Determining the Optimal Timing for Initiation of Adjuvant Chemotherapy After Resection for Stage II and III Colon Cancer
Determining the Optimal Timing for Initiation of Adjuvant Chemotherapy After Resection for Stage II and III Colon Cancer
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DOI：
10.1097/dcr.0000000000000518
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发表时间：
2016-02-01
影响因子：
3.9
通讯作者：
Migaly, John
中科院分区：
文献类型：
--
作者：
Sun, Zhifei;Adam, Mohamed A.;Migaly, John
背景技术背景：几份报告表明，辅助化疗对生存的疗效随着时间的推移减少结肠癌，但是，准确的时间损失的好处还没有established.Objective：本研究旨在确定时间之间的关系，辅助化疗和生存，并确定一个阈值增加的风险mortals.DESIGN：这是一项回顾性研究。多变量考克斯比例风险模型与限制性三次样条被用来评估调整后的辅助化疗时间与总生存率之间的关系，并建立一个最佳的阈值开始治疗。设置：数据收集自国家癌症数据库。患者：选择在II至II期结肠癌切除术后接受辅助化疗的成年人。主要观察指标：主要结果是总生存率。结果：共纳入7794例患者。在调整了临床、肿瘤和治疗特征后，我们的模型确定了手术后44天开始化疗的临界阈值，此后总体死亡率增加。在中位随访61个月时，手术后44天接受辅助化疗的患者死亡风险增加（校正HR，1.14; 95% CI，1.05-1.24; p = 0.002），但手术前44天接受化疗的患者死亡风险未增加（p = 0.11）。每延迟一周，生存率下降7%（HR，1.07; 95%CI，1.04-1.10; p < 0.001）。局限性：本研究受到选择偏倚和无法比较特定化疗方案的限制。结论：本研究客观地确定了结肠癌切除患者辅助化疗的最佳时机。延迟超过6周与生存率受损相关。这些发现强调了及时开始治疗的重要性，并表明努力提高术后恢复有可能通过减少辅助化疗的延迟来提高生存率。
BACKGROUND: 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.OBJECTIVE: This study aimed to determine the relationship between time to adjuvant chemotherapy and survival and to identify a threshold for increased risk of mortality.DESIGN: 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.SETTINGS: Data were collected from the National Cancer Data Base.PATIENTS: Adults who received adjuvant chemotherapy following resection of stage II to II colon cancers were selected.MAIN OUTCOME MEASURES: The primary outcome measured was overall survival.RESULTS: 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).LIMITATIONS: This study was limited by selection bias and the inability to compare specific chemotherapy regimens.CONCLUSIONS: 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.