Kakinoki Kaheita, Asai Jun, Kida Akihiko, Ogawa Norihiko, Niwa Hideki, Futatsuya Chizuru, Urabe Takeshi
Department of Gastroenterology, Public Central Hospital of Matto Ishikawa.
Department of Diagnostic Pathology, Public Central Hospital of Matto Ishikawa.
Nihon Shokakibyo Gakkai Zasshi. 2024;121(9):745-753. doi: 10.11405/nisshoshi.121.745.
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.
一名62岁男性自X月起出现发热和厌食症状。初始治疗无效，因意识改变和呕吐被转诊至我院。入院时，他表现出谵妄、嗜睡和定向障碍。血液检查正常，但胃镜检查发现其胃体下部有3型肿瘤，后来被诊断为低分化腺癌。免疫组化显示人表皮生长因子受体2阴性，程序性死亡配体1表达阳性，综合阳性评分≥5。此外，爱泼斯坦-巴尔病毒编码的小RNA原位杂交结果呈阳性。腹部增强CT和PET-CT扫描显示胃周围和肝脏有多处淋巴结转移，确诊为IVB期胃癌（T4aN2M1）。脑磁共振成像（MRI）显示脑干、小脑沟和右枕叶有强化病变。虽然脑脊液细胞学检查未发现恶性肿瘤，但临床症状和MRI结果证实为软脑膜癌病（LMC）。该患者接受了LMC放疗（共30Gy，分10次），随后接受纳武利尤单抗和SOX方案的联合治疗。治疗后，LMC症状缓解；然而，他出现了与肝功能障碍相关的3级免疫相关不良事件。纳武利尤单抗停药，经类固醇治疗后，不良事件有所改善。治疗后的影像学评估显示胃肿瘤缩小且无LMC。7个周期后，重新使用纳武利尤单抗，至15个周期未再出现肝功能障碍复发。发病1年后的内镜检查显示胃肿瘤已形成瘢痕，MRI未显示LMC复发迹象。在5%-8%的实体瘤中存在LMC并发症，导致治疗选择有限且预后不良。最近的报告表明免疫检查点抑制剂在治疗实体瘤颅内转移方面具有潜力。在日本，纳武利尤单抗于2017年被批准用于胃癌治疗，自2021年起被批准用于联合化疗的一线治疗。我们报告了一例放疗、化疗联合纳武利尤单抗对源自胃癌的LMC进行了超过1年的持久控制的病例。
