Al Masad Qusai, Sousa Aryanna, Pena Paola, Sammartino Cara J, Somasundar Ponnandai, Abdelfattah Thaer, Espat N Joseph, Calvino Abdul S, Kwon Steve
Department of Medicine, Roger Williams Medical Center, Providence, Rhode Island.
Department of Public Health, Johnson and Wales University, Providence, Rhode Island.
J Surg Res. 2025 Feb;306:111-121. doi: 10.1016/j.jss.2024.12.007. Epub 2025 Jan 3.
Evidence demonstrating overall survival benefit of neoadjuvant chemotherapy (NAC) followed by surgical resection over upfront surgical resection for resectable pancreatic ductal adenocarcinoma (PDAC) has been mixed. The time to first therapy (TTFT) variable has not been studied as a contributing factor.
A nationwide retrospective analysis using the National Cancer Database to evaluate patients with clinical stage T1 and T2 PDACs from 2010 to 2020. Cox proportional hazards model was used to evaluate the impact of NAC followed by definitive surgery compared to upfront surgery on overall survival with and without TTFT.
Total of 43,174 patients were included-9874 patients with clinical stage T1 and 33,300 patients with T2 PDACs. There were increasing trends in the NAC approach from 2.9% in 2010 to more than 25% by 2020 and decreasing trends in the upfront surgery approach from 69.34% in 2010 to 31.87% by 2020. There were significant differences in TTFT according to the treatment choice with upfront surgery group having a significantly shorter TTFT-proportion of those receiving first treatment within the first week was 24.32% in the upfront surgery compared to 4.22% in the NAC group. In the adjusted cox regression without the TTFT variable, there was a 25% higher rate of death in the upfront surgery compared to the NAC group (hazard ratio 1.25, 95% confidence interval 1.19-1.30). When the adjusted regression was performed with addition of a TTFT interaction term, there was survival disadvantage of upfront surgery approach in patients whose TTFT occurred after 1 wk, but not in those with TTFT occurring in less than 1 wk (hazard ratio 1.01, 95% confidence interval 0.86-1.17).
Our study emphasizes the importance of incorporating TTFT variable when comparing NAC versus upfront surgery approach in PDAC. Future studies comparing NAC to upfront surgery in resectable PDAC should consider incorporating the TTFT variable.
关于新辅助化疗（NAC）后手术切除与直接手术切除相比，对可切除性胰腺导管腺癌（PDAC）患者总生存期的益处，相关证据并不一致。首次治疗时间（TTFT）这一变量尚未作为一个影响因素进行研究。
利用国家癌症数据库进行全国性回顾性分析，以评估2010年至2020年临床分期为T1和T2的PDAC患者。采用Cox比例风险模型评估NAC后行确定性手术与直接手术相比，在有无TTFT情况下对总生存期的影响。
共纳入43174例患者，其中9874例临床分期为T1的患者，33300例临床分期为T2的PDAC患者。NAC治疗方法呈上升趋势，从2010年的2.9%增至2020年的25%以上，直接手术治疗方法呈下降趋势，从2010年的69.34%降至2020年的31.87%。根据治疗选择，TTFT存在显著差异，直接手术组的TTFT显著更短，直接手术组中在第一周内接受首次治疗的比例为24.32%，而NAC组为4.22%。在不包含TTFT变量的调整后Cox回归分析中，直接手术组的死亡率比NAC组高25%（风险比1.25，95%置信区间1.19 - 1.30）。当加入TTFT交互项进行调整回归分析时，TTFT发生在1周后的患者中，直接手术治疗方法存在生存劣势，但TTFT发生在1周以内的患者则不存在（风险比1.01，95%置信区间0.86 - 1.17）。
我们的研究强调了在比较PDAC患者的NAC与直接手术治疗方法时纳入TTFT变量的重要性。未来在可切除性PDAC中比较NAC与直接手术的研究应考虑纳入TTFT变量。
