Heidi Splete

Some of the best clinical trials of patients with antineutrophil cytoplasmic antibody–associated vasculitis (AAV) that were presented at the 21st International Vasculitis Workshop in Barcelona, Spain, included studies addressing relapse after stopping steroids, preventing relapse with abatacept, improving kidney function with plasma exchange, and vaccinating rituximab-treated patients.
 

Stopping Steroids After Remission in GPA

In the randomized, open-label TAPIR (The Assessment of Prednisone In Remission Trial) study of 159 adults with GPA in remission who had tapered to a prednisone dose of 5 mg/day, those who remained at that dosage had a significantly lower rate of relapse after 6 months than those who tapered to 0 mg/day (4.2% vs 15.5%; P = .227), according to results reported at the meeting.

However, use of a higher dose of prednisone for disease relapse by 6 months was similar for patients who used rituximab at baseline (8.8% with 0 mg/day vs 6.1% with 5 mg/day; P = .667), and the difference in this primary outcome was more pronounced among patients who did not take rituximab at baseline (20.0% with 0 mg/day vs 2.6% with 5 mg/day; P = .023).

A higher percentage of patients taking prednisone 0 mg/day had disease relapses that were considered minor (14.1% and 4.2%; P = .0391). Major relapses occurred in none of the patients taking 5 mg/day and in 1.4% receiving 0 mg/day. About 90% of patients in either treatment arm completed the trial.

The study, funded by the National Institute of Arthritis and Musculoskelatal and Skin Diseases and the National Heart Lung and Blood Institute, was unique in that half of patients randomized in the study were enrolled at community clinics and half were enrolled at Vasculitis Clinical Research Consortium clinical centers.
 

Abatacept Falls Short for Preventing Relapse in GPA

Adding abatacept to glucocorticoids failed to reduce risk of relapse, worsening disease, or failure to reach remission in adults with relapsing, nonsevere GPA, based on data from a randomized trial of 65 individuals.

In the 20-site, randomized, double-blind ABROGATE (Abatacept for the Treatment of Relapsing, Non-Severe, Granulomatosis With Polyangiitis) study, 34 patients received 125 mg subcutaneous abatacept once a week or a placebo in addition to 30 mg/day of prednisone that was tapered and discontinued after 12 weeks. Patients who were receiving methotrexate, azathioprine, mycophenolate, or leflunomide at baseline continued the medication at a stable dose.

The primary outcome of disease worsening or relapse occurred in 62% of the abatacept group and 68% of the placebo group, and no significant difference in treatment failure rate appeared between the groups. In addition, key secondary endpoints of time to full remission, duration of glucocorticoid-free remission, relapse severity, prevention of damage, and patient-reported quality of life outcomes were not significantly different between the groups.

A total of 112 adverse events occurred, with similar type and severity between the groups, including incidence of infections.

The findings were limited by the relatively small sample size, but the results suggest a need for further research to determine mechanisms of disease and explore additional novel treatments for this rare patient population, the researchers wrote in their abstract.

The study was funded by the National Institutes of Health and Bristol-Myers Squibb.
 

Plasma Exchange Improves Kidney Function in AAV

Use of therapeutic plasma exchange (PLEX) as an adjunct treatment improved early kidney function in adults with AAV and glomerulonephritis but did not extend beyond 8 weeks, and recovery of kidney function was no different between patients receiving a regular glucocorticoid regimen versus a reduced course, based on a post-hoc analysis of 691 individuals in the international randomized controlled trial called PEXIVAS.

The primary outcomes of change in kidney function based on estimated glomerular filtration rate (eGFR) from baseline over 1 year and the percentage of patients with improvement in eGFR of at least 15 mL/min/1.73 m² at weeks 12, 26, and 52.

The rate of improved eGFR was significantly greater in the PLEX group, compared with controls, at 2, 4, and 8 weeks. At 4 weeks, significantly more patients in the PLEX group had an increase in eGFR by at least 15 mL/min/1.73 m², compared with the control group (relative risk [RR], 1.41; P = .008). In addition, improved kidney function within 4 weeks was significantly associated with lower risk of kidney failure within 1 year, regardless of treatment group.

The original PEXIVAS trial was supported by various government institutes and agencies from multiple countries.
 

Reinforced Vaccine Strategy with Rituximab Improved Antibody Response in AAV

A vaccine strategy consisting of a double dose of 13-valent antipneumococcal conjugate vaccine (PCV13) at day 0 and day 7 followed by a single dose of 23-valent unconjugated pneumococcal polysaccharide vaccine (PPV23) at 5 months significantly improved antibody responses against Streptococcus pneumoniae in patients with AAV, compared with standard treatment, based on data from 95 individuals in the multicenter, open-label study called PNEUMOVAS.

Adults with newly diagnosed AAV were randomly assigned to one of three treatment arms: a standard regimen of one dose of PCV13 at day 0 and one dose of PPV23 at month 5 (arm 1); a double dose of PCV13 at day 0 and day 7 with a dose of PPV23 at month 5 (arm 2); or four doses of PCV13 at day 0 and one dose of PPV23 at month 5 (arm 3). These patients received PCV13 within 2 days before or after their first infusion of rituximab.

The primary endpoint was positive antibody response against 12 pneumococcal subtypes common to the PCV13 and PCV23 vaccines at 6 months. At 6 months, the immune response to 0-3, 4-6, 7-9, or 10-12 serotypes was 83.3%, 13.3%, 3.3%, and 0%, respectively, in arm 1; 56.3%, 28.1%, 15.6%, and 0% in arm 2; and 60.6%, 33.3%, 6.1%, and 0% in arm 3.

No severe adverse events related to vaccination were observed in any of the groups; a total of eight AAV flares occurred in six patients (one in arm 1, two in arm 2, and three in arm 3). Local and systemic reactions occurred more frequently with the reinforced dose regimens, but these were mostly grade 1 or 2 local reactions.

The study was supported by the French Ministry of Health.

Some of the best clinical trials of patients with antineutrophil cytoplasmic antibody–associated vasculitis (AAV) that were presented at the 21st International Vasculitis Workshop in Barcelona, Spain, included studies addressing relapse after stopping steroids, preventing relapse with abatacept, improving kidney function with plasma exchange, and vaccinating rituximab-treated patients.
 

Stopping Steroids After Remission in GPA

In the randomized, open-label TAPIR (The Assessment of Prednisone In Remission Trial) study of 159 adults with GPA in remission who had tapered to a prednisone dose of 5 mg/day, those who remained at that dosage had a significantly lower rate of relapse after 6 months than those who tapered to 0 mg/day (4.2% vs 15.5%; P = .227), according to results reported at the meeting.

However, use of a higher dose of prednisone for disease relapse by 6 months was similar for patients who used rituximab at baseline (8.8% with 0 mg/day vs 6.1% with 5 mg/day; P = .667), and the difference in this primary outcome was more pronounced among patients who did not take rituximab at baseline (20.0% with 0 mg/day vs 2.6% with 5 mg/day; P = .023).

A higher percentage of patients taking prednisone 0 mg/day had disease relapses that were considered minor (14.1% and 4.2%; P = .0391). Major relapses occurred in none of the patients taking 5 mg/day and in 1.4% receiving 0 mg/day. About 90% of patients in either treatment arm completed the trial.

The study, funded by the National Institute of Arthritis and Musculoskelatal and Skin Diseases and the National Heart Lung and Blood Institute, was unique in that half of patients randomized in the study were enrolled at community clinics and half were enrolled at Vasculitis Clinical Research Consortium clinical centers.
 

Abatacept Falls Short for Preventing Relapse in GPA

Adding abatacept to glucocorticoids failed to reduce risk of relapse, worsening disease, or failure to reach remission in adults with relapsing, nonsevere GPA, based on data from a randomized trial of 65 individuals.

In the 20-site, randomized, double-blind ABROGATE (Abatacept for the Treatment of Relapsing, Non-Severe, Granulomatosis With Polyangiitis) study, 34 patients received 125 mg subcutaneous abatacept once a week or a placebo in addition to 30 mg/day of prednisone that was tapered and discontinued after 12 weeks. Patients who were receiving methotrexate, azathioprine, mycophenolate, or leflunomide at baseline continued the medication at a stable dose.

The primary outcome of disease worsening or relapse occurred in 62% of the abatacept group and 68% of the placebo group, and no significant difference in treatment failure rate appeared between the groups. In addition, key secondary endpoints of time to full remission, duration of glucocorticoid-free remission, relapse severity, prevention of damage, and patient-reported quality of life outcomes were not significantly different between the groups.

A total of 112 adverse events occurred, with similar type and severity between the groups, including incidence of infections.

The findings were limited by the relatively small sample size, but the results suggest a need for further research to determine mechanisms of disease and explore additional novel treatments for this rare patient population, the researchers wrote in their abstract.

The study was funded by the National Institutes of Health and Bristol-Myers Squibb.
 

Plasma Exchange Improves Kidney Function in AAV

Use of therapeutic plasma exchange (PLEX) as an adjunct treatment improved early kidney function in adults with AAV and glomerulonephritis but did not extend beyond 8 weeks, and recovery of kidney function was no different between patients receiving a regular glucocorticoid regimen versus a reduced course, based on a post-hoc analysis of 691 individuals in the international randomized controlled trial called PEXIVAS.

The primary outcomes of change in kidney function based on estimated glomerular filtration rate (eGFR) from baseline over 1 year and the percentage of patients with improvement in eGFR of at least 15 mL/min/1.73 m² at weeks 12, 26, and 52.

The rate of improved eGFR was significantly greater in the PLEX group, compared with controls, at 2, 4, and 8 weeks. At 4 weeks, significantly more patients in the PLEX group had an increase in eGFR by at least 15 mL/min/1.73 m², compared with the control group (relative risk [RR], 1.41; P = .008). In addition, improved kidney function within 4 weeks was significantly associated with lower risk of kidney failure within 1 year, regardless of treatment group.

The original PEXIVAS trial was supported by various government institutes and agencies from multiple countries.
 

Reinforced Vaccine Strategy with Rituximab Improved Antibody Response in AAV

A vaccine strategy consisting of a double dose of 13-valent antipneumococcal conjugate vaccine (PCV13) at day 0 and day 7 followed by a single dose of 23-valent unconjugated pneumococcal polysaccharide vaccine (PPV23) at 5 months significantly improved antibody responses against Streptococcus pneumoniae in patients with AAV, compared with standard treatment, based on data from 95 individuals in the multicenter, open-label study called PNEUMOVAS.

Adults with newly diagnosed AAV were randomly assigned to one of three treatment arms: a standard regimen of one dose of PCV13 at day 0 and one dose of PPV23 at month 5 (arm 1); a double dose of PCV13 at day 0 and day 7 with a dose of PPV23 at month 5 (arm 2); or four doses of PCV13 at day 0 and one dose of PPV23 at month 5 (arm 3). These patients received PCV13 within 2 days before or after their first infusion of rituximab.

The primary endpoint was positive antibody response against 12 pneumococcal subtypes common to the PCV13 and PCV23 vaccines at 6 months. At 6 months, the immune response to 0-3, 4-6, 7-9, or 10-12 serotypes was 83.3%, 13.3%, 3.3%, and 0%, respectively, in arm 1; 56.3%, 28.1%, 15.6%, and 0% in arm 2; and 60.6%, 33.3%, 6.1%, and 0% in arm 3.

No severe adverse events related to vaccination were observed in any of the groups; a total of eight AAV flares occurred in six patients (one in arm 1, two in arm 2, and three in arm 3). Local and systemic reactions occurred more frequently with the reinforced dose regimens, but these were mostly grade 1 or 2 local reactions.

The study was supported by the French Ministry of Health.

Some of the best clinical trials of patients with antineutrophil cytoplasmic antibody–associated vasculitis (AAV) that were presented at the 21st International Vasculitis Workshop in Barcelona, Spain, included studies addressing relapse after stopping steroids, preventing relapse with abatacept, improving kidney function with plasma exchange, and vaccinating rituximab-treated patients.
 

Stopping Steroids After Remission in GPA

In the randomized, open-label TAPIR (The Assessment of Prednisone In Remission Trial) study of 159 adults with GPA in remission who had tapered to a prednisone dose of 5 mg/day, those who remained at that dosage had a significantly lower rate of relapse after 6 months than those who tapered to 0 mg/day (4.2% vs 15.5%; P = .227), according to results reported at the meeting.

However, use of a higher dose of prednisone for disease relapse by 6 months was similar for patients who used rituximab at baseline (8.8% with 0 mg/day vs 6.1% with 5 mg/day; P = .667), and the difference in this primary outcome was more pronounced among patients who did not take rituximab at baseline (20.0% with 0 mg/day vs 2.6% with 5 mg/day; P = .023).

A higher percentage of patients taking prednisone 0 mg/day had disease relapses that were considered minor (14.1% and 4.2%; P = .0391). Major relapses occurred in none of the patients taking 5 mg/day and in 1.4% receiving 0 mg/day. About 90% of patients in either treatment arm completed the trial.

The study, funded by the National Institute of Arthritis and Musculoskelatal and Skin Diseases and the National Heart Lung and Blood Institute, was unique in that half of patients randomized in the study were enrolled at community clinics and half were enrolled at Vasculitis Clinical Research Consortium clinical centers.
 

Abatacept Falls Short for Preventing Relapse in GPA

Adding abatacept to glucocorticoids failed to reduce risk of relapse, worsening disease, or failure to reach remission in adults with relapsing, nonsevere GPA, based on data from a randomized trial of 65 individuals.

In the 20-site, randomized, double-blind ABROGATE (Abatacept for the Treatment of Relapsing, Non-Severe, Granulomatosis With Polyangiitis) study, 34 patients received 125 mg subcutaneous abatacept once a week or a placebo in addition to 30 mg/day of prednisone that was tapered and discontinued after 12 weeks. Patients who were receiving methotrexate, azathioprine, mycophenolate, or leflunomide at baseline continued the medication at a stable dose.

The primary outcome of disease worsening or relapse occurred in 62% of the abatacept group and 68% of the placebo group, and no significant difference in treatment failure rate appeared between the groups. In addition, key secondary endpoints of time to full remission, duration of glucocorticoid-free remission, relapse severity, prevention of damage, and patient-reported quality of life outcomes were not significantly different between the groups.

A total of 112 adverse events occurred, with similar type and severity between the groups, including incidence of infections.

The findings were limited by the relatively small sample size, but the results suggest a need for further research to determine mechanisms of disease and explore additional novel treatments for this rare patient population, the researchers wrote in their abstract.

The study was funded by the National Institutes of Health and Bristol-Myers Squibb.
 

Plasma Exchange Improves Kidney Function in AAV

Use of therapeutic plasma exchange (PLEX) as an adjunct treatment improved early kidney function in adults with AAV and glomerulonephritis but did not extend beyond 8 weeks, and recovery of kidney function was no different between patients receiving a regular glucocorticoid regimen versus a reduced course, based on a post-hoc analysis of 691 individuals in the international randomized controlled trial called PEXIVAS.

The primary outcomes of change in kidney function based on estimated glomerular filtration rate (eGFR) from baseline over 1 year and the percentage of patients with improvement in eGFR of at least 15 mL/min/1.73 m² at weeks 12, 26, and 52.

The rate of improved eGFR was significantly greater in the PLEX group, compared with controls, at 2, 4, and 8 weeks. At 4 weeks, significantly more patients in the PLEX group had an increase in eGFR by at least 15 mL/min/1.73 m², compared with the control group (relative risk [RR], 1.41; P = .008). In addition, improved kidney function within 4 weeks was significantly associated with lower risk of kidney failure within 1 year, regardless of treatment group.

The original PEXIVAS trial was supported by various government institutes and agencies from multiple countries.
 

Reinforced Vaccine Strategy with Rituximab Improved Antibody Response in AAV

A vaccine strategy consisting of a double dose of 13-valent antipneumococcal conjugate vaccine (PCV13) at day 0 and day 7 followed by a single dose of 23-valent unconjugated pneumococcal polysaccharide vaccine (PPV23) at 5 months significantly improved antibody responses against Streptococcus pneumoniae in patients with AAV, compared with standard treatment, based on data from 95 individuals in the multicenter, open-label study called PNEUMOVAS.

Adults with newly diagnosed AAV were randomly assigned to one of three treatment arms: a standard regimen of one dose of PCV13 at day 0 and one dose of PPV23 at month 5 (arm 1); a double dose of PCV13 at day 0 and day 7 with a dose of PPV23 at month 5 (arm 2); or four doses of PCV13 at day 0 and one dose of PPV23 at month 5 (arm 3). These patients received PCV13 within 2 days before or after their first infusion of rituximab.

The primary endpoint was positive antibody response against 12 pneumococcal subtypes common to the PCV13 and PCV23 vaccines at 6 months. At 6 months, the immune response to 0-3, 4-6, 7-9, or 10-12 serotypes was 83.3%, 13.3%, 3.3%, and 0%, respectively, in arm 1; 56.3%, 28.1%, 15.6%, and 0% in arm 2; and 60.6%, 33.3%, 6.1%, and 0% in arm 3.

No severe adverse events related to vaccination were observed in any of the groups; a total of eight AAV flares occurred in six patients (one in arm 1, two in arm 2, and three in arm 3). Local and systemic reactions occurred more frequently with the reinforced dose regimens, but these were mostly grade 1 or 2 local reactions.

The study was supported by the French Ministry of Health.

Medicare reimbursement for common breast cancer surgeries decreased significantly over the past two decades, and the resulting shortage of funds could affect quality of care and access to services, especially for vulnerable patient populations.

These were findings of new research presented by Terry P. Gao, MD, at the American Society of Breast Surgeons annual meeting.

Medicare reimbursements often set a benchmark that is followed by private insurers, and the impact of changes on various breast surgeries have not been examined, Dr. Gao, a research resident at Temple University Hospital, Philadelphia, said during a press briefing in advance of the meeting.

“This study is important because it is the first to analyze trends in Medicare reimbursement for breast cancer surgery over a long period,” Dr. Gao said during an interview. The findings highlight a critical issue that could impact access to quality care, especially for vulnerable populations, she said.
 

How Were the Data Analyzed?

Dr. Gao and colleagues reviewed percent changes in reimbursement procedures over a 20-year period and compared them to changes in the consumer price index (CPI) to show the real-life impact of inflation.

The study examined reimbursements based on the Medicare Physician Fee Schedule Look-Up Tool from 2003 to 2023 for 10 procedures. The procedures were core needle biopsy, open incisional breast biopsy, open excisional breast biopsy, lumpectomy, lumpectomy with axillary lymph node dissection (ALND), simple mastectomy, radical mastectomy, modified radical mastectomy, biopsy/removal of lymph nodes, and sentinel lymph node biopsy.
 

What Does the New Study Show?

“Reimbursements did not keep pace with the price of goods and services,” Dr. Gao said during the press briefing.

After the researchers corrected data for inflation, the overall mean Medicare reimbursement for breast cancer surgeries decreased by approximately 21%, based in part on the 69% increase in the CPI over the study period, Dr. Gao said. The greatest change was in core needle biopsy, for which reimbursement decreased by 36%.

After inflation adjustment, reimbursement increases were seen for only two procedures, lumpectomy and simple mastectomy, of 0.37% and 3.58%, respectively, but these do not represent meaningful gains, Dr. Gao said.

The researchers also used a model to estimate the real-life impact of decreased reimbursement on clinicians. They subtracted the actual 2023 compensation from expected 2023 compensation based on inflation for a breast cancer case incidence of 297,790 patients who underwent axillary surgery, breast lumpectomy, or simple mastectomy. The calculated potential real-world compensation loss for that year was $107,604,444.
 

What are the Clinical Implications? 

The current study is the first to put specific numbers on the trend in declining breast cancer payments, and the findings should encourage physicians to advocate for equitable policies, Dr. Gao noted during the briefing.

The substantial decrease in inflation-adjusted reimbursement rates was significant, she said during the interview. Although the decrease reflects similar trends seen in other specialties, the magnitude is a potential cause for concern, she said.

Declining reimbursements could disproportionately hurt safety-net hospitals serving vulnerable populations by limiting their ability to invest in better care and potentially worsening existing racial disparities, Dr. Gao told this publication. “Additionally, surgeons may opt out of Medicare networks due to low rates, leading to access issues and longer wait times. Finally, these trends could discourage future generations from specializing in breast cancer surgery.”

The study findings should be considered in the context of the complex and rapidly changing clinical landscape in which breast cancer care is evolving, Mediget Teshome, MD, chief of breast surgery at UCLA Health, said during an interview.

“Surgery remains a critically important aspect to curative treatment,” Dr. Teshome said.

Surgical decision-making tailored to each patient’s goals involves coordination from a multidisciplinary team as well as skill and attention from surgeons, she added.

“This degree of specialization and nuance is not always captured in reimbursement models for breast surgery,” Dr. Teshome emphasized. The policy implications of any changes in Medicare reimbursement will be important given the American Cancer Society reports breast cancer as the most commonly diagnosed cancer in women in the United States, and as the second leading cause of cancer death in US women, she noted.
 

What Additional Research Is Needed?

Research is needed to understand how declining reimbursements affect patients’ access to care, treatment choices, and long-term outcomes, Dr. Gao said in the interview. Future studies also are needed to examine provider overhead costs, staffing structures, and profit margins to offer a more comprehensive understanding of financial sustainability.

Dr. Gao and Dr. Teshome had no financial conflicts to disclose.

Medicare reimbursement for common breast cancer surgeries decreased significantly over the past two decades, and the resulting shortage of funds could affect quality of care and access to services, especially for vulnerable patient populations.

These were findings of new research presented by Terry P. Gao, MD, at the American Society of Breast Surgeons annual meeting.

Medicare reimbursements often set a benchmark that is followed by private insurers, and the impact of changes on various breast surgeries have not been examined, Dr. Gao, a research resident at Temple University Hospital, Philadelphia, said during a press briefing in advance of the meeting.

“This study is important because it is the first to analyze trends in Medicare reimbursement for breast cancer surgery over a long period,” Dr. Gao said during an interview. The findings highlight a critical issue that could impact access to quality care, especially for vulnerable populations, she said.
 

How Were the Data Analyzed?

Dr. Gao and colleagues reviewed percent changes in reimbursement procedures over a 20-year period and compared them to changes in the consumer price index (CPI) to show the real-life impact of inflation.

The study examined reimbursements based on the Medicare Physician Fee Schedule Look-Up Tool from 2003 to 2023 for 10 procedures. The procedures were core needle biopsy, open incisional breast biopsy, open excisional breast biopsy, lumpectomy, lumpectomy with axillary lymph node dissection (ALND), simple mastectomy, radical mastectomy, modified radical mastectomy, biopsy/removal of lymph nodes, and sentinel lymph node biopsy.
 

What Does the New Study Show?

“Reimbursements did not keep pace with the price of goods and services,” Dr. Gao said during the press briefing.

After the researchers corrected data for inflation, the overall mean Medicare reimbursement for breast cancer surgeries decreased by approximately 21%, based in part on the 69% increase in the CPI over the study period, Dr. Gao said. The greatest change was in core needle biopsy, for which reimbursement decreased by 36%.

After inflation adjustment, reimbursement increases were seen for only two procedures, lumpectomy and simple mastectomy, of 0.37% and 3.58%, respectively, but these do not represent meaningful gains, Dr. Gao said.

The researchers also used a model to estimate the real-life impact of decreased reimbursement on clinicians. They subtracted the actual 2023 compensation from expected 2023 compensation based on inflation for a breast cancer case incidence of 297,790 patients who underwent axillary surgery, breast lumpectomy, or simple mastectomy. The calculated potential real-world compensation loss for that year was $107,604,444.
 

What are the Clinical Implications? 

The current study is the first to put specific numbers on the trend in declining breast cancer payments, and the findings should encourage physicians to advocate for equitable policies, Dr. Gao noted during the briefing.

The substantial decrease in inflation-adjusted reimbursement rates was significant, she said during the interview. Although the decrease reflects similar trends seen in other specialties, the magnitude is a potential cause for concern, she said.

Declining reimbursements could disproportionately hurt safety-net hospitals serving vulnerable populations by limiting their ability to invest in better care and potentially worsening existing racial disparities, Dr. Gao told this publication. “Additionally, surgeons may opt out of Medicare networks due to low rates, leading to access issues and longer wait times. Finally, these trends could discourage future generations from specializing in breast cancer surgery.”

The study findings should be considered in the context of the complex and rapidly changing clinical landscape in which breast cancer care is evolving, Mediget Teshome, MD, chief of breast surgery at UCLA Health, said during an interview.

“Surgery remains a critically important aspect to curative treatment,” Dr. Teshome said.

Surgical decision-making tailored to each patient’s goals involves coordination from a multidisciplinary team as well as skill and attention from surgeons, she added.

“This degree of specialization and nuance is not always captured in reimbursement models for breast surgery,” Dr. Teshome emphasized. The policy implications of any changes in Medicare reimbursement will be important given the American Cancer Society reports breast cancer as the most commonly diagnosed cancer in women in the United States, and as the second leading cause of cancer death in US women, she noted.
 

What Additional Research Is Needed?

Research is needed to understand how declining reimbursements affect patients’ access to care, treatment choices, and long-term outcomes, Dr. Gao said in the interview. Future studies also are needed to examine provider overhead costs, staffing structures, and profit margins to offer a more comprehensive understanding of financial sustainability.

Dr. Gao and Dr. Teshome had no financial conflicts to disclose.

Medicare reimbursement for common breast cancer surgeries decreased significantly over the past two decades, and the resulting shortage of funds could affect quality of care and access to services, especially for vulnerable patient populations.

These were findings of new research presented by Terry P. Gao, MD, at the American Society of Breast Surgeons annual meeting.

Medicare reimbursements often set a benchmark that is followed by private insurers, and the impact of changes on various breast surgeries have not been examined, Dr. Gao, a research resident at Temple University Hospital, Philadelphia, said during a press briefing in advance of the meeting.

“This study is important because it is the first to analyze trends in Medicare reimbursement for breast cancer surgery over a long period,” Dr. Gao said during an interview. The findings highlight a critical issue that could impact access to quality care, especially for vulnerable populations, she said.
 

How Were the Data Analyzed?

Dr. Gao and colleagues reviewed percent changes in reimbursement procedures over a 20-year period and compared them to changes in the consumer price index (CPI) to show the real-life impact of inflation.

The study examined reimbursements based on the Medicare Physician Fee Schedule Look-Up Tool from 2003 to 2023 for 10 procedures. The procedures were core needle biopsy, open incisional breast biopsy, open excisional breast biopsy, lumpectomy, lumpectomy with axillary lymph node dissection (ALND), simple mastectomy, radical mastectomy, modified radical mastectomy, biopsy/removal of lymph nodes, and sentinel lymph node biopsy.
 

What Does the New Study Show?

“Reimbursements did not keep pace with the price of goods and services,” Dr. Gao said during the press briefing.

After the researchers corrected data for inflation, the overall mean Medicare reimbursement for breast cancer surgeries decreased by approximately 21%, based in part on the 69% increase in the CPI over the study period, Dr. Gao said. The greatest change was in core needle biopsy, for which reimbursement decreased by 36%.

After inflation adjustment, reimbursement increases were seen for only two procedures, lumpectomy and simple mastectomy, of 0.37% and 3.58%, respectively, but these do not represent meaningful gains, Dr. Gao said.

The researchers also used a model to estimate the real-life impact of decreased reimbursement on clinicians. They subtracted the actual 2023 compensation from expected 2023 compensation based on inflation for a breast cancer case incidence of 297,790 patients who underwent axillary surgery, breast lumpectomy, or simple mastectomy. The calculated potential real-world compensation loss for that year was $107,604,444.
 

What are the Clinical Implications? 

The current study is the first to put specific numbers on the trend in declining breast cancer payments, and the findings should encourage physicians to advocate for equitable policies, Dr. Gao noted during the briefing.

The substantial decrease in inflation-adjusted reimbursement rates was significant, she said during the interview. Although the decrease reflects similar trends seen in other specialties, the magnitude is a potential cause for concern, she said.

Declining reimbursements could disproportionately hurt safety-net hospitals serving vulnerable populations by limiting their ability to invest in better care and potentially worsening existing racial disparities, Dr. Gao told this publication. “Additionally, surgeons may opt out of Medicare networks due to low rates, leading to access issues and longer wait times. Finally, these trends could discourage future generations from specializing in breast cancer surgery.”

The study findings should be considered in the context of the complex and rapidly changing clinical landscape in which breast cancer care is evolving, Mediget Teshome, MD, chief of breast surgery at UCLA Health, said during an interview.

“Surgery remains a critically important aspect to curative treatment,” Dr. Teshome said.

Surgical decision-making tailored to each patient’s goals involves coordination from a multidisciplinary team as well as skill and attention from surgeons, she added.

“This degree of specialization and nuance is not always captured in reimbursement models for breast surgery,” Dr. Teshome emphasized. The policy implications of any changes in Medicare reimbursement will be important given the American Cancer Society reports breast cancer as the most commonly diagnosed cancer in women in the United States, and as the second leading cause of cancer death in US women, she noted.
 

What Additional Research Is Needed?

Research is needed to understand how declining reimbursements affect patients’ access to care, treatment choices, and long-term outcomes, Dr. Gao said in the interview. Future studies also are needed to examine provider overhead costs, staffing structures, and profit margins to offer a more comprehensive understanding of financial sustainability.

Dr. Gao and Dr. Teshome had no financial conflicts to disclose.

Ultrasound for assessing lymph nodal involvement may be substituted for sentinel lymph node biopsy with no change in outcomes in patients with early breast cancer, a new study finds.

This was the conclusion of research on the agenda at the American Society of Breast Surgeons annual meeting.

Sentinel lymph node biopsy (SLNB) is the standard of care for individuals with early-stage HR+HER2- breast cancer to assess nodal involvement, but SLNB can bring complications including postoperative arm problems and lasting lymphedema, according to Andreas Giannakou, MD, of Brigham and Women’s Hospital and the Dana-Farber Cancer Institute, Boston, the presenter of this new research.

The SOUND (Sentinel Node vs. Observation After Axillary Ultra-Sound) trial, published in JAMA Oncology in 2023, showed that ultrasound nodal imaging was a safe and effective alternative to SLNB in certain patients with early-stage breast cancers, but real-world validation was needed, Dr. Giannakou said during a press briefing in advance of the meeting.

Why Was the SOUND Trial Important?

The SOUND trial randomized 1,463 individuals with early stage (cT1NO) breast cancer (tumors less than 2 cm) and negative findings on axillary ultrasound to either SLNB or no axillary surgical staging.

The 5-year rate of distant disease-free survival was 97.7% in the SLNB group vs. 98% in the no axillary surgery group, suggesting that omission of staging was noninferior to SLNB in these patients and a safe and effective option.

In current practice, nodal status remains a key factor in decision-making for adjuvant systemic therapy in premenopausal patients and in patients with HER2+ and triple-negative breast cancer, Dr. Giannakou said during the press briefing.

“The SOUND trial is a potentially practice-changing study that can spare a specific patient population from axillary surgical staging,” Dr. Giannakou said in an interview. “Before broadly applying clinical trial results to practice, it is important to ensure that the trial population is representative of the population being treated in real world practice,” he said.

What Did the New Study Show? 

In the new study, the researchers identified 312 patients meeting the SOUND trial eligibility criteria in a large database from a single center, and compared disease characteristics and outcomes with the 708 patients in the SLNB arm of the SOUND trial.

The researchers found a similarly high rate of negative SLNB results and very low recurrence in the study population. Notably, only 11.3% of the patients in the current study and 13.1% of patients in the SOUND trial had 1-3 positive lymph nodes, and less than 1% of patients in both cohorts had 4 or more positive nodes, Dr. Giannakou said.

The population of the current study was similar to that of the SOUND trial population with respect to treatment characteristics and nodal disease burden,” Dr. Giannakou said during the interview. These findings suggest that omission of sentinel lymph node in the new study cohort would have also likely been oncologically safe.

“These results are confirmatory but not surprising,” he said. Previous studies have shown that the sensitivity and accuracy of axillary ultrasound is comparable to the sentinel lymph node biopsy in patients with early breast cancer and only one abnormal lymph node on the ultrasound. 
 

What Are the Clinical Implications?

The current study findings make an important contribution to the effort to de-escalate axillary surgery in early breast cancer, Dr. Giannakou said during the interview. Although SLNB is less morbid than axillary lymph node dissection, the lymphedema risk still exists, and identifying which patients actually benefit from SLNB is critical, he said.

“In our multidisciplinary team, we are working to define selection criteria for postmenopausal patients with HR+HER2- breast cancer who would have met eligibility criteria for the SOUND trial and for whom omission of SLNB would not change adjuvant treatment considerations,” he said.

“Breast surgeons have been moving towards less aggressive axillary surgery based on evidence showing its safety in specific patient cohorts, particularly those with low-risk factors such as older age (70 years and above) and early-stage hormone receptor-positive breast cancer,” Sarah Blair, MD, professor and vice chair in the department of surgery at UC San Diego Health, said in an interview.

“The Choosing Wisely recommendations, issued by the Society of Surgical Oncology, advise against routine use of sentinel lymph node biopsy in women aged 70 and older with early-stage hormone receptor–positive breast cancer; these recommendations are based on clinical trials demonstrating oncologic safety in this population,” said Dr. Blair, who was not involved in the SOUND trial or the current study.

The data from the new study are encouraging and highlight the generalizability of the SOUND results, Mediget Teshome, MD, chief of breast surgery at UCLA Health, said in an interview. The results help to define a low-risk group of patients for which sentinel node staging may be omitted, after multidisciplinary discussion to ensure that nodal staging will not impact adjuvant systemic therapy or radiation decision-making, said Dr. Teshome, who was not involved in the SOUND trial or the current study.
 

What Are the Limitations of the SOUND trial and the New Study?

The current study limitations included its design having been a retrospective review of a prospective database with selection bias, lack of standard criteria for preoperative axillary ultrasound, and the lack of SLNB for many patients older than 70 years based on the Choosing Wisely criteria, Dr. Giannakou said in the press briefing.

“Despite the evidence supporting axillary surgery de-escalation, it can be challenging for surgeons to change their practice based on a single study,” Dr. Blair said an interview. However, the SOUND trial findings support current evidence, giving surgeons more confidence to discuss multidisciplinary treatment options, she said.
 

What Additional Research is Needed?

“Longer follow-up is needed to make definitive conclusions about the oncologic outcomes of axillary surgery de-escalation in this patient population,” said Dr. Blair. “Given that slow-growing tumors are involved, the time to recurrence may extend beyond the typical follow-up period of three years.

“Ongoing research and collaboration among multidisciplinary teams are essential to ensure optimal treatment decisions and patient outcomes,” she emphasized.

Dr. Giannakou, Dr. Blair, and Dr. Teshome had no financial conflicts to disclose.

Ultrasound for assessing lymph nodal involvement may be substituted for sentinel lymph node biopsy with no change in outcomes in patients with early breast cancer, a new study finds.

This was the conclusion of research on the agenda at the American Society of Breast Surgeons annual meeting.

Sentinel lymph node biopsy (SLNB) is the standard of care for individuals with early-stage HR+HER2- breast cancer to assess nodal involvement, but SLNB can bring complications including postoperative arm problems and lasting lymphedema, according to Andreas Giannakou, MD, of Brigham and Women’s Hospital and the Dana-Farber Cancer Institute, Boston, the presenter of this new research.

The SOUND (Sentinel Node vs. Observation After Axillary Ultra-Sound) trial, published in JAMA Oncology in 2023, showed that ultrasound nodal imaging was a safe and effective alternative to SLNB in certain patients with early-stage breast cancers, but real-world validation was needed, Dr. Giannakou said during a press briefing in advance of the meeting.

Why Was the SOUND Trial Important?

The SOUND trial randomized 1,463 individuals with early stage (cT1NO) breast cancer (tumors less than 2 cm) and negative findings on axillary ultrasound to either SLNB or no axillary surgical staging.

The 5-year rate of distant disease-free survival was 97.7% in the SLNB group vs. 98% in the no axillary surgery group, suggesting that omission of staging was noninferior to SLNB in these patients and a safe and effective option.

In current practice, nodal status remains a key factor in decision-making for adjuvant systemic therapy in premenopausal patients and in patients with HER2+ and triple-negative breast cancer, Dr. Giannakou said during the press briefing.

“The SOUND trial is a potentially practice-changing study that can spare a specific patient population from axillary surgical staging,” Dr. Giannakou said in an interview. “Before broadly applying clinical trial results to practice, it is important to ensure that the trial population is representative of the population being treated in real world practice,” he said.

What Did the New Study Show? 

In the new study, the researchers identified 312 patients meeting the SOUND trial eligibility criteria in a large database from a single center, and compared disease characteristics and outcomes with the 708 patients in the SLNB arm of the SOUND trial.

The researchers found a similarly high rate of negative SLNB results and very low recurrence in the study population. Notably, only 11.3% of the patients in the current study and 13.1% of patients in the SOUND trial had 1-3 positive lymph nodes, and less than 1% of patients in both cohorts had 4 or more positive nodes, Dr. Giannakou said.

The population of the current study was similar to that of the SOUND trial population with respect to treatment characteristics and nodal disease burden,” Dr. Giannakou said during the interview. These findings suggest that omission of sentinel lymph node in the new study cohort would have also likely been oncologically safe.

“These results are confirmatory but not surprising,” he said. Previous studies have shown that the sensitivity and accuracy of axillary ultrasound is comparable to the sentinel lymph node biopsy in patients with early breast cancer and only one abnormal lymph node on the ultrasound. 
 

What Are the Clinical Implications?

The current study findings make an important contribution to the effort to de-escalate axillary surgery in early breast cancer, Dr. Giannakou said during the interview. Although SLNB is less morbid than axillary lymph node dissection, the lymphedema risk still exists, and identifying which patients actually benefit from SLNB is critical, he said.

“In our multidisciplinary team, we are working to define selection criteria for postmenopausal patients with HR+HER2- breast cancer who would have met eligibility criteria for the SOUND trial and for whom omission of SLNB would not change adjuvant treatment considerations,” he said.

“Breast surgeons have been moving towards less aggressive axillary surgery based on evidence showing its safety in specific patient cohorts, particularly those with low-risk factors such as older age (70 years and above) and early-stage hormone receptor-positive breast cancer,” Sarah Blair, MD, professor and vice chair in the department of surgery at UC San Diego Health, said in an interview.

“The Choosing Wisely recommendations, issued by the Society of Surgical Oncology, advise against routine use of sentinel lymph node biopsy in women aged 70 and older with early-stage hormone receptor–positive breast cancer; these recommendations are based on clinical trials demonstrating oncologic safety in this population,” said Dr. Blair, who was not involved in the SOUND trial or the current study.

The data from the new study are encouraging and highlight the generalizability of the SOUND results, Mediget Teshome, MD, chief of breast surgery at UCLA Health, said in an interview. The results help to define a low-risk group of patients for which sentinel node staging may be omitted, after multidisciplinary discussion to ensure that nodal staging will not impact adjuvant systemic therapy or radiation decision-making, said Dr. Teshome, who was not involved in the SOUND trial or the current study.
 

What Are the Limitations of the SOUND trial and the New Study?

The current study limitations included its design having been a retrospective review of a prospective database with selection bias, lack of standard criteria for preoperative axillary ultrasound, and the lack of SLNB for many patients older than 70 years based on the Choosing Wisely criteria, Dr. Giannakou said in the press briefing.

“Despite the evidence supporting axillary surgery de-escalation, it can be challenging for surgeons to change their practice based on a single study,” Dr. Blair said an interview. However, the SOUND trial findings support current evidence, giving surgeons more confidence to discuss multidisciplinary treatment options, she said.
 

What Additional Research is Needed?

“Longer follow-up is needed to make definitive conclusions about the oncologic outcomes of axillary surgery de-escalation in this patient population,” said Dr. Blair. “Given that slow-growing tumors are involved, the time to recurrence may extend beyond the typical follow-up period of three years.

“Ongoing research and collaboration among multidisciplinary teams are essential to ensure optimal treatment decisions and patient outcomes,” she emphasized.

Dr. Giannakou, Dr. Blair, and Dr. Teshome had no financial conflicts to disclose.

Ultrasound for assessing lymph nodal involvement may be substituted for sentinel lymph node biopsy with no change in outcomes in patients with early breast cancer, a new study finds.

This was the conclusion of research on the agenda at the American Society of Breast Surgeons annual meeting.

Sentinel lymph node biopsy (SLNB) is the standard of care for individuals with early-stage HR+HER2- breast cancer to assess nodal involvement, but SLNB can bring complications including postoperative arm problems and lasting lymphedema, according to Andreas Giannakou, MD, of Brigham and Women’s Hospital and the Dana-Farber Cancer Institute, Boston, the presenter of this new research.

The SOUND (Sentinel Node vs. Observation After Axillary Ultra-Sound) trial, published in JAMA Oncology in 2023, showed that ultrasound nodal imaging was a safe and effective alternative to SLNB in certain patients with early-stage breast cancers, but real-world validation was needed, Dr. Giannakou said during a press briefing in advance of the meeting.

Why Was the SOUND Trial Important?

The SOUND trial randomized 1,463 individuals with early stage (cT1NO) breast cancer (tumors less than 2 cm) and negative findings on axillary ultrasound to either SLNB or no axillary surgical staging.

The 5-year rate of distant disease-free survival was 97.7% in the SLNB group vs. 98% in the no axillary surgery group, suggesting that omission of staging was noninferior to SLNB in these patients and a safe and effective option.

In current practice, nodal status remains a key factor in decision-making for adjuvant systemic therapy in premenopausal patients and in patients with HER2+ and triple-negative breast cancer, Dr. Giannakou said during the press briefing.

“The SOUND trial is a potentially practice-changing study that can spare a specific patient population from axillary surgical staging,” Dr. Giannakou said in an interview. “Before broadly applying clinical trial results to practice, it is important to ensure that the trial population is representative of the population being treated in real world practice,” he said.

What Did the New Study Show? 

In the new study, the researchers identified 312 patients meeting the SOUND trial eligibility criteria in a large database from a single center, and compared disease characteristics and outcomes with the 708 patients in the SLNB arm of the SOUND trial.

The researchers found a similarly high rate of negative SLNB results and very low recurrence in the study population. Notably, only 11.3% of the patients in the current study and 13.1% of patients in the SOUND trial had 1-3 positive lymph nodes, and less than 1% of patients in both cohorts had 4 or more positive nodes, Dr. Giannakou said.

The population of the current study was similar to that of the SOUND trial population with respect to treatment characteristics and nodal disease burden,” Dr. Giannakou said during the interview. These findings suggest that omission of sentinel lymph node in the new study cohort would have also likely been oncologically safe.

“These results are confirmatory but not surprising,” he said. Previous studies have shown that the sensitivity and accuracy of axillary ultrasound is comparable to the sentinel lymph node biopsy in patients with early breast cancer and only one abnormal lymph node on the ultrasound. 
 

What Are the Clinical Implications?

The current study findings make an important contribution to the effort to de-escalate axillary surgery in early breast cancer, Dr. Giannakou said during the interview. Although SLNB is less morbid than axillary lymph node dissection, the lymphedema risk still exists, and identifying which patients actually benefit from SLNB is critical, he said.

“In our multidisciplinary team, we are working to define selection criteria for postmenopausal patients with HR+HER2- breast cancer who would have met eligibility criteria for the SOUND trial and for whom omission of SLNB would not change adjuvant treatment considerations,” he said.

“Breast surgeons have been moving towards less aggressive axillary surgery based on evidence showing its safety in specific patient cohorts, particularly those with low-risk factors such as older age (70 years and above) and early-stage hormone receptor-positive breast cancer,” Sarah Blair, MD, professor and vice chair in the department of surgery at UC San Diego Health, said in an interview.

“The Choosing Wisely recommendations, issued by the Society of Surgical Oncology, advise against routine use of sentinel lymph node biopsy in women aged 70 and older with early-stage hormone receptor–positive breast cancer; these recommendations are based on clinical trials demonstrating oncologic safety in this population,” said Dr. Blair, who was not involved in the SOUND trial or the current study.

The data from the new study are encouraging and highlight the generalizability of the SOUND results, Mediget Teshome, MD, chief of breast surgery at UCLA Health, said in an interview. The results help to define a low-risk group of patients for which sentinel node staging may be omitted, after multidisciplinary discussion to ensure that nodal staging will not impact adjuvant systemic therapy or radiation decision-making, said Dr. Teshome, who was not involved in the SOUND trial or the current study.
 

What Are the Limitations of the SOUND trial and the New Study?

The current study limitations included its design having been a retrospective review of a prospective database with selection bias, lack of standard criteria for preoperative axillary ultrasound, and the lack of SLNB for many patients older than 70 years based on the Choosing Wisely criteria, Dr. Giannakou said in the press briefing.

“Despite the evidence supporting axillary surgery de-escalation, it can be challenging for surgeons to change their practice based on a single study,” Dr. Blair said an interview. However, the SOUND trial findings support current evidence, giving surgeons more confidence to discuss multidisciplinary treatment options, she said.
 

What Additional Research is Needed?

“Longer follow-up is needed to make definitive conclusions about the oncologic outcomes of axillary surgery de-escalation in this patient population,” said Dr. Blair. “Given that slow-growing tumors are involved, the time to recurrence may extend beyond the typical follow-up period of three years.

“Ongoing research and collaboration among multidisciplinary teams are essential to ensure optimal treatment decisions and patient outcomes,” she emphasized.

Dr. Giannakou, Dr. Blair, and Dr. Teshome had no financial conflicts to disclose.

High levels of tumor-infiltrating lymphocytes predicted increased survival in patients with early-stage triple-negative breast cancer who did not receive chemotherapy, a new analysis finds.

The association of abundant tumor-infiltrating lymphocytes (TILs) in breast cancer tissue with outcomes in patients with early-stage triple-negative breast cancer (TNBC) who do not receive chemotherapy has not been well studied, wrote Roberto A. Leon-Ferre, MD, of the Mayo Clinic, Rochester, Minnesota, and colleagues, in JAMA.

Biomarkers to guide systemic treatment and avoid overtreatment are lacking, and such markers could help identify patients who could achieve increased survival with less intensive therapy, continued the authors of the new study of nearly 2000 individuals.

“TNBC is the most aggressive subtype of breast cancer, and for this reason, current treatment guidelines recommend chemotherapy using multiple drugs either before or after surgery,” Dr. Leon-Ferre said in an interview. “We have learned over the last several years that TNBC is not a single disease, but that there are several subtypes of TNBC that have different risks and different vulnerabilities, and treating all patients similarly may not be optimal.”

  

What is Known About Tumor-Infiltrating Lymphocytes and Cancer?

Previous studies have shown improved survival in patients with early-stage TNBC and high levels of TILs who were treated with adjuvant and neoadjuvant chemotherapy, compared with those with lower TILs. In a pooled analysis of 2148 patients from nine studies published in the Journal of Clinical Oncology in 2019, a higher percentage of TILs in the stroma surrounding a tumor was significantly associated with improved survival in TNBC patients after adjuvant chemotherapy.

Another study published in the Journal of Clinical Oncology in 2022 showed that elevated TILs were significant predictors of overall survival, but the study included fewer than 500 patients.

The potential mechanisms that drive the association between elevated TILs and improved survival include the ability of TILs to attack cancer cells, Dr. Leon-Ferre said in an interview. 

The goal of this study was to evaluate whether TILs could identify a subset of patients with TNBC who had a very low risk of cancer recurrence even if chemotherapy was not given.

“Indeed, we found that patients with stage I TNBC and high TILs had a very low risk of recurrence even when chemotherapy was not administered. These findings will pave the way for future studies aiming to reduce the need for multiple chemotherapy drugs in patients with stage I TNBC and decrease the side effects that patients face,” he said.

 

What Does the New Study Add?

The current study included 1966 individuals from 13 sites in North America, Europe, and Asia who were diagnosed with TNBC between 1979 and 2017 and were treated with surgery, with or without radiotherapy but with no adjuvant or neoadjuvant chemotherapy. The researchers examined the abundance of TILs in the breast tissue of resected primary tumors; the primary outcome was invasive disease-free survival (iDFS), with recurrence-free survival, distant recurrence-free survival, and overall survival as secondary outcomes.

The median age of the patients was 56 years, 55% had stage I TNBC, and the median TIL level was 15%.

A total of 417 patients had a TIL level of 50% or more, and the 5-year iDFS for these patients was 94%, compared with 78% for those with a TIL level less than 30%. Similarly, 5-year overall survival was 95% in patients with a TIL level of 50% or more, compared with 82% for patients with TIL levels of less than 30%.

Additionally, each 10% increase in TILs was independently associated not only with improved iDFS (hazard ratio[HR], 0.92), but also improved recurrence-free survival (HR, 0.90), distant recurrence-free survival (HR, 0.87), and overall survival (HR, 0.88) over a median follow-up of 18 years.

The current study shows that cancer stage based on tumor size and the number of lymph nodes should not be the only considerations for making treatment decisions and predicting outcomes, Dr. Leon-Ferre said in an interview.

“In fact, our study shows that for tumors of the same stage (particularly for stage I), the risk of recurrence is different depending on the number of TILs seen in the breast cancer tissue. When chemo is not given, those with high TILs have lower risk of recurrence, whereas those with low TILs have a higher risk of recurrence,” he said.
 

What are the Limitations of This Research?

The current study findings are limited by the retrospective design and use of observational data, so the researchers could not make conclusions about causality. Other limitations included lack of data on germline mutations and race or ethnicity, and the potential irrelevance of data from patients treated as long as 45 years ago.

“Because most patients with TNBC receive chemotherapy in the modern times, we needed to work with 13 hospitals around the world to find data on patients with TNBC who never received chemotherapy for various reasons,” Dr. Leon-Ferre said.

To address these limitations, Dr. Leone-Ferre and his colleagues are planning prospective studies where TILs will be used to make treatment decisions.

“Many of the patients in our cohort were treated many years ago, when chemotherapy was not routinely given. Advances in cancer detection, surgical and radiation techniques may lead to different results in patients treated today,” he added.

What Do Oncologists Need to Know?

The current study findings may provide additional information on prognosis that is important to share with patients for decision-making on the risks versus benefits of chemotherapy, Dr. Leon-Ferre said.

“Like any test, TILs should not be used in isolation to make decisions, but should be integrated with other factors including the cancer stage, the overall patient health, patient preferences, and concerns about treatment complications,” he emphasized. “The results of this study allow oncologists to offer a more refined calculation of recurrence risk if patients opt to not receive chemotherapy.”

In the current study, although younger age was associated with higher TIL levels, a finding consistent with previous studies, increased TIL, remained significantly associated with improved survival after adjusting for age, tumor size, nodal status, and histological grade.

Overall, “the findings suggest that for patients with stage I TNBC and TILs greater than 50%, chemotherapy may not be as necessary as it was previously thought,” Dr. Leon-Ferre said.

What Additional Research is Needed?

Prospective studies are needed to validate the findings, including studies in diverse populations, and additional studies may investigate whether early TBNC patients with high TIL levels could achieve high cure rates with less intensive and less toxic chemotherapy regiments than those currently recommended, the researchers wrote in their discussion.

“There are many additional research questions that we need to answer, and look forward to working on,” Dr. Leon-Ferre said, in an interview. These topics include whether TILs can be used to decide on the number of chemotherapy drugs a patient really needs and whether artificial intelligence can be used to evaluate TILs more quickly and effectively than the human eye, he said. Other research topics include identifying which particular type of TILs attack cancer cells most effectively and whether TILs could be increased in patients with low levels in order to improve their prognosis, he added.

The study was supported by the National Research Agency and General Secretariat for Investment, Clinical and Translational Science Awards, the Mayo Clinic Breast Cancer SPORE grant, the Cancer Research Society of Canada, institutional grants from the Dutch Cancer Society, The Netherlands Organization for Health Research, and several foundations. Dr. Leon-Ferre disclosed consulting honoraria to his institution for research activities from AstraZeneca, Gilead Sciences, and Lyell Immunopharma, with no personal fees outside the submitted work.

High levels of tumor-infiltrating lymphocytes predicted increased survival in patients with early-stage triple-negative breast cancer who did not receive chemotherapy, a new analysis finds.

The association of abundant tumor-infiltrating lymphocytes (TILs) in breast cancer tissue with outcomes in patients with early-stage triple-negative breast cancer (TNBC) who do not receive chemotherapy has not been well studied, wrote Roberto A. Leon-Ferre, MD, of the Mayo Clinic, Rochester, Minnesota, and colleagues, in JAMA.

Biomarkers to guide systemic treatment and avoid overtreatment are lacking, and such markers could help identify patients who could achieve increased survival with less intensive therapy, continued the authors of the new study of nearly 2000 individuals.

“TNBC is the most aggressive subtype of breast cancer, and for this reason, current treatment guidelines recommend chemotherapy using multiple drugs either before or after surgery,” Dr. Leon-Ferre said in an interview. “We have learned over the last several years that TNBC is not a single disease, but that there are several subtypes of TNBC that have different risks and different vulnerabilities, and treating all patients similarly may not be optimal.”

  

What is Known About Tumor-Infiltrating Lymphocytes and Cancer?

Previous studies have shown improved survival in patients with early-stage TNBC and high levels of TILs who were treated with adjuvant and neoadjuvant chemotherapy, compared with those with lower TILs. In a pooled analysis of 2148 patients from nine studies published in the Journal of Clinical Oncology in 2019, a higher percentage of TILs in the stroma surrounding a tumor was significantly associated with improved survival in TNBC patients after adjuvant chemotherapy.

Another study published in the Journal of Clinical Oncology in 2022 showed that elevated TILs were significant predictors of overall survival, but the study included fewer than 500 patients.

The potential mechanisms that drive the association between elevated TILs and improved survival include the ability of TILs to attack cancer cells, Dr. Leon-Ferre said in an interview. 

The goal of this study was to evaluate whether TILs could identify a subset of patients with TNBC who had a very low risk of cancer recurrence even if chemotherapy was not given.

“Indeed, we found that patients with stage I TNBC and high TILs had a very low risk of recurrence even when chemotherapy was not administered. These findings will pave the way for future studies aiming to reduce the need for multiple chemotherapy drugs in patients with stage I TNBC and decrease the side effects that patients face,” he said.

 

What Does the New Study Add?

The current study included 1966 individuals from 13 sites in North America, Europe, and Asia who were diagnosed with TNBC between 1979 and 2017 and were treated with surgery, with or without radiotherapy but with no adjuvant or neoadjuvant chemotherapy. The researchers examined the abundance of TILs in the breast tissue of resected primary tumors; the primary outcome was invasive disease-free survival (iDFS), with recurrence-free survival, distant recurrence-free survival, and overall survival as secondary outcomes.

The median age of the patients was 56 years, 55% had stage I TNBC, and the median TIL level was 15%.

A total of 417 patients had a TIL level of 50% or more, and the 5-year iDFS for these patients was 94%, compared with 78% for those with a TIL level less than 30%. Similarly, 5-year overall survival was 95% in patients with a TIL level of 50% or more, compared with 82% for patients with TIL levels of less than 30%.

Additionally, each 10% increase in TILs was independently associated not only with improved iDFS (hazard ratio[HR], 0.92), but also improved recurrence-free survival (HR, 0.90), distant recurrence-free survival (HR, 0.87), and overall survival (HR, 0.88) over a median follow-up of 18 years.

The current study shows that cancer stage based on tumor size and the number of lymph nodes should not be the only considerations for making treatment decisions and predicting outcomes, Dr. Leon-Ferre said in an interview.

“In fact, our study shows that for tumors of the same stage (particularly for stage I), the risk of recurrence is different depending on the number of TILs seen in the breast cancer tissue. When chemo is not given, those with high TILs have lower risk of recurrence, whereas those with low TILs have a higher risk of recurrence,” he said.
 

What are the Limitations of This Research?

The current study findings are limited by the retrospective design and use of observational data, so the researchers could not make conclusions about causality. Other limitations included lack of data on germline mutations and race or ethnicity, and the potential irrelevance of data from patients treated as long as 45 years ago.

“Because most patients with TNBC receive chemotherapy in the modern times, we needed to work with 13 hospitals around the world to find data on patients with TNBC who never received chemotherapy for various reasons,” Dr. Leon-Ferre said.

To address these limitations, Dr. Leone-Ferre and his colleagues are planning prospective studies where TILs will be used to make treatment decisions.

“Many of the patients in our cohort were treated many years ago, when chemotherapy was not routinely given. Advances in cancer detection, surgical and radiation techniques may lead to different results in patients treated today,” he added.

What Do Oncologists Need to Know?

The current study findings may provide additional information on prognosis that is important to share with patients for decision-making on the risks versus benefits of chemotherapy, Dr. Leon-Ferre said.

“Like any test, TILs should not be used in isolation to make decisions, but should be integrated with other factors including the cancer stage, the overall patient health, patient preferences, and concerns about treatment complications,” he emphasized. “The results of this study allow oncologists to offer a more refined calculation of recurrence risk if patients opt to not receive chemotherapy.”

In the current study, although younger age was associated with higher TIL levels, a finding consistent with previous studies, increased TIL, remained significantly associated with improved survival after adjusting for age, tumor size, nodal status, and histological grade.

Overall, “the findings suggest that for patients with stage I TNBC and TILs greater than 50%, chemotherapy may not be as necessary as it was previously thought,” Dr. Leon-Ferre said.

What Additional Research is Needed?

Prospective studies are needed to validate the findings, including studies in diverse populations, and additional studies may investigate whether early TBNC patients with high TIL levels could achieve high cure rates with less intensive and less toxic chemotherapy regiments than those currently recommended, the researchers wrote in their discussion.

“There are many additional research questions that we need to answer, and look forward to working on,” Dr. Leon-Ferre said, in an interview. These topics include whether TILs can be used to decide on the number of chemotherapy drugs a patient really needs and whether artificial intelligence can be used to evaluate TILs more quickly and effectively than the human eye, he said. Other research topics include identifying which particular type of TILs attack cancer cells most effectively and whether TILs could be increased in patients with low levels in order to improve their prognosis, he added.

The study was supported by the National Research Agency and General Secretariat for Investment, Clinical and Translational Science Awards, the Mayo Clinic Breast Cancer SPORE grant, the Cancer Research Society of Canada, institutional grants from the Dutch Cancer Society, The Netherlands Organization for Health Research, and several foundations. Dr. Leon-Ferre disclosed consulting honoraria to his institution for research activities from AstraZeneca, Gilead Sciences, and Lyell Immunopharma, with no personal fees outside the submitted work.

High levels of tumor-infiltrating lymphocytes predicted increased survival in patients with early-stage triple-negative breast cancer who did not receive chemotherapy, a new analysis finds.

The association of abundant tumor-infiltrating lymphocytes (TILs) in breast cancer tissue with outcomes in patients with early-stage triple-negative breast cancer (TNBC) who do not receive chemotherapy has not been well studied, wrote Roberto A. Leon-Ferre, MD, of the Mayo Clinic, Rochester, Minnesota, and colleagues, in JAMA.

Biomarkers to guide systemic treatment and avoid overtreatment are lacking, and such markers could help identify patients who could achieve increased survival with less intensive therapy, continued the authors of the new study of nearly 2000 individuals.

“TNBC is the most aggressive subtype of breast cancer, and for this reason, current treatment guidelines recommend chemotherapy using multiple drugs either before or after surgery,” Dr. Leon-Ferre said in an interview. “We have learned over the last several years that TNBC is not a single disease, but that there are several subtypes of TNBC that have different risks and different vulnerabilities, and treating all patients similarly may not be optimal.”

  

What is Known About Tumor-Infiltrating Lymphocytes and Cancer?

Previous studies have shown improved survival in patients with early-stage TNBC and high levels of TILs who were treated with adjuvant and neoadjuvant chemotherapy, compared with those with lower TILs. In a pooled analysis of 2148 patients from nine studies published in the Journal of Clinical Oncology in 2019, a higher percentage of TILs in the stroma surrounding a tumor was significantly associated with improved survival in TNBC patients after adjuvant chemotherapy.

Another study published in the Journal of Clinical Oncology in 2022 showed that elevated TILs were significant predictors of overall survival, but the study included fewer than 500 patients.

The potential mechanisms that drive the association between elevated TILs and improved survival include the ability of TILs to attack cancer cells, Dr. Leon-Ferre said in an interview. 

The goal of this study was to evaluate whether TILs could identify a subset of patients with TNBC who had a very low risk of cancer recurrence even if chemotherapy was not given.

“Indeed, we found that patients with stage I TNBC and high TILs had a very low risk of recurrence even when chemotherapy was not administered. These findings will pave the way for future studies aiming to reduce the need for multiple chemotherapy drugs in patients with stage I TNBC and decrease the side effects that patients face,” he said.

 

What Does the New Study Add?

The current study included 1966 individuals from 13 sites in North America, Europe, and Asia who were diagnosed with TNBC between 1979 and 2017 and were treated with surgery, with or without radiotherapy but with no adjuvant or neoadjuvant chemotherapy. The researchers examined the abundance of TILs in the breast tissue of resected primary tumors; the primary outcome was invasive disease-free survival (iDFS), with recurrence-free survival, distant recurrence-free survival, and overall survival as secondary outcomes.

The median age of the patients was 56 years, 55% had stage I TNBC, and the median TIL level was 15%.

A total of 417 patients had a TIL level of 50% or more, and the 5-year iDFS for these patients was 94%, compared with 78% for those with a TIL level less than 30%. Similarly, 5-year overall survival was 95% in patients with a TIL level of 50% or more, compared with 82% for patients with TIL levels of less than 30%.

Additionally, each 10% increase in TILs was independently associated not only with improved iDFS (hazard ratio[HR], 0.92), but also improved recurrence-free survival (HR, 0.90), distant recurrence-free survival (HR, 0.87), and overall survival (HR, 0.88) over a median follow-up of 18 years.

The current study shows that cancer stage based on tumor size and the number of lymph nodes should not be the only considerations for making treatment decisions and predicting outcomes, Dr. Leon-Ferre said in an interview.

“In fact, our study shows that for tumors of the same stage (particularly for stage I), the risk of recurrence is different depending on the number of TILs seen in the breast cancer tissue. When chemo is not given, those with high TILs have lower risk of recurrence, whereas those with low TILs have a higher risk of recurrence,” he said.
 

What are the Limitations of This Research?

The current study findings are limited by the retrospective design and use of observational data, so the researchers could not make conclusions about causality. Other limitations included lack of data on germline mutations and race or ethnicity, and the potential irrelevance of data from patients treated as long as 45 years ago.

“Because most patients with TNBC receive chemotherapy in the modern times, we needed to work with 13 hospitals around the world to find data on patients with TNBC who never received chemotherapy for various reasons,” Dr. Leon-Ferre said.

To address these limitations, Dr. Leone-Ferre and his colleagues are planning prospective studies where TILs will be used to make treatment decisions.

“Many of the patients in our cohort were treated many years ago, when chemotherapy was not routinely given. Advances in cancer detection, surgical and radiation techniques may lead to different results in patients treated today,” he added.

What Do Oncologists Need to Know?

The current study findings may provide additional information on prognosis that is important to share with patients for decision-making on the risks versus benefits of chemotherapy, Dr. Leon-Ferre said.

“Like any test, TILs should not be used in isolation to make decisions, but should be integrated with other factors including the cancer stage, the overall patient health, patient preferences, and concerns about treatment complications,” he emphasized. “The results of this study allow oncologists to offer a more refined calculation of recurrence risk if patients opt to not receive chemotherapy.”

In the current study, although younger age was associated with higher TIL levels, a finding consistent with previous studies, increased TIL, remained significantly associated with improved survival after adjusting for age, tumor size, nodal status, and histological grade.

Overall, “the findings suggest that for patients with stage I TNBC and TILs greater than 50%, chemotherapy may not be as necessary as it was previously thought,” Dr. Leon-Ferre said.

What Additional Research is Needed?

Prospective studies are needed to validate the findings, including studies in diverse populations, and additional studies may investigate whether early TBNC patients with high TIL levels could achieve high cure rates with less intensive and less toxic chemotherapy regiments than those currently recommended, the researchers wrote in their discussion.

“There are many additional research questions that we need to answer, and look forward to working on,” Dr. Leon-Ferre said, in an interview. These topics include whether TILs can be used to decide on the number of chemotherapy drugs a patient really needs and whether artificial intelligence can be used to evaluate TILs more quickly and effectively than the human eye, he said. Other research topics include identifying which particular type of TILs attack cancer cells most effectively and whether TILs could be increased in patients with low levels in order to improve their prognosis, he added.

The study was supported by the National Research Agency and General Secretariat for Investment, Clinical and Translational Science Awards, the Mayo Clinic Breast Cancer SPORE grant, the Cancer Research Society of Canada, institutional grants from the Dutch Cancer Society, The Netherlands Organization for Health Research, and several foundations. Dr. Leon-Ferre disclosed consulting honoraria to his institution for research activities from AstraZeneca, Gilead Sciences, and Lyell Immunopharma, with no personal fees outside the submitted work.

TOPLINE:

C-reactive protein (CRP) levels and eosinophil-to-platelet ratio (EPR) are significant independent predictors of adverse events in patients with chronic obstructive pulmonary disease (COPD) hospitalized with acute exacerbations.

METHODOLOGY:

• Known risk factors for COPD exacerbations do not fully explain the variation in susceptibility among patients; data on potential biomarkers as predictors of COPD exacerbations are limited.
• In a prospective, observational study at a single center, the researchers examined clinical and lab data including serum CRP levels, EPR, sarcopenia, lung function, nutrition, and frailty.
• The study population included 200 adults older than 40 years with COPD who were hospitalized for acute exacerbations; 50 experienced adverse events.

TAKEAWAY:

• Both elevated CRP and low EPR were significant predictors of adverse events in adjusted analysis in patients with COPD exacerbations (area under the curve, 0.71 and 0.76, respectively).
• In a multivariate analysis, EPR and CRP, as well as sarcopenia, were significantly associated with adverse events (adjusted odds ratios, 2.33, 2.09, and 1.97, respectively).
• COPD symptom scores, frailty, and malnutrition showed predictive value in bivariate but not multivariate analysis.

IN PRACTICE:

“Screening for these biomarkers [EPR and CRP] on admission could help identify high-risk patients who need more aggressive monitoring and treatment,” the researchers wrote in their discussion.

SOURCE:

The lead author on the study was Rohankumar Gandhi, MD, of Guru Gobind Singh Government Hospital, Jamnagar, India. The study was published online in Cureus.

LIMITATIONS:

The use of data from a single center, lack of information on nutritional interventions and counseling, and lack of data on outpatient outcomes limited the study findings.

DISCLOSURES:

The study received no outside funding. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

C-reactive protein (CRP) levels and eosinophil-to-platelet ratio (EPR) are significant independent predictors of adverse events in patients with chronic obstructive pulmonary disease (COPD) hospitalized with acute exacerbations.

METHODOLOGY:

• Known risk factors for COPD exacerbations do not fully explain the variation in susceptibility among patients; data on potential biomarkers as predictors of COPD exacerbations are limited.
• In a prospective, observational study at a single center, the researchers examined clinical and lab data including serum CRP levels, EPR, sarcopenia, lung function, nutrition, and frailty.
• The study population included 200 adults older than 40 years with COPD who were hospitalized for acute exacerbations; 50 experienced adverse events.

TAKEAWAY:

• Both elevated CRP and low EPR were significant predictors of adverse events in adjusted analysis in patients with COPD exacerbations (area under the curve, 0.71 and 0.76, respectively).
• In a multivariate analysis, EPR and CRP, as well as sarcopenia, were significantly associated with adverse events (adjusted odds ratios, 2.33, 2.09, and 1.97, respectively).
• COPD symptom scores, frailty, and malnutrition showed predictive value in bivariate but not multivariate analysis.

IN PRACTICE:

“Screening for these biomarkers [EPR and CRP] on admission could help identify high-risk patients who need more aggressive monitoring and treatment,” the researchers wrote in their discussion.

SOURCE:

The lead author on the study was Rohankumar Gandhi, MD, of Guru Gobind Singh Government Hospital, Jamnagar, India. The study was published online in Cureus.

LIMITATIONS:

The use of data from a single center, lack of information on nutritional interventions and counseling, and lack of data on outpatient outcomes limited the study findings.

DISCLOSURES:

The study received no outside funding. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

C-reactive protein (CRP) levels and eosinophil-to-platelet ratio (EPR) are significant independent predictors of adverse events in patients with chronic obstructive pulmonary disease (COPD) hospitalized with acute exacerbations.

METHODOLOGY:

• Known risk factors for COPD exacerbations do not fully explain the variation in susceptibility among patients; data on potential biomarkers as predictors of COPD exacerbations are limited.
• In a prospective, observational study at a single center, the researchers examined clinical and lab data including serum CRP levels, EPR, sarcopenia, lung function, nutrition, and frailty.
• The study population included 200 adults older than 40 years with COPD who were hospitalized for acute exacerbations; 50 experienced adverse events.

TAKEAWAY:

• Both elevated CRP and low EPR were significant predictors of adverse events in adjusted analysis in patients with COPD exacerbations (area under the curve, 0.71 and 0.76, respectively).
• In a multivariate analysis, EPR and CRP, as well as sarcopenia, were significantly associated with adverse events (adjusted odds ratios, 2.33, 2.09, and 1.97, respectively).
• COPD symptom scores, frailty, and malnutrition showed predictive value in bivariate but not multivariate analysis.

IN PRACTICE:

“Screening for these biomarkers [EPR and CRP] on admission could help identify high-risk patients who need more aggressive monitoring and treatment,” the researchers wrote in their discussion.

SOURCE:

The lead author on the study was Rohankumar Gandhi, MD, of Guru Gobind Singh Government Hospital, Jamnagar, India. The study was published online in Cureus.

LIMITATIONS:

The use of data from a single center, lack of information on nutritional interventions and counseling, and lack of data on outpatient outcomes limited the study findings.

DISCLOSURES:

The study received no outside funding. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Infants born to women with obesity showed improved measures of cardiovascular health when their mothers adopted healthier lifestyles before and during pregnancy, based on data from a systematic review presented at the annual meeting of the Society for Reproductive Investigation.

Previous research has shown that children born to mothers with a high body mass index (BMI) are more likely to die from cardiovascular disease in later life, said presenting author Samuel J. Burden, PhD, in an interview.

“Surprisingly, early signs of these heart issues can start before birth and continue into childhood,” said Dr. Burden, a research associate in the Department of Women & Children’s Health, School of Life Course & Population Sciences, King’s College London, London, United Kingdom.

To examine the effect of interventions such as a healthy diet and exercise in pregnant women with obesity on the heart health of their infants, Dr. Burden and colleagues reviewed data from eight randomized, controlled trials involving diet and exercise for pregnant women with obesity. Of these, two used antenatal exercise, two used diet and physical activity, and one used preconception diet and physical activity. The studies ranged in size from 18 to 404 participants. Two studies included infants younger than 2 months of age, and four studies included children aged 3-7 years.

Overall, lifestyle interventions before conception and before birth were associated with significant changes in cardiac remodeling, specifically reduced interventricular septal wall thickness.

In addition, one of three studies of cardiac diastolic function and four of five studies of systolic function showed significant improvements. The five studies of cardiac systolic function and three studies of diastolic function also showed improvement in systolic and diastolic blood pressure in infants of mothers who took part in the interventions. The studies were limited mainly by large attrition rates, the researchers wrote in their presentation. However, more studies in larger populations that also include older children could confirm the findings and inform public health strategies to promote healthy lifestyles for pregnant women, they noted.

Encourage Healthy Lifestyle Before and During Pregnancy

The evidence supports the findings from animal studies showing that an offspring’s health is influenced by maternal lifestyle before and during pregnancy, Dr. Burden said in an interview. The data suggest that healthcare providers should encourage women with a high BMI who want to become pregnant to eat healthfully and become more active as a way to enhance the future cardiovascular health of their children, he said.

The full results of the current study are soon to be published, but more work is needed, said Dr. Burden. “While we observed a protective effect from these lifestyle programs, there is a need for more extensive studies involving a larger number of women (and their children) who were part of the initial research,” he said. “Additionally, it will be crucial to track these children into adulthood to determine whether these antenatal lifestyle interventions persist in lowering the risk of future cardiovascular disease.”

Beginning healthy lifestyle programs prior to pregnancy might yield the best results for promoting infant cardiovascular health, and more prepregnancy interventions for women with obesity are needed, Dr. Burden added.

The current study adds to the growing body of evidence that the in utero environment can have lifelong effects on offspring, Joseph R. Biggio Jr, MD, system chair of maternal fetal medicine at Ochsner Health, New Orleans, Louisiana, said in an interview.

“Several studies have previously shown that the children of mothers with diabetes, hypertension, or obesity are at increased risk for developing signs of metabolic syndrome and cardiovascular changes during childhood or adolescence,” said Dr. Biggio.

The data from this systematic review support the potential value of interventions aimed at improving maternal weight gain and cardiovascular performance before and during pregnancy that may result in reduced cardiovascular remodeling and myocardial thickening in infants, he said.   

The study was supported by a British Heart Foundation Special Project Grant. The researchers had no financial conflicts to disclose. Dr. Biggio had no financial conflicts to disclose.

Infants born to women with obesity showed improved measures of cardiovascular health when their mothers adopted healthier lifestyles before and during pregnancy, based on data from a systematic review presented at the annual meeting of the Society for Reproductive Investigation.

Previous research has shown that children born to mothers with a high body mass index (BMI) are more likely to die from cardiovascular disease in later life, said presenting author Samuel J. Burden, PhD, in an interview.

“Surprisingly, early signs of these heart issues can start before birth and continue into childhood,” said Dr. Burden, a research associate in the Department of Women & Children’s Health, School of Life Course & Population Sciences, King’s College London, London, United Kingdom.

To examine the effect of interventions such as a healthy diet and exercise in pregnant women with obesity on the heart health of their infants, Dr. Burden and colleagues reviewed data from eight randomized, controlled trials involving diet and exercise for pregnant women with obesity. Of these, two used antenatal exercise, two used diet and physical activity, and one used preconception diet and physical activity. The studies ranged in size from 18 to 404 participants. Two studies included infants younger than 2 months of age, and four studies included children aged 3-7 years.

Overall, lifestyle interventions before conception and before birth were associated with significant changes in cardiac remodeling, specifically reduced interventricular septal wall thickness.

In addition, one of three studies of cardiac diastolic function and four of five studies of systolic function showed significant improvements. The five studies of cardiac systolic function and three studies of diastolic function also showed improvement in systolic and diastolic blood pressure in infants of mothers who took part in the interventions. The studies were limited mainly by large attrition rates, the researchers wrote in their presentation. However, more studies in larger populations that also include older children could confirm the findings and inform public health strategies to promote healthy lifestyles for pregnant women, they noted.

Encourage Healthy Lifestyle Before and During Pregnancy

The evidence supports the findings from animal studies showing that an offspring’s health is influenced by maternal lifestyle before and during pregnancy, Dr. Burden said in an interview. The data suggest that healthcare providers should encourage women with a high BMI who want to become pregnant to eat healthfully and become more active as a way to enhance the future cardiovascular health of their children, he said.

The full results of the current study are soon to be published, but more work is needed, said Dr. Burden. “While we observed a protective effect from these lifestyle programs, there is a need for more extensive studies involving a larger number of women (and their children) who were part of the initial research,” he said. “Additionally, it will be crucial to track these children into adulthood to determine whether these antenatal lifestyle interventions persist in lowering the risk of future cardiovascular disease.”

Beginning healthy lifestyle programs prior to pregnancy might yield the best results for promoting infant cardiovascular health, and more prepregnancy interventions for women with obesity are needed, Dr. Burden added.

The current study adds to the growing body of evidence that the in utero environment can have lifelong effects on offspring, Joseph R. Biggio Jr, MD, system chair of maternal fetal medicine at Ochsner Health, New Orleans, Louisiana, said in an interview.

“Several studies have previously shown that the children of mothers with diabetes, hypertension, or obesity are at increased risk for developing signs of metabolic syndrome and cardiovascular changes during childhood or adolescence,” said Dr. Biggio.

The data from this systematic review support the potential value of interventions aimed at improving maternal weight gain and cardiovascular performance before and during pregnancy that may result in reduced cardiovascular remodeling and myocardial thickening in infants, he said.   

The study was supported by a British Heart Foundation Special Project Grant. The researchers had no financial conflicts to disclose. Dr. Biggio had no financial conflicts to disclose.

Infants born to women with obesity showed improved measures of cardiovascular health when their mothers adopted healthier lifestyles before and during pregnancy, based on data from a systematic review presented at the annual meeting of the Society for Reproductive Investigation.

Previous research has shown that children born to mothers with a high body mass index (BMI) are more likely to die from cardiovascular disease in later life, said presenting author Samuel J. Burden, PhD, in an interview.

“Surprisingly, early signs of these heart issues can start before birth and continue into childhood,” said Dr. Burden, a research associate in the Department of Women & Children’s Health, School of Life Course & Population Sciences, King’s College London, London, United Kingdom.

To examine the effect of interventions such as a healthy diet and exercise in pregnant women with obesity on the heart health of their infants, Dr. Burden and colleagues reviewed data from eight randomized, controlled trials involving diet and exercise for pregnant women with obesity. Of these, two used antenatal exercise, two used diet and physical activity, and one used preconception diet and physical activity. The studies ranged in size from 18 to 404 participants. Two studies included infants younger than 2 months of age, and four studies included children aged 3-7 years.

Overall, lifestyle interventions before conception and before birth were associated with significant changes in cardiac remodeling, specifically reduced interventricular septal wall thickness.

In addition, one of three studies of cardiac diastolic function and four of five studies of systolic function showed significant improvements. The five studies of cardiac systolic function and three studies of diastolic function also showed improvement in systolic and diastolic blood pressure in infants of mothers who took part in the interventions. The studies were limited mainly by large attrition rates, the researchers wrote in their presentation. However, more studies in larger populations that also include older children could confirm the findings and inform public health strategies to promote healthy lifestyles for pregnant women, they noted.

Encourage Healthy Lifestyle Before and During Pregnancy

The evidence supports the findings from animal studies showing that an offspring’s health is influenced by maternal lifestyle before and during pregnancy, Dr. Burden said in an interview. The data suggest that healthcare providers should encourage women with a high BMI who want to become pregnant to eat healthfully and become more active as a way to enhance the future cardiovascular health of their children, he said.

The full results of the current study are soon to be published, but more work is needed, said Dr. Burden. “While we observed a protective effect from these lifestyle programs, there is a need for more extensive studies involving a larger number of women (and their children) who were part of the initial research,” he said. “Additionally, it will be crucial to track these children into adulthood to determine whether these antenatal lifestyle interventions persist in lowering the risk of future cardiovascular disease.”

Beginning healthy lifestyle programs prior to pregnancy might yield the best results for promoting infant cardiovascular health, and more prepregnancy interventions for women with obesity are needed, Dr. Burden added.

The current study adds to the growing body of evidence that the in utero environment can have lifelong effects on offspring, Joseph R. Biggio Jr, MD, system chair of maternal fetal medicine at Ochsner Health, New Orleans, Louisiana, said in an interview.

“Several studies have previously shown that the children of mothers with diabetes, hypertension, or obesity are at increased risk for developing signs of metabolic syndrome and cardiovascular changes during childhood or adolescence,” said Dr. Biggio.

The data from this systematic review support the potential value of interventions aimed at improving maternal weight gain and cardiovascular performance before and during pregnancy that may result in reduced cardiovascular remodeling and myocardial thickening in infants, he said.   

The study was supported by a British Heart Foundation Special Project Grant. The researchers had no financial conflicts to disclose. Dr. Biggio had no financial conflicts to disclose.

A longer time between hysteroscopic polypectomy and frozen embryo transfer may improve the odds of successful pregnancy, based on data from a new analysis presented at the annual meeting of the Society for Reproductive Investigation.

Although uterine polyps have a negative effect on pregnancy rates, data supporting a specific time interval between hysteroscopic polypectomy (HP) and frozen embryo transfer (FET) are limited, according to Audrey Messelt, MD, of Baylor College of Medicine, Houston, Texas, and colleagues.

“Hysteroscopic polypectomy is a common procedure performed before embryo transfer to optimize the receptivity of the endometrium. Currently, there is no ideal recovery time lapse between surgery and an embryo transfer,” said senior author Laura Detti, MD, professor of obstetrics and gynecology at Baylor, in an interview. “This is often the last step prior to embryo transfer, and identifying a recovery time that allows the best outcome is important.”

In a retrospective analysis, the researchers examined the effect of the time between HP and FET on pregnancy outcomes. They identified 65 patients with uterine pathology based on saline-infusion sonogram who underwent hysteroscopy and FET between June 1, 2022, and September 30, 2023.

The endometrial preparation for FET included sequential administration of oral or transdermal estradiol and intramuscular progesterone.

Overall, 46 patients were diagnosed with endometrial polyps at the time of surgery; three had endometritis, one had a uterine septum that was resected, 15 had no abnormal pathology or had normal endometrium at the time of examination. No cases of hyperplasia or malignancy were identified.

A total of 58 patients underwent FET with a single euploid embryo, four with a single untested embryo, one with a low-mosaic embryo, and two with a double-embryo transfer (one euploid and one low mosaic).

After FET, 50 patients conceived and 15 did not. Patients with ongoing pregnancies who had a history of endometrial polyps had significantly more days from surgery to FET, compared to patients with a history of polyps who failed to conceive (median 70 days vs 45 days, P = .01).

By contrast, the time between hysteroscopy and FET was similar among patients with no endometrial pathology who did and did not have ongoing pregnancies (median 45 vs 52.5 days, P = .95).

The findings were limited by the relatively small sample size and exclusion of patients with pathologies other than polyps, as well as a lack of data on age group breakdowns. However, the results suggest that patients with uterine polyps may benefit from more time between HP and FET, while patients with normal surgical findings could undergo FET sooner, the researchers concluded.
 

Postpolypectomy Timing May Affect Pregnancy Outcomes

“We used to think that having had the first menses from surgery would be enough recovery time for the uterine cavity, even if it was just 2 weeks,” Dr. Detti said in an interview. “This still holds true when no endometrial polyps are diagnosed in the pathological specimen; however, we learned that if endometrial polyps are removed at the time of hysteroscopy, the ideal recovery time prior to an embryo transfer should be longer,” she said.

The current study is important because approximately 15% of women are diagnosed with endometrial polyps during their reproductive years, said Mark P. Trolice, MD, professor at the University of Central Florida, Orlando, and founder/medical director of the IVF Center of Central Florida in Winter Park, in an interview.

“Abnormalities of the uterine cavity have been shown to reduce embryo implantation and increase the risk of miscarriage,” said Dr. Trolice. Although the impact of small endometrial polyps on fertility and pregnancy are uncertain, most infertility specialists recommend removal of endometrial polyps via hysteroscopic polypectomy in general and prior to IVF embryo transfer in particular, he said.

Although infertility patients are anxious to undergo embryo transfer, the current study suggests a benefit in delaying the procedure following the removal of any polyps identified during the pretransfer evaluation, Dr. Trolice said in an interview. As for additional research, “it would be helpful to know the age group breakdown of patients and if the results were consistent among all categories,” he said.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Trolice had no financial conflicts to disclose and serves on the Editorial Advisory Board of Ob.Gyn. News.

A longer time between hysteroscopic polypectomy and frozen embryo transfer may improve the odds of successful pregnancy, based on data from a new analysis presented at the annual meeting of the Society for Reproductive Investigation.

Although uterine polyps have a negative effect on pregnancy rates, data supporting a specific time interval between hysteroscopic polypectomy (HP) and frozen embryo transfer (FET) are limited, according to Audrey Messelt, MD, of Baylor College of Medicine, Houston, Texas, and colleagues.

“Hysteroscopic polypectomy is a common procedure performed before embryo transfer to optimize the receptivity of the endometrium. Currently, there is no ideal recovery time lapse between surgery and an embryo transfer,” said senior author Laura Detti, MD, professor of obstetrics and gynecology at Baylor, in an interview. “This is often the last step prior to embryo transfer, and identifying a recovery time that allows the best outcome is important.”

In a retrospective analysis, the researchers examined the effect of the time between HP and FET on pregnancy outcomes. They identified 65 patients with uterine pathology based on saline-infusion sonogram who underwent hysteroscopy and FET between June 1, 2022, and September 30, 2023.

The endometrial preparation for FET included sequential administration of oral or transdermal estradiol and intramuscular progesterone.

Overall, 46 patients were diagnosed with endometrial polyps at the time of surgery; three had endometritis, one had a uterine septum that was resected, 15 had no abnormal pathology or had normal endometrium at the time of examination. No cases of hyperplasia or malignancy were identified.

A total of 58 patients underwent FET with a single euploid embryo, four with a single untested embryo, one with a low-mosaic embryo, and two with a double-embryo transfer (one euploid and one low mosaic).

After FET, 50 patients conceived and 15 did not. Patients with ongoing pregnancies who had a history of endometrial polyps had significantly more days from surgery to FET, compared to patients with a history of polyps who failed to conceive (median 70 days vs 45 days, P = .01).

By contrast, the time between hysteroscopy and FET was similar among patients with no endometrial pathology who did and did not have ongoing pregnancies (median 45 vs 52.5 days, P = .95).

The findings were limited by the relatively small sample size and exclusion of patients with pathologies other than polyps, as well as a lack of data on age group breakdowns. However, the results suggest that patients with uterine polyps may benefit from more time between HP and FET, while patients with normal surgical findings could undergo FET sooner, the researchers concluded.
 

Postpolypectomy Timing May Affect Pregnancy Outcomes

“We used to think that having had the first menses from surgery would be enough recovery time for the uterine cavity, even if it was just 2 weeks,” Dr. Detti said in an interview. “This still holds true when no endometrial polyps are diagnosed in the pathological specimen; however, we learned that if endometrial polyps are removed at the time of hysteroscopy, the ideal recovery time prior to an embryo transfer should be longer,” she said.

The current study is important because approximately 15% of women are diagnosed with endometrial polyps during their reproductive years, said Mark P. Trolice, MD, professor at the University of Central Florida, Orlando, and founder/medical director of the IVF Center of Central Florida in Winter Park, in an interview.

“Abnormalities of the uterine cavity have been shown to reduce embryo implantation and increase the risk of miscarriage,” said Dr. Trolice. Although the impact of small endometrial polyps on fertility and pregnancy are uncertain, most infertility specialists recommend removal of endometrial polyps via hysteroscopic polypectomy in general and prior to IVF embryo transfer in particular, he said.

Although infertility patients are anxious to undergo embryo transfer, the current study suggests a benefit in delaying the procedure following the removal of any polyps identified during the pretransfer evaluation, Dr. Trolice said in an interview. As for additional research, “it would be helpful to know the age group breakdown of patients and if the results were consistent among all categories,” he said.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Trolice had no financial conflicts to disclose and serves on the Editorial Advisory Board of Ob.Gyn. News.

A longer time between hysteroscopic polypectomy and frozen embryo transfer may improve the odds of successful pregnancy, based on data from a new analysis presented at the annual meeting of the Society for Reproductive Investigation.

Although uterine polyps have a negative effect on pregnancy rates, data supporting a specific time interval between hysteroscopic polypectomy (HP) and frozen embryo transfer (FET) are limited, according to Audrey Messelt, MD, of Baylor College of Medicine, Houston, Texas, and colleagues.

“Hysteroscopic polypectomy is a common procedure performed before embryo transfer to optimize the receptivity of the endometrium. Currently, there is no ideal recovery time lapse between surgery and an embryo transfer,” said senior author Laura Detti, MD, professor of obstetrics and gynecology at Baylor, in an interview. “This is often the last step prior to embryo transfer, and identifying a recovery time that allows the best outcome is important.”

In a retrospective analysis, the researchers examined the effect of the time between HP and FET on pregnancy outcomes. They identified 65 patients with uterine pathology based on saline-infusion sonogram who underwent hysteroscopy and FET between June 1, 2022, and September 30, 2023.

The endometrial preparation for FET included sequential administration of oral or transdermal estradiol and intramuscular progesterone.

Overall, 46 patients were diagnosed with endometrial polyps at the time of surgery; three had endometritis, one had a uterine septum that was resected, 15 had no abnormal pathology or had normal endometrium at the time of examination. No cases of hyperplasia or malignancy were identified.

A total of 58 patients underwent FET with a single euploid embryo, four with a single untested embryo, one with a low-mosaic embryo, and two with a double-embryo transfer (one euploid and one low mosaic).

After FET, 50 patients conceived and 15 did not. Patients with ongoing pregnancies who had a history of endometrial polyps had significantly more days from surgery to FET, compared to patients with a history of polyps who failed to conceive (median 70 days vs 45 days, P = .01).

By contrast, the time between hysteroscopy and FET was similar among patients with no endometrial pathology who did and did not have ongoing pregnancies (median 45 vs 52.5 days, P = .95).

The findings were limited by the relatively small sample size and exclusion of patients with pathologies other than polyps, as well as a lack of data on age group breakdowns. However, the results suggest that patients with uterine polyps may benefit from more time between HP and FET, while patients with normal surgical findings could undergo FET sooner, the researchers concluded.
 

Postpolypectomy Timing May Affect Pregnancy Outcomes

“We used to think that having had the first menses from surgery would be enough recovery time for the uterine cavity, even if it was just 2 weeks,” Dr. Detti said in an interview. “This still holds true when no endometrial polyps are diagnosed in the pathological specimen; however, we learned that if endometrial polyps are removed at the time of hysteroscopy, the ideal recovery time prior to an embryo transfer should be longer,” she said.

The current study is important because approximately 15% of women are diagnosed with endometrial polyps during their reproductive years, said Mark P. Trolice, MD, professor at the University of Central Florida, Orlando, and founder/medical director of the IVF Center of Central Florida in Winter Park, in an interview.

“Abnormalities of the uterine cavity have been shown to reduce embryo implantation and increase the risk of miscarriage,” said Dr. Trolice. Although the impact of small endometrial polyps on fertility and pregnancy are uncertain, most infertility specialists recommend removal of endometrial polyps via hysteroscopic polypectomy in general and prior to IVF embryo transfer in particular, he said.

Although infertility patients are anxious to undergo embryo transfer, the current study suggests a benefit in delaying the procedure following the removal of any polyps identified during the pretransfer evaluation, Dr. Trolice said in an interview. As for additional research, “it would be helpful to know the age group breakdown of patients and if the results were consistent among all categories,” he said.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Trolice had no financial conflicts to disclose and serves on the Editorial Advisory Board of Ob.Gyn. News.

Development of a DNA-based lung cancer vaccine in the United Kingdom received funding for 2 years of laboratory research and initial manufacture of 3000 doses, according to a press release from the University of Oxford, England.

A team of scientists from the University of Oxford, the Francis Crick Institute, and University College London (UCL) will receive funding from the Cancer Research UK and the CRIS Cancer Foundation.

The LungVax vaccine is based on technology similar to that used in the creation of the successful Oxford/AstraZeneca COVID-19 vaccine and will carry a DNA strand that trains the immune system to recognize the neoantigens that indicate abnormal lung cancer cells and then activate the immune system to kill these cells and stop the cancer, according to the statement.

Initially, scientists are working to develop a vaccine that triggers an immune response in the lab setting. If successful, the vaccine will move directly into a clinical trial. “If the subsequent early trial delivers promising results, the vaccine could then be scaled up to bigger trials for people at high risk of lung cancer,” according to the release.
 

Help for High-Risk Patients

Lung cancer is diagnosed in approximately 48,000 individuals in the United Kingdom each year, and the average 10-year survival is only 10%, Tim Elliott, MD, professor of immuno-oncology at the University of Oxford and lead researcher on the LungVax project, said in an interview. Nearly three-quarters of the 35,000 annual deaths are preventable by quitting smoking, which remains the best risk reduction strategy to date, he said. However, “an intervention such as a vaccine, given when people are healthy and are more likely to have a strong immune system, could benefit many thousands per year in the UK and 1.8 million patients worldwide,” he said.
 

Preliminary Trial Plans

The initial trial of the vaccine is a collaboration between Oxford University, UCL, and the Francis Crick Institute, Dr. Elliott said. The trial is a culmination of research into the biology and genetics of lung cancer at UCL and vaccine design research at the University of Oxford.

“We are at a very early stage of the program, which will develop over the next 6 years if all goes to plan,” said Dr. Elliott. The vaccine is designed on the basis of shared lung cancer antigens and packaged into the ChAdOx delivery system that proved successful as the Oxford-AstraZeneca COVID-19 vaccine, he said.

“We intend to vaccinate individuals who have had curative surgery for their lung cancer after being diagnosed with a very early stage of the disease,” Dr. Elliott said.

Challenges to vaccine development include knowing whether there is a clinical benefit, Dr. Elliott noted. “Our clinical trial is calculated to show up to 15% reduction in risk over 3-5 years, but only long-term follow-up will really tell us whether the immune responses we see to the vaccine within the first few weeks will have a long-term effect,” he emphasized.

In clinical practice, “these people are cancer-free and healthy after surgery,” said Dr. Elliott. However, “they are at a high risk of recurrence; 30%-70% of ex-patients will develop new cancer in their lifetime and in the majority of cases that will happen within 2 years after surgery,” he said. “We think that vaccinating them against common lung cancer antigens could reduce this risk significantly and remove some of the uncertainty that they live with after their operation.”
 

Vaccine Has Potential for Immense Impact

Lung cancer remains one of the most frequently diagnosed cancers. “In the past few decades, public health measures including tobacco cessation and lung cancer screening have contributed to the reduction of lung cancer incidence and improved survival in high-income countries, but lung cancer continues to be the leading cause of cancer-related deaths worldwide,” Saadia A. Faiz, MD, a member of the CHEST Physician editorial board, said in an interview.

“Further, new cancer diagnoses continue to increase in low-income countries where there may not be widespread public health initiatives and/or access to healthcare. Thus, development of a vaccine to prevent lung cancer could be very impactful,” she said.

Challenges to vaccine development include the heterogeneous nature of the disease, which may occur in smokers and nonsmokers, said Dr. Faiz. “Targeting the various molecular markers may be challenging,” she said. However, building on the success of other vaccine initiatives, such as the human papillomavirus vaccine for cervical cancer, and COVID-19 vaccines with collaboration and clinical research will ideally overcome these challenges, she added.

“The potential implications for a lung cancer vaccine are immense,” said Dr. Faiz.

A lung cancer vaccine could prevent a deadly disease, but continued efforts in risk factor reduction and lung cancer screening will also be important, she said.

“Depending on the results of this clinical research, longitudinal data regarding efficacy, side effects, and prevention will be vital prior to application in high-risk patients in clinical practice,” she emphasized.

The development of the lung cancer vaccine is supported in part by Cancer Research UK and the CRIS Cancer Foundation. Dr. Elliott has received support from Cancer Research UK but had no financial conflicts to disclose. Dr. Faiz had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Development of a DNA-based lung cancer vaccine in the United Kingdom received funding for 2 years of laboratory research and initial manufacture of 3000 doses, according to a press release from the University of Oxford, England.

A team of scientists from the University of Oxford, the Francis Crick Institute, and University College London (UCL) will receive funding from the Cancer Research UK and the CRIS Cancer Foundation.

The LungVax vaccine is based on technology similar to that used in the creation of the successful Oxford/AstraZeneca COVID-19 vaccine and will carry a DNA strand that trains the immune system to recognize the neoantigens that indicate abnormal lung cancer cells and then activate the immune system to kill these cells and stop the cancer, according to the statement.

Initially, scientists are working to develop a vaccine that triggers an immune response in the lab setting. If successful, the vaccine will move directly into a clinical trial. “If the subsequent early trial delivers promising results, the vaccine could then be scaled up to bigger trials for people at high risk of lung cancer,” according to the release.
 

Help for High-Risk Patients

Lung cancer is diagnosed in approximately 48,000 individuals in the United Kingdom each year, and the average 10-year survival is only 10%, Tim Elliott, MD, professor of immuno-oncology at the University of Oxford and lead researcher on the LungVax project, said in an interview. Nearly three-quarters of the 35,000 annual deaths are preventable by quitting smoking, which remains the best risk reduction strategy to date, he said. However, “an intervention such as a vaccine, given when people are healthy and are more likely to have a strong immune system, could benefit many thousands per year in the UK and 1.8 million patients worldwide,” he said.
 

Preliminary Trial Plans

The initial trial of the vaccine is a collaboration between Oxford University, UCL, and the Francis Crick Institute, Dr. Elliott said. The trial is a culmination of research into the biology and genetics of lung cancer at UCL and vaccine design research at the University of Oxford.

“We are at a very early stage of the program, which will develop over the next 6 years if all goes to plan,” said Dr. Elliott. The vaccine is designed on the basis of shared lung cancer antigens and packaged into the ChAdOx delivery system that proved successful as the Oxford-AstraZeneca COVID-19 vaccine, he said.

“We intend to vaccinate individuals who have had curative surgery for their lung cancer after being diagnosed with a very early stage of the disease,” Dr. Elliott said.

Challenges to vaccine development include knowing whether there is a clinical benefit, Dr. Elliott noted. “Our clinical trial is calculated to show up to 15% reduction in risk over 3-5 years, but only long-term follow-up will really tell us whether the immune responses we see to the vaccine within the first few weeks will have a long-term effect,” he emphasized.

In clinical practice, “these people are cancer-free and healthy after surgery,” said Dr. Elliott. However, “they are at a high risk of recurrence; 30%-70% of ex-patients will develop new cancer in their lifetime and in the majority of cases that will happen within 2 years after surgery,” he said. “We think that vaccinating them against common lung cancer antigens could reduce this risk significantly and remove some of the uncertainty that they live with after their operation.”
 

Vaccine Has Potential for Immense Impact

Lung cancer remains one of the most frequently diagnosed cancers. “In the past few decades, public health measures including tobacco cessation and lung cancer screening have contributed to the reduction of lung cancer incidence and improved survival in high-income countries, but lung cancer continues to be the leading cause of cancer-related deaths worldwide,” Saadia A. Faiz, MD, a member of the CHEST Physician editorial board, said in an interview.

“Further, new cancer diagnoses continue to increase in low-income countries where there may not be widespread public health initiatives and/or access to healthcare. Thus, development of a vaccine to prevent lung cancer could be very impactful,” she said.

Challenges to vaccine development include the heterogeneous nature of the disease, which may occur in smokers and nonsmokers, said Dr. Faiz. “Targeting the various molecular markers may be challenging,” she said. However, building on the success of other vaccine initiatives, such as the human papillomavirus vaccine for cervical cancer, and COVID-19 vaccines with collaboration and clinical research will ideally overcome these challenges, she added.

“The potential implications for a lung cancer vaccine are immense,” said Dr. Faiz.

A lung cancer vaccine could prevent a deadly disease, but continued efforts in risk factor reduction and lung cancer screening will also be important, she said.

“Depending on the results of this clinical research, longitudinal data regarding efficacy, side effects, and prevention will be vital prior to application in high-risk patients in clinical practice,” she emphasized.

The development of the lung cancer vaccine is supported in part by Cancer Research UK and the CRIS Cancer Foundation. Dr. Elliott has received support from Cancer Research UK but had no financial conflicts to disclose. Dr. Faiz had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Development of a DNA-based lung cancer vaccine in the United Kingdom received funding for 2 years of laboratory research and initial manufacture of 3000 doses, according to a press release from the University of Oxford, England.

A team of scientists from the University of Oxford, the Francis Crick Institute, and University College London (UCL) will receive funding from the Cancer Research UK and the CRIS Cancer Foundation.

The LungVax vaccine is based on technology similar to that used in the creation of the successful Oxford/AstraZeneca COVID-19 vaccine and will carry a DNA strand that trains the immune system to recognize the neoantigens that indicate abnormal lung cancer cells and then activate the immune system to kill these cells and stop the cancer, according to the statement.

Initially, scientists are working to develop a vaccine that triggers an immune response in the lab setting. If successful, the vaccine will move directly into a clinical trial. “If the subsequent early trial delivers promising results, the vaccine could then be scaled up to bigger trials for people at high risk of lung cancer,” according to the release.
 

Help for High-Risk Patients

Lung cancer is diagnosed in approximately 48,000 individuals in the United Kingdom each year, and the average 10-year survival is only 10%, Tim Elliott, MD, professor of immuno-oncology at the University of Oxford and lead researcher on the LungVax project, said in an interview. Nearly three-quarters of the 35,000 annual deaths are preventable by quitting smoking, which remains the best risk reduction strategy to date, he said. However, “an intervention such as a vaccine, given when people are healthy and are more likely to have a strong immune system, could benefit many thousands per year in the UK and 1.8 million patients worldwide,” he said.
 

Preliminary Trial Plans

The initial trial of the vaccine is a collaboration between Oxford University, UCL, and the Francis Crick Institute, Dr. Elliott said. The trial is a culmination of research into the biology and genetics of lung cancer at UCL and vaccine design research at the University of Oxford.

“We are at a very early stage of the program, which will develop over the next 6 years if all goes to plan,” said Dr. Elliott. The vaccine is designed on the basis of shared lung cancer antigens and packaged into the ChAdOx delivery system that proved successful as the Oxford-AstraZeneca COVID-19 vaccine, he said.

“We intend to vaccinate individuals who have had curative surgery for their lung cancer after being diagnosed with a very early stage of the disease,” Dr. Elliott said.

Challenges to vaccine development include knowing whether there is a clinical benefit, Dr. Elliott noted. “Our clinical trial is calculated to show up to 15% reduction in risk over 3-5 years, but only long-term follow-up will really tell us whether the immune responses we see to the vaccine within the first few weeks will have a long-term effect,” he emphasized.

In clinical practice, “these people are cancer-free and healthy after surgery,” said Dr. Elliott. However, “they are at a high risk of recurrence; 30%-70% of ex-patients will develop new cancer in their lifetime and in the majority of cases that will happen within 2 years after surgery,” he said. “We think that vaccinating them against common lung cancer antigens could reduce this risk significantly and remove some of the uncertainty that they live with after their operation.”
 

Vaccine Has Potential for Immense Impact

Lung cancer remains one of the most frequently diagnosed cancers. “In the past few decades, public health measures including tobacco cessation and lung cancer screening have contributed to the reduction of lung cancer incidence and improved survival in high-income countries, but lung cancer continues to be the leading cause of cancer-related deaths worldwide,” Saadia A. Faiz, MD, a member of the CHEST Physician editorial board, said in an interview.

“Further, new cancer diagnoses continue to increase in low-income countries where there may not be widespread public health initiatives and/or access to healthcare. Thus, development of a vaccine to prevent lung cancer could be very impactful,” she said.

Challenges to vaccine development include the heterogeneous nature of the disease, which may occur in smokers and nonsmokers, said Dr. Faiz. “Targeting the various molecular markers may be challenging,” she said. However, building on the success of other vaccine initiatives, such as the human papillomavirus vaccine for cervical cancer, and COVID-19 vaccines with collaboration and clinical research will ideally overcome these challenges, she added.

“The potential implications for a lung cancer vaccine are immense,” said Dr. Faiz.

A lung cancer vaccine could prevent a deadly disease, but continued efforts in risk factor reduction and lung cancer screening will also be important, she said.

“Depending on the results of this clinical research, longitudinal data regarding efficacy, side effects, and prevention will be vital prior to application in high-risk patients in clinical practice,” she emphasized.

The development of the lung cancer vaccine is supported in part by Cancer Research UK and the CRIS Cancer Foundation. Dr. Elliott has received support from Cancer Research UK but had no financial conflicts to disclose. Dr. Faiz had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Many women with cancer want advice for managing sexual function issues, and clinicians are tuning in, new studies suggest.

Decreased sexual function is a side effect of many types of cancer, notably uterine, cervical, ovarian, and breast cancer, that often goes unaddressed, according to the authors of several studies presented at the Society of Gynecologic Oncology (SGO)’s Annual Meeting on Women’s Cancer.

Patients want to talk about sex, but not necessarily at the start of their diagnosis or treatment, suggest the findings of a study presented at the meeting. Jesse T. Brewer of Weill Cornell Medicine in New York City and colleagues enrolled 63 patients who underwent surgery with documented hereditary breast cancer, ovarian cancer, or Lynch syndrome in a cross-sectional survey.

Overall, 86% said that sexuality and intimacy were very or somewhat important, and 78% said that the healthcare team addressing the issue was very or somewhat important, the researchers found. However, only 40% of the respondents said that they wanted to discuss sexuality at the time of diagnosis because the idea was too overwhelming.

Oncologists are more aware of sexual side effects and the potential for sexual issues that persist long after treatment, but many patients may not have opportunities to talk about sexual concerns, said Don S. Dizon, MD, an oncologist specializing in women’s cancers at Brown University, Providence, Rhode Island, in an interview.

“It is important that we [oncologists] be the ones to open the door to these conversations; people with cancer will not bring it up spontaneously, for fear of making their provider uncomfortable, especially if they’ve never been asked about it before,” Dr. Dizon said in an interview.

He advised clinicians to find a network within their health systems so they can refer patients to specialized services, such as sex therapy, couples counseling, pelvic rehabilitation, or menopausal experts as needed.

In another study presented at the meeting, Naaman Mehta, MD, of NYU Langone Health, and colleagues reviewed data from 166 healthcare providers who completed a 23-item survey about evaluating and managing sexual health concerns of their patients. Most of the respondents were gynecologic oncologists (93.4%), but one radiation oncologist and 10 other healthcare providers also completed the survey.

Overall, approximately 60% of the respondents routinely asked about the sexual health concerns of their patients, and 98% of these said they believed that sexual health discussions should be held with a gynecologic oncologist. Just over half (54%) also said that the patient should be the one to initiate a discussion of sexual health concerns.

Female providers were significantly more likely to discuss sexual health with patients, compared with male providers, after controlling for the hospital setting and training level, the researchers noted (odds ratio, 1.4;P < .01).

The results suggest a need for more ways to integrate sexual health screening into gynecologic oncologic clinics, the researchers concluded.

The provider survey findings are similar to the results of a survey conducted by Dr. Dizon and colleagues in 2007. In that study, less than half of respondents took a sexual history, but 80% felt there was insufficient time to explore sexual issues.

“It is critical to understand that people with cancer do not expect their oncologists to be sexual health experts, but as with all other side effects caused by treatment and the diagnosis, we can be the ones who recognize it,” Dr. Dizon noted, in an interview.
 

Common Complaints and Causes

In Dr. Dizon’s experience, local symptoms including vaginal dryness, pain with penetration, and vaginal thinning, are common sexual complaints in women with cancer, as are systemic issues such as lack of interest and menopause-type symptoms.

“For those undergoing radiation, the vaginal tunnel can actually develop adhesions, and if not treated proactively this can lead to vaginal stenosis,” said Dr. Dizon, who was not involved in the studies presented at the meeting.

Comorbidities such as diabetes, cardiovascular disease, and musculoskeletal conditions can contribute to sexual issues in women with cancer, according to Nora Lersch, DNP, FNP-BC, AOCNP, and Nicole Dreibelbis, CRNP, the authors of other research presented at the meeting.

Culture, religion, fitness level, history of sexual violence, and gender spectrum health also play a role, as do anxiety and depression, dementia, and substance abuse disorders, the authors wrote in their presentation, “Prioritizing Sexual Health in Gynecological Oncology Care.”

Low libido is a frequent complaint across all cancer types, Ms. Dreibelbis, a nurse practitioner specializing in gynecologic oncology at the UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, said in an interview.

“Breast cancer patients, especially those on [aromatase inhibitor] therapy, often experience vaginal dryness and therefore dyspareunia,” she added.

The pelvic floor muscles, with their important role in sexual response, can be weakened by cancer treatment or surgery, and the pudendal nerves, which are the primary nerves responsible for sexual response in women, can be affected as well, Dr. Lersch and Ms. Dreibelbis wrote.
 

Taking Sex Seriously

Researchers are exploring the impact of different cancer prevention treatments for women to mitigate sexual side effects, as illustrated by another study presented at the meeting.

Dr. Barbara Norquist, MD, a gynecologic oncologist at the University of Washington, Seattle, and colleagues compared the sexual function and menopausal symptoms of patients at high risk of ovarian carcinoma who underwent either interval salpingectomy/delayed oophorectomy (ISDO) or risk-reducing salpingo-oophorectomy (RRSO).

“For patients at high risk for ovarian cancer, surgical removal of the tubes and ovaries is the mainstay of prevention, as screening is not effective at reducing death from ovarian cancer. As a result of surgery, many patients become suddenly postmenopausal from losing their ovaries,” Dr. Norquist said in an interview.

Some patients delay surgery out of concern for health and quality of life, including sexual function, she said.

In the study (known as the WISP trial) the researchers compared data from 166 patients who underwent immediate removal of the fallopian tubes and ovaries and 171 who underwent fallopian tube removal and delayed oophorectomy. All patients completed questionnaires about sexual function. The primary outcome was change in sexual function based on the sexual function index (FSFI) from baseline to 6 months after surgery.

Overall, changes in sexual function were significantly greater in the immediate oophorectomy group, compared with the delayed oophorectomy group at 6 months (33% vs 17%) and also at 12 months (43% vs 20%).

A further review of patients using hormone therapy showed that those in the immediate oophorectomy group still had greater decreases in sexual function, compared with the delayed group, though the difference between groups of patients using hormone therapy was less dramatic.

“I was surprised that, even with hormone replacement therapy, patients undergoing removal of the ovaries still had significant detrimental changes to sexual function when compared to those having the tubes removed, although this was even worse in those who could not take HRT,” Dr. Norquist said, in an interview. “I was reassured that menopausal symptoms in general were well managed with HRT, as these patients did not score differently on menopause symptoms, compared with those having their tubes removed,” she said.

Patients deserve accurate information about predicted changes in menopausal symptoms and sexual function as a result of ovary removal, and HRT should be provided when there is no contraindication, Dr. Norquist told this news organization.

Dr. Norquist and colleagues are awaiting the results of clinical trials investigating the safety of salpingectomy with delayed oophorectomy in terms of ovarian cancer prevention, but more research is needed to identify optimal management of the menopausal and sexual side effects associated with surgical menopause, she noted.

“Findings from the WISP study show the importance of hormones in women undergoing prophylactic surgery,” Dr. Dizon said. The findings indicate that salpingectomy has less of a negative influence on sexual function compared to removal of the ovaries, and the impact of hormone therapy and the relatively young age of the patients who took hormones reinforces current knowledge about hormones and sex, he added.
 

Barriers and Solutions

Barriers to asking women with cancer about sexual issues reported by providers include limited time, lack of training in sexual health, a desire to avoid offending the patient or making them uncomfortable, and uncertainty about how to answer the questions, Dr. Lersch and Ms. Dreibelbis wrote in their presentation.

Barriers to asking healthcare providers about their sexual issues reported by patients include the beliefs that the clinician should initiate the discussion, that sexual function will not be taken seriously, and that they might make the provider uncomfortable.

“Fortunately, more information and research has been done on sexual health and gynecological cancer in recent years, so oncologists are becoming more aware of the issues women may have,” said Dr. Lersch who is an oncology nurse practitioner at Providence Franz Cancer Institute in Portland, Oregon, in an interview.

Telling patients early in their cancer treatment about potential sexual side effects and opportunities for help is essential, she added.

Although oncologists have become more aware of the importance of sexual health and well-being for their patients, “I think there has historically been a disconnect in including sexual health education in medical training,” Ms. Dreibelbis said in an interview.

Dr. Lersch and Ms. Dreibelbis advised a multidimensional approach to managing sexual problems in cancer patients that includes consideration of biological and psychological symptoms, but also social, cultural, and interpersonal factors, in their presentation.

Their suggestions include discussing dyspareunia with their patients, asking for details such as whether the pain is internal or external, whether it occurs with activities outside of sex including masturbation, and whether bleeding is present.

Oncology therapies and surgeries can decrease or eliminate an individual’s ability to produce their own lubricant; for example, removal of the cervix eliminates cervical mucous, which helps with internal lubrication, they wrote in their presentation.

For patients with dyspareunia, Dr. Lersch and Ms. Dreibelbis recommend a vaginal moisturizer especially formulated for vaginal tissue that can be absorbed by the mucosal tissue of the vagina. Use of this type of product can increase the effectiveness of lubricants and help restore integrity of the vaginal tissue. Such moisturizers are available as gels, creams, or suppositories over the counter, and do not contain hormones.

Vaginal estrogen can be helpful for burning, itching, irritation, tissue fragility, and pain with sex, according to Dr. Lersch and Ms. Dreibelbis. Adequate estrogen therapy can promote normalization of vaginal pH and microflora, as well increase vaginal secretion and reduce pain and dryness with intercourse, the presenters stated in their presentation. In addition, dilator therapy can be used to help prevent vaginal stenosis, and penetration bumpers can help relieve discomfort during intercourse, they wrote.

Looking ahead, more research is needed to serve a wider patient population, Ms. Dreibelbis said, in an interview.

“LGBTQIA [individuals] have not been included in sexual health research and there are more people than ever who identify within this group of people. I know there has also been some very early work on shielding the clitoris from the impacts of radiation, and I believe this is extremely important up-and-coming research,” she said.

Dr. Lersch, Ms. Dreibelbi, Dr. Dizon, Dr. Norquist, Ms. Brewer, and Dr. Mehta had no financial conflicts to disclose.

Many women with cancer want advice for managing sexual function issues, and clinicians are tuning in, new studies suggest.

Decreased sexual function is a side effect of many types of cancer, notably uterine, cervical, ovarian, and breast cancer, that often goes unaddressed, according to the authors of several studies presented at the Society of Gynecologic Oncology (SGO)’s Annual Meeting on Women’s Cancer.

Patients want to talk about sex, but not necessarily at the start of their diagnosis or treatment, suggest the findings of a study presented at the meeting. Jesse T. Brewer of Weill Cornell Medicine in New York City and colleagues enrolled 63 patients who underwent surgery with documented hereditary breast cancer, ovarian cancer, or Lynch syndrome in a cross-sectional survey.

Overall, 86% said that sexuality and intimacy were very or somewhat important, and 78% said that the healthcare team addressing the issue was very or somewhat important, the researchers found. However, only 40% of the respondents said that they wanted to discuss sexuality at the time of diagnosis because the idea was too overwhelming.

Oncologists are more aware of sexual side effects and the potential for sexual issues that persist long after treatment, but many patients may not have opportunities to talk about sexual concerns, said Don S. Dizon, MD, an oncologist specializing in women’s cancers at Brown University, Providence, Rhode Island, in an interview.

“It is important that we [oncologists] be the ones to open the door to these conversations; people with cancer will not bring it up spontaneously, for fear of making their provider uncomfortable, especially if they’ve never been asked about it before,” Dr. Dizon said in an interview.

He advised clinicians to find a network within their health systems so they can refer patients to specialized services, such as sex therapy, couples counseling, pelvic rehabilitation, or menopausal experts as needed.

In another study presented at the meeting, Naaman Mehta, MD, of NYU Langone Health, and colleagues reviewed data from 166 healthcare providers who completed a 23-item survey about evaluating and managing sexual health concerns of their patients. Most of the respondents were gynecologic oncologists (93.4%), but one radiation oncologist and 10 other healthcare providers also completed the survey.

Overall, approximately 60% of the respondents routinely asked about the sexual health concerns of their patients, and 98% of these said they believed that sexual health discussions should be held with a gynecologic oncologist. Just over half (54%) also said that the patient should be the one to initiate a discussion of sexual health concerns.

Female providers were significantly more likely to discuss sexual health with patients, compared with male providers, after controlling for the hospital setting and training level, the researchers noted (odds ratio, 1.4;P < .01).

The results suggest a need for more ways to integrate sexual health screening into gynecologic oncologic clinics, the researchers concluded.

The provider survey findings are similar to the results of a survey conducted by Dr. Dizon and colleagues in 2007. In that study, less than half of respondents took a sexual history, but 80% felt there was insufficient time to explore sexual issues.

“It is critical to understand that people with cancer do not expect their oncologists to be sexual health experts, but as with all other side effects caused by treatment and the diagnosis, we can be the ones who recognize it,” Dr. Dizon noted, in an interview.
 

Common Complaints and Causes

In Dr. Dizon’s experience, local symptoms including vaginal dryness, pain with penetration, and vaginal thinning, are common sexual complaints in women with cancer, as are systemic issues such as lack of interest and menopause-type symptoms.

“For those undergoing radiation, the vaginal tunnel can actually develop adhesions, and if not treated proactively this can lead to vaginal stenosis,” said Dr. Dizon, who was not involved in the studies presented at the meeting.

Comorbidities such as diabetes, cardiovascular disease, and musculoskeletal conditions can contribute to sexual issues in women with cancer, according to Nora Lersch, DNP, FNP-BC, AOCNP, and Nicole Dreibelbis, CRNP, the authors of other research presented at the meeting.

Culture, religion, fitness level, history of sexual violence, and gender spectrum health also play a role, as do anxiety and depression, dementia, and substance abuse disorders, the authors wrote in their presentation, “Prioritizing Sexual Health in Gynecological Oncology Care.”

Low libido is a frequent complaint across all cancer types, Ms. Dreibelbis, a nurse practitioner specializing in gynecologic oncology at the UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, said in an interview.

“Breast cancer patients, especially those on [aromatase inhibitor] therapy, often experience vaginal dryness and therefore dyspareunia,” she added.

The pelvic floor muscles, with their important role in sexual response, can be weakened by cancer treatment or surgery, and the pudendal nerves, which are the primary nerves responsible for sexual response in women, can be affected as well, Dr. Lersch and Ms. Dreibelbis wrote.
 

Taking Sex Seriously

Researchers are exploring the impact of different cancer prevention treatments for women to mitigate sexual side effects, as illustrated by another study presented at the meeting.

Dr. Barbara Norquist, MD, a gynecologic oncologist at the University of Washington, Seattle, and colleagues compared the sexual function and menopausal symptoms of patients at high risk of ovarian carcinoma who underwent either interval salpingectomy/delayed oophorectomy (ISDO) or risk-reducing salpingo-oophorectomy (RRSO).

“For patients at high risk for ovarian cancer, surgical removal of the tubes and ovaries is the mainstay of prevention, as screening is not effective at reducing death from ovarian cancer. As a result of surgery, many patients become suddenly postmenopausal from losing their ovaries,” Dr. Norquist said in an interview.

Some patients delay surgery out of concern for health and quality of life, including sexual function, she said.

In the study (known as the WISP trial) the researchers compared data from 166 patients who underwent immediate removal of the fallopian tubes and ovaries and 171 who underwent fallopian tube removal and delayed oophorectomy. All patients completed questionnaires about sexual function. The primary outcome was change in sexual function based on the sexual function index (FSFI) from baseline to 6 months after surgery.

Overall, changes in sexual function were significantly greater in the immediate oophorectomy group, compared with the delayed oophorectomy group at 6 months (33% vs 17%) and also at 12 months (43% vs 20%).

A further review of patients using hormone therapy showed that those in the immediate oophorectomy group still had greater decreases in sexual function, compared with the delayed group, though the difference between groups of patients using hormone therapy was less dramatic.

“I was surprised that, even with hormone replacement therapy, patients undergoing removal of the ovaries still had significant detrimental changes to sexual function when compared to those having the tubes removed, although this was even worse in those who could not take HRT,” Dr. Norquist said, in an interview. “I was reassured that menopausal symptoms in general were well managed with HRT, as these patients did not score differently on menopause symptoms, compared with those having their tubes removed,” she said.

Patients deserve accurate information about predicted changes in menopausal symptoms and sexual function as a result of ovary removal, and HRT should be provided when there is no contraindication, Dr. Norquist told this news organization.

Dr. Norquist and colleagues are awaiting the results of clinical trials investigating the safety of salpingectomy with delayed oophorectomy in terms of ovarian cancer prevention, but more research is needed to identify optimal management of the menopausal and sexual side effects associated with surgical menopause, she noted.

“Findings from the WISP study show the importance of hormones in women undergoing prophylactic surgery,” Dr. Dizon said. The findings indicate that salpingectomy has less of a negative influence on sexual function compared to removal of the ovaries, and the impact of hormone therapy and the relatively young age of the patients who took hormones reinforces current knowledge about hormones and sex, he added.
 

Barriers and Solutions

Barriers to asking women with cancer about sexual issues reported by providers include limited time, lack of training in sexual health, a desire to avoid offending the patient or making them uncomfortable, and uncertainty about how to answer the questions, Dr. Lersch and Ms. Dreibelbis wrote in their presentation.

Barriers to asking healthcare providers about their sexual issues reported by patients include the beliefs that the clinician should initiate the discussion, that sexual function will not be taken seriously, and that they might make the provider uncomfortable.

“Fortunately, more information and research has been done on sexual health and gynecological cancer in recent years, so oncologists are becoming more aware of the issues women may have,” said Dr. Lersch who is an oncology nurse practitioner at Providence Franz Cancer Institute in Portland, Oregon, in an interview.

Telling patients early in their cancer treatment about potential sexual side effects and opportunities for help is essential, she added.

Although oncologists have become more aware of the importance of sexual health and well-being for their patients, “I think there has historically been a disconnect in including sexual health education in medical training,” Ms. Dreibelbis said in an interview.

Dr. Lersch and Ms. Dreibelbis advised a multidimensional approach to managing sexual problems in cancer patients that includes consideration of biological and psychological symptoms, but also social, cultural, and interpersonal factors, in their presentation.

Their suggestions include discussing dyspareunia with their patients, asking for details such as whether the pain is internal or external, whether it occurs with activities outside of sex including masturbation, and whether bleeding is present.

Oncology therapies and surgeries can decrease or eliminate an individual’s ability to produce their own lubricant; for example, removal of the cervix eliminates cervical mucous, which helps with internal lubrication, they wrote in their presentation.

For patients with dyspareunia, Dr. Lersch and Ms. Dreibelbis recommend a vaginal moisturizer especially formulated for vaginal tissue that can be absorbed by the mucosal tissue of the vagina. Use of this type of product can increase the effectiveness of lubricants and help restore integrity of the vaginal tissue. Such moisturizers are available as gels, creams, or suppositories over the counter, and do not contain hormones.

Vaginal estrogen can be helpful for burning, itching, irritation, tissue fragility, and pain with sex, according to Dr. Lersch and Ms. Dreibelbis. Adequate estrogen therapy can promote normalization of vaginal pH and microflora, as well increase vaginal secretion and reduce pain and dryness with intercourse, the presenters stated in their presentation. In addition, dilator therapy can be used to help prevent vaginal stenosis, and penetration bumpers can help relieve discomfort during intercourse, they wrote.

Looking ahead, more research is needed to serve a wider patient population, Ms. Dreibelbis said, in an interview.

“LGBTQIA [individuals] have not been included in sexual health research and there are more people than ever who identify within this group of people. I know there has also been some very early work on shielding the clitoris from the impacts of radiation, and I believe this is extremely important up-and-coming research,” she said.

Dr. Lersch, Ms. Dreibelbi, Dr. Dizon, Dr. Norquist, Ms. Brewer, and Dr. Mehta had no financial conflicts to disclose.

Many women with cancer want advice for managing sexual function issues, and clinicians are tuning in, new studies suggest.

Decreased sexual function is a side effect of many types of cancer, notably uterine, cervical, ovarian, and breast cancer, that often goes unaddressed, according to the authors of several studies presented at the Society of Gynecologic Oncology (SGO)’s Annual Meeting on Women’s Cancer.

Patients want to talk about sex, but not necessarily at the start of their diagnosis or treatment, suggest the findings of a study presented at the meeting. Jesse T. Brewer of Weill Cornell Medicine in New York City and colleagues enrolled 63 patients who underwent surgery with documented hereditary breast cancer, ovarian cancer, or Lynch syndrome in a cross-sectional survey.

Overall, 86% said that sexuality and intimacy were very or somewhat important, and 78% said that the healthcare team addressing the issue was very or somewhat important, the researchers found. However, only 40% of the respondents said that they wanted to discuss sexuality at the time of diagnosis because the idea was too overwhelming.

Oncologists are more aware of sexual side effects and the potential for sexual issues that persist long after treatment, but many patients may not have opportunities to talk about sexual concerns, said Don S. Dizon, MD, an oncologist specializing in women’s cancers at Brown University, Providence, Rhode Island, in an interview.

“It is important that we [oncologists] be the ones to open the door to these conversations; people with cancer will not bring it up spontaneously, for fear of making their provider uncomfortable, especially if they’ve never been asked about it before,” Dr. Dizon said in an interview.

He advised clinicians to find a network within their health systems so they can refer patients to specialized services, such as sex therapy, couples counseling, pelvic rehabilitation, or menopausal experts as needed.

In another study presented at the meeting, Naaman Mehta, MD, of NYU Langone Health, and colleagues reviewed data from 166 healthcare providers who completed a 23-item survey about evaluating and managing sexual health concerns of their patients. Most of the respondents were gynecologic oncologists (93.4%), but one radiation oncologist and 10 other healthcare providers also completed the survey.

Overall, approximately 60% of the respondents routinely asked about the sexual health concerns of their patients, and 98% of these said they believed that sexual health discussions should be held with a gynecologic oncologist. Just over half (54%) also said that the patient should be the one to initiate a discussion of sexual health concerns.

Female providers were significantly more likely to discuss sexual health with patients, compared with male providers, after controlling for the hospital setting and training level, the researchers noted (odds ratio, 1.4;P < .01).

The results suggest a need for more ways to integrate sexual health screening into gynecologic oncologic clinics, the researchers concluded.

The provider survey findings are similar to the results of a survey conducted by Dr. Dizon and colleagues in 2007. In that study, less than half of respondents took a sexual history, but 80% felt there was insufficient time to explore sexual issues.

“It is critical to understand that people with cancer do not expect their oncologists to be sexual health experts, but as with all other side effects caused by treatment and the diagnosis, we can be the ones who recognize it,” Dr. Dizon noted, in an interview.
 

Common Complaints and Causes

In Dr. Dizon’s experience, local symptoms including vaginal dryness, pain with penetration, and vaginal thinning, are common sexual complaints in women with cancer, as are systemic issues such as lack of interest and menopause-type symptoms.

“For those undergoing radiation, the vaginal tunnel can actually develop adhesions, and if not treated proactively this can lead to vaginal stenosis,” said Dr. Dizon, who was not involved in the studies presented at the meeting.

Comorbidities such as diabetes, cardiovascular disease, and musculoskeletal conditions can contribute to sexual issues in women with cancer, according to Nora Lersch, DNP, FNP-BC, AOCNP, and Nicole Dreibelbis, CRNP, the authors of other research presented at the meeting.

Culture, religion, fitness level, history of sexual violence, and gender spectrum health also play a role, as do anxiety and depression, dementia, and substance abuse disorders, the authors wrote in their presentation, “Prioritizing Sexual Health in Gynecological Oncology Care.”

Low libido is a frequent complaint across all cancer types, Ms. Dreibelbis, a nurse practitioner specializing in gynecologic oncology at the UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, said in an interview.

“Breast cancer patients, especially those on [aromatase inhibitor] therapy, often experience vaginal dryness and therefore dyspareunia,” she added.

The pelvic floor muscles, with their important role in sexual response, can be weakened by cancer treatment or surgery, and the pudendal nerves, which are the primary nerves responsible for sexual response in women, can be affected as well, Dr. Lersch and Ms. Dreibelbis wrote.
 

Taking Sex Seriously

Researchers are exploring the impact of different cancer prevention treatments for women to mitigate sexual side effects, as illustrated by another study presented at the meeting.

Dr. Barbara Norquist, MD, a gynecologic oncologist at the University of Washington, Seattle, and colleagues compared the sexual function and menopausal symptoms of patients at high risk of ovarian carcinoma who underwent either interval salpingectomy/delayed oophorectomy (ISDO) or risk-reducing salpingo-oophorectomy (RRSO).

“For patients at high risk for ovarian cancer, surgical removal of the tubes and ovaries is the mainstay of prevention, as screening is not effective at reducing death from ovarian cancer. As a result of surgery, many patients become suddenly postmenopausal from losing their ovaries,” Dr. Norquist said in an interview.

Some patients delay surgery out of concern for health and quality of life, including sexual function, she said.

In the study (known as the WISP trial) the researchers compared data from 166 patients who underwent immediate removal of the fallopian tubes and ovaries and 171 who underwent fallopian tube removal and delayed oophorectomy. All patients completed questionnaires about sexual function. The primary outcome was change in sexual function based on the sexual function index (FSFI) from baseline to 6 months after surgery.

Overall, changes in sexual function were significantly greater in the immediate oophorectomy group, compared with the delayed oophorectomy group at 6 months (33% vs 17%) and also at 12 months (43% vs 20%).

A further review of patients using hormone therapy showed that those in the immediate oophorectomy group still had greater decreases in sexual function, compared with the delayed group, though the difference between groups of patients using hormone therapy was less dramatic.

“I was surprised that, even with hormone replacement therapy, patients undergoing removal of the ovaries still had significant detrimental changes to sexual function when compared to those having the tubes removed, although this was even worse in those who could not take HRT,” Dr. Norquist said, in an interview. “I was reassured that menopausal symptoms in general were well managed with HRT, as these patients did not score differently on menopause symptoms, compared with those having their tubes removed,” she said.

Patients deserve accurate information about predicted changes in menopausal symptoms and sexual function as a result of ovary removal, and HRT should be provided when there is no contraindication, Dr. Norquist told this news organization.

Dr. Norquist and colleagues are awaiting the results of clinical trials investigating the safety of salpingectomy with delayed oophorectomy in terms of ovarian cancer prevention, but more research is needed to identify optimal management of the menopausal and sexual side effects associated with surgical menopause, she noted.

“Findings from the WISP study show the importance of hormones in women undergoing prophylactic surgery,” Dr. Dizon said. The findings indicate that salpingectomy has less of a negative influence on sexual function compared to removal of the ovaries, and the impact of hormone therapy and the relatively young age of the patients who took hormones reinforces current knowledge about hormones and sex, he added.
 

Barriers and Solutions

Barriers to asking women with cancer about sexual issues reported by providers include limited time, lack of training in sexual health, a desire to avoid offending the patient or making them uncomfortable, and uncertainty about how to answer the questions, Dr. Lersch and Ms. Dreibelbis wrote in their presentation.

Barriers to asking healthcare providers about their sexual issues reported by patients include the beliefs that the clinician should initiate the discussion, that sexual function will not be taken seriously, and that they might make the provider uncomfortable.

“Fortunately, more information and research has been done on sexual health and gynecological cancer in recent years, so oncologists are becoming more aware of the issues women may have,” said Dr. Lersch who is an oncology nurse practitioner at Providence Franz Cancer Institute in Portland, Oregon, in an interview.

Telling patients early in their cancer treatment about potential sexual side effects and opportunities for help is essential, she added.

Although oncologists have become more aware of the importance of sexual health and well-being for their patients, “I think there has historically been a disconnect in including sexual health education in medical training,” Ms. Dreibelbis said in an interview.

Dr. Lersch and Ms. Dreibelbis advised a multidimensional approach to managing sexual problems in cancer patients that includes consideration of biological and psychological symptoms, but also social, cultural, and interpersonal factors, in their presentation.

Their suggestions include discussing dyspareunia with their patients, asking for details such as whether the pain is internal or external, whether it occurs with activities outside of sex including masturbation, and whether bleeding is present.

Oncology therapies and surgeries can decrease or eliminate an individual’s ability to produce their own lubricant; for example, removal of the cervix eliminates cervical mucous, which helps with internal lubrication, they wrote in their presentation.

For patients with dyspareunia, Dr. Lersch and Ms. Dreibelbis recommend a vaginal moisturizer especially formulated for vaginal tissue that can be absorbed by the mucosal tissue of the vagina. Use of this type of product can increase the effectiveness of lubricants and help restore integrity of the vaginal tissue. Such moisturizers are available as gels, creams, or suppositories over the counter, and do not contain hormones.

Vaginal estrogen can be helpful for burning, itching, irritation, tissue fragility, and pain with sex, according to Dr. Lersch and Ms. Dreibelbis. Adequate estrogen therapy can promote normalization of vaginal pH and microflora, as well increase vaginal secretion and reduce pain and dryness with intercourse, the presenters stated in their presentation. In addition, dilator therapy can be used to help prevent vaginal stenosis, and penetration bumpers can help relieve discomfort during intercourse, they wrote.

Looking ahead, more research is needed to serve a wider patient population, Ms. Dreibelbis said, in an interview.

“LGBTQIA [individuals] have not been included in sexual health research and there are more people than ever who identify within this group of people. I know there has also been some very early work on shielding the clitoris from the impacts of radiation, and I believe this is extremely important up-and-coming research,” she said.

Dr. Lersch, Ms. Dreibelbi, Dr. Dizon, Dr. Norquist, Ms. Brewer, and Dr. Mehta had no financial conflicts to disclose.

Children and adolescents with functional constipation showed significantly greater increases in spontaneous bowel movements with linaclotide compared with placebo, according to data from 330 individuals.

“Functional constipation is prevalent in pediatrics and is associated with chronic burdensome symptoms and impaired quality of life with an unmet need for treatment options for this age group,” corresponding study author Julie Khlevner, MD, AGAF, a pediatric gastroenterologist at Columbia University Vagelos College of Physicians and Surgeons, New York, said in an interview.

Jörg Meyer

“Linaclotide has been approved for adults with chronic idiopathic constipation and irritable bowel syndrome with constipation, but its efficacy and safety in pediatric patients were unknown. Therefore, evaluating its use in this population was crucial to provide evidence-based treatment option,” she said.

In a study published in The Lancet Gastroenterology & Hepatology, the researchers randomized 166 pediatric patients with functional constipation to 72 micrograms of linaclotide once daily for 12 weeks and 164 to a placebo. The study was conducted at 64 clinic or hospital sites across 7 countries between October 1, 2019, and March 21, 2022. Approximately half (55%) of the patients were female.

The primary outcome was a change from baseline to 12 weeks in the frequency of spontaneous bowel movements (SBMs) per week, with no rescue medication on the day of or before the bowel movement. The secondary endpoint was change in stool consistency from baseline to 12 weeks. The mean frequency for SBMs at baseline was 1.16 per week in patients randomized to linaclotide and 1.28 for those randomized to placebo; these rates increased to 3.41 and 2.29, respectively, over the study period. The linaclotide patients showed a significantly greater improvement over placebo patients based on least-squares mean change from baseline (2.22 vs. 1.05, P = .0001).

In a subgroup analysis by age, the response was stronger in younger patients aged 6-11 years than in those aged 12-17 years, the researchers noted. This difference might stem from different pathophysiological mechanisms between older and younger ages, such as withholding behavior, they added.

Linaclotide was well tolerated overall; the most frequently reported treatment-emergent events were diarrhea (seven linaclotide patients and three placebo patients). In addition, five linaclotide patients and four placebo patients developed COVID-19 during treatment. No deaths occurred during the study, but one serious adverse event involving severe diarrhea, dehydration, and hospitalization, occurred in a 17-year-old female patient, but resolved after administration of intravenous fluids, the researchers noted.
 

Clinical Implications and Next Steps

The study findings reflect previous research on linaclotide in adults, Dr. Khlevner said. “The significant improvement in spontaneous bowel movements frequency and stool consistency with linaclotide compared to placebo is consistent with its mechanism of action as a guanylate cyclase C agonist,” she noted.

In clinical practice, barriers to the use of linaclotide may include lack of awareness of linaclotide’s safety and efficacy profile, and of its Food and Drug Administration approval for use in children aged 6-17 years with functional constipation, said Dr. Khlevner. “Additionally, access to the medication and insurance coverage may be potential barriers for some patients.” However, “some of these barriers can be overcome through education and training of healthcare providers regarding the appropriate use of linaclotide in pediatric patients with functional constipation,” she added.

The findings were limited by several factors including potential measurement bias and selection bias, lack of assessment of lifestyle modifications as confounding factors, and lack of quality-of-life assessment, the researchers noted. Other limitations included the relatively short 12-week treatment duration, which may not fully capture long-term safety and efficacy, and the focus on patients aged 6-17 years, Dr. Khlevner told this news organization.

“Future research could address these limitations through longer-term studies with broader age ranges and incorporating patient-reported outcomes in real world situations to assess the overall impact of linaclotide treatment on pediatric patients with functional constipation,” she said.

Study Supports Noninvasive Treatment Option

An alternative medication for children with functional constipation who do not respond to current therapies could prevent the use of more invasive interventions such as frequent enemas or antegrade enemas, Stephen M. Borowitz, MD, professor of pediatrics at the University of Virginia, Charlottesville, said in an interview.

Dr. Borowitz said he was not surprised by study findings. “Given the mechanism of action of the drug, I would expect the majority of children with functional constipation to respond in the sense of having more frequent and softer stools,” he said. “The bigger question, which wasn’t answered, is whether children who fail more conservative therapies respond to linaclotide,” said Dr. Borowitz, who was not involved in the study. “This was a phase 3 trial of otherwise healthy children with functional constipation and we know the majority of these children will respond to aggressive management with osmotic stool softeners, plus or minus a stimulant like senna coupled with lifestyle modifications (such as drinking more fluid, regular toileting, and appropriate toileting behaviors),” he said.

The greatest short-term barrier to the expanded use of linaclotide in clinical practice will likely be cost, and whether insurance will cover the drug, Dr. Borowitz told this news organization. Insurance coverage may not be an option until the child has failed more conservative, less expensive therapies, he said.

Also, the current study was a placebo-controlled trial, and not a comparison between linaclotide and polyethylene glycol, plus or minus senna, with other routine interventions, he said.

Looking ahead, “now that we know linaclotide is better than placebo, we need to know if it is as good, better, or worse than other proven interventions, and perhaps even more importantly, is it effective among children who have failed more conservative management,” Dr. Borowitz said. “We also need to know long-term risks, and given that the majority of childhood constipation develops before age 6 years, whether the drug can be used in younger children,” he emphasized. If so, studies need to examine whether linaclotide alters the natural history of the problem, he added. Previous studies suggest that the longer the symptom goes on, the harder it is to undo the secondary behaviors that result, such as withholding, pelvic floor dysfunction, and toileting refusal, he noted.

The study was supported by AbbVie and Ironwood Pharmaceuticals. The lead author, Carlo Di Lorenzo, MD, disclosed consulting fees from AbbVie, Ironwood Pharmaceuticals, Mallinckrodt, NeurAxis, QOL Medical, and Takeda. Dr. Khlevner disclosed honoraria from Abbott Pediatric Nutrition and participation on a data safety monitoring board and advisory board for AbbVie. Dr. Borowitz had no financial conflicts to disclose.

Children and adolescents with functional constipation showed significantly greater increases in spontaneous bowel movements with linaclotide compared with placebo, according to data from 330 individuals.

“Functional constipation is prevalent in pediatrics and is associated with chronic burdensome symptoms and impaired quality of life with an unmet need for treatment options for this age group,” corresponding study author Julie Khlevner, MD, AGAF, a pediatric gastroenterologist at Columbia University Vagelos College of Physicians and Surgeons, New York, said in an interview.

Jörg Meyer

“Linaclotide has been approved for adults with chronic idiopathic constipation and irritable bowel syndrome with constipation, but its efficacy and safety in pediatric patients were unknown. Therefore, evaluating its use in this population was crucial to provide evidence-based treatment option,” she said.

In a study published in The Lancet Gastroenterology & Hepatology, the researchers randomized 166 pediatric patients with functional constipation to 72 micrograms of linaclotide once daily for 12 weeks and 164 to a placebo. The study was conducted at 64 clinic or hospital sites across 7 countries between October 1, 2019, and March 21, 2022. Approximately half (55%) of the patients were female.

The primary outcome was a change from baseline to 12 weeks in the frequency of spontaneous bowel movements (SBMs) per week, with no rescue medication on the day of or before the bowel movement. The secondary endpoint was change in stool consistency from baseline to 12 weeks. The mean frequency for SBMs at baseline was 1.16 per week in patients randomized to linaclotide and 1.28 for those randomized to placebo; these rates increased to 3.41 and 2.29, respectively, over the study period. The linaclotide patients showed a significantly greater improvement over placebo patients based on least-squares mean change from baseline (2.22 vs. 1.05, P = .0001).

In a subgroup analysis by age, the response was stronger in younger patients aged 6-11 years than in those aged 12-17 years, the researchers noted. This difference might stem from different pathophysiological mechanisms between older and younger ages, such as withholding behavior, they added.

Linaclotide was well tolerated overall; the most frequently reported treatment-emergent events were diarrhea (seven linaclotide patients and three placebo patients). In addition, five linaclotide patients and four placebo patients developed COVID-19 during treatment. No deaths occurred during the study, but one serious adverse event involving severe diarrhea, dehydration, and hospitalization, occurred in a 17-year-old female patient, but resolved after administration of intravenous fluids, the researchers noted.
 

Clinical Implications and Next Steps

The study findings reflect previous research on linaclotide in adults, Dr. Khlevner said. “The significant improvement in spontaneous bowel movements frequency and stool consistency with linaclotide compared to placebo is consistent with its mechanism of action as a guanylate cyclase C agonist,” she noted.

In clinical practice, barriers to the use of linaclotide may include lack of awareness of linaclotide’s safety and efficacy profile, and of its Food and Drug Administration approval for use in children aged 6-17 years with functional constipation, said Dr. Khlevner. “Additionally, access to the medication and insurance coverage may be potential barriers for some patients.” However, “some of these barriers can be overcome through education and training of healthcare providers regarding the appropriate use of linaclotide in pediatric patients with functional constipation,” she added.

The findings were limited by several factors including potential measurement bias and selection bias, lack of assessment of lifestyle modifications as confounding factors, and lack of quality-of-life assessment, the researchers noted. Other limitations included the relatively short 12-week treatment duration, which may not fully capture long-term safety and efficacy, and the focus on patients aged 6-17 years, Dr. Khlevner told this news organization.

“Future research could address these limitations through longer-term studies with broader age ranges and incorporating patient-reported outcomes in real world situations to assess the overall impact of linaclotide treatment on pediatric patients with functional constipation,” she said.

Study Supports Noninvasive Treatment Option

An alternative medication for children with functional constipation who do not respond to current therapies could prevent the use of more invasive interventions such as frequent enemas or antegrade enemas, Stephen M. Borowitz, MD, professor of pediatrics at the University of Virginia, Charlottesville, said in an interview.

Dr. Borowitz said he was not surprised by study findings. “Given the mechanism of action of the drug, I would expect the majority of children with functional constipation to respond in the sense of having more frequent and softer stools,” he said. “The bigger question, which wasn’t answered, is whether children who fail more conservative therapies respond to linaclotide,” said Dr. Borowitz, who was not involved in the study. “This was a phase 3 trial of otherwise healthy children with functional constipation and we know the majority of these children will respond to aggressive management with osmotic stool softeners, plus or minus a stimulant like senna coupled with lifestyle modifications (such as drinking more fluid, regular toileting, and appropriate toileting behaviors),” he said.

The greatest short-term barrier to the expanded use of linaclotide in clinical practice will likely be cost, and whether insurance will cover the drug, Dr. Borowitz told this news organization. Insurance coverage may not be an option until the child has failed more conservative, less expensive therapies, he said.

Also, the current study was a placebo-controlled trial, and not a comparison between linaclotide and polyethylene glycol, plus or minus senna, with other routine interventions, he said.

Looking ahead, “now that we know linaclotide is better than placebo, we need to know if it is as good, better, or worse than other proven interventions, and perhaps even more importantly, is it effective among children who have failed more conservative management,” Dr. Borowitz said. “We also need to know long-term risks, and given that the majority of childhood constipation develops before age 6 years, whether the drug can be used in younger children,” he emphasized. If so, studies need to examine whether linaclotide alters the natural history of the problem, he added. Previous studies suggest that the longer the symptom goes on, the harder it is to undo the secondary behaviors that result, such as withholding, pelvic floor dysfunction, and toileting refusal, he noted.

The study was supported by AbbVie and Ironwood Pharmaceuticals. The lead author, Carlo Di Lorenzo, MD, disclosed consulting fees from AbbVie, Ironwood Pharmaceuticals, Mallinckrodt, NeurAxis, QOL Medical, and Takeda. Dr. Khlevner disclosed honoraria from Abbott Pediatric Nutrition and participation on a data safety monitoring board and advisory board for AbbVie. Dr. Borowitz had no financial conflicts to disclose.

Children and adolescents with functional constipation showed significantly greater increases in spontaneous bowel movements with linaclotide compared with placebo, according to data from 330 individuals.

“Functional constipation is prevalent in pediatrics and is associated with chronic burdensome symptoms and impaired quality of life with an unmet need for treatment options for this age group,” corresponding study author Julie Khlevner, MD, AGAF, a pediatric gastroenterologist at Columbia University Vagelos College of Physicians and Surgeons, New York, said in an interview.

Jörg Meyer

“Linaclotide has been approved for adults with chronic idiopathic constipation and irritable bowel syndrome with constipation, but its efficacy and safety in pediatric patients were unknown. Therefore, evaluating its use in this population was crucial to provide evidence-based treatment option,” she said.

In a study published in The Lancet Gastroenterology & Hepatology, the researchers randomized 166 pediatric patients with functional constipation to 72 micrograms of linaclotide once daily for 12 weeks and 164 to a placebo. The study was conducted at 64 clinic or hospital sites across 7 countries between October 1, 2019, and March 21, 2022. Approximately half (55%) of the patients were female.

The primary outcome was a change from baseline to 12 weeks in the frequency of spontaneous bowel movements (SBMs) per week, with no rescue medication on the day of or before the bowel movement. The secondary endpoint was change in stool consistency from baseline to 12 weeks. The mean frequency for SBMs at baseline was 1.16 per week in patients randomized to linaclotide and 1.28 for those randomized to placebo; these rates increased to 3.41 and 2.29, respectively, over the study period. The linaclotide patients showed a significantly greater improvement over placebo patients based on least-squares mean change from baseline (2.22 vs. 1.05, P = .0001).

In a subgroup analysis by age, the response was stronger in younger patients aged 6-11 years than in those aged 12-17 years, the researchers noted. This difference might stem from different pathophysiological mechanisms between older and younger ages, such as withholding behavior, they added.

Linaclotide was well tolerated overall; the most frequently reported treatment-emergent events were diarrhea (seven linaclotide patients and three placebo patients). In addition, five linaclotide patients and four placebo patients developed COVID-19 during treatment. No deaths occurred during the study, but one serious adverse event involving severe diarrhea, dehydration, and hospitalization, occurred in a 17-year-old female patient, but resolved after administration of intravenous fluids, the researchers noted.
 

Clinical Implications and Next Steps

The study findings reflect previous research on linaclotide in adults, Dr. Khlevner said. “The significant improvement in spontaneous bowel movements frequency and stool consistency with linaclotide compared to placebo is consistent with its mechanism of action as a guanylate cyclase C agonist,” she noted.

In clinical practice, barriers to the use of linaclotide may include lack of awareness of linaclotide’s safety and efficacy profile, and of its Food and Drug Administration approval for use in children aged 6-17 years with functional constipation, said Dr. Khlevner. “Additionally, access to the medication and insurance coverage may be potential barriers for some patients.” However, “some of these barriers can be overcome through education and training of healthcare providers regarding the appropriate use of linaclotide in pediatric patients with functional constipation,” she added.

The findings were limited by several factors including potential measurement bias and selection bias, lack of assessment of lifestyle modifications as confounding factors, and lack of quality-of-life assessment, the researchers noted. Other limitations included the relatively short 12-week treatment duration, which may not fully capture long-term safety and efficacy, and the focus on patients aged 6-17 years, Dr. Khlevner told this news organization.

“Future research could address these limitations through longer-term studies with broader age ranges and incorporating patient-reported outcomes in real world situations to assess the overall impact of linaclotide treatment on pediatric patients with functional constipation,” she said.

Study Supports Noninvasive Treatment Option

An alternative medication for children with functional constipation who do not respond to current therapies could prevent the use of more invasive interventions such as frequent enemas or antegrade enemas, Stephen M. Borowitz, MD, professor of pediatrics at the University of Virginia, Charlottesville, said in an interview.

Dr. Borowitz said he was not surprised by study findings. “Given the mechanism of action of the drug, I would expect the majority of children with functional constipation to respond in the sense of having more frequent and softer stools,” he said. “The bigger question, which wasn’t answered, is whether children who fail more conservative therapies respond to linaclotide,” said Dr. Borowitz, who was not involved in the study. “This was a phase 3 trial of otherwise healthy children with functional constipation and we know the majority of these children will respond to aggressive management with osmotic stool softeners, plus or minus a stimulant like senna coupled with lifestyle modifications (such as drinking more fluid, regular toileting, and appropriate toileting behaviors),” he said.

The greatest short-term barrier to the expanded use of linaclotide in clinical practice will likely be cost, and whether insurance will cover the drug, Dr. Borowitz told this news organization. Insurance coverage may not be an option until the child has failed more conservative, less expensive therapies, he said.

Also, the current study was a placebo-controlled trial, and not a comparison between linaclotide and polyethylene glycol, plus or minus senna, with other routine interventions, he said.

Looking ahead, “now that we know linaclotide is better than placebo, we need to know if it is as good, better, or worse than other proven interventions, and perhaps even more importantly, is it effective among children who have failed more conservative management,” Dr. Borowitz said. “We also need to know long-term risks, and given that the majority of childhood constipation develops before age 6 years, whether the drug can be used in younger children,” he emphasized. If so, studies need to examine whether linaclotide alters the natural history of the problem, he added. Previous studies suggest that the longer the symptom goes on, the harder it is to undo the secondary behaviors that result, such as withholding, pelvic floor dysfunction, and toileting refusal, he noted.

The study was supported by AbbVie and Ironwood Pharmaceuticals. The lead author, Carlo Di Lorenzo, MD, disclosed consulting fees from AbbVie, Ironwood Pharmaceuticals, Mallinckrodt, NeurAxis, QOL Medical, and Takeda. Dr. Khlevner disclosed honoraria from Abbott Pediatric Nutrition and participation on a data safety monitoring board and advisory board for AbbVie. Dr. Borowitz had no financial conflicts to disclose.