重照射（reRT）以质子束放疗（PBT）的方式可能为非小细胞肺癌（NSCLC）局部胸内复发患者提供治愈的机会，同时最大程度地减少毒性。然而，远距离复发仍然常见，需要采取更有效的全身性治疗策略。本研究是一项II期单臂试验（NCT03087760），旨在研究PBT reRT后联合应用帕珠单抗巩固治疗NSCLC局部区域复发。 完成60-70 Gy PBT reRT后的4至12周内，没有疾病进展的患者接受帕珠单抗治疗，治疗持续时间最长为12个月。主要终点是从reRT开始算起的无进展生存期（PFS）。次要终点是总生存期（OS）和CTCAE v5.0毒性反应。在2017年至2021年期间，共有22名患者接受了PBT reRT。先前放疗结束到reRT开始的中位间隔为20个月。大多数复发（91%）位于中心部位。大多数患者接受了同步化疗（95%）和铅笔束扫描PBT（77%），36%的患者曾接受过durvalumab治疗。15名患者（68%）开始进行帕珠单抗巩固治疗试验，并接受了中位数为3个周期（范围为2-17个周期）的治疗。帕珠单抗的终止最常见原因是毒性反应（n=5；其中两例与帕珠单抗相关）、疾病进展（n=4）和治疗一年的时间到期（n=3）。中位随访时间为38.7个月。中位PFS和OS分别为8.8个月（95% CI 4.2-23.7）和22.8个月（95% CI 6.9-尚未达到）。只发生了一个孤立的领域内失败。10名患者（45%）出现≥3级毒性反应，其中两例与帕珠单抗相关。发生了两例5级毒性反应，分别是在6.9个月时发生的主动脉-食管瘘和在46.8个月时发生的咯血，两例可能均与reRT有关。该试验因免疫治疗药物在非研究方案中的广泛应用而提前停止。 在首次前瞻性试验中，将PBT reRT与巩固免疫治疗相结合，所得到的PFS是可以接受的，OS也是有利的。2名患者发生了后期5级毒性反应。在具有孤立胸部复发的NSCLC选定患者中，可以考虑采用这种治疗方法。 版权所有 © 2023. Elsevier Inc.出版

Reirradiation (reRT) with proton beam therapy (PBT) may offer a chance of cure while minimizing toxicity for patients with isolated intrathoracic recurrences of non-small cell lung cancer (NSCLC). However, distant failure remains common, necessitating strategies to integrate more effective systemic therapy.This was a phase II, single-arm trial (NCT03087760) of consolidation pembrolizumab after PBT reRT for locoregional recurrences of NSCLC. Four to twelve weeks after completion of 60-70 Gy PBT reRT, patients without progressive disease received pembrolizumab for up to 12 months. Primary endpoint was progression-free survival (PFS), measured from the start of reRT. Secondary endpoints were overall survival (OS) and CTCAE v5.0 toxicity.Between 2017 and 2021, 22 patients received PBT reRT. Median interval from prior radiation end to reRT start was 20 months. Most recurrences (91%) were centrally located. Most patients received concurrent chemotherapy (95%) and pencil beam scanning PBT (77%), and 36% had received prior durvalumab. Fifteen patients (68%) initiated consolidation pembrolizumab on trial and received a median of 3 cycles (range 2-17). Pembrolizumab was discontinued most commonly due to toxicity (n=5; two were pembrolizumab-related), disease progression (n=4), and completion of one year (n=3). Median follow-up was 38.7 months. Median PFS and OS were 8.8 months (95% CI 4.2-23.7) and 22.8 months (95% CI 6.9-not reached), respectively. There was only one isolated in-field failure. Grade ≥3 toxicities occurred in 10 patients (45%); two were pembrolizumab-related. There were two grade 5 toxicities, an aorto-esophageal fistula at 6.9 months and hemoptysis at 46.8 months, both probably from reRT. The trial closed early due to widespread adoption of immunotherapy off-protocol.In the first-ever prospective trial combining PBT reRT with consolidation immunotherapy, PFS was acceptable and OS favorable. Late grade 5 toxicity occurred in 2/22 patients. This approach may be considered in selected patients with isolated thoracic recurrences of NSCLC.Copyright © 2023. Published by Elsevier Inc.