[Efficacy of nivolumab in combination with chemotherapy after radiotherapy for meningeal carcinomatosis in patients with Epstein-Barr virus-associated gastric cancer:a case report].

Abstract

A 62-year-old man presented with fever and anorexia since July X. Initial treatments were rendered ineffective, and due to altered consciousness and vomiting, he was referred to our hospital. On admission, he manifested delirium, drowsiness, and disorientation. While blood tests were normal, gastroscopy identified a type 3 tumor in his lower gastric body, later diagnosed as a poorly differentiated adenocarcinoma. Immunohistochemistry demonstrated negative human epidermal growth factor receptor 2 and positive programmed death-ligand 1 expression with a combined positive score ≥5. Furthermore, a positive Epstein-Barr virus-encoded small RNA in situ hybridization result was noted. Abdominal contrast-enhanced CT and PET-CT scans demonstrated multiple lymph node metastases around the stomach and liver, establishing the diagnosis of stage IVB gastric cancer (T4aN2M1). Brain magnetic resonance imaging (MRI) demonstrated enhanced lesions in the brainstem, cerebellar sulci, and right occipital lobe. Although cerebrospinal fluid cytology was negative for malignancy, the clinical symptoms and MRI findings confirmed leptomeningeal carcinomatosis (LMC). The patient underwent radiotherapy for LMC (total of 30Gy in 10 fractions), followed by combination therapy with a nivolumab and SOX regimen. Posttreatment, the LMC symptoms resolved;however, he experienced grade 3 immune-related adverse events related to liver dysfunction. Nivolumab was discontinued, and with steroid administration, the adverse events improved. Imaging evaluations posttreatment showed gastric tumor reduction and the absence of LMC. After 7 cycles, nivolumab was reintroduced, with no liver dysfunction recurrence noted through 15 cycles. Endoscopic examination 1 year postonset demonstrated that the gastric tumor had scarred, and MRI showed no signs of LMC recurrence. In 5-8% of solid tumors, LMC complications are present, resulting in limited treatment options and poor prognosis. Recent reports suggest the potential of immune checkpoint inhibitors in treating intracranial metastasis from solid tumors. In Japan, nivolumab was approved for gastric cancer treatment in 2017 and for first-line therapy in combination with chemotherapy since 2021. We report a case in which radiotherapy and chemotherapy combined with nivolumab provided durable control of LMC originating from gastric cancer for more than 1 year.