放疗剂量和靶向策略相关毒性：局部晚期非小细胞肺癌联合治疗合作组试验的汇总分析。
Toxicity Related to Radiotherapy Dose and Targeting Strategy: A Pooled Analysis of Cooperative Group Trials of Combined Modality Therapy for Locally Advanced Non-Small Cell Lung Cancer.
机构信息
Department of Radiation Oncology, Mayo Clinic, Phoenix, Arizona.
Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, North Carolina.
出版信息
J Thorac Oncol. 2019 Feb;14(2):298-303. doi: 10.1016/j.jtho.2018.09.021. Epub 2018 Oct 4.
OBJECTIVE
Concurrent chemoradiotherapy (CRT) was the standard treatment for locally advanced NSCLC (LA-NSCLC). This study was performed to examine thoracic radiotherapy (TRT) parameters and their impact on adverse events (AEs).
METHODS
We collected individual patient data from 3600 patients with LA-NSCLC who participated in 16 cooperative group trials of concurrent CRT. The TRT parameters examined included field design strategy (elective nodal irradiation [ENI] versus involved-field [IF] TRT [IF-TRT]) and TRT dose (60 Gy versus ≥60 Gy). The primary end point of this analysis was the occurrence of AEs. ORs for AEs were calculated with univariable and multivariable logistic models.
RESULTS
TRT doses ranged from 60 to 74 Gy. ENI was not associated with more grade 3 or higher AEs than IF-TRT was (multivariable OR = 0.77, 95% confidence interval [CI]: 0.543-1.102, p = 0.1545). Doses higher than 60 Gy (high-dose TRT) were associated with significantly more grade 3 or higher AEs (multivariable OR = 1.82, 95% CI: 1.501-2.203, p < 0.0001). In contrast, ENI was associated with significantly more grade 4 or higher AEs (multivariable OR = 1.33, 95% CI: 1.035-1.709, p = 0.0258). Doses higher than 60 Gy were also associated with more grade 4 or higher AEs (multivariate OR = 1.42, 95% CI: 1.191-1.700, p = 0.0001). Grade 5 AEs plus treatment-related deaths were more frequent with higher-dose TRT (p = 0.0012) but not ENI (p = 0.099).
CONCLUSIONS
For patients with LA-NSCLC treated with concurrent CRT, IF-TRT was not associated with the overall risk of grade 3 or higher AEs but was associated with significantly fewer grade 4 or higher AEs than ENI TRT. This is likely the result of irradiation of a lesser amount of adjacent critical normal tissue. Higher TRT doses were associated significantly with grade 3 or higher and grade 4 or higher AEs. On the basis of these findings and our prior report on survival, CRT using IF-TRT and 60 Gy (conventionally fractionated) were associated with more favorable patient survival and less toxicity than was the use of ENI or higher radiotherapy doses.
目的
同期放化疗（CRT）是局部晚期非小细胞肺癌（LA-NSCLC）的标准治疗方法。本研究旨在研究胸部放疗（TRT）参数及其对不良事件（AEs）的影响。
方法
我们从参加 16 项同期 CRT 合作组试验的 3600 例 LA-NSCLC 患者中收集了个体患者数据。检查的 TRT 参数包括野设计策略（选择性淋巴结照射[ENI]与累及野[IF] TRT[IF-TRT]）和 TRT 剂量（60 Gy 与≥60 Gy）。该分析的主要终点是 AEs 的发生。使用单变量和多变量逻辑模型计算 AEs 的比值比（OR）。
结果
TRT 剂量范围为 60 至 74 Gy。ENI 与 IF-TRT 相比，并未导致更多 3 级或更高等级的 AEs（多变量 OR=0.77，95%置信区间[CI]：0.543-1.102，p=0.1545）。剂量高于 60 Gy（高剂量 TRT）与明显更多的 3 级或更高等级的 AEs 相关（多变量 OR=1.82，95%CI：1.501-2.203，p<0.0001）。相比之下，ENI 与明显更多的 4 级或更高等级的 AEs 相关（多变量 OR=1.33，95%CI：1.035-1.709，p=0.0258）。剂量高于 60 Gy 也与更多的 4 级或更高等级的 AEs 相关（多变量 OR=1.42，95%CI：1.191-1.700，p=0.0001）。高剂量 TRT 导致更频繁的 5 级 AE 和治疗相关死亡（p=0.0012），而不是 ENI（p=0.099）。
结论
对于接受同期 CRT 治疗的 LA-NSCLC 患者，IF-TRT 与 3 级或更高等级 AEs 的总体风险无关，但与 ENI TRT 相比，与明显更少的 4 级或更高等级 AEs 相关。这可能是由于照射到的相邻关键正常组织较少所致。更高的 TRT 剂量与 3 级或更高等级和 4 级或更高等级的 AEs 显著相关。基于这些发现和我们之前关于生存的报告，使用 IF-TRT 和 60 Gy（常规分割）的 CRT 与更有利的患者生存和更少的毒性相关，而不是使用 ENI 或更高的放疗剂量。
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