{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:09:01Z","timestamp":1773965341400,"version":"3.50.1"},"reference-count":36,"publisher":"American Medical Association (AMA)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>Randomized clinical trials examining the effectiveness of neoadjuvant chemotherapy (NACT) for advanced ovarian cancer predominantly included patients with high-grade serous carcinomas. The use and outcomes of NACT in less common epithelial carcinomas are understudied.<\/jats:p><\/jats:sec>Objective<\/jats:title>To investigate the uptake and survival outcomes in treatment with NACT for less common histologic subtypes of epithelial ovarian cancer.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>A retrospective cohort study and systematic literature review with meta-analysis was conducted using the National Cancer Database from 2006 to 2017 and the National Cancer Institute\u2019s Surveillance, Epidemiology, and End Results Program from 2006 to 2019. Data analysis was performed from July 2022 to April 2023. The evaluation included patients with stage III to IV ovarian cancer with clear cell, mucinous, or low-grade serous histologic subtypes who received multimodal treatment with surgery and chemotherapy.<\/jats:p><\/jats:sec>Exposures<\/jats:title>Exposure assignment per the sequence of treatment: primary debulking surgery (PDS) followed by chemotherapy (PDS group) or NACT followed by interval surgery (NACT group).<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>Temporal trends and characteristics of NACT use were assessed using multivariable analysis, and overall survival (OS) was assessed with the inverse probability of treatment weighting propensity score.<\/jats:p><\/jats:sec>Results<\/jats:title>A total of 3880 patients were examined in the National Cancer Database including 1829 women (median age, 56 [IQR, 49-63] years) with clear cell, 1156 women (median age, 53 [IQR, 42-64] years) with low-grade serous, and 895 women (median age, 57 [IQR, 48-66] years) with mucinous carcinomas. NACT use increased in patients with clear cell (from 10.2% to 16.2%, 58.8% relative increase; P<\/jats:italic>\u2009&amp;lt;\u2009.001 for trend) or low-grade serous (from 7.7% to 14.2%, 84.4% relative increase; P<\/jats:italic>\u2009=\u2009.007 for trend) carcinoma during the study period. This association remained consistent in multivariable analysis. NACT use also increased, but nonsignificantly, in mucinous carcinomas (from 8.6% to 13.9%, 61.6% relative increase; P<\/jats:italic>\u2009=\u2009.07 for trend). Across the 3 histologic subtypes, older age and stage IV disease were independently associated with NACT use. In a propensity score\u2013weighted model, the NACT and PDS groups had comparable OS for clear cell (4-year rates, 31.4% vs 37.7%; hazard ratio [HR], 1.12; 95% CI, 0.95-1.33) and mucinous (27.0% vs 26.7%; HR, 0.90; 95% CI, 0.68-1.19) carcinomas. For patients with low-grade serous carcinoma, NACT was associated with decreased OS compared with PDS (4-year rates, 56.4% vs 81.0%; HR, 2.12; 95% CI, 1.55-2.90). Increasing NACT use and histologic subtype\u2013specific survival association were also found in the Surveillance, Epidemiology, and End Results Program cohort (n\u2009=\u20091447). A meta-analysis of 4 studies, including the current study, observed similar OS associations for clear cell (HR, 1.13; 95% CI, 0.96-1.34; 2 studies), mucinous (HR, 0.93; 95% CI, 0.71-1.21; 2 studies), and low-grade serous (HR, 2.11; 95% CI, 1.63-2.74; 3 studies) carcinomas.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>Despite the lack of data on outcomes of NACT among patients with less common carcinomas, this study noted that NACT use for advanced disease has gradually increased in the US. Primary chemotherapy for advanced-stage, low-grade serous ovarian cancer may be associated with worse survival compared with PDS.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2023.18602","type":"journal-article","created":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T15:34:12Z","timestamp":1686929652000},"page":"e2318602","source":"Crossref","is-referenced-by-count":23,"title":["Uptake and Outcomes of Neoadjuvant Chemotherapy Among US Patients With Less Common Epithelial Ovarian Carcinomas"],"prefix":"10.1001","volume":"6","author":[{"given":"Koji","family":"Matsuo","sequence":"first","affiliation":[{"name":"Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles"},{"name":"Norris Comprehensive Cancer Center, University of Southern California, Los Angeles"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinya","family":"Matsuzaki","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Osaka International Cancer Institute, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michihide","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Osaka International Cancer Institute, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alesandra R.","family":"Rau","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kosuke","family":"Yoshihara","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Niigata University School of Medicine, Niigata, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryo","family":"Tamura","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Niigata University School of Medicine, Niigata, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muneaki","family":"Shimada","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Tohoku University School of Medicine, Miyagi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroko","family":"Machida","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Tokai University School of Medicine, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikio","family":"Mikami","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Tokai University School of Medicine, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maximilian","family":"Klar","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Freiburg Faculty of Medicine, Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynda D.","family":"Roman","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles"},{"name":"Norris Comprehensive Cancer Center, University of Southern California, Los Angeles"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason D.","family":"Wright","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anil K.","family":"Sood","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M.","family":"Gershenson","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"10","published-online":{"date-parts":[[2023,6,16]]},"reference":[{"issue":"1","key":"zoi230566r1","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3322\/caac.v73.1","article-title":"Cancer statistics, 2023.","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J Clin"},{"issue":"4","key":"zoi230566r4","doi-asserted-by":"publisher","first-page":"626","DOI":"10.3390\/cancers13040626","article-title":"Emerging trends in neoadjuvant chemotherapy for ovarian cancer.","volume":"13","author":"Patel","year":"2021","journal-title":"Cancers (Basel)"},{"issue":"1","key":"zoi230566r5","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.ygyno.2020.10.027","article-title":"Possible candidate population for neoadjuvant chemotherapy in women with advanced ovarian cancer.","volume":"160","author":"Matsuo","year":"2021","journal-title":"Gynecol Oncol"},{"issue":"10","key":"zoi230566r6","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1056\/NEJMoa0908806","article-title":"Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer.","volume":"363","author":"Vergote","year":"2010","journal-title":"N Engl J Med"},{"issue":"9990","key":"zoi230566r7","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/S0140-6736(14)62223-6","article-title":"Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial.","volume":"386","author":"Kehoe","year":"2015","journal-title":"Lancet"},{"key":"zoi230566r8","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.ejca.2020.02.020","article-title":"Comparison of survival between primary debulking surgery and neoadjuvant chemotherapy for stage III\/IV ovarian, tubal and peritoneal cancers in phase III randomised trial.","volume":"130","author":"Onda","year":"2020","journal-title":"Eur J Cancer"},{"issue":"11","key":"zoi230566r9","doi-asserted-by":"publisher","first-page":"1657","DOI":"10.1136\/ijgc-2020-001640","article-title":"Randomized trial of primary debulking surgery versus neoadjuvant chemotherapy for advanced epithelial ovarian cancer (SCORPION-NCT01461850).","volume":"30","author":"Fagotti","year":"2020","journal-title":"Int J Gynecol Cancer"},{"issue":"10","key":"zoi230566r10","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1038\/nrc3144","article-title":"Rethinking ovarian cancer: recommendations for improving outcomes.","volume":"11","author":"Vaughan","year":"2011","journal-title":"Nat Rev Cancer"},{"issue":"1","key":"zoi230566r11","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.ygyno.2019.11.122","article-title":"Evolving population-based statistics for rare epithelial ovarian cancers.","volume":"157","author":"Matsuo","year":"2020","journal-title":"Gynecol Oncol"},{"issue":"3","key":"zoi230566r12","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1016\/j.ygyno.2007.11.013","article-title":"Neoadjuvant chemotherapy for low-grade serous carcinoma of the ovary or peritoneum.","volume":"108","author":"Schmeler","year":"2008","journal-title":"Gynecol Oncol"},{"issue":"1","key":"zoi230566r13","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.ygyno.2010.09.024","article-title":"Interaction between preoperative CA-125 level and survival benefit of neoadjuvant chemotherapy in advanced epithelial ovarian cancer.","volume":"120","author":"Kang","year":"2011","journal-title":"Gynecol Oncol"},{"issue":"1","key":"zoi230566r14","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1186\/s12885-019-5514-7","article-title":"Outcomes of non-high grade serous carcinoma after neoadjuvant chemotherapy for advanced-stage ovarian cancer: a Korean gynecologic oncology group study (OV 1708).","volume":"19","author":"Chung","year":"2019","journal-title":"BMC Cancer"},{"issue":"1","key":"zoi230566r15","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.ygyno.2020.01.021","article-title":"Low-grade serous carcinoma (LGSC): a Canadian multicenter review of practice patterns and patient outcomes.","volume":"157","author":"Scott","year":"2020","journal-title":"Gynecol Oncol"},{"issue":"3","key":"zoi230566r16","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1016\/j.ygyno.2020.06.498","article-title":"The role of neoadjuvant chemotherapy in the management of low-grade serous carcinoma of the ovary and peritoneum: further evidence of relative chemoresistance.","volume":"158","author":"Cobb","year":"2020","journal-title":"Gynecol Oncol"},{"issue":"9","key":"zoi230566r17","doi-asserted-by":"publisher","first-page":"2345","DOI":"10.3390\/cancers14092345","article-title":"Surgical implications of advanced low-grade serous ovarian cancer: analysis of the database of the Tumeurs Malignes Rares Gyn\u00e9cologiques Network.","volume":"14","author":"Bonsang-Kitzis","year":"2022","journal-title":"Cancers (Basel)"},{"issue":"28","key":"zoi230566r18","doi-asserted-by":"publisher","first-page":"3460","DOI":"10.1200\/JCO.2016.68.6907","article-title":"Neoadjuvant chemotherapy for newly diagnosed, advanced ovarian cancer: Society of Gynecologic Oncology and American Society of Clinical Oncology Clinical Practice Guideline.","volume":"34","author":"Wright","year":"2016","journal-title":"J Clin Oncol"},{"issue":"1","key":"zoi230566r22","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.ygyno.2019.08.030","article-title":"Diagnosis-shift between low-grade serous ovarian cancer and serous borderline ovarian tumor: a population-based study.","volume":"157","author":"Matsuo","year":"2020","journal-title":"Gynecol Oncol"},{"issue":"2","key":"zoi230566r23","doi-asserted-by":"publisher","DOI":"10.3802\/jgo.2018.29.e22","article-title":"Trends of uterine carcinosarcoma in the United States.","volume":"29","author":"Matsuo","year":"2018","journal-title":"J Gynecol Oncol"},{"issue":"6","key":"zoi230566r24","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1016\/0895-4356(92)90133-8","article-title":"Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases.","volume":"45","author":"Deyo","year":"1992","journal-title":"J Clin Epidemiol"},{"issue":"2","key":"zoi230566r26","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1093\/ije\/dyw040","article-title":"Outcome modelling strategies in epidemiology: traditional methods and basic alternatives.","volume":"45","author":"Greenland","year":"2016","journal-title":"Int J Epidemiol"},{"issue":"28","key":"zoi230566r27","doi-asserted-by":"crossref","first-page":"3661","DOI":"10.1002\/sim.6607","article-title":"Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies.","volume":"34","author":"Austin","year":"2015","journal-title":"Stat Med"},{"issue":"32","key":"zoi230566r29","doi-asserted-by":"crossref","first-page":"3854","DOI":"10.1200\/JCO.2016.68.1239","article-title":"Use and effectiveness of neoadjuvant chemotherapy for treatment of ovarian cancer.","volume":"34","author":"Meyer","year":"2016","journal-title":"J Clin Oncol"},{"issue":"6","key":"zoi230566r30","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1136\/ijgc-2019-001124","article-title":"Interval debulking surgery is not worth the wait: a National Cancer Database study comparing primary cytoreductive surgery versus neoadjuvant chemotherapy.","volume":"30","author":"Lyons","year":"2020","journal-title":"Int J Gynecol Cancer"},{"issue":"3","key":"zoi230566r31","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1097\/AOG.0000000000002796","article-title":"Laparoscopic surgical algorithm to triage the timing of tumor reductive surgery in advanced ovarian cancer.","volume":"132","author":"Fleming","year":"2018","journal-title":"Obstet Gynecol"},{"issue":"11","key":"zoi230566r32","doi-asserted-by":"crossref","first-page":"2584","DOI":"10.1002\/1097-0142(20000601)88:11<2584::AID-CNCR22>3.0.CO;2-5","article-title":"Clinical characteristics of clear cell carcinoma of the ovary: a distinct histologic type with poor prognosis and resistance to platinum-based chemotherapy.","volume":"88","author":"Sugiyama","year":"2000","journal-title":"Cancer"},{"issue":"3","key":"zoi230566r33","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.ygyno.2009.02.010","article-title":"Clinicopathological characteristics of mucinous adenocarcinoma of the ovary.","volume":"113","author":"Shimada","year":"2009","journal-title":"Gynecol Oncol"},{"issue":"24","key":"zoi230566r34","doi-asserted-by":"crossref","first-page":"2675","DOI":"10.1200\/JCO.2015.61.0873","article-title":"Impact of age and primary disease site on outcome in women with low-grade serous carcinoma of the ovary or peritoneum: results of a large single-institution registry of a rare tumor.","volume":"33","author":"Gershenson","year":"2015","journal-title":"J Clin Oncol"},{"issue":"3","key":"zoi230566r35","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.ygyno.2019.03.256","article-title":"An international, phase III randomized trial in patients with mucinous epithelial ovarian cancer (mEOC\/GOG 0241) with long-term follow-up: and experience of conducting a clinical trial in a rare gynecological tumor.","volume":"153","author":"Gore","year":"2019","journal-title":"Gynecol Oncol"},{"key":"zoi230566r2","first-page":"1525","volume-title":"Abeloff\u2019s Clinical Oncology","author":"Coleman","year":"2019","edition":"6th ed"},{"key":"zoi230566r28","volume-title":"Statistical Power Analysis for the Behavioral Sciences","author":"Cohen","year":"1988","edition":"2nd ed"},{"key":"zoi230566r3","unstructured":"National Comprehensive Cancer Network. Ovarian cancer including fallopian tube cancer and primary peritoneal cancer. NCCN clinical practice guidelines in Oncology (NCCN Guidelines). Accessed September 30, 2022. https:\/\/www.nccn.org\/"},{"key":"zoi230566r19","unstructured":"American College of Surgeons. National Cancer Database. Accessed October 1, 2022. https:\/\/www.facs.org\/quality-programs\/cancer-programs\/national-cancer-database\/"},{"key":"zoi230566r20","unstructured":"National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Accessed October 1, 2022. https:\/\/seer.cancer.gov\/"},{"key":"zoi230566r21","unstructured":"World Health Organization. International Classification of Diseases for Oncology. 3rd ed (ICD-O-3). Accessed October 1, 2022. World Health Organization. https:\/\/www.who.int\/standards\/classifications\/other-classifications\/international-classification-of-diseases-for-oncology"},{"key":"zoi230566r25","unstructured":"Ovary: collaborative stage version 2 schema list v.02.05.00. Accessed October 1, 2022. https:\/\/web2.facs.org\/cstage0205\/ovary\/Ovaryschema.html"},{"key":"zoi230566r36","unstructured":"Cobb? LP, Davis? J, Hull? S, . A pilot phase II study of neoadjuvant fulvestrant plus abemaciclib in women with advanced low-grade serous carcinoma. J Clin Oncol. Accessed May 11, 2023. https:\/\/ascopubs.org\/doi\/pdf\/10.1200\/JCO.2022.40.16_suppl.5522?role=tab"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2806184\/matsuo_2023_oi_230566_1686250804.7296.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T15:34:21Z","timestamp":1686929661000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2806184"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,16]]},"references-count":36,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,6,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2023.18602","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,16]]}}}