Su Chung-Wei, Hou Ming-Mo, Huang Pei-Wei, Chou Yung-Chih, Huang Bing-Shen, Tseng Jeng-Hwei, Hsu Chao-Wei, Chang Tung-Chieh, Lin Shi-Ming, Lin Chen-Chun
Department of Gastroenterology and Hepatology, Linkuo Chang Gung Memorial Hospital, Chang Gung University Taiwan.
Department of Oncology, Linkuo Chang Gung Memorial Hospital, Chang Gung University Taiwan.
Am J Cancer Res. 2022 Apr 15;12(4):1606-1620. eCollection 2022.
Anti-Programmed cell Death protein 1 (Anti-PD1) or Programmed Death-Ligand 1 (PDL1) immune checkpoint inhibitors provide treatment options for advanced HCC patients with low response rates. Combination therapy is becoming a major issue to improve the unmet need. Proton beam radiotherapy (PBT) could effectively control the local tumor with a low-risk injury to peripheral liver parenchyma. We retrospectively reviewed the patients who have received PBT combined with anti-PD1/PDL1 to evaluate the efficacy and safety of the advanced HCC patients. This study reviewed 29 advanced HCC patients who have received PBT and anti-PD1/PDL1 during 2016 and 2019. All were Child-Pugh A and performance status 0-1. Seventeen patients (58.6%) had extrahepatic spreading. Concurrent PBT started during anti-PD1/PDL1 with a median of 96.6 grays equivalent dose. The PBT field covered all tumors in 13 (44.8%) patients under curative intent. Other patients (55.2%) received palliative PBT that covered only the principal tumors. All patients have completed the concurrent PBT protocol. The median anti-PD1/PDL1 duration was 3.9 months. After a median follow-up of 13.2 months, the rates of 1-year PBT infield tumor control, 1-year outfield tumor control, and overall response were 90.5%, 90.9%, and 61.5%, and 70.8%, 69.2%, and 43.8%, respectively for curative-intent and palliative-control PBT. Complete response was found in 4 (30.8%) curative-intent and 1 (6.3%) palliative-control patients. The median overall progression-free survival was 27.2 months for curative-intent patients and 15.9 months for palliative-control patients. The overall survival was non-reached for both groups. The ALBI grade and Child-Pugh score change at 3-month and 6-month after PBT initiation were nonsignificant. No unexpected adverse event occurred except nine patients (31.0%) had treatment-related adverse events higher than or equal to Grade 3, including 2 (6.9%) had a radiation-induced liver injury. PBT combined with anti-PD1/PDL1 was safe without unexpected adverse events. The concurrent therapy could effectively treat advanced HCC through sustained local tumor necrosis and effective systemic tumor control for the patients who received curative-intent or palliative-control PBT combined with anti-PD1/PDL1.
抗程序性细胞死亡蛋白1（Anti-PD1）或程序性死亡配体1（PDL1）免疫检查点抑制剂为晚期肝癌患者提供了治疗选择，但缓解率较低。联合治疗正成为满足未满足需求的一个主要问题。质子束放疗（PBT）可以有效控制局部肿瘤，对周围肝实质的损伤风险较低。我们回顾性分析了接受PBT联合抗PD1/PDL1治疗的患者，以评估晚期肝癌患者的疗效和安全性。本研究回顾了2016年至2019年期间接受PBT和抗PD1/PDL1治疗的29例晚期肝癌患者。所有患者均为Child-Pugh A级，体能状态为0-1级。17例患者（58.6%）有肝外转移。在抗PD1/PDL1治疗期间同时开始PBT，中位等效剂量为96.6格雷。PBT照射野在根治性意图下覆盖了13例（44.8%）患者的所有肿瘤。其他患者（55.2%）接受姑息性PBT，仅覆盖主要肿瘤。所有患者均完成了同步PBT方案。抗PD1/PDL1的中位持续时间为3.9个月。中位随访13.2个月后，根治性意图和姑息性对照PBT的1年PBT野内肿瘤控制率、1年野外肿瘤控制率和总缓解率分别为90.5%、90.9%和61.5%以及70.8%、69.2%和43.8%。根治性意图患者中有4例（30.8%）和姑息性对照患者中有1例（6.3%）达到完全缓解。根治性意图患者的中位总无进展生存期为27.2个月，姑息性对照患者为15.9个月。两组的总生存期均未达到。PBT开始后3个月和6个月时，ALBI分级和Child-Pugh评分变化不显著。除9例患者（31.0%）出现高于或等于3级的治疗相关不良事件外，未发生意外不良事件，其中2例（6.9%）发生放射性肝损伤。PBT联合抗PD1/PDL1治疗安全，未发生意外不良事件。对于接受根治性意图或姑息性对照PBT联合抗PD1/PDL1治疗的患者，同步治疗可通过持续的局部肿瘤坏死和有效的全身肿瘤控制有效治疗晚期肝癌。
