Supplementary Material for: A case of long-term survival with recurrent liver metastases from gastric cancer treated with nivolumab

Introduction: Improvements in overall survival from advanced gastric cancer have recently been reported with nivolumab. However, few reports have described long-term survival after discontinuing treatment. Case presentation: A 67-year-old man diagnosed with advanced gastric cancer and abdominal aortic aneurysm initially underwent distal gastrectomy with D2 dissection. Histological examination revealed tub2 and T2N1M0 stage IIA. One month later, endovascular aneurysm repair was performed. Six weeks after gastrectomy, adjuvant chemotherapy with S-1 was started. Six months later, liver metastases were identified and liver segments S1 and S7 were resected. S-1 and oxaliplatin were added postoperatively, but multiple liver metastases recurred. Paclitaxel and ramucirumab, irinotecan, and docetaxel were administered. Liver metastases showed a temporary reduction in size then enlarged again. Nivolumab was therefore administered and the liver metastases showed a significant reduction in size. The interval between doses gradually increased due to persistent general fatigue. At 28 months after starting nivolumab therapy, bronchitis and adrenal insufficiency appeared, so treatment was discontinued. As of 3.5 years after cessation of nivolumab immunotherapy, tumor regression continued to be maintained. The patient remains alive as of 8 years after recurrence of liver metastases. Conclusion: We encountered a case in which the patient received nivolumab therapy for recurrent liver metastases from gastric cancer and survived long-term after discontinuing treatment.

引言：近期有研究报道，纳武利尤单抗（nivolumab）可改善晚期胃癌患者的总生存期，但目前鲜有研究阐述停药后的长期生存情况。
病例报告：1例确诊为晚期胃癌合并腹主动脉瘤（abdominal aortic aneurysm）的67岁男性患者，初始接受联合D2淋巴结清扫术的远端胃切除术。病理检查提示肿瘤为管状腺癌2级（tub2），分期为T2N1M0 ⅡA期。术后1个月，患者接受血管腔内动脉瘤修复术（endovascular aneurysm repair）。胃切除术后6周，患者开始接受S-1辅助化疗。术后6个月检出肝转移灶，遂行肝S1段及S7段切除术。术后加用S-1联合奥沙利铂（oxaliplatin）化疗，但肝内多发转移灶复发。随后先后予以紫杉醇（paclitaxel）联合雷莫芦单抗（ramucirumab）、伊立替康（irinotecan）及多西他赛（docetaxel）治疗，肝转移灶曾一度缩小后再次增大。因此予纳武利尤单抗治疗，肝转移灶显著缩小。因持续出现全身乏力，给药间隔逐渐延长。纳武利尤单抗治疗启动后28个月时，患者出现支气管炎及肾上腺功能不全（adrenal insufficiency），遂停止治疗。截至纳武利尤单抗免疫治疗停药后3.5年，患者仍维持肿瘤退缩状态。截至肝转移复发后8年，患者仍存活。
结论：本病例报告1例胃癌肝转移复发患者接受纳武利尤单抗治疗后，停药后仍获得长期生存的临床案例。