Unusual Ovarian Cancer Relapse Managed by Nivolumab in a Long-term Surviving Patient with PD-L1 Mutation

case rePorT This report is approved by the Institutional Review Board of Peking Union Medical College Hospital. A 70‐year‐old female with acute abdomen referred to our hospital and received an emergency laparoscopic exploration in July 2008. Right inguinal hernia with small intestine protrusion was found, as well as ascites with peritoneal dissemination and large omental cake. Although bilateral ovaries were grossly normal, biopsy of both ovaries and peritoneal was done in addition to hernia repair. Pathology examination demonstrated serous papillary carcinoma in both ovaries. Two cycles neoadjuvant chemotherapy of taxol and carboplatin (TC, taxol 175 mg/m2, carboplatin area under the curve = 5, every 3 weeks) were added. Subsequently, a comprehensive cytoreductive surgery was performed. Surgical pathology examination established a Stage IIIc ovarian serous papillary carcinoma. The patient received another six cycles of TC chemotherapy, during which the CA125 level slopped from 1010 to normal after 2 cycles of postoperative chemotherapy. Then, she was under regular surveillance without any sign of relapse till the 7th year in 2015; a tender mass was palpated at the right sternocostal region. PET‐CT demonstrated a 3.7 cm × 4.8 cm soft‐tissue mass with high standardized uptake values (SUV) in anterior mediastinum. Thoracotomy and lower sternum resection were performed and pathology revealed poorly differentiated adenocarcinoma with immunohistochemistry compatible with ovarian cancer metastasis. Thoracic radiation was added as well as four courses of taxol chemotherapy. Platinum was omitted due to late onset allergy of carboplatin. CA125 level remained normal after the initial treatment. Seven months later, the patient noticed a fixed protuberance of 2 cm in diameter on her left forehead. Cranial magnetic resonance imaging demonstrated left parietal and frontal bone osteolytic osseous metastasis. PET/CT showed multiple nodules in both lungs with high SUV as well as the eighth posterior rib, right sacral bone, and left frontal bone, which highly indicated cancer metastasis. The patient received cranial radiation and zoledronic acids for osteolytic osseous metastasis. The whole-exome sequencing revealed CD274 (PD-L1), JAK2, and PDCD1LG2 (PD-L2) gene amplification and functional loss of p53 due to pretermination of transcription. Thus, nivolumab was administered at a dosage of 3 mg/kg every 2 weeks for seven cycles. Five months later, cranial MRI revealed regression of subcutaneous involvement on left frontal bone leaving bone erosion, and pulmonary metastases were also greatly relieved in CT examination [Figure 1]. Unusual Ovarian Cancer Relapse Managed by Nivolumab in a Long-term Surviving Patient with PD-L1 Mutation