Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Chin Med J (Engl). 2024 Jun 5;137(11):1332-1342. doi: 10.1097/CM9.0000000000003124. Epub 2024 May 9.
To address the need for immunotherapy in patients with advanced primary hepatocellular carcinoma (HCC), combination with radiotherapy (RT) has emerged as a promising strategy. In preclinical studies, irradiated tumors released tumor antigens to synergistically increase the antitumor effect of immunotherapy. Hence, we investigated whether RT enhances the efficacy of anti-programmed death receptor-1 (PD-1) inhibitors in advanced HCC in real-world practice.
Between August 2018 and June 2021, 172 patients with advanced primary HCC were enrolled in the tertiary center (Zhongshan Hospital of Fudan University); 95 were treated with a combination of RT and the inhibitor of PD-1 (RT-PD1 cohort), and 77 were administered anti-PD-1 therapy (PD1 cohort). The first cycle of PD-1 inhibitors was administered within 60 days or concurrently with RT. Propensity score matching for bias reduction was used to evaluate the clinical outcomes.
Among 71 propensity-matched pairs, median progression-free survival was 5.7 months in the RT-PD1 cohort vs. 2.9 months in the PD1 cohort ( P <0.001). Median overall survival was 20.9 months in the RT-PD1 cohort vs. 11.2 months in the PD1 cohort ( P = 0.018). Compared with patients in the PD1 cohort, patients in the RT-PD1 cohort had significantly higher objective response rates (40.8%, 29/71 vs. 19.7%, 14/71, P = 0.006) and disease control rates (62.0%, 44/71 vs. 31.0%, 22/71, P <0.001). The incidences of toxic effects were not significantly different between the two cohorts.
RT plus anti-PD-1 therapy is well tolerated. RT enhances the efficacy of anti-PD-1 therapy in patients with advanced primary HCC by improving survival outcomes without increased toxic effects.
为了满足晚期原发性肝细胞癌（HCC）患者的免疫治疗需求，联合放疗（RT）已成为一种很有前途的策略。在临床前研究中，放射治疗后的肿瘤释放肿瘤抗原，从而协同增强免疫治疗的抗肿瘤作用。因此，我们研究了在真实世界的实践中，RT 是否能增强晚期 HCC 患者对 PD-1 抑制剂的疗效。
2018 年 8 月至 2021 年 6 月，我们在复旦大学附属中山医院的一个三级中心招募了 172 名晚期原发性 HCC 患者；其中 95 名患者接受 RT 和 PD-1 抑制剂联合治疗（RT-PD1 组），77 名患者接受 PD-1 抑制剂治疗（PD1 组）。PD-1 抑制剂的第一个周期在 60 天内或与 RT 同时给药。采用倾向评分匹配来减少偏倚，以评估临床结局。
在 71 对匹配的患者中，RT-PD1 组的中位无进展生存期为 5.7 个月，而 PD1 组为 2.9 个月（ P ＜0.001）。RT-PD1 组的中位总生存期为 20.9 个月，而 PD1 组为 11.2 个月（ P ＝0.018）。与 PD1 组相比，RT-PD1 组患者的客观缓解率（40.8%，29/71 对 19.7%，14/71， P ＝0.006）和疾病控制率（62.0%，44/71 对 31.0%，22/71， P ＜0.001）明显更高。两组患者的毒性反应发生率无显著差异。
RT 联合抗 PD-1 治疗具有良好的耐受性。RT 通过改善生存结局，而不增加毒性作用，增强了晚期原发性 HCC 患者抗 PD-1 治疗的疗效。
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