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MMR/MSI Testing for CRC Climbs, But Variations Persist
TOPLINE:
with testing rates differing by cancer stage, individual hospital, patient sex, race, and insurance status.
METHODOLOGY:
- In 2017, the National Comprehensive Cancer Network (NCCN) recommended universal testing for MMR and MSI among patients with CRC, but studies suggest that testing may still be underused.
- To assess trends and factors associated with MMR/MSI testing in the United States, researchers evaluated 834,797 patients diagnosed with stage I-IV CRC between 2012 and 2021 across 1366 Commission on Cancer–accredited hospitals in the National Cancer Database.
- The variability in MMR/MSI testing was assessed in relation to both patient and hospital-level factors.
- Overall, 70.7% patients had colon cancer, 7.3% had rectosigmoid cancer, and 22.0% had rectal cancer. The median patient age was 66 years; just over half (53%) were men, 81.8% were White, and 11.9% were Black.
TAKEAWAY:
- Overall, 43.9% patients underwent MMR/MSI testing, but testing rates increased more than threefold between 2012 and 2021 — from 22.7% to 71.5%. Still, testing rates varied depending on a range of factors.
- About 22% variability in MMR/MSI testing was attributed to hospital-level variations, with the best vs worst performing hospitals reporting testing rates of 90% vs 2%. This hospital-level variation may be caused by testing protocol differences at individual institutions, the authors said.
- The likelihood of undergoing MMR/MSI testing was lower in patients with stage IV vs stage I disease (adjusted odds ratio [aOR], 0.78) but higher in those with stage II (aOR, 1.53) and III (aOR, 1.40) disease.
- The likelihood of undergoing MMR/MSI testing was slightly lower for men than for women (aOR, 0.98) and for Black patients than for White patients (aOR, 0.97). Having a lower household income, public or no insurance (vs private insurance), or living a longer distance (more than 5 miles) from the treatment facility was also associated with lower odds of testing.
IN PRACTICE:
“This cohort study indicated that MMR/MSI testing increased markedly, suggesting increased NCCN guideline adherence,” the authors said. However, variations still exist by cancer stage, hospital, and patient factors. Implementing “widespread institution-level reflexive testing for every initial diagnostic biopsy” can improve testing rates and reduce disparities, the authors suggested.
SOURCE:
This study, led by Totadri Dhimal, MD, University of Rochester Medical Center in New York, was published online in JAMA Oncology.
LIMITATIONS:
The study lacked clinical granularity, and potential coding inaccuracies and incomplete data could have affected the interpretation and generalizability of the findings.
DISCLOSURES:
No funding information was provided for the study. One author reported receiving author royalties from UpToDate outside the submitted work.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
with testing rates differing by cancer stage, individual hospital, patient sex, race, and insurance status.
METHODOLOGY:
- In 2017, the National Comprehensive Cancer Network (NCCN) recommended universal testing for MMR and MSI among patients with CRC, but studies suggest that testing may still be underused.
- To assess trends and factors associated with MMR/MSI testing in the United States, researchers evaluated 834,797 patients diagnosed with stage I-IV CRC between 2012 and 2021 across 1366 Commission on Cancer–accredited hospitals in the National Cancer Database.
- The variability in MMR/MSI testing was assessed in relation to both patient and hospital-level factors.
- Overall, 70.7% patients had colon cancer, 7.3% had rectosigmoid cancer, and 22.0% had rectal cancer. The median patient age was 66 years; just over half (53%) were men, 81.8% were White, and 11.9% were Black.
TAKEAWAY:
- Overall, 43.9% patients underwent MMR/MSI testing, but testing rates increased more than threefold between 2012 and 2021 — from 22.7% to 71.5%. Still, testing rates varied depending on a range of factors.
- About 22% variability in MMR/MSI testing was attributed to hospital-level variations, with the best vs worst performing hospitals reporting testing rates of 90% vs 2%. This hospital-level variation may be caused by testing protocol differences at individual institutions, the authors said.
- The likelihood of undergoing MMR/MSI testing was lower in patients with stage IV vs stage I disease (adjusted odds ratio [aOR], 0.78) but higher in those with stage II (aOR, 1.53) and III (aOR, 1.40) disease.
- The likelihood of undergoing MMR/MSI testing was slightly lower for men than for women (aOR, 0.98) and for Black patients than for White patients (aOR, 0.97). Having a lower household income, public or no insurance (vs private insurance), or living a longer distance (more than 5 miles) from the treatment facility was also associated with lower odds of testing.
IN PRACTICE:
“This cohort study indicated that MMR/MSI testing increased markedly, suggesting increased NCCN guideline adherence,” the authors said. However, variations still exist by cancer stage, hospital, and patient factors. Implementing “widespread institution-level reflexive testing for every initial diagnostic biopsy” can improve testing rates and reduce disparities, the authors suggested.
SOURCE:
This study, led by Totadri Dhimal, MD, University of Rochester Medical Center in New York, was published online in JAMA Oncology.
LIMITATIONS:
The study lacked clinical granularity, and potential coding inaccuracies and incomplete data could have affected the interpretation and generalizability of the findings.
DISCLOSURES:
No funding information was provided for the study. One author reported receiving author royalties from UpToDate outside the submitted work.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
with testing rates differing by cancer stage, individual hospital, patient sex, race, and insurance status.
METHODOLOGY:
- In 2017, the National Comprehensive Cancer Network (NCCN) recommended universal testing for MMR and MSI among patients with CRC, but studies suggest that testing may still be underused.
- To assess trends and factors associated with MMR/MSI testing in the United States, researchers evaluated 834,797 patients diagnosed with stage I-IV CRC between 2012 and 2021 across 1366 Commission on Cancer–accredited hospitals in the National Cancer Database.
- The variability in MMR/MSI testing was assessed in relation to both patient and hospital-level factors.
- Overall, 70.7% patients had colon cancer, 7.3% had rectosigmoid cancer, and 22.0% had rectal cancer. The median patient age was 66 years; just over half (53%) were men, 81.8% were White, and 11.9% were Black.
TAKEAWAY:
- Overall, 43.9% patients underwent MMR/MSI testing, but testing rates increased more than threefold between 2012 and 2021 — from 22.7% to 71.5%. Still, testing rates varied depending on a range of factors.
- About 22% variability in MMR/MSI testing was attributed to hospital-level variations, with the best vs worst performing hospitals reporting testing rates of 90% vs 2%. This hospital-level variation may be caused by testing protocol differences at individual institutions, the authors said.
- The likelihood of undergoing MMR/MSI testing was lower in patients with stage IV vs stage I disease (adjusted odds ratio [aOR], 0.78) but higher in those with stage II (aOR, 1.53) and III (aOR, 1.40) disease.
- The likelihood of undergoing MMR/MSI testing was slightly lower for men than for women (aOR, 0.98) and for Black patients than for White patients (aOR, 0.97). Having a lower household income, public or no insurance (vs private insurance), or living a longer distance (more than 5 miles) from the treatment facility was also associated with lower odds of testing.
IN PRACTICE:
“This cohort study indicated that MMR/MSI testing increased markedly, suggesting increased NCCN guideline adherence,” the authors said. However, variations still exist by cancer stage, hospital, and patient factors. Implementing “widespread institution-level reflexive testing for every initial diagnostic biopsy” can improve testing rates and reduce disparities, the authors suggested.
SOURCE:
This study, led by Totadri Dhimal, MD, University of Rochester Medical Center in New York, was published online in JAMA Oncology.
LIMITATIONS:
The study lacked clinical granularity, and potential coding inaccuracies and incomplete data could have affected the interpretation and generalizability of the findings.
DISCLOSURES:
No funding information was provided for the study. One author reported receiving author royalties from UpToDate outside the submitted work.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Crisugabalin Alleviates Postherpetic Neuralgia Symptoms in Phase 3 Study
TOPLINE:
METHODOLOGY:
- Researchers conducted a phase 3 multicenter, double-blind study involving 366 patients in China (median age, 63 years; 52.7% men) with PHN with an average daily pain score (ADPS) of 4 or greater on the numeric pain rating scale who were randomly assigned to receive either crisugabalin 40 mg/d (n = 121), 80 mg/d (n = 121), or placebo (n = 124) for 12 weeks.
- Patients who did not experience any serious toxic effects in these 12 weeks entered a 14-week open-label extension phase and received crisugabalin 40 mg twice daily.
- The primary efficacy endpoint was the change in ADPS from baseline at week 12.
- Secondary efficacy endpoints included the proportion of patients achieving at least 30% and 50% reduction in ADPS at week 12; changes in the Short-Form McGill Pain Questionnaire (SF-MPQ), Visual Analog Scale, and Average Daily Sleep Interference Scale scores at week 12; and change in the SF-MPQ Present Pain Intensity scores at weeks 12 and 26.
TAKEAWAY:
- At week 12, among those on crisugabalin 40 mg/d and 80 mg/d, there were significant reductions in ADPS compared with placebo (least squares mean [LSM] change from baseline, −2.2 and −2.6 vs −1.1, respectively; P < .001).
- A greater proportion of patients on crisugabalin 40 mg/d (61.2%) and 80 mg/d (54.5%) achieved 30% or greater reduction in ADPS (P < .001) than patients who received placebo (35.5%). Similarly, a 50% or greater reduction in ADPS was achieved by 37.2% of patients on crisugabalin 40 mg/d (P = .002) and 38% on 80 mg/d (P < .001), compared with 20.2% for placebo.
- Crisugabalin 40 mg/d and crisugabalin 80 mg/d were associated with greater reductions in the pain intensity at week 12 than placebo (LSM, −1.0 and −1.2 vs −0.5, respectively; P < .001). Similar patterns were noted for other pain-related measures at weeks 12 and 26.
- Serious treatment-emergent adverse events occurred in four patients in each group; only 2.4% of those on 40 mg/d and 1.6% on 80 mg/d discontinued treatment because of side effects.
IN PRACTICE:
“Crisugabalin 40 mg/d or crisugabalin 80 mg/d was well-tolerated and significantly improved ADPS compared to placebo,” the authors wrote, adding that “crisugabalin can be flexibly selected depending on individual patient response and tolerability at 40 mg/d or 80 mg/d.”
SOURCE:
The study was led by Daying Zhang, PhD, of the Department of Pain Medicine at The First Affiliated Hospital of Nanchang University, Nanchang, China. It was published online in JAMA Dermatology.
LIMITATIONS:
The findings may not be generalizable to the global population as the study population was limited to Chinese patients. The study only provided short-term efficacy and safety data on crisugabalin, lacked an active comparator, and did not reflect the standard of care observed in the United States or Europe, where oral tricyclic antidepressants, pregabalin, and the lidocaine patch are recommended as first-line therapies.
DISCLOSURES:
The study was sponsored and funded by Haisco Pharmaceutical. Dr. Zhang and another author reported receiving support from Haisco. Two authors are company employees.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Researchers conducted a phase 3 multicenter, double-blind study involving 366 patients in China (median age, 63 years; 52.7% men) with PHN with an average daily pain score (ADPS) of 4 or greater on the numeric pain rating scale who were randomly assigned to receive either crisugabalin 40 mg/d (n = 121), 80 mg/d (n = 121), or placebo (n = 124) for 12 weeks.
- Patients who did not experience any serious toxic effects in these 12 weeks entered a 14-week open-label extension phase and received crisugabalin 40 mg twice daily.
- The primary efficacy endpoint was the change in ADPS from baseline at week 12.
- Secondary efficacy endpoints included the proportion of patients achieving at least 30% and 50% reduction in ADPS at week 12; changes in the Short-Form McGill Pain Questionnaire (SF-MPQ), Visual Analog Scale, and Average Daily Sleep Interference Scale scores at week 12; and change in the SF-MPQ Present Pain Intensity scores at weeks 12 and 26.
TAKEAWAY:
- At week 12, among those on crisugabalin 40 mg/d and 80 mg/d, there were significant reductions in ADPS compared with placebo (least squares mean [LSM] change from baseline, −2.2 and −2.6 vs −1.1, respectively; P < .001).
- A greater proportion of patients on crisugabalin 40 mg/d (61.2%) and 80 mg/d (54.5%) achieved 30% or greater reduction in ADPS (P < .001) than patients who received placebo (35.5%). Similarly, a 50% or greater reduction in ADPS was achieved by 37.2% of patients on crisugabalin 40 mg/d (P = .002) and 38% on 80 mg/d (P < .001), compared with 20.2% for placebo.
- Crisugabalin 40 mg/d and crisugabalin 80 mg/d were associated with greater reductions in the pain intensity at week 12 than placebo (LSM, −1.0 and −1.2 vs −0.5, respectively; P < .001). Similar patterns were noted for other pain-related measures at weeks 12 and 26.
- Serious treatment-emergent adverse events occurred in four patients in each group; only 2.4% of those on 40 mg/d and 1.6% on 80 mg/d discontinued treatment because of side effects.
IN PRACTICE:
“Crisugabalin 40 mg/d or crisugabalin 80 mg/d was well-tolerated and significantly improved ADPS compared to placebo,” the authors wrote, adding that “crisugabalin can be flexibly selected depending on individual patient response and tolerability at 40 mg/d or 80 mg/d.”
SOURCE:
The study was led by Daying Zhang, PhD, of the Department of Pain Medicine at The First Affiliated Hospital of Nanchang University, Nanchang, China. It was published online in JAMA Dermatology.
LIMITATIONS:
The findings may not be generalizable to the global population as the study population was limited to Chinese patients. The study only provided short-term efficacy and safety data on crisugabalin, lacked an active comparator, and did not reflect the standard of care observed in the United States or Europe, where oral tricyclic antidepressants, pregabalin, and the lidocaine patch are recommended as first-line therapies.
DISCLOSURES:
The study was sponsored and funded by Haisco Pharmaceutical. Dr. Zhang and another author reported receiving support from Haisco. Two authors are company employees.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Researchers conducted a phase 3 multicenter, double-blind study involving 366 patients in China (median age, 63 years; 52.7% men) with PHN with an average daily pain score (ADPS) of 4 or greater on the numeric pain rating scale who were randomly assigned to receive either crisugabalin 40 mg/d (n = 121), 80 mg/d (n = 121), or placebo (n = 124) for 12 weeks.
- Patients who did not experience any serious toxic effects in these 12 weeks entered a 14-week open-label extension phase and received crisugabalin 40 mg twice daily.
- The primary efficacy endpoint was the change in ADPS from baseline at week 12.
- Secondary efficacy endpoints included the proportion of patients achieving at least 30% and 50% reduction in ADPS at week 12; changes in the Short-Form McGill Pain Questionnaire (SF-MPQ), Visual Analog Scale, and Average Daily Sleep Interference Scale scores at week 12; and change in the SF-MPQ Present Pain Intensity scores at weeks 12 and 26.
TAKEAWAY:
- At week 12, among those on crisugabalin 40 mg/d and 80 mg/d, there were significant reductions in ADPS compared with placebo (least squares mean [LSM] change from baseline, −2.2 and −2.6 vs −1.1, respectively; P < .001).
- A greater proportion of patients on crisugabalin 40 mg/d (61.2%) and 80 mg/d (54.5%) achieved 30% or greater reduction in ADPS (P < .001) than patients who received placebo (35.5%). Similarly, a 50% or greater reduction in ADPS was achieved by 37.2% of patients on crisugabalin 40 mg/d (P = .002) and 38% on 80 mg/d (P < .001), compared with 20.2% for placebo.
- Crisugabalin 40 mg/d and crisugabalin 80 mg/d were associated with greater reductions in the pain intensity at week 12 than placebo (LSM, −1.0 and −1.2 vs −0.5, respectively; P < .001). Similar patterns were noted for other pain-related measures at weeks 12 and 26.
- Serious treatment-emergent adverse events occurred in four patients in each group; only 2.4% of those on 40 mg/d and 1.6% on 80 mg/d discontinued treatment because of side effects.
IN PRACTICE:
“Crisugabalin 40 mg/d or crisugabalin 80 mg/d was well-tolerated and significantly improved ADPS compared to placebo,” the authors wrote, adding that “crisugabalin can be flexibly selected depending on individual patient response and tolerability at 40 mg/d or 80 mg/d.”
SOURCE:
The study was led by Daying Zhang, PhD, of the Department of Pain Medicine at The First Affiliated Hospital of Nanchang University, Nanchang, China. It was published online in JAMA Dermatology.
LIMITATIONS:
The findings may not be generalizable to the global population as the study population was limited to Chinese patients. The study only provided short-term efficacy and safety data on crisugabalin, lacked an active comparator, and did not reflect the standard of care observed in the United States or Europe, where oral tricyclic antidepressants, pregabalin, and the lidocaine patch are recommended as first-line therapies.
DISCLOSURES:
The study was sponsored and funded by Haisco Pharmaceutical. Dr. Zhang and another author reported receiving support from Haisco. Two authors are company employees.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Phase3 Data: Atopic Dermatitis Symptoms Improved with Topical Roflumilast
TOPLINE:
(AD) in two phase 3 trials.
METHODOLOGY:
- Two randomized, parallel-group, double-blind, vehicle-controlled phase 3 trials, INTEGUMENT-1 (n = 654) and INTEGUMENT-2 (n = 683), enrolled patients aged ≥ 6 years with mild to moderate AD who were randomly assigned in a 2:1 ratio to roflumilast cream 0.15%, a phosphodiesterase 4 inhibitor, or vehicle cream once daily for 4 weeks.
- The primary efficacy endpoint was the Validated Investigator Global Assessment for AD (vIGA-AD) success at week 4, defined as a score of 0 (clear) or 1 (almost clear) plus improvement of at least two grades from baseline.
- Secondary endpoints included vIGA-AD success at week 4 in patients with a baseline score of 3, at least a four-point reduction in the Worst Itch Numeric Rating Scale (WI-NRS), and at least a 75% reduction in the Eczema Area and Severity Index (EASI-75) at weeks 1, 2, and 4.
TAKEAWAY:
- Significantly more patients receiving roflumilast achieved vIGA-AD success at week 4 vs those in the vehicle group in INTEGUMENT-1 (32.0% vs 15.2%; P < .001) and INTEGUMENT-2 (28.9% vs 12.0%; P < .001), which was consistent across all age groups and in those with a baseline score of 3.
- Similarly, a greater proportion of patients treated with roflumilast vs vehicle achieved at least a four-point reduction in WI-NRS at weeks 1, 2, and 4, with improvements noted as early as 24 hours after the first application (P < .05 at all subsequent timepoints).
- The number of patients achieving EASI-75 and vIGA-AD scores of 0 or 1 was significantly higher with roflumilast than with vehicle at weeks 1, 2, and 4.
- Most treatment-emergent adverse events (TEAEs) were mild to moderate, with only 0.9% of the patients experiencing serious TEAEs in each trial. More than 95% of the patients showed no signs of irritation, and over 90% reported no or mild sensation at the application site.
IN PRACTICE:
The two phase 3 randomized clinical trials of patients with AD treated with roflumilast cream 0.15% “demonstrated improvement across multiple efficacy endpoints, including reducing pruritus within 24 hours after application, with favorable safety and tolerability,” the authors wrote. “Additional research, including subgroup analyses, will provide more data regarding the efficacy and safety of roflumilast cream 0.15%, in patients with AD,” they added.
SOURCE:
The study was led by Eric L. Simpson, MD, of the Department of Dermatology, Oregon Health & Science University, Portland, Oregon, and was published online on September 18 in JAMA Dermatology.
LIMITATIONS:
A short duration, a minimum age limit of 6 years, and the lack of an active comparator may influence the interpretation and generalizability of the results.
DISCLOSURES:
The study was sponsored by Arcutis Biotherapeutics. Simpson received grants and personal fees from Arcutis during this study. Three authors reported being employees and/or stockholders of Arcutis, two other authors reported patents for Arcutis, and several authors declared having various ties with various sources, including Arcutis.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
(AD) in two phase 3 trials.
METHODOLOGY:
- Two randomized, parallel-group, double-blind, vehicle-controlled phase 3 trials, INTEGUMENT-1 (n = 654) and INTEGUMENT-2 (n = 683), enrolled patients aged ≥ 6 years with mild to moderate AD who were randomly assigned in a 2:1 ratio to roflumilast cream 0.15%, a phosphodiesterase 4 inhibitor, or vehicle cream once daily for 4 weeks.
- The primary efficacy endpoint was the Validated Investigator Global Assessment for AD (vIGA-AD) success at week 4, defined as a score of 0 (clear) or 1 (almost clear) plus improvement of at least two grades from baseline.
- Secondary endpoints included vIGA-AD success at week 4 in patients with a baseline score of 3, at least a four-point reduction in the Worst Itch Numeric Rating Scale (WI-NRS), and at least a 75% reduction in the Eczema Area and Severity Index (EASI-75) at weeks 1, 2, and 4.
TAKEAWAY:
- Significantly more patients receiving roflumilast achieved vIGA-AD success at week 4 vs those in the vehicle group in INTEGUMENT-1 (32.0% vs 15.2%; P < .001) and INTEGUMENT-2 (28.9% vs 12.0%; P < .001), which was consistent across all age groups and in those with a baseline score of 3.
- Similarly, a greater proportion of patients treated with roflumilast vs vehicle achieved at least a four-point reduction in WI-NRS at weeks 1, 2, and 4, with improvements noted as early as 24 hours after the first application (P < .05 at all subsequent timepoints).
- The number of patients achieving EASI-75 and vIGA-AD scores of 0 or 1 was significantly higher with roflumilast than with vehicle at weeks 1, 2, and 4.
- Most treatment-emergent adverse events (TEAEs) were mild to moderate, with only 0.9% of the patients experiencing serious TEAEs in each trial. More than 95% of the patients showed no signs of irritation, and over 90% reported no or mild sensation at the application site.
IN PRACTICE:
The two phase 3 randomized clinical trials of patients with AD treated with roflumilast cream 0.15% “demonstrated improvement across multiple efficacy endpoints, including reducing pruritus within 24 hours after application, with favorable safety and tolerability,” the authors wrote. “Additional research, including subgroup analyses, will provide more data regarding the efficacy and safety of roflumilast cream 0.15%, in patients with AD,” they added.
SOURCE:
The study was led by Eric L. Simpson, MD, of the Department of Dermatology, Oregon Health & Science University, Portland, Oregon, and was published online on September 18 in JAMA Dermatology.
LIMITATIONS:
A short duration, a minimum age limit of 6 years, and the lack of an active comparator may influence the interpretation and generalizability of the results.
DISCLOSURES:
The study was sponsored by Arcutis Biotherapeutics. Simpson received grants and personal fees from Arcutis during this study. Three authors reported being employees and/or stockholders of Arcutis, two other authors reported patents for Arcutis, and several authors declared having various ties with various sources, including Arcutis.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
(AD) in two phase 3 trials.
METHODOLOGY:
- Two randomized, parallel-group, double-blind, vehicle-controlled phase 3 trials, INTEGUMENT-1 (n = 654) and INTEGUMENT-2 (n = 683), enrolled patients aged ≥ 6 years with mild to moderate AD who were randomly assigned in a 2:1 ratio to roflumilast cream 0.15%, a phosphodiesterase 4 inhibitor, or vehicle cream once daily for 4 weeks.
- The primary efficacy endpoint was the Validated Investigator Global Assessment for AD (vIGA-AD) success at week 4, defined as a score of 0 (clear) or 1 (almost clear) plus improvement of at least two grades from baseline.
- Secondary endpoints included vIGA-AD success at week 4 in patients with a baseline score of 3, at least a four-point reduction in the Worst Itch Numeric Rating Scale (WI-NRS), and at least a 75% reduction in the Eczema Area and Severity Index (EASI-75) at weeks 1, 2, and 4.
TAKEAWAY:
- Significantly more patients receiving roflumilast achieved vIGA-AD success at week 4 vs those in the vehicle group in INTEGUMENT-1 (32.0% vs 15.2%; P < .001) and INTEGUMENT-2 (28.9% vs 12.0%; P < .001), which was consistent across all age groups and in those with a baseline score of 3.
- Similarly, a greater proportion of patients treated with roflumilast vs vehicle achieved at least a four-point reduction in WI-NRS at weeks 1, 2, and 4, with improvements noted as early as 24 hours after the first application (P < .05 at all subsequent timepoints).
- The number of patients achieving EASI-75 and vIGA-AD scores of 0 or 1 was significantly higher with roflumilast than with vehicle at weeks 1, 2, and 4.
- Most treatment-emergent adverse events (TEAEs) were mild to moderate, with only 0.9% of the patients experiencing serious TEAEs in each trial. More than 95% of the patients showed no signs of irritation, and over 90% reported no or mild sensation at the application site.
IN PRACTICE:
The two phase 3 randomized clinical trials of patients with AD treated with roflumilast cream 0.15% “demonstrated improvement across multiple efficacy endpoints, including reducing pruritus within 24 hours after application, with favorable safety and tolerability,” the authors wrote. “Additional research, including subgroup analyses, will provide more data regarding the efficacy and safety of roflumilast cream 0.15%, in patients with AD,” they added.
SOURCE:
The study was led by Eric L. Simpson, MD, of the Department of Dermatology, Oregon Health & Science University, Portland, Oregon, and was published online on September 18 in JAMA Dermatology.
LIMITATIONS:
A short duration, a minimum age limit of 6 years, and the lack of an active comparator may influence the interpretation and generalizability of the results.
DISCLOSURES:
The study was sponsored by Arcutis Biotherapeutics. Simpson received grants and personal fees from Arcutis during this study. Three authors reported being employees and/or stockholders of Arcutis, two other authors reported patents for Arcutis, and several authors declared having various ties with various sources, including Arcutis.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Biomarkers in Cord Blood May Predict AD Onset in Newborns, Study Suggests
TOPLINE:
and interleukin (IL) 31.
METHODOLOGY:
- Researchers conducted a prospective study to evaluate the predictive role of serologic biomarkers and cutaneous markers and the development of AD in 40 full-term newborns from a university hospital in Italy.
- Cord blood was collected at birth and analyzed for serum biomarkers such as CCL17/TARC and IL-31.
- TEWL and skin hydration rates were measured at 1, 6, and 12 months, and dermatological features such as dryness, cradle cap, and eczematous lesions were also monitored during visits.
TAKEAWAY:
- At 6 months, 16 infants had symptoms of AD, which included dry skin, pruritus, and keratosis pilaris, which persisted at 12 months. Their mean Eczema Area and Severity Index score was 6.6 at 6 months and 2.9 at 12 months.
- Infants with signs of AD had significantly higher TEWL levels at the anterior cubital fossa at 1, 6, and 12 months than those without AD.
- Cord blood levels of CCL17/TARC and IL-31 were significantly higher in infants with AD.
- A correlation was found between TEWL values and CCL17 levels at 1, 6, and 12 months.
IN PRACTICE:
“,” the authors wrote. “Stratified interventions based on these variables, family history, FLG [filaggrin] variations, and other biomarkers could offer more targeted approaches to AD prevention and management, especially during the first year of life,” they added.
SOURCE:
The study was led by Angelo Massimiliano D’Erme, MD, PhD, of the Dermatology Unit, in the Department of Medical and Oncology, University of Pisa, Pisa, Italy, and was published online in JAMA Dermatology.
LIMITATIONS:
The limitations included the observational design and small sample size, and it was a single-center study.
DISCLOSURES:
The authors did not disclose any funding information. One author disclosed receiving personal fees from various pharmaceutical companies and serving as a founder and chairman of a nonprofit organization.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.A version of this article appeared on Medscape.com.
TOPLINE:
and interleukin (IL) 31.
METHODOLOGY:
- Researchers conducted a prospective study to evaluate the predictive role of serologic biomarkers and cutaneous markers and the development of AD in 40 full-term newborns from a university hospital in Italy.
- Cord blood was collected at birth and analyzed for serum biomarkers such as CCL17/TARC and IL-31.
- TEWL and skin hydration rates were measured at 1, 6, and 12 months, and dermatological features such as dryness, cradle cap, and eczematous lesions were also monitored during visits.
TAKEAWAY:
- At 6 months, 16 infants had symptoms of AD, which included dry skin, pruritus, and keratosis pilaris, which persisted at 12 months. Their mean Eczema Area and Severity Index score was 6.6 at 6 months and 2.9 at 12 months.
- Infants with signs of AD had significantly higher TEWL levels at the anterior cubital fossa at 1, 6, and 12 months than those without AD.
- Cord blood levels of CCL17/TARC and IL-31 were significantly higher in infants with AD.
- A correlation was found between TEWL values and CCL17 levels at 1, 6, and 12 months.
IN PRACTICE:
“,” the authors wrote. “Stratified interventions based on these variables, family history, FLG [filaggrin] variations, and other biomarkers could offer more targeted approaches to AD prevention and management, especially during the first year of life,” they added.
SOURCE:
The study was led by Angelo Massimiliano D’Erme, MD, PhD, of the Dermatology Unit, in the Department of Medical and Oncology, University of Pisa, Pisa, Italy, and was published online in JAMA Dermatology.
LIMITATIONS:
The limitations included the observational design and small sample size, and it was a single-center study.
DISCLOSURES:
The authors did not disclose any funding information. One author disclosed receiving personal fees from various pharmaceutical companies and serving as a founder and chairman of a nonprofit organization.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.A version of this article appeared on Medscape.com.
TOPLINE:
and interleukin (IL) 31.
METHODOLOGY:
- Researchers conducted a prospective study to evaluate the predictive role of serologic biomarkers and cutaneous markers and the development of AD in 40 full-term newborns from a university hospital in Italy.
- Cord blood was collected at birth and analyzed for serum biomarkers such as CCL17/TARC and IL-31.
- TEWL and skin hydration rates were measured at 1, 6, and 12 months, and dermatological features such as dryness, cradle cap, and eczematous lesions were also monitored during visits.
TAKEAWAY:
- At 6 months, 16 infants had symptoms of AD, which included dry skin, pruritus, and keratosis pilaris, which persisted at 12 months. Their mean Eczema Area and Severity Index score was 6.6 at 6 months and 2.9 at 12 months.
- Infants with signs of AD had significantly higher TEWL levels at the anterior cubital fossa at 1, 6, and 12 months than those without AD.
- Cord blood levels of CCL17/TARC and IL-31 were significantly higher in infants with AD.
- A correlation was found between TEWL values and CCL17 levels at 1, 6, and 12 months.
IN PRACTICE:
“,” the authors wrote. “Stratified interventions based on these variables, family history, FLG [filaggrin] variations, and other biomarkers could offer more targeted approaches to AD prevention and management, especially during the first year of life,” they added.
SOURCE:
The study was led by Angelo Massimiliano D’Erme, MD, PhD, of the Dermatology Unit, in the Department of Medical and Oncology, University of Pisa, Pisa, Italy, and was published online in JAMA Dermatology.
LIMITATIONS:
The limitations included the observational design and small sample size, and it was a single-center study.
DISCLOSURES:
The authors did not disclose any funding information. One author disclosed receiving personal fees from various pharmaceutical companies and serving as a founder and chairman of a nonprofit organization.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.A version of this article appeared on Medscape.com.
Diabetes Drug Improved Symptoms in Small Study of Women With Central Centrifugal Cicatricial Alopecia
TOPLINE:
in a retrospective case series.
METHODOLOGY:
- Researchers conducted a case series involving 12 Black women in their 30s, 40s, and 50s, with biopsy-confirmed, treatment-refractory CCCA, a chronic inflammatory hair disorder characterized by permanent hair loss, from the Johns Hopkins University alopecia clinic.
- Participants received CCCA treatment for at least 6 months and had stagnant or worsening symptoms before oral extended-release metformin (500 mg daily) was added to treatment. (Treatments included topical clobetasol, compounded minoxidil, and platelet-rich plasma injections.)
- Scalp biopsies were collected from four patients before and after metformin treatment to evaluate gene expression changes.
- Changes in clinical symptoms were assessed, including pruritus, inflammation, pain, scalp resistance, and hair regrowth, following initiation of metformin treatment.
TAKEAWAY:
- Metformin led to significant clinical improvement in eight patients, which included reductions in scalp pain, scalp resistance, pruritus, and inflammation. However, two patients experienced worsening symptoms.
- Six patients showed clinical evidence of hair regrowth after at least 6 months of metformin treatment with one experiencing hair loss again 3 months after discontinuing treatment.
- Transcriptomic analysis revealed 34 up-regulated genes, which included up-regulated of 23 hair keratin–associated proteins, and pathways related to keratinization, epidermis development, and the hair cycle. In addition, eight genes were down-regulated, with pathways that included those associated with extracellular matrix organization, collagen fibril organization, and collagen metabolism.
- Gene set variation analysis showed reduced expression of T helper 17 cell and epithelial-mesenchymal transition pathways and elevated adenosine monophosphate kinase signaling and keratin-associated proteins after treatment with metformin.
IN PRACTICE:
“Metformin’s ability to concomitantly target fibrosis and inflammation provides a plausible mechanism for its therapeutic effects in CCCA and other fibrosing alopecia disorders,” the authors concluded. But, they added, “larger prospective, placebo-controlled randomized clinical trials are needed to rigorously evaluate metformin’s efficacy and optimal dosing for treatment of cicatricial alopecias.”
SOURCE:
The study was led by Aaron Bao, Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, and was published online on September 4 in JAMA Dermatology.
LIMITATIONS:
A small sample size, retrospective design, lack of a placebo control group, and the single-center setting limited the generalizability of the study findings. Additionally, the absence of a validated activity or severity scale for CCCA and the single posttreatment sampling limit the assessment and comparison of clinical symptoms and transcriptomic changes.
DISCLOSURES:
The study was supported by the American Academy of Dermatology. One author reported several ties with pharmaceutical companies, a pending patent, and authorship for the UpToDate section on CCCA.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
in a retrospective case series.
METHODOLOGY:
- Researchers conducted a case series involving 12 Black women in their 30s, 40s, and 50s, with biopsy-confirmed, treatment-refractory CCCA, a chronic inflammatory hair disorder characterized by permanent hair loss, from the Johns Hopkins University alopecia clinic.
- Participants received CCCA treatment for at least 6 months and had stagnant or worsening symptoms before oral extended-release metformin (500 mg daily) was added to treatment. (Treatments included topical clobetasol, compounded minoxidil, and platelet-rich plasma injections.)
- Scalp biopsies were collected from four patients before and after metformin treatment to evaluate gene expression changes.
- Changes in clinical symptoms were assessed, including pruritus, inflammation, pain, scalp resistance, and hair regrowth, following initiation of metformin treatment.
TAKEAWAY:
- Metformin led to significant clinical improvement in eight patients, which included reductions in scalp pain, scalp resistance, pruritus, and inflammation. However, two patients experienced worsening symptoms.
- Six patients showed clinical evidence of hair regrowth after at least 6 months of metformin treatment with one experiencing hair loss again 3 months after discontinuing treatment.
- Transcriptomic analysis revealed 34 up-regulated genes, which included up-regulated of 23 hair keratin–associated proteins, and pathways related to keratinization, epidermis development, and the hair cycle. In addition, eight genes were down-regulated, with pathways that included those associated with extracellular matrix organization, collagen fibril organization, and collagen metabolism.
- Gene set variation analysis showed reduced expression of T helper 17 cell and epithelial-mesenchymal transition pathways and elevated adenosine monophosphate kinase signaling and keratin-associated proteins after treatment with metformin.
IN PRACTICE:
“Metformin’s ability to concomitantly target fibrosis and inflammation provides a plausible mechanism for its therapeutic effects in CCCA and other fibrosing alopecia disorders,” the authors concluded. But, they added, “larger prospective, placebo-controlled randomized clinical trials are needed to rigorously evaluate metformin’s efficacy and optimal dosing for treatment of cicatricial alopecias.”
SOURCE:
The study was led by Aaron Bao, Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, and was published online on September 4 in JAMA Dermatology.
LIMITATIONS:
A small sample size, retrospective design, lack of a placebo control group, and the single-center setting limited the generalizability of the study findings. Additionally, the absence of a validated activity or severity scale for CCCA and the single posttreatment sampling limit the assessment and comparison of clinical symptoms and transcriptomic changes.
DISCLOSURES:
The study was supported by the American Academy of Dermatology. One author reported several ties with pharmaceutical companies, a pending patent, and authorship for the UpToDate section on CCCA.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
in a retrospective case series.
METHODOLOGY:
- Researchers conducted a case series involving 12 Black women in their 30s, 40s, and 50s, with biopsy-confirmed, treatment-refractory CCCA, a chronic inflammatory hair disorder characterized by permanent hair loss, from the Johns Hopkins University alopecia clinic.
- Participants received CCCA treatment for at least 6 months and had stagnant or worsening symptoms before oral extended-release metformin (500 mg daily) was added to treatment. (Treatments included topical clobetasol, compounded minoxidil, and platelet-rich plasma injections.)
- Scalp biopsies were collected from four patients before and after metformin treatment to evaluate gene expression changes.
- Changes in clinical symptoms were assessed, including pruritus, inflammation, pain, scalp resistance, and hair regrowth, following initiation of metformin treatment.
TAKEAWAY:
- Metformin led to significant clinical improvement in eight patients, which included reductions in scalp pain, scalp resistance, pruritus, and inflammation. However, two patients experienced worsening symptoms.
- Six patients showed clinical evidence of hair regrowth after at least 6 months of metformin treatment with one experiencing hair loss again 3 months after discontinuing treatment.
- Transcriptomic analysis revealed 34 up-regulated genes, which included up-regulated of 23 hair keratin–associated proteins, and pathways related to keratinization, epidermis development, and the hair cycle. In addition, eight genes were down-regulated, with pathways that included those associated with extracellular matrix organization, collagen fibril organization, and collagen metabolism.
- Gene set variation analysis showed reduced expression of T helper 17 cell and epithelial-mesenchymal transition pathways and elevated adenosine monophosphate kinase signaling and keratin-associated proteins after treatment with metformin.
IN PRACTICE:
“Metformin’s ability to concomitantly target fibrosis and inflammation provides a plausible mechanism for its therapeutic effects in CCCA and other fibrosing alopecia disorders,” the authors concluded. But, they added, “larger prospective, placebo-controlled randomized clinical trials are needed to rigorously evaluate metformin’s efficacy and optimal dosing for treatment of cicatricial alopecias.”
SOURCE:
The study was led by Aaron Bao, Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, and was published online on September 4 in JAMA Dermatology.
LIMITATIONS:
A small sample size, retrospective design, lack of a placebo control group, and the single-center setting limited the generalizability of the study findings. Additionally, the absence of a validated activity or severity scale for CCCA and the single posttreatment sampling limit the assessment and comparison of clinical symptoms and transcriptomic changes.
DISCLOSURES:
The study was supported by the American Academy of Dermatology. One author reported several ties with pharmaceutical companies, a pending patent, and authorship for the UpToDate section on CCCA.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Is Minimal Access Nipple-Sparing Mastectomy a Safer Option?
TOPLINE:
Given that both procedures appear safe overall, the choice may be guided by patients’ preference.
METHODOLOGY:
- Compared with a conventional mastectomy, a nipple-sparing mastectomy offers superior esthetic outcomes in patients with breast cancer. However, even the typical nipple-sparing approach often results in visible scarring and a high risk for nipple or areola necrosis. A minimal access approach, using endoscopic or robotic techniques, offers the potential to minimize scarring and better outcomes, but the complication risks are not well understood.
- Researchers performed a retrospective study that included 1583 patients with breast cancer who underwent conventional nipple-sparing mastectomy (n = 1356) or minimal access nipple-sparing mastectomy (n = 227) between 2018 and 2020 across 21 institutions in the Republic of Korea.
- Postoperative complications, categorized as short term (< 30 days) and long term (< 90 days), were compared between the two groups.
- The minimal access group had a higher percentage of premenopausal patients (73.57% vs 66.67%) and women with firm breasts (66.08% vs 31.27%).
TAKEAWAY:
- In total, 72 individuals (5.31%) in the conventional nipple-sparing mastectomy group and 7 (3.08%) in the minimal access nipple-sparing mastectomy group developed postoperative complications of grade IIIb or higher.
- The rate of complications between the conventional and minimal access nipple-sparing mastectomy groups in the short term (34.29% for conventional vs 32.16% for minimal access; P = .53) and long term (38.72% vs 32.16%, respectively; P = .06) was not significantly different.
- The conventional group experienced significantly fewer wound infections — both in the short term (1.62% vs 7.49%) and long term (4.28% vs 7.93%) — but a significantly higher rate of seroma (14.23% vs 9.25%), likely because of the variations in surgical instruments used during the procedures.
- Necrosis of the nipple or areola occurred more often in the minimal access group in the short term (8.81% vs 3.91%) but occurred more frequently in the conventional group in the long term (6.71% vs 2.20%).
IN PRACTICE:
“The similar complication rates suggest that both C-NSM [conventional nipple-sparing mastectomy] and M-NSM [minimal access nipple-sparing mastectomy] may be equally safe options,” the authors wrote. “Therefore, the choice of surgical approach should be tailored to patient preferences and individual needs.”
SOURCE:
The study, led by Joo Heung Kim, MD, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, South Korea, was published online on August 14, 2024, in JAMA Surgery.
LIMITATIONS:
The retrospective design comes with inherent biases. The nonrandom assignment of the participants to the two groups and the relatively small number of cases of minimal access nipple-sparing mastectomy may have affected the findings. The involvement of different surgeons and use of early robotic surgery techniques may have introduced bias as well.
DISCLOSURES:
This study was supported by Yonsei University College of Medicine and the National Research Foundation of Korea. Two authors reported receiving grants and consulting fees outside of this work.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
Given that both procedures appear safe overall, the choice may be guided by patients’ preference.
METHODOLOGY:
- Compared with a conventional mastectomy, a nipple-sparing mastectomy offers superior esthetic outcomes in patients with breast cancer. However, even the typical nipple-sparing approach often results in visible scarring and a high risk for nipple or areola necrosis. A minimal access approach, using endoscopic or robotic techniques, offers the potential to minimize scarring and better outcomes, but the complication risks are not well understood.
- Researchers performed a retrospective study that included 1583 patients with breast cancer who underwent conventional nipple-sparing mastectomy (n = 1356) or minimal access nipple-sparing mastectomy (n = 227) between 2018 and 2020 across 21 institutions in the Republic of Korea.
- Postoperative complications, categorized as short term (< 30 days) and long term (< 90 days), were compared between the two groups.
- The minimal access group had a higher percentage of premenopausal patients (73.57% vs 66.67%) and women with firm breasts (66.08% vs 31.27%).
TAKEAWAY:
- In total, 72 individuals (5.31%) in the conventional nipple-sparing mastectomy group and 7 (3.08%) in the minimal access nipple-sparing mastectomy group developed postoperative complications of grade IIIb or higher.
- The rate of complications between the conventional and minimal access nipple-sparing mastectomy groups in the short term (34.29% for conventional vs 32.16% for minimal access; P = .53) and long term (38.72% vs 32.16%, respectively; P = .06) was not significantly different.
- The conventional group experienced significantly fewer wound infections — both in the short term (1.62% vs 7.49%) and long term (4.28% vs 7.93%) — but a significantly higher rate of seroma (14.23% vs 9.25%), likely because of the variations in surgical instruments used during the procedures.
- Necrosis of the nipple or areola occurred more often in the minimal access group in the short term (8.81% vs 3.91%) but occurred more frequently in the conventional group in the long term (6.71% vs 2.20%).
IN PRACTICE:
“The similar complication rates suggest that both C-NSM [conventional nipple-sparing mastectomy] and M-NSM [minimal access nipple-sparing mastectomy] may be equally safe options,” the authors wrote. “Therefore, the choice of surgical approach should be tailored to patient preferences and individual needs.”
SOURCE:
The study, led by Joo Heung Kim, MD, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, South Korea, was published online on August 14, 2024, in JAMA Surgery.
LIMITATIONS:
The retrospective design comes with inherent biases. The nonrandom assignment of the participants to the two groups and the relatively small number of cases of minimal access nipple-sparing mastectomy may have affected the findings. The involvement of different surgeons and use of early robotic surgery techniques may have introduced bias as well.
DISCLOSURES:
This study was supported by Yonsei University College of Medicine and the National Research Foundation of Korea. Two authors reported receiving grants and consulting fees outside of this work.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
Given that both procedures appear safe overall, the choice may be guided by patients’ preference.
METHODOLOGY:
- Compared with a conventional mastectomy, a nipple-sparing mastectomy offers superior esthetic outcomes in patients with breast cancer. However, even the typical nipple-sparing approach often results in visible scarring and a high risk for nipple or areola necrosis. A minimal access approach, using endoscopic or robotic techniques, offers the potential to minimize scarring and better outcomes, but the complication risks are not well understood.
- Researchers performed a retrospective study that included 1583 patients with breast cancer who underwent conventional nipple-sparing mastectomy (n = 1356) or minimal access nipple-sparing mastectomy (n = 227) between 2018 and 2020 across 21 institutions in the Republic of Korea.
- Postoperative complications, categorized as short term (< 30 days) and long term (< 90 days), were compared between the two groups.
- The minimal access group had a higher percentage of premenopausal patients (73.57% vs 66.67%) and women with firm breasts (66.08% vs 31.27%).
TAKEAWAY:
- In total, 72 individuals (5.31%) in the conventional nipple-sparing mastectomy group and 7 (3.08%) in the minimal access nipple-sparing mastectomy group developed postoperative complications of grade IIIb or higher.
- The rate of complications between the conventional and minimal access nipple-sparing mastectomy groups in the short term (34.29% for conventional vs 32.16% for minimal access; P = .53) and long term (38.72% vs 32.16%, respectively; P = .06) was not significantly different.
- The conventional group experienced significantly fewer wound infections — both in the short term (1.62% vs 7.49%) and long term (4.28% vs 7.93%) — but a significantly higher rate of seroma (14.23% vs 9.25%), likely because of the variations in surgical instruments used during the procedures.
- Necrosis of the nipple or areola occurred more often in the minimal access group in the short term (8.81% vs 3.91%) but occurred more frequently in the conventional group in the long term (6.71% vs 2.20%).
IN PRACTICE:
“The similar complication rates suggest that both C-NSM [conventional nipple-sparing mastectomy] and M-NSM [minimal access nipple-sparing mastectomy] may be equally safe options,” the authors wrote. “Therefore, the choice of surgical approach should be tailored to patient preferences and individual needs.”
SOURCE:
The study, led by Joo Heung Kim, MD, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, South Korea, was published online on August 14, 2024, in JAMA Surgery.
LIMITATIONS:
The retrospective design comes with inherent biases. The nonrandom assignment of the participants to the two groups and the relatively small number of cases of minimal access nipple-sparing mastectomy may have affected the findings. The involvement of different surgeons and use of early robotic surgery techniques may have introduced bias as well.
DISCLOSURES:
This study was supported by Yonsei University College of Medicine and the National Research Foundation of Korea. Two authors reported receiving grants and consulting fees outside of this work.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Should Genetic Testing Be Routine for Breast Cancer?
TOPLINE:
METHODOLOGY:
- Traditional risk-based criteria, including family history and ancestry, are used to guide genetic testing decisions in women with breast cancer. However, these criteria may overlook patients with actionable genetic variants, particularly those outside the typical risk profile.
- To assess the efficacy of universal genetic testing, researchers conducted a cross-sectional study that included 729 women (median age at diagnosis, 53 years; 65.4% White women) newly diagnosed with invasive breast cancer between September 2019 and April 2022 at three Canadian institutions.
- All patients received genetic counseling followed by testing for the presence of germline pathogenic variants in 17 breast cancer susceptibility genes. The primary gene panel included screening for BRCA1, BRCA2, and PALB2, and the optional secondary panel included 14 additional breast cancer susceptibility genes.
- Of the participants, 659 (90.4%) were tested for both primary and secondary gene panels, whereas 70 (9.6%) underwent testing for only the primary panel. The majority of the cohort (66.8) were diagnosed with estrogen receptor–positive breast cancer, while 15.4% had triple-negative breast cancer.
TAKEAWAY:
- The prevalence of germline pathogenic variants was 7.3% (53 patients) — 5.3% for the primary gene panel and 2.1% for the secondary panel.
- Younger age (< 40 years; odds ratio [OR], 6.83), family history of ovarian cancer (OR, 9.75), high-grade disease (OR, 1.68), and triple-negative breast cancer (OR, 3.19) were independently associated with the presence of pathogenic genetic variants in BRCA1, BRCA2, or PALB2.
- Overall, 34.3% of patients with germline pathogenic variants in BRCA1, BRCA2, or PALB2, and 85.7% of carriers of secondary panel variants would not have qualified for traditional genetic testing according to the current risk factors.
- A total of 13 patients with BRCA1, BRCA2, or PALB2 variants had confirmed pathogenic mutations and were eligible for poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors.
IN PRACTICE:
These findings have “informed our clinical practice, and we now offer mainstream, oncology-led genetic testing to all women diagnosed with incident invasive breast cancer younger than 50 years of age, those with triple-negative breast cancer and/or bilateral breast cancer, those potentially eligible for PARP inhibitors,” as well as to men with breast cancer, the authors wrote.
SOURCE:
The study was led by Zoulikha Rezoug, MSc, Lady Davis Institute of the Jewish General Hospital, McGill University in Montreal, Québec, Canada. It was published online on September 3, 2024, in JAMA Network Open.
LIMITATIONS:
The COVID-19 pandemic resulted in a 6-month recruitment pause. Adjustments in recruitment criteria, focus on younger patients and those with triple-negative breast cancer could have overestimated prevalence of genetic pathogenic variants among women aged ≥ 70 years.
DISCLOSURES:
The study was supported by grants from the Jewish General Hospital Foundation and the Québec Breast Cancer Foundation, as well as an award from the Fonds de Recherche du Québec - Santé. Two authors reported receiving grants or personal fees from various sources.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Traditional risk-based criteria, including family history and ancestry, are used to guide genetic testing decisions in women with breast cancer. However, these criteria may overlook patients with actionable genetic variants, particularly those outside the typical risk profile.
- To assess the efficacy of universal genetic testing, researchers conducted a cross-sectional study that included 729 women (median age at diagnosis, 53 years; 65.4% White women) newly diagnosed with invasive breast cancer between September 2019 and April 2022 at three Canadian institutions.
- All patients received genetic counseling followed by testing for the presence of germline pathogenic variants in 17 breast cancer susceptibility genes. The primary gene panel included screening for BRCA1, BRCA2, and PALB2, and the optional secondary panel included 14 additional breast cancer susceptibility genes.
- Of the participants, 659 (90.4%) were tested for both primary and secondary gene panels, whereas 70 (9.6%) underwent testing for only the primary panel. The majority of the cohort (66.8) were diagnosed with estrogen receptor–positive breast cancer, while 15.4% had triple-negative breast cancer.
TAKEAWAY:
- The prevalence of germline pathogenic variants was 7.3% (53 patients) — 5.3% for the primary gene panel and 2.1% for the secondary panel.
- Younger age (< 40 years; odds ratio [OR], 6.83), family history of ovarian cancer (OR, 9.75), high-grade disease (OR, 1.68), and triple-negative breast cancer (OR, 3.19) were independently associated with the presence of pathogenic genetic variants in BRCA1, BRCA2, or PALB2.
- Overall, 34.3% of patients with germline pathogenic variants in BRCA1, BRCA2, or PALB2, and 85.7% of carriers of secondary panel variants would not have qualified for traditional genetic testing according to the current risk factors.
- A total of 13 patients with BRCA1, BRCA2, or PALB2 variants had confirmed pathogenic mutations and were eligible for poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors.
IN PRACTICE:
These findings have “informed our clinical practice, and we now offer mainstream, oncology-led genetic testing to all women diagnosed with incident invasive breast cancer younger than 50 years of age, those with triple-negative breast cancer and/or bilateral breast cancer, those potentially eligible for PARP inhibitors,” as well as to men with breast cancer, the authors wrote.
SOURCE:
The study was led by Zoulikha Rezoug, MSc, Lady Davis Institute of the Jewish General Hospital, McGill University in Montreal, Québec, Canada. It was published online on September 3, 2024, in JAMA Network Open.
LIMITATIONS:
The COVID-19 pandemic resulted in a 6-month recruitment pause. Adjustments in recruitment criteria, focus on younger patients and those with triple-negative breast cancer could have overestimated prevalence of genetic pathogenic variants among women aged ≥ 70 years.
DISCLOSURES:
The study was supported by grants from the Jewish General Hospital Foundation and the Québec Breast Cancer Foundation, as well as an award from the Fonds de Recherche du Québec - Santé. Two authors reported receiving grants or personal fees from various sources.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Traditional risk-based criteria, including family history and ancestry, are used to guide genetic testing decisions in women with breast cancer. However, these criteria may overlook patients with actionable genetic variants, particularly those outside the typical risk profile.
- To assess the efficacy of universal genetic testing, researchers conducted a cross-sectional study that included 729 women (median age at diagnosis, 53 years; 65.4% White women) newly diagnosed with invasive breast cancer between September 2019 and April 2022 at three Canadian institutions.
- All patients received genetic counseling followed by testing for the presence of germline pathogenic variants in 17 breast cancer susceptibility genes. The primary gene panel included screening for BRCA1, BRCA2, and PALB2, and the optional secondary panel included 14 additional breast cancer susceptibility genes.
- Of the participants, 659 (90.4%) were tested for both primary and secondary gene panels, whereas 70 (9.6%) underwent testing for only the primary panel. The majority of the cohort (66.8) were diagnosed with estrogen receptor–positive breast cancer, while 15.4% had triple-negative breast cancer.
TAKEAWAY:
- The prevalence of germline pathogenic variants was 7.3% (53 patients) — 5.3% for the primary gene panel and 2.1% for the secondary panel.
- Younger age (< 40 years; odds ratio [OR], 6.83), family history of ovarian cancer (OR, 9.75), high-grade disease (OR, 1.68), and triple-negative breast cancer (OR, 3.19) were independently associated with the presence of pathogenic genetic variants in BRCA1, BRCA2, or PALB2.
- Overall, 34.3% of patients with germline pathogenic variants in BRCA1, BRCA2, or PALB2, and 85.7% of carriers of secondary panel variants would not have qualified for traditional genetic testing according to the current risk factors.
- A total of 13 patients with BRCA1, BRCA2, or PALB2 variants had confirmed pathogenic mutations and were eligible for poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors.
IN PRACTICE:
These findings have “informed our clinical practice, and we now offer mainstream, oncology-led genetic testing to all women diagnosed with incident invasive breast cancer younger than 50 years of age, those with triple-negative breast cancer and/or bilateral breast cancer, those potentially eligible for PARP inhibitors,” as well as to men with breast cancer, the authors wrote.
SOURCE:
The study was led by Zoulikha Rezoug, MSc, Lady Davis Institute of the Jewish General Hospital, McGill University in Montreal, Québec, Canada. It was published online on September 3, 2024, in JAMA Network Open.
LIMITATIONS:
The COVID-19 pandemic resulted in a 6-month recruitment pause. Adjustments in recruitment criteria, focus on younger patients and those with triple-negative breast cancer could have overestimated prevalence of genetic pathogenic variants among women aged ≥ 70 years.
DISCLOSURES:
The study was supported by grants from the Jewish General Hospital Foundation and the Québec Breast Cancer Foundation, as well as an award from the Fonds de Recherche du Québec - Santé. Two authors reported receiving grants or personal fees from various sources.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Mortality Risk From Early-Onset CRC Higher in Rural, Poor Areas
TOPLINE:
Patients with early-onset colorectal cancer (CRC) living in rural and impoverished areas face a significantly higher risk of dying from CRC.
METHODOLOGY:
- Previous research has shown that patients living in impoverished and rural areas have an increased risk of dying from CRC, but it is unclear if this trend applies to patients with early-onset CRC.
- Researchers analyzed 58,200 patients with early-onset CRC from the Surveillance, Epidemiology, and End Results Program between 2006 and 2015.
- Of these patients, 1346 (21%) lived in rural areas with persistent poverty. Persistent poverty was defined as having 20% or more of the population living below the poverty level for about 30 years, and rural locations were identified using specific US Department of Agriculture codes.
- The primary outcome was cancer-specific survival.
TAKEAWAY:
- The cancer-specific survival at 5 years was highest for patients who lived in neither poverty-stricken nor rural areas (72%) and the lowest for those who lived in impoverished areas irrespective of rural status (67%).
- Patients who lived in rural areas had a significantly higher risk of dying from CRC than those living in nonrural areas, with younger individuals facing the highest risk. More specifically, patients aged between 20 and 29 years had a 35% higher risk of dying from CRC, those aged between 30 and 39 years had a 26% higher risk, and those aged between 40 and 49 years had a 12% higher risk.
- Patients who lived in poverty and rural areas had a 29% increased risk of dying from CRC compared with those in nonrural areas — with the highest 51% greater risk for those aged between 30 and 39 years.
IN PRACTICE:
“Our results can be used to inform health system policies for ongoing investments in cancer diagnosis and treatment resources in rural or impoverished areas for younger CRC patients and their communities,” the authors wrote.
SOURCE:
The study, led by Meng-Han Tsai, PhD, Georgia Prevention Institute, Augusta University, Augusta, Georgia, was published online in JAMA Network Open.
LIMITATIONS:
Confounders, such as lifestyle factors, comorbidities, and structural barriers, could affect the findings.
DISCLOSURES:
This study was partially supported by a grant from the Georgia Cancer Center Paceline funding mechanism at Augusta University. The authors did not declare any conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
Patients with early-onset colorectal cancer (CRC) living in rural and impoverished areas face a significantly higher risk of dying from CRC.
METHODOLOGY:
- Previous research has shown that patients living in impoverished and rural areas have an increased risk of dying from CRC, but it is unclear if this trend applies to patients with early-onset CRC.
- Researchers analyzed 58,200 patients with early-onset CRC from the Surveillance, Epidemiology, and End Results Program between 2006 and 2015.
- Of these patients, 1346 (21%) lived in rural areas with persistent poverty. Persistent poverty was defined as having 20% or more of the population living below the poverty level for about 30 years, and rural locations were identified using specific US Department of Agriculture codes.
- The primary outcome was cancer-specific survival.
TAKEAWAY:
- The cancer-specific survival at 5 years was highest for patients who lived in neither poverty-stricken nor rural areas (72%) and the lowest for those who lived in impoverished areas irrespective of rural status (67%).
- Patients who lived in rural areas had a significantly higher risk of dying from CRC than those living in nonrural areas, with younger individuals facing the highest risk. More specifically, patients aged between 20 and 29 years had a 35% higher risk of dying from CRC, those aged between 30 and 39 years had a 26% higher risk, and those aged between 40 and 49 years had a 12% higher risk.
- Patients who lived in poverty and rural areas had a 29% increased risk of dying from CRC compared with those in nonrural areas — with the highest 51% greater risk for those aged between 30 and 39 years.
IN PRACTICE:
“Our results can be used to inform health system policies for ongoing investments in cancer diagnosis and treatment resources in rural or impoverished areas for younger CRC patients and their communities,” the authors wrote.
SOURCE:
The study, led by Meng-Han Tsai, PhD, Georgia Prevention Institute, Augusta University, Augusta, Georgia, was published online in JAMA Network Open.
LIMITATIONS:
Confounders, such as lifestyle factors, comorbidities, and structural barriers, could affect the findings.
DISCLOSURES:
This study was partially supported by a grant from the Georgia Cancer Center Paceline funding mechanism at Augusta University. The authors did not declare any conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
Patients with early-onset colorectal cancer (CRC) living in rural and impoverished areas face a significantly higher risk of dying from CRC.
METHODOLOGY:
- Previous research has shown that patients living in impoverished and rural areas have an increased risk of dying from CRC, but it is unclear if this trend applies to patients with early-onset CRC.
- Researchers analyzed 58,200 patients with early-onset CRC from the Surveillance, Epidemiology, and End Results Program between 2006 and 2015.
- Of these patients, 1346 (21%) lived in rural areas with persistent poverty. Persistent poverty was defined as having 20% or more of the population living below the poverty level for about 30 years, and rural locations were identified using specific US Department of Agriculture codes.
- The primary outcome was cancer-specific survival.
TAKEAWAY:
- The cancer-specific survival at 5 years was highest for patients who lived in neither poverty-stricken nor rural areas (72%) and the lowest for those who lived in impoverished areas irrespective of rural status (67%).
- Patients who lived in rural areas had a significantly higher risk of dying from CRC than those living in nonrural areas, with younger individuals facing the highest risk. More specifically, patients aged between 20 and 29 years had a 35% higher risk of dying from CRC, those aged between 30 and 39 years had a 26% higher risk, and those aged between 40 and 49 years had a 12% higher risk.
- Patients who lived in poverty and rural areas had a 29% increased risk of dying from CRC compared with those in nonrural areas — with the highest 51% greater risk for those aged between 30 and 39 years.
IN PRACTICE:
“Our results can be used to inform health system policies for ongoing investments in cancer diagnosis and treatment resources in rural or impoverished areas for younger CRC patients and their communities,” the authors wrote.
SOURCE:
The study, led by Meng-Han Tsai, PhD, Georgia Prevention Institute, Augusta University, Augusta, Georgia, was published online in JAMA Network Open.
LIMITATIONS:
Confounders, such as lifestyle factors, comorbidities, and structural barriers, could affect the findings.
DISCLOSURES:
This study was partially supported by a grant from the Georgia Cancer Center Paceline funding mechanism at Augusta University. The authors did not declare any conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Metformin Led to Improvements in Women with Central Centrifugal Cicatricial Alopecia
TOPLINE:
, in a retrospective case series.
METHODOLOGY:
- Researchers conducted a case series involving 12 Black women in their 30s, 40s, and 50s, with biopsy-confirmed, treatment-refractory CCCA, a chronic inflammatory hair disorder characterized by permanent hair loss, from the Johns Hopkins University alopecia clinic.
- Participants received CCCA treatment for at least 6 months and had stagnant or worsening symptoms before oral extended-release metformin (500 mg daily) was added to treatment. (Treatments included topical clobetasol, compounded minoxidil, and platelet-rich plasma injections.)
- Scalp biopsies were collected from four patients before and after metformin treatment to evaluate gene expression changes.
- Changes in clinical symptoms were assessed, including pruritus, inflammation, pain, scalp resistance, and hair regrowth, following initiation of metformin treatment.
TAKEAWAY:
- Metformin led to significant clinical improvement in eight patients, which included reductions in scalp pain, scalp resistance, pruritus, and inflammation. However, two patients experienced worsening symptoms.
- Six patients showed clinical evidence of hair regrowth after at least 6 months of metformin treatment with one experiencing hair loss again 3 months after discontinuing treatment.
- Transcriptomic analysis revealed 34 upregulated genes, which included upregulated of 23 hair keratin-associated proteins, and pathways related to keratinization, epidermis development, and the hair cycle. In addition, eight genes were downregulated, with pathways that included those associated with extracellular matrix organization, collagen fibril organization, and collagen metabolism.
- Gene set variation analysis showed reduced expression of T helper 17 cell and epithelial-mesenchymal transition pathways and elevated adenosine monophosphate kinase signaling and keratin-associated proteins after treatment with metformin.
IN PRACTICE:
“Metformin’s ability to concomitantly target fibrosis and inflammation provides a plausible mechanism for its therapeutic effects in CCCA and other fibrosing alopecia disorders,” the authors concluded. But, they added, “larger prospective, placebo-controlled randomized clinical trials are needed to rigorously evaluate metformin’s efficacy and optimal dosing for treatment of cicatricial alopecias.”
SOURCE:
The study was led by Aaron Bao, Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, and was published online on September 4 in JAMA Dermatology.
LIMITATIONS:
A small sample size, retrospective design, lack of a placebo control group, and the single-center setting limited the generalizability of the study findings. In addition, the absence of a validated activity or severity scale for CCCA and the single posttreatment sampling limit the assessment and comparison of clinical symptoms and transcriptomic changes.
DISCLOSURES:
The study was supported by the American Academy of Dermatology. One author reported several ties with pharmaceutical companies, a pending patent, and authorship for the UpToDate section on CCCA.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
, in a retrospective case series.
METHODOLOGY:
- Researchers conducted a case series involving 12 Black women in their 30s, 40s, and 50s, with biopsy-confirmed, treatment-refractory CCCA, a chronic inflammatory hair disorder characterized by permanent hair loss, from the Johns Hopkins University alopecia clinic.
- Participants received CCCA treatment for at least 6 months and had stagnant or worsening symptoms before oral extended-release metformin (500 mg daily) was added to treatment. (Treatments included topical clobetasol, compounded minoxidil, and platelet-rich plasma injections.)
- Scalp biopsies were collected from four patients before and after metformin treatment to evaluate gene expression changes.
- Changes in clinical symptoms were assessed, including pruritus, inflammation, pain, scalp resistance, and hair regrowth, following initiation of metformin treatment.
TAKEAWAY:
- Metformin led to significant clinical improvement in eight patients, which included reductions in scalp pain, scalp resistance, pruritus, and inflammation. However, two patients experienced worsening symptoms.
- Six patients showed clinical evidence of hair regrowth after at least 6 months of metformin treatment with one experiencing hair loss again 3 months after discontinuing treatment.
- Transcriptomic analysis revealed 34 upregulated genes, which included upregulated of 23 hair keratin-associated proteins, and pathways related to keratinization, epidermis development, and the hair cycle. In addition, eight genes were downregulated, with pathways that included those associated with extracellular matrix organization, collagen fibril organization, and collagen metabolism.
- Gene set variation analysis showed reduced expression of T helper 17 cell and epithelial-mesenchymal transition pathways and elevated adenosine monophosphate kinase signaling and keratin-associated proteins after treatment with metformin.
IN PRACTICE:
“Metformin’s ability to concomitantly target fibrosis and inflammation provides a plausible mechanism for its therapeutic effects in CCCA and other fibrosing alopecia disorders,” the authors concluded. But, they added, “larger prospective, placebo-controlled randomized clinical trials are needed to rigorously evaluate metformin’s efficacy and optimal dosing for treatment of cicatricial alopecias.”
SOURCE:
The study was led by Aaron Bao, Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, and was published online on September 4 in JAMA Dermatology.
LIMITATIONS:
A small sample size, retrospective design, lack of a placebo control group, and the single-center setting limited the generalizability of the study findings. In addition, the absence of a validated activity or severity scale for CCCA and the single posttreatment sampling limit the assessment and comparison of clinical symptoms and transcriptomic changes.
DISCLOSURES:
The study was supported by the American Academy of Dermatology. One author reported several ties with pharmaceutical companies, a pending patent, and authorship for the UpToDate section on CCCA.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
, in a retrospective case series.
METHODOLOGY:
- Researchers conducted a case series involving 12 Black women in their 30s, 40s, and 50s, with biopsy-confirmed, treatment-refractory CCCA, a chronic inflammatory hair disorder characterized by permanent hair loss, from the Johns Hopkins University alopecia clinic.
- Participants received CCCA treatment for at least 6 months and had stagnant or worsening symptoms before oral extended-release metformin (500 mg daily) was added to treatment. (Treatments included topical clobetasol, compounded minoxidil, and platelet-rich plasma injections.)
- Scalp biopsies were collected from four patients before and after metformin treatment to evaluate gene expression changes.
- Changes in clinical symptoms were assessed, including pruritus, inflammation, pain, scalp resistance, and hair regrowth, following initiation of metformin treatment.
TAKEAWAY:
- Metformin led to significant clinical improvement in eight patients, which included reductions in scalp pain, scalp resistance, pruritus, and inflammation. However, two patients experienced worsening symptoms.
- Six patients showed clinical evidence of hair regrowth after at least 6 months of metformin treatment with one experiencing hair loss again 3 months after discontinuing treatment.
- Transcriptomic analysis revealed 34 upregulated genes, which included upregulated of 23 hair keratin-associated proteins, and pathways related to keratinization, epidermis development, and the hair cycle. In addition, eight genes were downregulated, with pathways that included those associated with extracellular matrix organization, collagen fibril organization, and collagen metabolism.
- Gene set variation analysis showed reduced expression of T helper 17 cell and epithelial-mesenchymal transition pathways and elevated adenosine monophosphate kinase signaling and keratin-associated proteins after treatment with metformin.
IN PRACTICE:
“Metformin’s ability to concomitantly target fibrosis and inflammation provides a plausible mechanism for its therapeutic effects in CCCA and other fibrosing alopecia disorders,” the authors concluded. But, they added, “larger prospective, placebo-controlled randomized clinical trials are needed to rigorously evaluate metformin’s efficacy and optimal dosing for treatment of cicatricial alopecias.”
SOURCE:
The study was led by Aaron Bao, Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, and was published online on September 4 in JAMA Dermatology.
LIMITATIONS:
A small sample size, retrospective design, lack of a placebo control group, and the single-center setting limited the generalizability of the study findings. In addition, the absence of a validated activity or severity scale for CCCA and the single posttreatment sampling limit the assessment and comparison of clinical symptoms and transcriptomic changes.
DISCLOSURES:
The study was supported by the American Academy of Dermatology. One author reported several ties with pharmaceutical companies, a pending patent, and authorship for the UpToDate section on CCCA.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Tool Can Help Predict Futile Surgery in Pancreatic Cancer
TOPLINE:
METHODOLOGY:
- Immediate resection is associated with a high incidence of postoperative complications and disease recurrence within a year of surgery in patients with pancreatic ductal adenocarcinoma. Predicting which patients likely won’t benefit from upfront pancreatectomy is important.
- To identify preoperative risk factors for futile pancreatectomy, researchers evaluated 1426 patients (median age, 69 years; 53.2% men) with anatomically resectable pancreatic ductal adenocarcinoma who underwent pancreatic resection between January 2010 and December 2021.
- The patients were divided into derivation (n = 885) and validation (n = 541) cohorts.
- The primary outcome was the rate of futile upfront pancreatectomy, defined as death or disease recurrence within 6 months of surgery. Patients were divided into three risk categories — low, intermediate, and high risk — each with escalating likelihoods of futile resection, worse pathological features, and worse outcomes.
- The secondary endpoint was to develop criteria for surgical candidacy, setting a futility likelihood threshold of < 20%. This threshold corresponds to the lower bound of the 95% confidence interval (CI) for postneoadjuvant resection rates (resection rate, 0.90; 95% CI, 0.80-1.01) from recent meta-analyses.
TAKEAWAY:
- The futility rate for pancreatectomy was 18.9% — 19.2% in the development cohort and 18.6% in the validation cohort. Three independent risk factors for futile resection included American Society of Anesthesiologists (ASA) class (95% CI for coefficients, 0.68-0.87), preoperative cancer antigen 19.9 serum levels (95% CI for coefficients, 0.05-0.75), and radiologic tumor size (95% CI for coefficients, 0.28-0.46).
- Using these independent risk factors, the predictive model demonstrated adequate calibration and discrimination in both the derivation and validation cohorts.
- The researchers then identified three risk groups. In the derivation cohort, the rate of futile pancreatectomy was 9.2% in the low-risk group, 18.0% in the intermediate-risk group, and 28.7% in the high-risk group (P < .001 for trend). In the validation cohort, the futility rate was 10.9% in the low-risk group, 20.2% in the intermediate-risk group, and 29.2% in the high-risk group (P < .001 for trend).
- Researchers identified four conditions associated with a futility likelihood below 20%, where larger tumor size is paired with lower cancer antigen 19.9 levels (defined as cancer antigen 19.9–adjusted-to-size). Patients who met these criteria experienced significantly longer disease-free survival (median 18.4 months vs 11.2 months) and overall survival (38.5 months vs 22.1 months).
IN PRACTICE:
“Although the study provides an easy-to-use calculator for clinical decision-making, there are some methodological limitations,” according to the authors of accompanying commentary. These limitations include failing to accurately describe how ASA class, cancer antigen 19.9 level, and tumor size were chosen for the model. “While we do not think the model is yet ready for standard clinical use, it may prove to be a viable tool if tested in future randomized trials comparing the neoadjuvant approach to upfront surgery in resectable pancreatic cancer,” the editorialists added.
SOURCE:
This study, led by Stefano Crippa, MD, PhD, Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, and the accompanying commentary were published online in JAMA Surgery.
LIMITATIONS:
In addition to the limitations noted by the editorialists, others include the study’s retrospective design, which could introduce bias. Because preoperative imaging was not revised, the assigned resectability classes could show variability. Institutional differences existed in the selection process for upfront pancreatectomy. The model cannot be applied to cancer antigen 19.9 nonsecretors and was not externally validated.
DISCLOSURES:
The Italian Association for Cancer Research Special Program in Metastatic Disease and Italian Ministry of Health/Italian Foundation for the Research of Pancreatic Diseases supported the study in the form of a grant. Two authors reported receiving personal fees outside the submitted work. No other disclosures were reported.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Immediate resection is associated with a high incidence of postoperative complications and disease recurrence within a year of surgery in patients with pancreatic ductal adenocarcinoma. Predicting which patients likely won’t benefit from upfront pancreatectomy is important.
- To identify preoperative risk factors for futile pancreatectomy, researchers evaluated 1426 patients (median age, 69 years; 53.2% men) with anatomically resectable pancreatic ductal adenocarcinoma who underwent pancreatic resection between January 2010 and December 2021.
- The patients were divided into derivation (n = 885) and validation (n = 541) cohorts.
- The primary outcome was the rate of futile upfront pancreatectomy, defined as death or disease recurrence within 6 months of surgery. Patients were divided into three risk categories — low, intermediate, and high risk — each with escalating likelihoods of futile resection, worse pathological features, and worse outcomes.
- The secondary endpoint was to develop criteria for surgical candidacy, setting a futility likelihood threshold of < 20%. This threshold corresponds to the lower bound of the 95% confidence interval (CI) for postneoadjuvant resection rates (resection rate, 0.90; 95% CI, 0.80-1.01) from recent meta-analyses.
TAKEAWAY:
- The futility rate for pancreatectomy was 18.9% — 19.2% in the development cohort and 18.6% in the validation cohort. Three independent risk factors for futile resection included American Society of Anesthesiologists (ASA) class (95% CI for coefficients, 0.68-0.87), preoperative cancer antigen 19.9 serum levels (95% CI for coefficients, 0.05-0.75), and radiologic tumor size (95% CI for coefficients, 0.28-0.46).
- Using these independent risk factors, the predictive model demonstrated adequate calibration and discrimination in both the derivation and validation cohorts.
- The researchers then identified three risk groups. In the derivation cohort, the rate of futile pancreatectomy was 9.2% in the low-risk group, 18.0% in the intermediate-risk group, and 28.7% in the high-risk group (P < .001 for trend). In the validation cohort, the futility rate was 10.9% in the low-risk group, 20.2% in the intermediate-risk group, and 29.2% in the high-risk group (P < .001 for trend).
- Researchers identified four conditions associated with a futility likelihood below 20%, where larger tumor size is paired with lower cancer antigen 19.9 levels (defined as cancer antigen 19.9–adjusted-to-size). Patients who met these criteria experienced significantly longer disease-free survival (median 18.4 months vs 11.2 months) and overall survival (38.5 months vs 22.1 months).
IN PRACTICE:
“Although the study provides an easy-to-use calculator for clinical decision-making, there are some methodological limitations,” according to the authors of accompanying commentary. These limitations include failing to accurately describe how ASA class, cancer antigen 19.9 level, and tumor size were chosen for the model. “While we do not think the model is yet ready for standard clinical use, it may prove to be a viable tool if tested in future randomized trials comparing the neoadjuvant approach to upfront surgery in resectable pancreatic cancer,” the editorialists added.
SOURCE:
This study, led by Stefano Crippa, MD, PhD, Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, and the accompanying commentary were published online in JAMA Surgery.
LIMITATIONS:
In addition to the limitations noted by the editorialists, others include the study’s retrospective design, which could introduce bias. Because preoperative imaging was not revised, the assigned resectability classes could show variability. Institutional differences existed in the selection process for upfront pancreatectomy. The model cannot be applied to cancer antigen 19.9 nonsecretors and was not externally validated.
DISCLOSURES:
The Italian Association for Cancer Research Special Program in Metastatic Disease and Italian Ministry of Health/Italian Foundation for the Research of Pancreatic Diseases supported the study in the form of a grant. Two authors reported receiving personal fees outside the submitted work. No other disclosures were reported.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Immediate resection is associated with a high incidence of postoperative complications and disease recurrence within a year of surgery in patients with pancreatic ductal adenocarcinoma. Predicting which patients likely won’t benefit from upfront pancreatectomy is important.
- To identify preoperative risk factors for futile pancreatectomy, researchers evaluated 1426 patients (median age, 69 years; 53.2% men) with anatomically resectable pancreatic ductal adenocarcinoma who underwent pancreatic resection between January 2010 and December 2021.
- The patients were divided into derivation (n = 885) and validation (n = 541) cohorts.
- The primary outcome was the rate of futile upfront pancreatectomy, defined as death or disease recurrence within 6 months of surgery. Patients were divided into three risk categories — low, intermediate, and high risk — each with escalating likelihoods of futile resection, worse pathological features, and worse outcomes.
- The secondary endpoint was to develop criteria for surgical candidacy, setting a futility likelihood threshold of < 20%. This threshold corresponds to the lower bound of the 95% confidence interval (CI) for postneoadjuvant resection rates (resection rate, 0.90; 95% CI, 0.80-1.01) from recent meta-analyses.
TAKEAWAY:
- The futility rate for pancreatectomy was 18.9% — 19.2% in the development cohort and 18.6% in the validation cohort. Three independent risk factors for futile resection included American Society of Anesthesiologists (ASA) class (95% CI for coefficients, 0.68-0.87), preoperative cancer antigen 19.9 serum levels (95% CI for coefficients, 0.05-0.75), and radiologic tumor size (95% CI for coefficients, 0.28-0.46).
- Using these independent risk factors, the predictive model demonstrated adequate calibration and discrimination in both the derivation and validation cohorts.
- The researchers then identified three risk groups. In the derivation cohort, the rate of futile pancreatectomy was 9.2% in the low-risk group, 18.0% in the intermediate-risk group, and 28.7% in the high-risk group (P < .001 for trend). In the validation cohort, the futility rate was 10.9% in the low-risk group, 20.2% in the intermediate-risk group, and 29.2% in the high-risk group (P < .001 for trend).
- Researchers identified four conditions associated with a futility likelihood below 20%, where larger tumor size is paired with lower cancer antigen 19.9 levels (defined as cancer antigen 19.9–adjusted-to-size). Patients who met these criteria experienced significantly longer disease-free survival (median 18.4 months vs 11.2 months) and overall survival (38.5 months vs 22.1 months).
IN PRACTICE:
“Although the study provides an easy-to-use calculator for clinical decision-making, there are some methodological limitations,” according to the authors of accompanying commentary. These limitations include failing to accurately describe how ASA class, cancer antigen 19.9 level, and tumor size were chosen for the model. “While we do not think the model is yet ready for standard clinical use, it may prove to be a viable tool if tested in future randomized trials comparing the neoadjuvant approach to upfront surgery in resectable pancreatic cancer,” the editorialists added.
SOURCE:
This study, led by Stefano Crippa, MD, PhD, Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, and the accompanying commentary were published online in JAMA Surgery.
LIMITATIONS:
In addition to the limitations noted by the editorialists, others include the study’s retrospective design, which could introduce bias. Because preoperative imaging was not revised, the assigned resectability classes could show variability. Institutional differences existed in the selection process for upfront pancreatectomy. The model cannot be applied to cancer antigen 19.9 nonsecretors and was not externally validated.
DISCLOSURES:
The Italian Association for Cancer Research Special Program in Metastatic Disease and Italian Ministry of Health/Italian Foundation for the Research of Pancreatic Diseases supported the study in the form of a grant. Two authors reported receiving personal fees outside the submitted work. No other disclosures were reported.
A version of this article first appeared on Medscape.com.