Sun Zhifei, Adam Mohamed A, Kim Jina, Nussbaum Daniel P, Benrashid Ehsan, Mantyh Christopher R, Migaly John
Department of Surgery, Duke University, Durham, North Carolina.
Dis Colon Rectum. 2016 Feb;59(2):87-93. doi: 10.1097/DCR.0000000000000518.
Several reports suggest that the efficacy of adjuvant chemotherapy on survival diminishes over time for colon cancer; however, precise timing of its loss of benefit has not been established.
This study aimed to determine the relationship between time to adjuvant chemotherapy and survival and to identify a threshold for increased risk of mortality.
This was a retrospective study. Multivariable Cox proportional hazard modeling with restricted cubic splines was used to evaluate the adjusted association between time to adjuvant chemotherapy and overall survival and to establish an optimal threshold for the initiation of therapy.
Data were collected from the National Cancer Data Base.
Adults who received adjuvant chemotherapy following resection of stage II to III colon cancers were selected.
The primary outcome measured was overall survival.
A total of 7794 patients were included. After adjusting for clinical, tumor, and treatment characteristics, our model determined a critical threshold of chemotherapy initiation at 44 days from surgery, after which there was an increase in the overall mortality. At a median follow-up of 61 months, the risk of mortality was increased in those who received adjuvant chemotherapy after 44 days from surgery (adjusted HR, 1.14; 95% CI, 1.05-1.24; p = 0.002), but not in those who received chemotherapy before 44 days from surgery (p = 0.11). Each additional week of delay was associated with a 7% decrease in survival (HR, 1.07; 95% CI, 1.04-1.10; p < 0.001).
This study was limited by selection bias and the inability to compare specific chemotherapy regimens.
This study objectively determines the optimal timing of adjuvant chemotherapy for patients with resected colon cancer. Delay beyond 6 weeks is associated with compromised survival. These findings emphasize the importance of the timely initiation of therapy, and suggest that efforts to enhance recovery following surgery have the potential to improve survival by decreasing delay to adjuvant chemotherapy.
多项报告表明，辅助化疗对结肠癌生存的疗效会随时间推移而降低；然而，其益处丧失的确切时间尚未确定。
本研究旨在确定辅助化疗时间与生存之间的关系，并确定死亡率增加风险的阈值。
这是一项回顾性研究。采用带有受限立方样条的多变量Cox比例风险模型来评估辅助化疗时间与总生存之间的校正关联，并确定治疗开始的最佳阈值。
数据收集自国家癌症数据库。
选取了在II至III期结肠癌切除术后接受辅助化疗的成年人。
测量的主要结局是总生存。
共纳入7794例患者。在对临床、肿瘤和治疗特征进行校正后，我们的模型确定了术后44天为化疗开始的关键阈值，此后总死亡率增加。在中位随访61个月时，术后44天之后接受辅助化疗的患者死亡率增加（校正风险比，1.14；95%置信区间，1.05 - 1.24；p = 0.002），但术后44天之前接受化疗的患者死亡率未增加（p = 0.11）。每延迟一周生存下降7%（风险比，1.07；95%置信区间，1.04 - 1.10；p < 0.001）。
本研究受选择偏倚限制，且无法比较特定化疗方案。
本研究客观地确定了切除术后结肠癌患者辅助化疗的最佳时机。延迟超过6周与生存受损相关。这些发现强调了及时开始治疗的重要性，并表明努力改善术后恢复有可能通过减少辅助化疗延迟来提高生存率。
