Department of Radiation Oncology, Tenon Hospital, Institut Universitaire du Cancer, AP-HP, Sorbonne Université, Paris, France.
Department of Radiation Oncology, Centre Léon Bérard, Lyon, France.
Int J Radiat Oncol Biol Phys. 2021 Jul 15;110(4):993-1002. doi: 10.1016/j.ijrobp.2021.01.055. Epub 2021 Feb 6.
The LAP07 multicenter randomized study assessed whether chemoradiation therapy increases overall survival versus continuation chemotherapy in patients whose locally advanced pancreatic cancer was controlled after 4 months of induction chemotherapy. This analysis investigated whether failure to adhere to radiation therapy (RT) guidelines influenced survival and toxicity.
This is a planned analysis of secondary objectives in the framework of a randomized international phase 3 trial. The protocol included detailed written RT guidelines. All participating institutions undertook an initial benchmark case to check adherence to protocol guidelines. Centers with major deviation were not allowed to include patients until they achieved a significant improvement and rigorously followed the guidelines. On-trial RT quality assurance consisted of a central review of treatment plan with dose-volume histograms for each patient. Adherence to guidelines was graded as per protocol (PP), minor deviation (MiD), or major deviation (MaD).
Fifty-seven benchmark cases were evaluated, 26% were classified as PP, 60% were MiD, and 14% were MaD. Among the 442 included patients, 133 patients were randomized in the chemoradiation therapy arm, and 117 patients were assessable for RT quality analysis. RT quality was graded as PP in 38.5% of patients, MiD in 43.6% of patients, and MaD in 17.9% of patients. The most frequent protocol violations were dose distribution heterogeneities. Median overall survival was 17 months with PP and MiD versus 13.4 months with MaD (hazard ratio [HR], 1.63; 95% confidence interval [CI], 0.99-2.71; P = .055). There was no difference in terms of progression-free survival (HR, 1.09; 95% CI, 0.66-1.8; P = .72). Patients with MaD had more nausea than patients treated PP or with MiD (P = .0045).
MaD was associated with a trend for worst survival. There was no difference in terms of progression-free survival. Because of the low rate of major deviations, their effects on the LAP07 trial results may be negligeable.
LAP07 多中心随机研究评估了在接受 4 个月诱导化疗后局部晚期胰腺癌得到控制的患者中，与继续化疗相比，放化疗是否能提高总生存期。本分析探讨了未能遵守放射治疗（RT）指南是否会影响生存和毒性。
这是一项在随机国际 3 期试验框架内进行的次要目标的计划分析。该方案包括详细的书面 RT 指南。所有参与机构都进行了初始基准案例检查，以检查对方案指南的遵守情况。存在重大偏差的中心在未达到显著改善并严格遵守指南之前，不允许纳入患者。试验期间的 RT 质量保证包括对每个患者的治疗计划进行中央审查，并绘制剂量-体积直方图。指南的遵守情况按方案（PP）、轻微偏差（MiD）或重大偏差（MaD）进行分级。
评估了 57 个基准案例，26%为 PP，60%为 MiD，14%为 MaD。在 442 名纳入的患者中，133 名患者被随机分配到放化疗组，117 名患者可进行 RT 质量分析。38.5%的患者 RT 质量被评为 PP，43.6%的患者为 MiD，17.9%的患者为 MaD。最常见的违反方案的情况是剂量分布不均匀。PP 和 MiD 的中位总生存期为 17 个月，MaD 为 13.4 个月（风险比 [HR]，1.63；95%置信区间 [CI]，0.99-2.71；P=0.055）。无进展生存期（HR，1.09；95%CI，0.66-1.8；P=0.72）无差异。MaD 组患者的恶心发生率高于 PP 或 MiD 组（P=0.0045）。
MaD 与生存最差的趋势相关。无进展生存期无差异。由于重大偏差率较低，它们对 LAP07 试验结果的影响可能可以忽略不计。
