Multi-modality therapies for advanced small cell carcinoma of the ovary, hypercalcemic type (SCCOHT): three case reports and literature review
1Department of Obstetrics and Gynecology, The Third Hospital of Peking University, 100191 Beijing, China
DOI: 10.31083/j.ejgo4301002 Vol.43,Issue 1,February 2022 pp.153-159
Submitted: 22 September 2021 Accepted: 01 November 2021
Published: 15 February 2022
Background: Small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare but highly undifferentiated, aggressive malignancy that primarily affects young women. Most SCCOHT patients present with advanced disease and have a very poor prognosis. Although several therapeutic regimens have been proposed, there is no consensus on the optimal treatment strategy. Case: Herein, we describe three cases of advanced-stage SCCOHT aged from16 to 36 treated with cytoreductive surgery and chemotherapy with or without immune checkpoint blockade treatment. With different strategy, the patients showed utterly different outcomes. Conclusion: The cases highlight the importance of prompt diagnosis as well as early, aggressive, and combined modality treatment of SCCOHT. We believe that improved therapies could result in more young patients surviving SCCOHT.
Small cell carcinoma of the ovary hypercalcemic type (SCCOHT); Advanced stage; Tumor immunotargeted therapy
Qin Han,Hongyan Guo. Multi-modality therapies for advanced small cell carcinoma of the ovary, hypercalcemic type (SCCOHT): three case reports and literature review. European Journal of Gynaecological Oncology. 2022. 43(1);153-159.
 Richard Dickersin G, Kline IW, Scully RE. Small cell carcinoma of the ovary with hypercalcemia: a report of eleven cases. Cancer. 1982; 49: 188–197.
 Young RH, Oliva E, Scully RE. Small cell carcinama of the ovary, hypercalcemic type. American Journal of Surgical Pathology. 1994; 18: 1102–1116.
 Matias-Guiu X, Prat J, Young RH, Capen CC, Rosol TJ, Delellis RA, et al. Human parathyroid hormone-related protein in ovarian small cell carcinoma. an immunohistochemical study. Cancer. 1994; 73: 1878–1881.
 Estel R, Hackethal A, Kalder M, Münstedt K. Small cell carcinoma of the ovary of the hypercalcaemic type: an analysis of clinical and prognostic aspects of a rare disease on the basis of cases published in the literature. Archives of Gynecology and Obstetrics. 2011; 284: 1277–1282.
 Witkowski L, Goudie C, Ramos P, Boshari T, Brunet J, Karnezis AN, et al. The influence of clinical and genetic factors on patient outcome in small cell carcinoma of the ovary, hypercalcemic type. Gynecologic Oncology. 2016; 141: 454–460.
 Harrison ML, Hoskins P, du Bois A, Quinn M, Rustin GJS, Ledermann JA, et al. Small cell of the ovary, hypercalcemic type –analysis of combined experience and recommendation for management. A GCIG study. Gynecologic Oncology. 2006; 100: 233–238.
 Jamy O, Yaghmour G, Hare F, Martin MG. Population- based analysis of the clinical features of primary small cell carcinoma of the ovary. Anticancer Research. 2015; 35: 3091.
 Karanian-Philippe M, Velasco V, Longy M, Floquet A, Arnould L, Coindre J, et al. SMARCA4 (BRG1) loss of expression is a useful marker for the diagnosis of ovarian small cell carcinoma of the hypercalcemic type (ovarian rhabdoid tumor): a comprehensive analysis of 116 rare gynecologic tumors, 9 soft tissue tumors, and 9 melanomas. The American Journal of Surgical Pathology. 2015; 39: 1197–1205.
 Ramos P, Karnezis AN, Craig DW, Sekulic A, Russell ML, Hendricks WPD, et al. Small cell carcinoma of the ovary, hypercalcemic type, displays frequent inactivating germline and somatic mutations in SMARCA4. Nature Genetics. 2014; 46: 427–429.
 Pautier P, Ribrag V, Duvillard P, Rey A, Elghissassi I, Sillet-Bach I, et al. Results of a prospective dose-intensive regimen in 27 patients with small cell carcinoma of the ovary of the hypercalcemic type. Annals of Oncology. 2007; 18: 1985–1989.
 Tischkowitz M, Huang S, Banerjee S, Hague J, Hendricks WPD, Huntsman DG, et al. Small-Cell Carcinoma of the Ovary, Hypercalcemic Type–Genetics, New Treatment Targets, and Current Management Guidelines. Clinical Cancer Research. 2020; 26: 3908–3917.
 Kim KH, Kim W, Howard TP, Vazquez F, Tsherniak A, Wu JN, et al. SWI/SNF-mutant cancers depend on catalytic and noncatalytic activity of EZH2. Nature Medicine. 2015; 21: 1491–1496.
 Wang Y, Chen SY, Karnezis AN, Colborne S, Santos ND, Lang JD, et al. The histone methyltransferase EZH2 is a therapeutic target in small cell carcinoma of the ovary, hypercalcaemic type. The Journal of Pathology. 2017; 242: 371–383.
 Chan-Penebre E, Armstrong K, Drew A, Grassian AR, Feldman I, Knutson SK, et al. Selective Killing of SMARCA2- and SMARCA4-deficient Small Cell Carcinoma of the Ovary, Hypercalcemic Type Cells by Inhibition of EZH2: in Vitro and in Vivo Preclinical Models. Molecular Cancer Therapeutics. 2017; 16: 850–860.
 Shorstova T, Marques M, Su J, Johnston J, Kleinman CL, Hamel N, et al. SWI/SNF-Compromised Cancers are Susceptible to Bromodomain Inhibitors. Cancer Research. 2019; 79: 2761–2774.
 Adeegbe DO, Liu S, Hattersley MM, Bowden M, Zhou CW, Li S, et al. BET Bromodomain Inhibition Cooperates with PD-1 Blockade to Facilitate Antitumor Response in Kras-Mutant Non–Small Cell Lung Cancer. Cancer Immunology Research. 2018; 6: 1234–1245.
 Wang Y, Chen SY, Colborne S, Lambert G, Shin CY, Santos ND, et al. Histone Deacetylase Inhibitors Synergize with Catalytic Inhibitors of EZH2 to Exhibit Antitumor Activity in Small Cell Carcinoma of the Ovary, Hypercalcemic Type. Molecular Cancer Therapeutics. 2018; 17: 2767–2779.
 Lang JD, Hendricks WPD, Orlando KA, Yin H, Kiefer J, Ramos P, et al. Ponatinib Shows Potent Antitumor Activity in Small Cell Carcinoma of the Ovary Hypercalcemic Type (SCCOHT) through Multikinase Inhibition. Clinical Cancer Research. 2018; 24: 1932–1943.
 Wong J, Todd J, Finetti M, McCarthy F, Broncel M, Vyse S, et al. Dual Targeting of PDGFRα and FGFR1 Displays Synergistic Efficacy in Malignant Rhabdoid Tumors. Cell Reports. 2016; 17: 1265–1275.
 Xue Y, Meehan B, Macdonald E, Venneti S, Wang XQD, Witkowski L, et al. CDK4/6 inhibitors target SMARCA4-determined cyclin D1 deficiency in hypercalcemic small cell carcinoma of the ovary. Nature Communications. 2019; 10: 558.
 Xue Y, Meehan B, Fu Z, Wang XQD, Fiset PO, Rieker R, et al. SMARCA4 loss is synthetic lethal with CDK4/6 inhibition in non-small cell lung cancer. Nature Communications. 2019; 10: 557.
 Jelinic P, Ricca J, Van Oudenhove E, Olvera N, Merghoub T, Levine DA, et al. Immune-Active Microenvironment in Small Cell Carcinoma of the Ovary, Hypercalcemic Type: Rationale for Immune Checkpoint Blockade. Journal of the National Cancer Institute. 2018; 110: 787–790.
 Pejovic T, McCluggage WG, Krieg AJ, Xu F, Lee DM, Witkowski L, et al. The dilemma of early preventive oophorectomy in familial small cell carcinoma of the ovary of hypercalcemic type. Gynecologic Oncology Reports. 2019; 28: 47–49.
Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,500 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.
Biological Abstracts Easily discover critical journal coverage of the life sciences with Biological Abstracts, produced by the Web of Science Group, with topics ranging from botany to microbiology to pharmacology. Including BIOSIS indexing and MeSH terms, specialized indexing in Biological Abstracts helps you to discover more accurate, context-sensitive results.
Google Scholar Google Scholar is a freely accessible web search engine that indexes the full text or metadata of scholarly literature across an array of publishing formats and disciplines.
JournalSeek Genamics JournalSeek is the largest completely categorized database of freely available journal information available on the internet. The database presently contains 39226 titles. Journal information includes the description (aims and scope), journal abbreviation, journal homepage link, subject category and ISSN.
Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.
BIOSIS Previews BIOSIS Previews is an English-language, bibliographic database service, with abstracts and citation indexing. It is part of Clarivate Analytics Web of Science suite. BIOSIS Previews indexes data from 1926 to the present.
Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.