局部晚期非小细胞肺癌自适应放化疗后PD-1抑制剂巩固治疗的征招挑战

Challenges of Recruitmen t for Immunoconsolidation Therapy After Adaptive Chemoradiotherapy in Patients with Locally Advanced Non-Small Cell Lung Cancer

[目的]评估不可切除的Ⅲ期非小细胞肺癌患者在自适应放化疗后接受免疫巩固治疗的征招情况。[方法]2018年11月到2019年12月不可切除Ⅲ期非小细胞肺癌行标准含铂同步放化疗,肿瘤靶区放疗处方剂量为64~66 Gy,计划靶区放疗处方剂量为54 Gy/30 f,同步推量,在放疗20次后给予离线自适应重新定位CT和重新计划,并在放疗后根据入组标准确认符合性。同意入组并符合条件在放疗完成后45 d内给予信迪利单抗(Sintilimab),200 mg q3w,维持1年。主要终点是同步放化疗后≥2级的毒性反应。[结果]107例潜在符合条件的患者接受了自适应同步放化疗。在放化疗前拒绝接受信迪利单抗巩固治疗88例,19例患者同意接受信迪利单抗巩固治疗。不同意入组患者中,有16例(18.2%)放疗结束后不符合纳入标准,主要不符合条件包括7例未解决的2级及以上放射性肺炎,5例未解决的2级及以上放射性食管炎,2例两者都有,2例未解决的3级白细胞减少。同意入组患者中,4例(21.1%)不符合条件,包括2例未解决的2级放射性肺炎,1例未解决的3级放射性食管炎,1例未解决的3级白细胞减少。[结论]在20次离线自适应放化疗后,约有20%患者在同步放化疗结束后不符合免疫巩固治疗入组标准。不符合入组的主要原因是急性放化疗毒性,特别是放射性肺炎和放射性食管炎。

[Objective]To analyze the challenges of enrollment for immunoconsolidation therapy after adaptive chemoradiotherapy in patients with locally advanced non-small-cell lung cancer(NSCLC).[Methods]A total of 107 patients with unresectable stageⅢNSCLC were treated with standard platinumbased concurrent chemoradiotherapy from November 2018 to December 2019.The prescription dose of radiotherapy was 64~66 Gy for gross tumor volume and 54 Gy for planning target volume with 30 fractions of radiation.After 20 fractions of radiotherapy,off-line adaptive re-simulated CT and replanning were performed.Before radiotherapy patients were initially asked for consensus to receive consolidation immunotherapy after chemoradiotherapy.After radiotherapy,patients who agreed to immunoconsolidation therapy and met the enrollment criteria received sintilimab,200 mg q3w,within 45 d of completion of radiotherapy and maintained for one year.The primary end point was grade 2 toxicity.[Results]In 107 potentially eligible patients received off-line adaptive concurrent chemoradiotherapy,88 declined enrollment before chemoradiotherapy,19 agreed to receive consolidation sintilimab.Among the patients who did not agree to be enrolled,16(18.2%)patients did not meet the inclusion criteria,including 7 cases with unresolved grade 2 or higher radiation pneumonitis,5 cases with unresolved grade 2 or higher esophagitis,2 cases with both of above conditions,and 2 cases with unresolved grade 3 leukopenia.Among the patients who agreed to be enrolled,4(21.1%)were ineligible,including 2 cases with unresolved grade 2 radiation pneumonitis,1 case with unresolved grade 3 esophagitis,and 1 case with unresolved grade 3 leukopenia.[Conclusion]The study shows that about 20%patients who agreed or refused for consolidation immunotherapy after adaptive chemoradiotherapy did not meet the inclusion criteria,the main reasons of which are acute chemoradiotherapy toxicities,especially radiation pneumonia and radiation esophagitis.