{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T10:26:54Z","timestamp":1778495214105,"version":"3.51.4"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T00:00:00Z","timestamp":1657584000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and highly aggressive malignancy with a poor prognosis. Most patients experience recurrence even after surgery and chemotherapy, and there are no standard treatment options for recurrent disease. Here, we report the case of a 36-year-old woman with SCCOHT who underwent primary cytoreductive surgery without adjuvant chemotherapy and remained disease-free for 9 months. She then developed retroperitoneal lymph node metastasis and was treated with two cycles of bleomycin\/etoposide\/cisplatin chemotherapy. However, the disease progressed and the patient received four cycles of liposomal doxorubicin\/ifosfamide chemotherapy, followed by local radiation to the enlarged retroperitoneal lymph nodes. She achieved partial remission for 13 months, after which the disease progressed again. Tumor tissues and blood samples were sent for next-generation sequencing. The results indicated a somatic SWI\/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (<jats:italic>SMARCA4<\/jats:italic>) mutation, microsatellite stability, and a tumor mutation burden of 1.0 muts\/Mb without any germline mutations. An anti-PD-1 antibody, camrelizumab, and an antiangiogenic agent, apatinib, were administered, and the patient achieved partial remission for 28 months. Our study provides the first clinical evidence that the combination therapy of camrelizumab and apatinib could be an effective treatment for recurrent SCCOHT.<\/jats:p>","DOI":"10.3389\/fonc.2022.916790","type":"journal-article","created":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T06:04:44Z","timestamp":1657605884000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Case Report: A Durable Response to Camrelizumab and Apatinib Combination Therapy in a Heavily Treated Small Cell Carcinoma of the Ovary, Hypercalcemic Type"],"prefix":"10.3389","volume":"12","author":[{"given":"Guiling","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yao","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcpc1000272","article-title":"Case Records of the MassachusettsGeneral Hospital. Case 8-2010. A 22-Year-Old Woman With Hypercalcemia and a Pelvic Mass","volume":"362","author":"Young","year":"2010","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-199411000-00004","article-title":"Small Cell Carcinoma of the Ovary, Hypercalcemic Type. A Clinicopathological Analysis of 150 Cases","volume":"18","author":"Young","year":"1994","journal-title":"Am J Surg Pathol"},{"key":"B3","article-title":"[Epithelial Cancer of the Ovary in Adults: Prognostic and Therapeutic Study of 95 Cases]","volume":"44","author":"Fignon","year":"1990","journal-title":"Ann Chir"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2015.11.004","article-title":"Small Cell Carcinoma of the Ovary-Hypercalcemic Type (SCCOHT): A Review of 47 Cases","volume":"140","author":"Callegaro-Filho","year":"2016","journal-title":"Gynecol Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdm376","article-title":"Results of a Prospective Dose-Intensive Regimen in 27 Patients With Small Cell Carcinoma of the Ovary of the Hypercalcemic Type","volume":"18","author":"Pautier","year":"2007","journal-title":"Ann Oncol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.22213","article-title":"Ovarian Small Cell Carcinoma of the Hypercalcemic Type in Children and Adolescents: A Prognostically Unfavorable But Curable Disease","volume":"107","author":"Distelmaier","year":"2006","journal-title":"Cancer"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2005.10.024","article-title":"Small Cell of the Ovary, Hypercalcemic Type \u2013 Analysis of Combined Experience and Recommendation for Management","volume":"100","author":"Harrison","year":"2006","journal-title":"A GCIG study Gynecol Oncol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.5114\/pjp.2013.39331","article-title":"Ovarian Small Cell Carcinoma of Hypercalcemic Type - Evidence of Germline Origin and SMARCA4 Gene Inactivation. A Pilot Study","volume":"64","author":"Kupryja\u0144czyk","year":"2013","journal-title":"Pol J Pathol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2922","article-title":"Recurrent SMARCA4 Mutations in Small Cell Carcinoma of the Ovary","volume":"46","author":"Jelinic","year":"2014","journal-title":"Nat Genet"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2928","article-title":"Small Cell Carcinoma of the Ovary, Hypercalcemic Type, Displays Frequent Inactivating Germline and Somatic Mutations in SMARCA4","volume":"46","author":"Ramos","year":"2014","journal-title":"Nat Genet"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2931","article-title":"Germline and Somatic SMARCA4 Mutations Characterize Small Cell Carcinoma of the Ovary, Hypercalcemic Type","volume":"46","author":"Witkowski","year":"2014","journal-title":"Nat Genet"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2017.09.031","article-title":"Comprehensive Genomic Profiling Reveals Inactivating SMARCA4 Mutations and Low Tumor Mutational Burden in Small Cell Carcinoma of the Ovary, Hypercalcemic-Type","volume":"147","author":"Lin","year":"2017","journal-title":"Gynecol Oncol"},{"key":"B13","unstructured":"ItalianoAHK\n          A Phase 1 Study of Tazemetostat (EPZ-6438), an Enhancer of Zeste -Homolog 2 (EZH2) Inhibitor: Preliminary Activity in INI1-Negative Tumors"},{"key":"B14","doi-asserted-by":"publisher","first-page":"VIII581","DOI":"10.1093\/annonc\/mdy299.014","article-title":"A Phase II, Multicenter Study of the EZH2 Inhibitor Tazemetostat in Adults: Epithelioid Sarcoma Cohort (NCT02601950)","volume":"29","author":"Gounder","year":"2018","journal-title":"Ann Oncol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-18-0348","article-title":"Histone Deacetylase Inhibitors Synergize With Catalytic Inhibitors of EZH2 to Exhibit Antitumor Activity in Small Cell Carcinoma of the Ovary, Hypercalcemic Type","volume":"17","author":"Wang","year":"2018","journal-title":"Mol Cancer Ther"},{"key":"B16","doi-asserted-by":"publisher","first-page":"4319","DOI":"10.1038\/s41467-021-24618-3","article-title":"SMARCA4 Deficient Tumours are Vulnerable to KDM6A\/UTX and KDM6B\/JMJD3 Blockade","volume":"12","author":"Romero","year":"2021","journal-title":"Nat Commun"},{"key":"B17","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1038\/s41467-018-06958-9","article-title":"CDK4\/6 Inhibitors Target SMARCA4-Determined Cyclin D1 Deficiency in Hypercalcemic Small Cell Carcinoma of the Ovary","volume":"10","author":"Xue","year":"2019","journal-title":"Nat Commun"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djx277","article-title":"Immune-Active Microenvironment in Small Cell Carcinoma of the Ovary, Hypercalcemic Type: Rationale for Immune Checkpoint Blockade","volume":"110","author":"Jelinic","year":"2018","journal-title":"J Natl Cancer Inst"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2020.03.030","article-title":"Efficacy of Immune Checkpoint Inhibitors in SMARCA4-Mutant NSCLC","volume":"15","author":"Zhou","year":"2020","journal-title":"J Thorac Oncol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2018.9","article-title":"Improving Immunotherapy Outcomes With Anti-Angiogenic Treatments and Vice Versa","volume":"15","author":"Khan","year":"2018","journal-title":"Nat Rev Clin Oncol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1186\/s12943-019-0974-6","article-title":"Synergistic Effect of Immune Checkpoint Blockade and Anti-Angiogenesis in Cancer Treatment","volume":"18","author":"Yi","year":"2019","journal-title":"Mol Cancer"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1111\/IGC.0b013e3181a1a116","article-title":"Clinical Management of Ovarian Small-Cell Carcinoma of the Hypercalcemic Type: A Proposal for Conservative Surgery in an Advanced Stage of Disease","volume":"19","author":"Dykgraaf","year":"2009","journal-title":"Int J Gynecol Cancer"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.1016\/j.cell.2018.09.032","article-title":"Modular Organization and Assembly of SWI\/SNF Family Chromatin Remodeling Complexes","volume":"175","author":"Mashtalir","year":"2018","journal-title":"Cell"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-20-1825","article-title":"The Genomic Landscape of SMARCA4 Alterations and Associations With Outcomes in Patients With Lung Cancer","volume":"26","author":"Schoenfeld","year":"2020","journal-title":"Clin Cancer Res"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.762598","article-title":"A Pan-Cancer Analysis of SMARCA4 Alterations in Human Cancers","volume":"12","author":"Peng","year":"2021","journal-title":"Front Immunol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-18-1545","article-title":"SWI\/SNF-Compromised Cancers Are Susceptible to Bromodomain Inhibitors","volume":"79","author":"Shorstova","year":"2019","journal-title":"Cancer Res"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.02.023","article-title":"Large-Scale Profiling of Kinase Dependencies in Cancer Cell Lines","volume":"14","author":"Campbell","year":"2016","journal-title":"Cell Rep"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-1928","article-title":"Ponatinib Shows Potent Antitumor Activity in Small Cell Carcinoma of the Ovary Hypercalcemic Type (SCCOHT) Through Multikinase Inhibition","volume":"24","author":"Lang","year":"2018","journal-title":"Clin Cancer Res"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)00007-8","article-title":"Radiation and Checkpoint Blockade Immunotherapy: Radiosensitisation and Potential Mechanisms of Synergy","volume":"16","author":"Sharabi","year":"2015","journal-title":"Lancet Oncol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1016\/S1470-2045(17)30380-7","article-title":"Previous Radiotherapy and the Clinical Activity and Toxicity of Pembrolizumab in the Treatment of non-Small-Cell Lung Cancer: A Secondary Analysis of the KEYNOTE-001 Phase 1 Trial","volume":"18","author":"Shaverdian","year":"2017","journal-title":"Lancet Oncol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1111\/ajco.13242","article-title":"Prior or Concurrent Radiotherapy and Nivolumab Immunotherapy in non-Small Cell Lung Cancer","volume":"16","author":"Ratnayake","year":"2020","journal-title":"Asia Pac J Clin Oncol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1200\/PO.20.00063","article-title":"Combined CDK4\/6 and PD-1 Inhibition in Refractory SMARCA4-Deficient Small-Cell Carcinoma of the Ovary, Hypercalcemic Type","volume":"4","author":"Lee","year":"2020","journal-title":"JCO Precis Oncol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-019-01167-0","article-title":"Camrelizumab: First Global Approval","volume":"79","author":"Markham","year":"2019","journal-title":"Drugs"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2018.29","article-title":"Enhancing Cancer Immunotherapy Using Antiangiogenics: Opportunities and Challenges","volume":"15","author":"Fukumura","year":"2018","journal-title":"Nat Rev Clin Oncol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-020-00500-y","article-title":"Combination of Anti-Angiogenic Therapy and Immune Checkpoint Blockade Normalizes Vascular-Immune Crosstalk to Potentiate Cancer Immunity","volume":"52","author":"Lee","year":"2020","journal-title":"Exp Mol Med"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1816714","article-title":"Pembrolizumab Plus Axitinib Versus Sunitinib for Advanced Renal-Cell Carcinoma","volume":"380","author":"Rini","year":"2019","journal-title":"N Engl J Med"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1816047","article-title":"Avelumab Plus Axitinib Versus Sunitinib for Advanced Renal-Cell Carcinoma","volume":"380","author":"Motzer","year":"2019","journal-title":"N Engl J Med"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-1044-8","article-title":"Avelumab Plus Axitinib Versus Sunitinib in Advanced Renal Cell Carcinoma: Biomarker Analysis of the Phase 3 JAVELIN Renal 101 Trial","volume":"26","author":"Motzer","year":"2020","journal-title":"Nat Med"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2011.01939.x","article-title":"YN968D1 is a Novel and Selective Inhibitor of Vascular Endothelial Growth Factor Receptor-2 Tyrosine Kinase With Potent Activity","volume":"102","author":"Tian","year":"2011","journal-title":"Vitro vivo Cancer Sci"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-018-0903-9","article-title":"Apatinib: A Review in Advanced Gastric Cancer and Other Advanced Cancers","volume":"78","author":"Scott","year":"2018","journal-title":"Drugs"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-17-0640","article-title":"Low-Dose Apatinib Optimizes Tumor Microenvironment and Potentiates Antitumor Effect of PD-1\/PD-L1 Blockade in Lung Cancer","volume":"7","author":"Zhao","year":"2019","journal-title":"Cancer Immunol Res"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.01920","article-title":"Camrelizumab Plus Apatinib in Patients With Advanced Cervical Cancer (CLAP): A Multicenter, Open-Label, Single-Arm, Phase II Trial","volume":"38","author":"Lan","year":"2020","journal-title":"J Clin Oncol"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2022.916790\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T06:04:52Z","timestamp":1657605892000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2022.916790\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,12]]},"references-count":42,"alternative-id":["10.3389\/fonc.2022.916790"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2022.916790","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,12]]},"article-number":"916790"}}