{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T15:13:05Z","timestamp":1788880385678,"version":"build-2803163510"},"reference-count":110,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"<jats:sec id=\"ab-zoi260891-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>The impact of sex on the efficacy of immune checkpoint inhibitors (ICIs) in curative treatments of solid tumors remains insufficiently explored. Optimal timing of ICIs is clinically relevant, with practice shifting toward broader adoption of neoadjuvant approaches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi260891-5\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To assess the association of patient sex and treatment timing with outcomes of ICI administration in curative treatments for solid tumors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi260891-6\">\n                    <jats:title>Data Sources<\/jats:title>\n                    <jats:p>In this systematic review and meta-analysis, MEDLINE, Embase, the Cochrane Library, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform were systematically searched from January 1, 2010, to June 23, 2025, using controlled vocabulary combined with free-text search terms. A manual search in PubMed was conducted through August 10, 2025.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi260891-7\">\n                    <jats:title>Study Selection<\/jats:title>\n                    <jats:p>Reports of randomized phase 3 clinical trials investigating ICI treatment in non\u2013sex-specific solid cancer types in curative settings, including surgery and radiotherapy or chemoradiotherapy as local therapies, were included.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi260891-8\">\n                    <jats:title>Data Extraction and Synthesis<\/jats:title>\n                    <jats:p>Three authors were involved in data abstraction; data from each record were extracted independently by 2 of these 3 authors. Hazard ratios (HRs) and corresponding 95% CIs were calculated using random-effects meta-analysis. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi260891-9\">\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>Pooled HRs for overall survival (OS) and for time to the combined end point of disease-free, event-free, progression-free, and recurrence-free survival were analyzed overall, by sex, and by treatment timing relative to surgery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi260891-10\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 62 reports of 38 trials comprising 31\u202f721 patients (29.7% female and 70.3% male) were analyzed. ICIs were associated with improvement in OS (HR, 0.83; 95% CI, 0.79-0.89;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001) and the combined end points (HR, 0.73; 95% CI, 0.68-0.77;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001). No statistically significant sex-specific differences were observed for OS (females: HR, 0.76 [95% CI, 0.67-0.86]; males: HR, 0.78 [95% CI, 0.72-0.85]) or the combined end points (females: HR, 0.74 [95% CI, 0.69-0.79]; males: HR, 0.73 [95% CI, 0.67-0.78]). Neoadjuvant or perioperative ICIs were associated with better OS (HR, 0.77 [95% CI, 0.69-0.86]) and combined end point outcomes (HR, 0.64 [95% CI, 0.57-0.73]) compared with adjuvant-only use (OS: HR, 0.84 [95% CI, 0.78-0.91]; combined end points: HR, 0.74 [95% CI, 0.68-0.81]).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi260891-11\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>This systematic review and meta-analysis detected no statistically significant difference in survival outcomes associated with ICIs by patient sex, although female patients were underrepresented. In exploratory analyses, neoadjuvant or perioperative ICIs were associated with superior survival outcomes compared with strictly adjuvant administration, a finding that supports increased adoption of neoadjuvant ICI therapy approaches.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.32635","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T15:00:18Z","timestamp":1788879618000},"page":"e2632635","source":"Crossref","is-referenced-by-count":0,"title":["Sex, Timing, and Outcomes of Curative-Intent Immunotherapy"],"prefix":"10.1001","volume":"9","author":[{"given":"Anne-Murielle","family":"Hollinger","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille L.","family":"Gerard","sequence":"additional","affiliation":[{"name":"Department of Medicine, Lausanne 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