Department of Radiation Oncology, London Regional Cancer Program, London, Ontario, Canada.
Int J Radiat Oncol Biol Phys. 2013 Nov 15;87(4):690-6. doi: 10.1016/j.ijrobp.2013.07.029. Epub 2013 Sep 10.
Concurrent chemoradiation therapy (CCRT) improves survival compared with sequential treatment for locally advanced non-small cell lung cancer, but it increases toxicity, particularly radiation esophagitis (RE). Validated predictors of RE for clinical use are lacking. We performed an individual-patient-data meta-analysis to determine factors predictive of clinically significant RE.
After a systematic review of the literature, data were obtained on 1082 patients who underwent CCRT, including patients from Europe, North America, Asia, and Australia. Patients were randomly divided into training and validation sets (2/3 vs 1/3 of patients). Factors predictive of RE (grade≥2 and grade≥3) were assessed using logistic modeling, with the concordance statistic (c statistic) used to evaluate the performance of each model.
The median radiation therapy dose delivered was 65 Gy, and the median follow-up time was 2.1 years. Most patients (91%) received platinum-containing CCRT regimens. The development of RE was common, scored as grade 2 in 348 patients (32.2%), grade 3 in 185 (17.1%), and grade 4 in 10 (0.9%). There were no RE-related deaths. On univariable analysis using the training set, several baseline factors were statistically predictive of RE (P<.05), but only dosimetric factors had good discrimination scores (c>.60). On multivariable analysis, the esophageal volume receiving ≥60 Gy (V60) alone emerged as the best predictor of grade≥2 and grade≥3 RE, with good calibration and discrimination. Recursive partitioning identified 3 risk groups: low (V60<0.07%), intermediate (V60 0.07% to 16.99%), and high (V60≥17%). With use of the validation set, the predictive model performed inferiorly for the grade≥2 endpoint (c=.58) but performed well for the grade≥3 endpoint (c=.66).
Clinically significant RE is common, but life-threatening complications occur in <1% of patients. Although several factors are statistically predictive of RE, the V60 alone provides the best predictive ability. Efforts to reduce the V60 should be prioritized, with further research needed to identify and validate new predictive factors.
与序贯治疗相比，同期放化疗（CCRT）可提高局部晚期非小细胞肺癌的生存率，但会增加毒性，尤其是放射性食管炎（RE）。目前缺乏用于临床的 RE 有效预测因子。我们进行了一项个体患者数据的荟萃分析，以确定具有临床意义的 RE 的预测因素。
在对文献进行系统回顾后，获取了 1082 名接受 CCRT 的患者的数据，包括来自欧洲、北美、亚洲和澳大利亚的患者。患者被随机分为训练集和验证集（2/3 和 1/3 的患者）。使用逻辑模型评估预测 RE（≥2 级和≥3 级）的因素，使用一致性统计量（c 统计量）评估每个模型的性能。
中位放射治疗剂量为 65 Gy，中位随访时间为 2.1 年。大多数患者（91%）接受了含铂的 CCRT 方案。RE 的发生较为常见，348 例（32.2%）为 2 级，185 例（17.1%）为 3 级，10 例（0.9%）为 4 级。没有与 RE 相关的死亡。在使用训练集的单变量分析中，有几个基线因素与 RE 有统计学上的相关性（P<.05），但只有剂量学因素的区分评分较好（c>.60）。在多变量分析中，仅食管体积接受≥60 Gy（V60）一项就成为预测≥2 级和≥3 级 RE 的最佳预测因子，且具有良好的校准和区分能力。递归分区确定了 3 个风险组：低（V60<0.07%）、中（V60 0.07%至 16.99%）和高（V60≥17%）。使用验证集，预测模型在≥2 级终点的预测性能较差（c=.58），但在≥3 级终点的预测性能较好（c=.66）。
具有临床意义的 RE 较为常见，但危及生命的并发症发生率<1%。虽然有几个因素在统计学上与 RE 相关，但仅 V60 提供了最佳的预测能力。应优先考虑降低 V60，需要进一步研究以确定和验证新的预测因子。
