Departments of Radiation Oncology.
Interventional Radiology.
Int J Radiat Oncol Biol Phys. 2022 Oct 1;114(2):221-230. doi: 10.1016/j.ijrobp.2022.05.021. Epub 2022 May 26.
Patients with hepatocellular carcinoma (HCC) at Barcelona Clinic Liver Cancer (BCLC) early-stage A (BCLC A) not suitable for surgery are first considered for ablation. Nonetheless, objective responses and long-term results for ablation in tumors larger than 3 to 4 cm are suboptimal, creating an unmet clinical need. This phase 2 trial studied combination of transarterial chemoembolization (TACE) and stereotactic body radiation therapy (SBRT) for BCLC A patients with a solitary HCC from 4 to 7 cm.
Eligible patients were BCLC A, Child-Pugh score ≤7, Eastern Cooperative Oncology Group performance status 0 presenting with a single HCC from 4 to 7 cm not suitable for resection or liver transplantation. Treatment consisted of 2 sessions of drug-eluting bead-TACE within 1 month followed by immediate SBRT. SBRT delivered 35 to 50 Gy in 5 fractions. The primary endpoint was best objective response rate (ORR) by modified Response Evaluation Criteria in Solid Tumours (mRECIST). Secondary endpoints were overall survival (OS), progression-free survival (PFS), and toxic effects.
From 2014 to 2020, 32 were enrolled in a single institution with median follow-up of 37 months. Thirty patients had at least 1 posttreatment scan to assess response. ORR in the target lesion was 91%: 63% complete response (CR; n = 20), 28% partial response (n = 9), and 3% progression of disease (n = 1). Median time to CR was 10.1 months. Median OS was not yet reached and median PFS was 35 months. Patients achieving CR had a trend toward improved PFS (P = .09). Toxic effects were low.
This phase 2 trial showed very promising ORR when combining TACE + SBRT in large, unresectable HCC, which translates into excellent OS and PFS. These results provide the rationale for exploring this combination in larger phase 2 and 3 clinical trials and a space where SBRT might offer unique clinical advantage.
巴塞罗那临床肝癌（BCLC）早期 A 期（BCLC A）不适合手术的肝细胞癌（HCC）患者首先考虑消融治疗。然而，对于 3 至 4 厘米以上肿瘤的消融治疗，客观反应和长期结果并不理想，这就产生了未满足的临床需求。这项 2 期试验研究了经动脉化疗栓塞（TACE）联合立体定向体部放射治疗（SBRT）治疗 BCLC A 期单个直径 4 至 7 厘米 HCC 患者。
符合条件的患者为 BCLC A 期，Child-Pugh 评分≤7，东部合作肿瘤学组体能状态 0 分，有单个直径 4 至 7 厘米且不适合切除或肝移植的 HCC。治疗包括 1 个月内 2 次载药微球 TACE，随后立即进行 SBRT。SBRT 采用 35 至 50Gy 分 5 次给予。主要终点是改良实体瘤反应评价标准（mRECIST）评估的最佳客观缓解率（ORR）。次要终点是总生存期（OS）、无进展生存期（PFS）和毒性反应。
2014 年至 2020 年，在一家机构共入组 32 例患者，中位随访时间为 37 个月。30 例患者至少有 1 次治疗后扫描来评估疗效。靶病灶的 ORR 为 91%：完全缓解（CR）63%（n=20），部分缓解（PR）28%（n=9），疾病进展（PD）3%（n=1）。CR 的中位时间为 10.1 个月。中位 OS 尚未达到，中位 PFS 为 35 个月。获得 CR 的患者有改善 PFS 的趋势（P=0.09）。毒性反应低。
本 2 期试验表明，在大型不可切除 HCC 患者中联合应用 TACE+SBRT 具有非常有前景的 ORR，这转化为极佳的 OS 和 PFS。这些结果为在更大的 2 期和 3 期临床试验中探索这种联合治疗以及 SBRT 可能提供独特临床优势的空间提供了依据。
