Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Division of Hematology and Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Int J Radiat Oncol Biol Phys. 2024 May 1;119(1):56-65. doi: 10.1016/j.ijrobp.2023.08.047. Epub 2023 Aug 29.
PURPOSE: 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. METHODS AND MATERIALS: This was a phase 2, single-arm trial (NCT03087760) of consolidation pembrolizumab after PBT reRT for locoregional recurrences of NSCLC. Four to 12 weeks after completion of 60 to 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 National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 toxicity. RESULTS: 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; 2 were pembrolizumab-related), disease progression (n = 4), and completion of 1 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 after reRT. Grade ≥3 toxicities occurred in 10 patients (45%); 2 were pembrolizumab-related. There were 2 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. CONCLUSIONS: 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 of 22 patients. This approach may be considered in selected patients with isolated thoracic recurrences of NSCLC.
目的：对于非小细胞肺癌（NSCLC）孤立性胸内复发患者，质子束治疗（PBT）的再放疗（reRT）可能提供治愈机会，同时最大程度降低毒性。然而，远处转移仍很常见，需要采用更有效的系统治疗策略。
方法和材料：这是一项 2 期、单臂试验（NCT03087760），对 NSCLC 局部区域复发患者，在完成 60-70Gy PBT reRT 后 4-12 周，无疾病进展的患者接受最多 12 个月的帕博利珠单抗巩固治疗。主要终点为从 reRT 开始的无进展生存期（PFS）。次要终点为总生存期（OS）和美国国立癌症研究所不良事件通用术语标准，版本 5.0 毒性。
结果：2017 年至 2021 年，22 例患者接受了 PBT reRT。从上次放疗结束到 reRT 开始的中位时间为 20 个月。大多数复发（91%）位于中央部位。大多数患者接受了同期化疗（95%）和笔形束扫描 PBT（77%），36%曾接受过 durvalumab 治疗。15 例患者（68%）入组开始接受帕博利珠单抗巩固治疗，中位数接受了 3 个周期（范围：2-17 个周期）。帕博利珠单抗最常见的停药原因是毒性（n=5；2 例与帕博利珠单抗相关）、疾病进展（n=4）和完成 1 年治疗（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-未达到）。reRT 后仅发生 1 例孤立的场内失败。10 例患者（45%）发生≥3 级毒性；2 例与帕博利珠单抗相关。有 2 例 5 级毒性，6.9 个月时发生主动脉食管瘘，46.8 个月时发生咯血，均可能由 reRT 引起。由于免疫治疗方案外的广泛应用，该试验提前关闭。
结论：在首次前瞻性试验中，将 PBT reRT 与巩固免疫治疗相结合，PFS 可接受，OS 较好。22 例患者中有 2 例发生晚期 5 级毒性。对于 NSCLC 孤立性胸部复发的患者，这种方法可能是可以考虑的。
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