Chiang Chi Leung, Lee Francis Ann Shing, Chan Kenneth Sik Kwan, Lee Venus Wan Yan, Chiu Keith Wan Hang, Ho Ryan Lok Man, Fong John Ka Shun, Wong Natalie Sean Man, Yip Winnie Wing Ling, Yeung Cynthia Sin Yu, Lau Vince Wing Hang, Man Kwan, Kong Feng Ming Spring, Chan Albert Chi Yan
Department of Clinical Oncology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR.
Department of Clinical Oncology, Tuen Mun Hospital, Hong Kong, Hong Kong SAR.
Liver Cancer. 2023 Oct 1;13(3):265-276. doi: 10.1159/000533425. eCollection 2024 Jun.
While combination of stereotactic body radiotherapy (SBRT) and immunotherapy are promising, their efficacy and safety have not been compared with SBRT-alone in patients with unresectable hepatocellular carcinoma (HCC).
This retrospective study included 100 patients with nonmetastatic, unresectable HCC in two hospitals. Eligible patients had tumor nodules ≤3 and Child-Pugh liver function score of A5 to B7. Seventy patients received SBRT-alone, and 30 patients underwent combined SBRT and immunotherapy (SBRT-IO). Overall survival (OS), time to progression (TTP), overall response rate (ORR), and toxicity were analyzed. We adjusted for the potential confounding factors using propensity score matching.
The median tumor size was 7.3 cm (range, 2.6-18 cm). Twenty-five (25%) of patients had vascular invasion. Before propensity score matching, the 1-year and 3-year OS rate was 89.9% and 59.8% in the SBRT-IO group and 75.7% and 42.3% in SBRT-alone group ( = 0.039). After propensity score matching (1:2), 25 and 50 patients were selected from the SBRT-IO and SBRT-alone group. The 1-year and 3-year OS was 92.0% and 63.9% in the SBRT-IO group versus 74.0% and 43.3% in the SBRT-alone group ( = 0.034). The 1-year and 3-year TTP was better in SBRT-IO group (1-year: 68.9% vs. 58.9% and 3-year: 61.3% vs. 32.5%, = 0.057). The ORR of 88% (complete response [CR]: 56%, partial response [PR]: 22%) in SBRT-IO arm was significantly better than 50% (CR: 20%, PR: 30%) in the SBRT-alone arm ( = 0.006). Three patients (12%) developed ≥grade 3 immune-related treatment adverse events ( = 2 hepatitis, = 1 dermatitis) leading to permanent treatment discontinuation.
Adding immunotherapy to SBRT resulted in better survival with manageable toxicities. Prospective randomized trial is warranted.
立体定向体部放疗（SBRT）与免疫疗法联合应用前景广阔，但在不可切除肝细胞癌（HCC）患者中，其疗效和安全性尚未与单纯SBRT进行比较。
这项回顾性研究纳入了两家医院的100例非转移性、不可切除HCC患者。符合条件的患者肿瘤结节≤3个，Child-Pugh肝功能评分为A5至B7。70例患者接受单纯SBRT，30例患者接受SBRT与免疫疗法联合治疗（SBRT-IO）。分析总生存期（OS）、疾病进展时间（TTP）、总缓解率（ORR）和毒性。我们使用倾向评分匹配法对潜在混杂因素进行了校正。
肿瘤中位大小为7.3 cm（范围2.6 - 18 cm）。25例（25%）患者有血管侵犯。在倾向评分匹配前，SBRT-IO组的1年和3年OS率分别为89.9%和59.8%，单纯SBRT组分别为75.7%和42.3%（P = 0.039）。倾向评分匹配（1:2）后，从SBRT-IO组和单纯SBRT组分别选出25例和50例患者。SBRT-IO组的1年和3年OS分别为92.0%和63.9%，单纯SBRT组分别为74.0%和43.3%（P = 0.034）。SBRT-IO组的1年和3年TTP更好（1年：68.9%对58.9%，3年：61.3%对32.5%，P = 0.057）。SBRT-IO组的ORR为88%（完全缓解[CR]：56%，部分缓解[PR]：22%），显著优于单纯SBRT组的50%（CR：20%，PR：30%）（P = 0.006）。3例患者（12%）发生≥3级免疫相关治疗不良事件（2例肝炎，1例皮炎），导致永久停药。
SBRT联合免疫疗法可提高生存率，且毒性可控。有必要进行前瞻性随机试验。
