between the groups. Metastatic disease was present at the start of treatment among 87.0% of the DT group, 79.2% of the pembrolizumab group prior to or after disease progression, and 65.2% of the neoadjuvant pembrolizumab group.

The median follow-up of the three groups was 102 months, 28 months, and 42 months, respectively. The median overall survival was 9 months with DT alone, vs. 17 months with DT plus pembrolizumab before or after progression and 63 months with neoadjuvant pembrolizumab plus DT (P < .001).

The 12- and 24-month survival rates with DT alone were 33.7% and 28.9%, respectively; for DT plus pembrolizumab before or after progression, the rates were 60.2% and 36.5%; and for neoadjuvant pembrolizumab plus DT, the rates were 80.7% and 74.5%.

In an analysis that did not include the neoadjuvant group, median progression-free survival was significantly longer with DT plus pembrolizumab as an initial treatment (11.0 months) compared with DT alone (4.0 months; P  =  .049).

A subanalysis that evaluated the timing of the addition of pembrolizumab to DT before or after disease progression showed no significant differences between the two in median overall survival (17 months vs. 16 months; P = .554).

“This is valuable information, especially for centers where pembrolizumab cannot be easily obtained as a first-line therapy for anaplastic thyroid cancer,” Dr. Hamidi said in presenting the findings.

She noted, however, that the results should be interpreted with caution, given the small number of patients who received pembrolizumab before progression (n = 34) and especially after progression (n = 14).

In terms of safety, there were no grade 5 adverse events (AEs); 32.4% of patients experienced immune‐related AEs, most frequently, colitis and hepatitis.
 

Therapies “improve survival”

Overall, the results are important, Dr. Cabanillas said.

The results are “very exciting when you think about the fact that 10 years ago, patients with anaplastic thyroid cancer had a median overall survival measured in months, and now we see that those with a BRAF mutation have a real chance at survival when managed appropriately from the start,” she told this news organization.

She noted that a key caveat is the study’s retrospective nature. Other important considerations are that pembrolizumab adds toxicity as well as cost, and it is largely used off label in anaplastic thyroid cancer.

Nevertheless, “it does feel like there needs to be a call to action in the guidelines for this disease so that it includes neoadjuvant DT or DT plus pembrolizumab as the primary treatment of patients with BRAF-mutated anaplastic thyroid cancer because the initial treatment is critical here,” Dr. Cabanillas said.

She added that a phase 2 trial with neoadjuvant DT plus pembrolizumab is ongoing. Enrollment is expected to be completed soon.

Commenting on the findings, Sarimar Agosto Salgado, MD, of the department of head and neck – endocrine oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla., who was a comoderator of the session, said the results are encouraging.

“These findings are promising because they open the landscape of options of therapies that we can provide these patients,” she said in an interview.

“Anaplastic thyroid cancer has been a disease with a very short survival despite aggressive therapies, but we are seeing that not only have these therapies been able to improve survival but also patients’ quality of life.”

Particularly encouraging is how quickly the therapies can work, Dr. Salgado added.

“Many times when patients present to the clinic, the rapid response to these systemic therapies can even [allow them to avoid] having a tracheostomy, and we’re also seeing that some of these patients are able to go from unresectable disease to resectable disease, and then by having the main tumor out, their survival improves.

“So, this is definitely a big ray of hope for these patients.”

Dr. Cabanillas has received research funding from Merck. Dr. Hamidi has disclosed no relevant financial relationships. Dr. Salgado has relationships with Lilly and Exelixis.
 

A version of this article appeared on Medscape.com.