Yang Jingyun, Cui Tianxiang, Zhang Yang, Chen Guangpeng, Wang Xinxin, Sun Jianguo, Zhang Anmei, Li Guanghui
Institute of Cancer, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
Front Immunol. 2025 Apr 9;16:1557154. doi: 10.3389/fimmu.2025.1557154. eCollection 2025.
Non-Small Cell Lung Cancer (NSCLC) patients with low tumor mutational burden (TMB) showed low sensitive to conventional fractionated radiotherapy in our previous study. This study aimed to evaluate the efficacy and safety of hypofractionated radiotherapy (HFRT) in locally advanced NSCLC patients with low-TMB compared to conventional fractionated radiotherapy (CFRT).
We retrospectively analyzed clinical outcomes of 74 locally advanced NSCLC patients with low-TMB undergoing definitive radiotherapy from January 2017 to July 2023, with 31 patients received HFRT (received radiation doses of >2Gy and ≤5 Gy per fraction) and 43 received CFRT (received radiation doses of 1.8-2 Gy per fraction). Progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) to radiotherapy was analyzed in the two groups. Univariate analysis was performed to assess the impact of clinical characteristics on PFS. We also analyzed PFS in subgroups receiving HFRT or CFRT combined with immunotherapy and chemotherapy.
Survival analysis revealed the median PFS of 13 months in the HFRT group was significantly better than the 10 months in the CFRT group (p = 0.024). The 6-month and 12-month PFS rates were 80.6% and 61.3% for the HFRT group, versus 81.4% and 39.5% for the CFRT group, respectively. Median OS was 27 months in the HFRT group and 20 months in the CFRT group (p = 0.079). There were no statistically significant differences in major adverse events between the HFRT and CFRT groups (all p>0.05). In the subgroup receiving combined immunotherapy and chemotherapy, the median PFS was 10 months in the HFRT group and 9 months in the CFRT group (p = 0.092).
HFRT was superior to CFRT in prolonging PFS for patients with low-TMB locally advanced NSCLC. It was a safely and effective approach for these patients and was worth further prospective studies with larger sample sizes.
在我们之前的研究中，肿瘤突变负荷（TMB）低的非小细胞肺癌（NSCLC）患者对传统分割放疗敏感性较低。本研究旨在评估与传统分割放疗（CFRT）相比，大分割放疗（HFRT）在TMB低的局部晚期NSCLC患者中的疗效和安全性。
我们回顾性分析了2017年1月至2023年7月期间74例接受根治性放疗的TMB低的局部晚期NSCLC患者的临床结局，其中31例患者接受了HFRT（每次分割剂量>2Gy且≤5Gy），43例接受了CFRT（每次分割剂量1.8 - 2Gy）。分析了两组患者的无进展生存期（PFS）、总生存期（OS）以及放疗的客观缓解率（ORR）。进行单因素分析以评估临床特征对PFS的影响。我们还分析了接受HFRT或CFRT联合免疫治疗和化疗的亚组中的PFS。
生存分析显示，HFRT组的中位PFS为13个月，显著优于CFRT组的10个月（p = 0.024）。HFRT组的6个月和12个月PFS率分别为80.6%和61.3%，而CFRT组分别为81.4%和39.5%。HFRT组的中位OS为27个月，CFRT组为20个月（p = 0.079）。HFRT组和CFRT组之间的主要不良事件无统计学显著差异（所有p>0.05）。在接受联合免疫治疗和化疗的亚组中，HFRT组的中位PFS为10个月，CFRT组为9个月（p = 0.092）。
对于TMB低的局部晚期NSCLC患者，HFRT在延长PFS方面优于CFRT。这是一种安全有效的方法，值得进一步开展更大样本量的前瞻性研究。
