Supplementary Material for: Post-Progression Survival Highly Influences Overall Survival in Driver Gene Mutation/Translocation Negative or Unknown Type of Non-Small Cell Lung Cancer

Introduction: In stage I–III non-small cell lung cancer (NSCLC), which is considered operable, surgical resection is the most efficacious treatment and is considered to provide a cure. However, after complete surgical resection, approximately 50% of patients with stage I–IIIA NSCLC experience recurrence and death. Once postoperative recurrence of NSCLC occurs, the prognosis is significantly poor, and the course of treatment after recurrence may influence overall survival (OS). Consequently, we investigated the relationship between relapse-free survival (RFS), post-progression survival (PPS), and OS in patients with postoperative recurrence of NSCLC with driver gene mutation/translocation negative or unknown status. Methods: Between January 2007 and September 2019, 101 patients with driver gene mutation/translocation negative or unknown status of NSCLC who underwent complete resection and in whom recurrence occurred were analyzed. The associations between RFS, PPS, and OS were analyzed at the individual patient level. Results: Linear regression and Spearman rank correlation analyses revealed that PPS was strongly associated with OS (r = 0.83, p < 0.0001, R2 = 0.71), whereas RFS was moderately correlated with OS (r = 0.65, p < 0.0001, R2 = 0.48). In the multivariate analysis, performance status at relapse, administration of immune checkpoint inhibitors, and radiotherapy for oligo-recurrences were significantly associated with PPS (p < 0.001). Conclusion: Current analysis of individual-level data of patients who underwent complete resection implied that PPS had a higher impact on OS than RFS in patients with postoperative recurrence of driver gene mutation/translocation negative or unknown status of NSCLC. Additionally, current perceptions indicate that treatment beyond progression after complete surgical resection might strongly affect OS.

引言：I~III期可手术非小细胞肺癌（non-small cell lung cancer, NSCLC）中，手术切除是最为有效的治疗手段，被认为可实现治愈。但在接受完全手术切除后，约50%的I~IIIA期NSCLC患者会出现复发并死亡。一旦NSCLC发生术后复发，患者预后将显著变差，且复发后的治疗过程可能对总生存期（overall survival, OS）产生影响。为此，本研究探讨了驱动基因突变/易位阴性或状态未知的NSCLC术后复发患者的无复发生存期（relapse-free survival, RFS）、进展后生存期（post-progression survival, PPS）与总生存期之间的关联。

方法：2007年1月至2019年9月，共纳入101例接受完全切除术、术后出现复发且驱动基因突变/易位阴性或状态未知的NSCLC患者进行分析。在个体患者层面，对RFS、PPS与OS的相关性进行了分析。

结果：线性回归与Spearman秩相关分析结果显示，PPS与OS存在强相关性（r=0.83，p<0.0001，R²=0.71），而RFS与OS呈中度相关（r=0.65，p<0.0001，R²=0.48）。多因素分析表明，复发时的体能状态、免疫检查点抑制剂给药以及寡复发放射治疗均与PPS显著相关（p<0.001）。

结论：本项个体水平数据分析提示，在驱动基因突变/易位阴性或状态未知的NSCLC术后复发患者中，PPS对OS的影响强于RFS。此外，现有认知表明，完全手术切除后进展阶段的治疗或可对OS产生显著影响。