Objective: To investigate the safety and efficacy of oxaliplatin combined with S-1 (SOX) as adjuvant chemotherapy after D2 radical gastrectomy for locally advanced gastric cancer. Methods: A descriptive case series study was applied. Case inclusion criteria: (1) locally advanced gastric cancer confirmed by endoscopic biopsy or surgical specimen pathology as gastric adenocarcinoma; (2) receiving D2 radical gastric resection followed by SOX regimen adjuvant chemotherapy. Case exclusion criteria: (1) postoperative pathological TNM stage I or IV; (2) acute complications and emergency surgeries; (3) receiving neoadjuvant therapy; (4) concurrent malignancies and complications compromising patients' treatment or survival; (5) without receiving adjuvant SOX chemotherapy. A total of 94 patients with stage II-III gastric cancer who underwent D2 radical gastrectomy and postoperative adjuvant SOX chemotherapy at department of Gastrointestinal Surgery, Peking University People's Hospital from January 2014 to December 2019 were retrospectively enrolled. Chemotherapy-related adverse events, overall survival (OS) and progression-free survival (PFS) were analyzed. Kaplan-Meier survival analysis was performed and log rank test was used to analyze the difference between groups. P<0.2 or clinically significant indicators in univariate analysis were included in Cox regression model for multivariate survival analysis. Results: Among these 94 patients, there were 65 males and 29 females with an average age of (58.2±12.1) years; 33 patients with hypertension, diabetes mellitus, or cardiovascular and cerebrovascular diseases, 11 patients with family history of gastrointestinal tumors; 59 patients with tumors locating in the antrum or pylorus, 16 patients in the gastric body, 19 patients in the gastric fundus or cardia; 29 patients underwent total gastrectomy, 5 patients underwent proximal subtotal gastrectomy, and 60 patients underwent distal subtotal gastrectomy. In this study, 73 patients (77.7%) completed at least 5 cycles of adjuvant SOX regimen chemotherapy. Grade 3-4 adverse reactions included thrombocytopenia (23.4%, 22/94), nausea and vomiting (18.1%, 17/94) and peripheral neurotoxicity (6.4%, 6/94). Eighty-nine patients (94.7%) completed follow-up with a median follow-up time of 32 months. The 3-year and 5-year OS rates were 89.8% and 83.7%, respectively, and the 3-year and 5-year PFS rates were 81.4% and 78.1%, respectively. Taking 5 chemotherapy cycles as the cut-off point, the 3-year OS rate and 3-year PFS rate were 72.2% and 53.9% in the adjuvant chemotherapy < 5 cycles group, and 93.7% and 87.1% in the adjuvant chemotherapy ≥5 cycles group, respectively; the differences were statistically significant (P=0.029, P=0.006). Univariate analysis showed that the adjuvant chemotherapy < 5 cycles group was associated with worse 3-year OS (P=0.029). Multivariate analysis showed that insufficient chemotherapy cycle (HR=9.419, 95% CI: 2.330-38.007, P=0.002) was an independent risk factor for 3-year OS. Meanwhile, univariate analysis showed that the adjuvant chemotherapy <5 cycles (P=0.006), preoperative CEA > 4.70 μg/L (P=0.035) and adjacent organ resection (P=0.024) were associated with worse 3-year PFS. Multivariate analysis showed that adjuvant chemotherapy <5 cycles (HR=10.493, 95% CI: 2.466-44.655, P=0.001) and adjacent organ resection (HR=127.518, 95% CI: 8.885-1 830.136, P<0.001) were independent risk factors for 3-year PFS. Conclusions: Oxaliplatin combined with S-1 as an adjuvant chemotherapy regimen for locally advanced gastric cancer has high efficacy and low incidence of adverse reactions. At least 5 cycles of SOX regimen adjuvant chemotherapy can significantly improve prognosis of patients with stage II-III gastric cancer.
目的： 探究奥沙利铂联合替吉奥（SOX）方案作为局部进展期胃癌D(2)根治术后辅助化疗方案的安全性和有效性。 方法： 采用描述性病例系列研究方法。病例纳入标准：（1）经胃镜活检或手术标本病理证实为胃腺癌；（2）接受D(2)根治手术，且术后接受SOX方案辅助化疗。排除标准：（1）术后病理分期为TNM分期Ⅰ期或Ⅳ期；（2）有急性并发症且接受急诊手术；（3）接受过新辅助治疗；（4）合并其他恶性肿瘤及有严重的、影响患者治疗及生存的合并症。回顾性纳入2014年1月至2019年12月于北京大学人民医院胃肠外科行D(2)根治手术的Ⅱ~Ⅲ期胃癌患者94例，分析患者化疗相关不良反应、总体生存（OS）和无进展生存（PFS）情况，并应用Kaplan-Meier进行生存分析，Log-rank法检验组间差异进行单因素分析；将单因素分析中P<0.2或临床有意义的指标纳入Cox回归模型进行多因素生存分析。 结果： 本研究共纳入94例接受D(2)手术和术后辅助SOX方案化疗的Ⅱ~Ⅲ期胃癌患者，其中男性65例，女性29例，年龄（58.2±12.1）岁。存在高血压、糖尿病、心脑血管疾病等合并症患者33例，消化道肿瘤家族史11例；肿瘤位于胃窦或幽门部59例，胃体16例，胃底或贲门19例；行全胃切除患者29例，近端胃大部切除患者5例，远端胃大部切除患者60例。73例（77.7%）患者术后完成至少5周期的SOX辅助化疗方案。3~4级不良反应主要为血小板降低（23.4%, 22/94）、恶心呕吐（18.1%, 17/94）和外周神经毒性（6.4%, 6/94）。本组中位随访时间32（3~78）个月，89例（94.7%）完成随访，3年和5年OS分别为89.8%和83.7%，3年和5年PFS分别为81.4%和78.1%。术后化疗<5周期的患者3年OS为72.2%，3年PFS为53.9%，≥5周期患者的3年OS为93.7%，3年PFS为87.1%，差异均有统计学意义（P=0.029，P=0.006）。单因素分析显示，术后化疗<5周期（P=0.029）与本组患者3年OS有关；多因素分析显示，术后化疗<5周期（HR=9.419，95% CI：2.330~38.007，P=0.002）为接受D(2)根治手术的局部进展期胃癌患者3年OS的独立危险因素。同样地，单因素分析显示，术后化疗<5周期（P=0.006）、术前癌胚抗原>4.70 μg/L（P=0.035）和进行联合脏器切除（P=0.024）与本组患者3年PFS有关；多因素分析显示，术后化疗<5周期（HR=10.493，95% CI：2.466~44.655，P=0.001）和联合脏器切除（HR=127.518，95% CI：8.885~1 830.136，P<0.001）为接受D(2)根治手术的局部进展期胃癌患者3年PFS的独立危险因素。 结论： 奥沙利铂联合替吉奥作为辅助化疗方案，对于局部进展期胃癌安全有效，完成至少5周期的SOX方案辅助化疗可以改善Ⅱ~Ⅲ期胃癌患者预后。.
Keywords: Adjuvant chemotherapy; D2 resection; Oxaliplatin; S-1; Stomach neoplasms.