Objective: To evaluate the short-term efficacy and safety of a preoperative combination of programmed cell death protein-1 (PD-1) inhibitor with either oxaliplatin + capecitabine (CapeOx) or oxaliplatin + tegafur gimeracil oteracil potassium (SOX) in the treatment of locally advanced immunotherapy-sensitive gastric cancer (LAGC) or adenocarcinoma of the esophagogastric junction (AEG). Methods: The cohort of this retrospective descriptive case series comprised patients with LAGC or AEG whose cancers had been determined to be immunotherapy- sensitive by endoscopic biopsy before treatment in the Gastrointestinal Cancer Center, Unit III, Peking University Cancer Hospital and Institute from 1 August 1 2021 to 31 January 2024. Patients with any one of the following three characteristics were immunotherapy-sensitive: (i) PD-L1 combined positive score (CPS) ≥5; (ii) microsatellite instability-high (MSI-H) / mismatch repair deficiency (dMMR); or (iii) Epstein-Barr virus-encoded RNA (EBER) positivity. All study patients received PD-1 inhibitors combined with CapeOx or SOX as a neoadjuvant or conversion treatment strategy before surgery. Patients with immune system diseases, distant metastases, or human epidermal growth factor receptor 2 positivity were excluded. Factors analyzed included pathological complete response, clinical complete response, major pathological response, R0 resection rate, surgical conversion rate, and safety of the treatment, including immune-related adverse events (irAEs) and surgical complications. Results: The study cohort comprised 39 patients (28 men and 11 women) of median age 62 (range 44-79) years. After the above-described preoperative treatment, radical resection of the 14 tumors that were initially considered unresectable was achieved (surgical conversion rate: 14/14). Twenty-three of the remaining 25 patients underwent radical resection. The last two patients achieved clinical complete responses and opted for a "non-surgical strategy" (watch and wait). Overall, 37 patients (94.9%) underwent radical resection, with an R0 resection rate of 100% (37/37), pathological complete response rate of 48.6% (18/37), and major pathological response rate of 62.2% (23/37). Of the 24 patients with CPS ≥ 5 (non-MSI-H/dMMR and non-EBER positive), 11 achieved pathological complete responses and one with CPS=95 achieved a clinical complete response. Of the eight patients with MSI-H/dMMR, six achieved pathological complete responses and one a clinical complete response. Of the seven patients with EBER positivity, one achieved a pathological complete response. After excluding patients with major pathological complete responses, there was a statistically significant difference in CPS scores between preoperative biopsy specimens and postoperative surgical specimens in 13 patients (7.769±5.570 vs. 15.538±16.870, t=2.287, P=0.041). All patients tolerated preoperative immunotherapy well; nine patients (9/39, 23.1%) had Grade I-II irAEs. There were no Grade III-IV irAEs. The five patients with pyloric obstruction before treatment tolerated normal diets after treatment. The incidence of postoperative complications among all patients who underwent surgery was 18.9% (7/37), including one case of Grade IIIA anastomotic leakage, one of Grade IIIA intestinal obstruction, one of Grade II abdominal hemorrhage, two of Grade II abdominal infection, one of Grade I intestinal obstruction. Additionally, one patient developed COVID-19 postoperatively. All patients recovered with symptomatic treatment. Conclusion: We found that preoperative treatment of patients with LAGC or AEG of one of three types (CPS≥5, dMMR+MSI-H, and EBER positivity) with a PD-1 inhibitor combined with CapeOx or SOX chemotherapy achieved promising effectiveness and safety, with high surgical conversion, R0 resection, and complete response rates.
目的： 评估术前程序性细胞死亡蛋白-1（PD-1）抑制剂联合CapeOx（奥沙利铂+卡培他滨）或SOX（奥沙利铂+替吉奥）化疗方案治疗免疫治疗敏感型局部进展期胃癌（LAGC）或食管胃结合部腺癌（AEG）的近期疗效和安全性。 方法： 采用描述性病例系列研究方法，回顾性纳入2021年8月1日至2024年1月31日期间，在北京大学肿瘤医院胃肠肿瘤中心三病区治疗前经内镜活检证实为免疫治疗敏感的LAGC或AEG患者，包括PD-L1综合阳性评分（CPS）≥5、微卫星高度不稳定（MSI-H）/错配修复缺陷（dMMR）和Epstein-Barr病毒编码RNA（EBER）阳性3种类型患者，术前均给予PD-1抑制剂联合CapeOx或SOX作为新辅助或转化治疗策略。排除免疫系统疾病、发生远处转移及人表皮生长因子受体-2阳性患者。主要观察指标为病理完全缓解、临床完全缓解、主要病理缓解、R0切除率、手术转化率以及治疗安全性［包括免疫相关不良事件（irAE）和手术并发症情况］。 结果： 共纳入39例患者，男28例，女11例；中位年龄62（44~79）岁。全组患者中，14例最初被认为不可切除者经治疗后均转化为可根治性切除（手术转化率：14/14）；其余25例患者中23例行根治性手术切除，另外2例达到临床完全缓解并接受“去手术策略”，选择等待观察。全组37例（94.9%）患者接受了根治性切除术，R0切除率为100%（37/37），病理完全缓解率为48.6%（18/37），主要病理缓解率为62.2%（23/37）。24例CPS≥5（非MSI-H/dMMR和非EBER阳性）患者中，有11例达到病理完全缓解；1例CPS=95的患者达到临床完全缓解。8例MSI-H/dMMR患者中，6例达到病理完全缓解，1例临床完全缓解。7例EBER阳性患者中，有1例达到病理完全缓解。13例患者术前活检标本与术后手术标本（不包括主要病理缓解患者）CPS评分差异有统计学意义［（7.769±5.570）比（15.538±16.870），t=2.287，P=0.041］。全组39例患者术前免疫治疗耐受良好，9例（23.1%）出现Ⅰ~Ⅱ级irAE，未发生Ⅲ~Ⅳ级irAE。5例患者治疗前伴有幽门梗阻，经治疗后恢复正常饮食。全组接受手术的患者术后并发症发生率为18.9%（7/37），其中ⅢA级吻合口漏1例，ⅢA级肠梗阻1例，Ⅱ级腹腔出血1例，Ⅱ级腹腔感染2例，术后Ⅰ级肠梗阻1例，1例患者术后感染COVID-19，均经对症治疗后康复。 结论： 术前应用PD-1抑制剂联合CapeOx或SOX方案治疗CPS≥5、MSI-H/dMMR和EBER阳性这3种类型的LAGC或AEG患者，显示出良好的有效性和安全性，具有较高的手术转化率、R0切除率和完全缓解率。.