Background/Objectives: This retrospective study evaluates outcomes of 66 patients who underwent reirradiation (re-RT) with proton beam therapy (PBT) for recurrent non-small cell lung cancer. Methods: Toxicity was scored via the CTCAE v5.0, and outcomes estimated using the Kaplan–Meier method, with associations evaluated via Cox proportional hazards and logistic regression analyses. Results: Patients were treated to a median re-RT prescription of 66 Gy/33 fxs (BED10 = 79 Gy; IQR: 71–84 Gy) at an interval of 1.4 years from prior RT. Half (50%) received concurrent chemotherapy. At 14 months follow-up, the median OS and PFS were 5 months (95%CI: 13–17) and 12.5 months (95%CI: 10–15), respectively. On multivariable analysis, a higher RT dose (BED10 > 70 Gy) [HR0.37; 95%CI: 0.20–0.68,p= 0.001] and concurrent chemotherapy (HR0.48; 95%CI: 0.28–0.81,p= 0.007) were associated with improved PFS, while treatment site overlap was adversely associated (HR1.78; 95%CI: 1.05–3.02,p= 0.031). The median PFS for definitive RT with concurrent chemotherapy (n= 28), definitive RT alone (BED10 > 70 Gy) [n= 22], and lower prescription RT (BED10 < 70 Gy) [n= 16] was 15.5 months (95%CI: 7.3–23.7), 14.1 months (95%CI: 10.9–17.3), and 3.3 months (95%CI: 0–12.3), respectively (log-rank,p= 0.006), with corresponding 2-year estimates of 37% (±9), 18% (±8), and 12.5% (±8), respectively. The incidence of Grade 3+ toxicity was 10.5% (6% pulmonary; 3% esophageal; and 1.5% skin), including one Grade 4 bronchopulmonary hemorrhage but no Grade 5 events. Cases with central site overlap had higher composite Dmax to the esophagus (median 87 Gy [IQR:77–90]), great vessels (median 120 Gy [IQR:110–138]), and proximal bronchial tree (median 120 Gy [IQR:110–138]) as compared to other cases (p≤ 0.001 for all). However, no significant associations were identified with Grade 3+ events. Conclusions: Thoracic re-RT with PBT is an option for recurrent NSCLC with acceptable outcomes and toxicity for select patients. When feasible, higher prescription doses (BED10 > 70 Gy) should be delivered for definitive intent, and concurrent chemotherapy may benefit individual cases.
背景/目的：本研究通过回顾性分析，评估了66例接受质子束治疗（PBT）再程放疗（re-RT）的复发性非小细胞肺癌患者的临床结局。方法：采用CTCAE v5.0标准评估毒性反应，通过Kaplan-Meier法估算生存结局，并运用Cox比例风险模型和逻辑回归分析进行相关性评估。结果：患者接受中位处方剂量为66 Gy/33次（BED10 = 79 Gy；IQR：71-84 Gy）的再程放疗，距前次放疗中位间隔时间为1.4年。半数患者（50%）接受了同步化疗。中位随访14个月后，总生存期（OS）和无进展生存期（PFS）分别为5个月（95%CI：13-17）和12.5个月（95%CI：10-15）。多变量分析显示，较高放疗剂量（BED10 > 70 Gy）[HR 0.37；95%CI：0.20-0.68，p=0.001]和同步化疗（HR 0.48；95%CI：0.28-0.81，p=0.007）与PFS改善显著相关，而治疗区域重叠则呈负相关（HR 1.78；95%CI：1.05-3.02，p=0.031）。根治性放疗联合同步化疗组（n=28）、单纯根治性放疗组（BED10 > 70 Gy）[n=22]与低处方剂量组（BED10 < 70 Gy）[n=16]的中位PFS分别为15.5个月（95%CI：7.3-23.7）、14.1个月（95%CI：10.9-17.3）和3.3个月（95%CI：0-12.3）（时序检验p=0.006），对应的2年PFS率分别为37%（±9）、18%（±8）和12.5%（±8）。3级及以上毒性发生率为10.5%（肺部6%；食管3%；皮肤1.5%），包括1例4级支气管肺出血事件，无5级毒性事件发生。与对照组相比，中央区重叠病例的食管（中位87 Gy [IQR:77-90]）、大血管（中位120 Gy [IQR:110-138]）及近端支气管树（中位120 Gy [IQR:110-138]）复合最大剂量显著升高（所有比较p≤0.001），但未发现与3级及以上毒性事件的显著关联。结论：对于经筛选的复发性非小细胞肺癌患者，质子束再程放疗是可考虑的治疗选择，其疗效与毒性反应在可接受范围内。在条件允许时，应采用较高处方剂量（BED10 > 70 Gy）以达到根治目的，同步化疗可能使部分患者获益。
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