Li Guangxin, Shu Bin, Zheng Zhuozhao, Yin Hongfang, Zhang Chen, Xiao Ying, Yang Yanmei, Yan Zhe, Zhang Xiaofei, Yang Shizhong, Li Gong, Dong Jiahong
Department of Radiation Oncology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
Hepatopancereatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
Front Oncol. 2022 Nov 24;12:1051916. doi: 10.3389/fonc.2022.1051916. eCollection 2022.
Surgical resection is a mainstay to treat hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) in east Asia. However, the postoperative recurrence rate is high. It is necessary to explore neo-adjuvant therapy to increase the surgical resection rate and improve overall survival. Evidence has shown that lenvatinib combined with PD-1 inhibitors is safe and effective in the treatment of advanced unresectable HCC. Radiotherapy is also an effective treatment method for PVTT and has a synergistic effect in combination with PD-1 inhibitors. Surgical resection after Lenvatinib and sintilimab combined with radiotherapy as a neoadjuvant treatment regimen may be a new exploration of HCC with PVTT, but there were not any reported.
This open-label, single-arm, prospective, multi-center Phase I trial will enroll 20 HCC patients with PVTT who have a resectable primary tumor and no extra-hepatic metastasis. Eligible patients will be given radiotherapy, 3Gy*10 fraction, and will receive lenvatinib 8-12mg once daily and sintilimab 200mg once every three weeks. Surgical resection will be performed 6-8 weeks after radiotherapy. The primary endpoint is safety (number of patients ≥3G TRAE) and the number of patients who complete pre-op treatment and proceed to surgery. The secondary study endpoints include Major Pathological Response (MPR), 1-year tumor recurrence-free rate, Objective Response Rate (ORR), Imaging-Pathology Concordance Rate (IPCR), PVTT regression rate, Median Overall Survival (OS) and Recurrence Free Survival (RFS).
This trial may confirm that surgical resection following intensive neoadjuvant therapy can provide a safe and efficient regimen for BCLC stage C patients with PVTT.
https://clinicaltrials.gov/, identifier (NCT05225116).
手术切除是东亚地区治疗伴有门静脉癌栓（PVTT）的肝细胞癌（HCC）的主要方法。然而，术后复发率很高。有必要探索新辅助治疗以提高手术切除率并改善总生存期。有证据表明，乐伐替尼联合PD-1抑制剂治疗晚期不可切除HCC安全有效。放疗也是治疗PVTT的有效方法，与PD-1抑制剂联合有协同作用。乐伐替尼和信迪利单抗联合放疗作为新辅助治疗方案后进行手术切除可能是对伴有PVTT的HCC的新探索，但尚无相关报道。
这项开放标签、单臂、前瞻性、多中心I期试验将纳入20例伴有PVTT且原发性肿瘤可切除且无肝外转移的HCC患者。符合条件的患者将接受放疗，3Gy×10次分割，并将接受乐伐替尼每日一次8-12mg和信迪利单抗每三周一次200mg。放疗后6-8周进行手术切除。主要终点是安全性（≥3级治疗相关不良反应的患者数量）以及完成术前治疗并进行手术的患者数量。次要研究终点包括主要病理缓解（MPR）、1年无肿瘤复发率、客观缓解率（ORR）、影像-病理符合率（IPCR）、PVTT退缩率、中位总生存期（OS）和无复发生存期（RFS）。
本试验可能证实，强化新辅助治疗后进行手术切除可为BCLC C期伴有PVTT的患者提供一种安全有效的治疗方案。
