Molecular Characterization of Ovarian Yolk Sac Tumor (OYST)

SIMPLE SUMMARY: Ovarian yolk sac tumors (OYSTs) are rare and specific therapeutic strategies are needed after the failure of platinum-based first-line and salvage regimens. This retrospective study included ten patients with OYST, including patients with relapsed disease and disease-free patients. Three patients (33.3%) harbored oncogenic mutations in KRAS, KIT and ARID1A, which may be used as a target. Our series shows that relapsed patients with molecular analysis had clinically relevant molecular alterations. Future research with dedicated trials and multicenter international collaborations are needed to demonstrate the efficacy of specific therapeutic strategies after failure of platinum-based first-line and salvage regimens. ABSTRACT: Most patients with malignant ovarian germ cell tumors (MOGTCs) have a very good prognosis and chemotherapy provides curative treatment; however, patients with yolk sac tumors (OYSTs) have a significantly worse prognosis. OYSTs are rare tumors and promising results are expected with the use of specific therapeutic strategies after the failure of platinum-based first-line and salvage regimens. We initiated a project in collaboration with EORTC SPECTA, to explore the molecular characteristics of OYSTs. The pilot project used retrospective samples from ten OYST relapsed and disease-free patients. Each patient had a molecular analysis performed with FoundationOne CDx describing the following variables according to the Foundation Medicine Incorporation (FMI): alteration type (SNV, deletion), actionable gene alteration, therapies approved in EU (for patient’s tumor type and other tumor types), tumor mutational burden (TMB), and microsatellite instability (MSI) status. A total of 10 patients with OYST diagnosed between 2007 and 2017 had a molecular analysis. A molecular alteration was identified in four patients (40%). A subset of three patients (33.3% of all patients) harbored targetable oncogenic mutations in KRAS, KIT, ARID1A. Two patients at relapse harbored a targetable mutation. This retrospective study identifies clinically relevant molecular alterations for all relapsed patients with molecular analysis. Dedicated studies are needed to demonstrate the efficacy of specific therapeutic strategies after the failure of platinum-based first-line and salvage regimens and to explore the potential relationship of a molecular alteration and patient outcome.