Zhai Yirui, Wang Liming, Zhao Hong, Wu Fan, Xin Lingxia, Ye Feng, Sun Wei, Song Yan, Niu Lijuan, Zeng Huiying, Wang Jingbo, Tang Yuan, Song Yongwen, Liu Yueping, Fang Hui, Lu Ningning, Jing Hao, Qi Shunan, Zhang Wenwen, Wang Shulian, Li Ye-Xiong, Wu Jianxiong, Chen Bo
Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
JHEP Rep. 2024 Nov 28;7(3):101287. doi: 10.1016/j.jhepr.2024.101287. eCollection 2025 Mar.
BACKGROUND & AIMS: Portal and hepatic vein tumor thrombosis is associated with inferior outcomes in patients with hepatocellular carcinoma (HCC), and systemic treatment alone is often insufficient. This phase II trial evaluated the efficacy and safety of combining sorafenib with radiotherapy in advanced HCC with thrombosis.
Registered at ClinicalTrials.gov (NCT03535259), this phase II single-arm prospective trial targeted patients with HCC with portal or hepatic vein tumor thrombosis, liver minus gross tumor volume >700 ml, and Eastern Cooperative Oncology Group Performance Status scores of 0 or 1. Participants underwent 40-66 Gy radiotherapy for the hepatic primary tumor and vein tumor thrombosis, with concurrent oral sorafenib (400 mg twice daily) until disease progression or unacceptable adverse events. The primary endpoint was median overall survival (mOS) and the secondary endpoints included overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and Modified Response Evaluation Criteria in Solid Tumors (mRECIST), median progression-free survival (mPFS), time to tumor progression (TTP), tumor thrombosis control, and grade ≥3 adverse events.
Between May 2018 and January 2020, 86 patients were enrolled with a median radiotherapy dose of 54 Gy (40-65 Gy). At a median follow-up of 17.2 months, mOS, mPFS, and TTP stood at 16.5, 6.1, and 6.8 months, respectively. ORR reached 47.7% and 52.3% per RECIST and mRECIST, respectively. For the tumor thrombosis, 2-year control rates per mRECIST were 93.1%. No grade 5 adverse events were noted, whereas thrombocytopenia (22.1%) and leukopenia (14.0%) were the main grade 3 adverse events.
Concurrent sorafenib and radiotherapy is an effective and well-tolerated treatment for patients with HCC with portal or hepatic vein tumor thrombosis.
Treatment options for patients with hepatocellular carcinoma (HCC) and vascular tumor thrombus are limited. The efficacy and safety of concurrent sorafenib and radiation for HCC with portal or hepatic vein tumor thrombosis has not been elucidated. This phase II trial shows that concurrent sorafenib and radiotherapy is effective and well-tolerated in the treatment of advanced HCC with portal vein or hepatic vein tumor thrombosis.
This study is registered at ClinicalTrials.gov (NCT03535259).
门静脉和肝静脉肿瘤血栓形成与肝细胞癌（HCC）患者的不良预后相关，单纯的系统治疗往往不足。本II期试验评估了索拉非尼联合放疗在伴有血栓形成的晚期HCC中的疗效和安全性。
本II期单臂前瞻性试验在ClinicalTrials.gov（NCT03535259）注册，目标人群为患有门静脉或肝静脉肿瘤血栓形成、肝脏减去大体肿瘤体积>700 ml且东部肿瘤协作组体能状态评分为0或1的HCC患者。参与者对肝脏原发性肿瘤和静脉肿瘤血栓进行40 - 66 Gy的放疗，同时口服索拉非尼（每日两次，每次400 mg），直至疾病进展或出现不可接受的不良事件。主要终点是中位总生存期（mOS），次要终点包括根据实体瘤疗效评价标准（RECIST）1.1版和改良实体瘤疗效评价标准（mRECIST）的总缓解率（ORR）、中位无进展生存期（mPFS）、肿瘤进展时间（TTP）、肿瘤血栓控制情况以及≥3级不良事件。
2018年5月至2020年1月期间，共纳入86例患者，中位放疗剂量为54 Gy（40 - 65 Gy）。中位随访17.2个月时，mOS、mPFS和TTP分别为16.5个月、6.1个月和6.8个月。根据RECIST和mRECIST标准，ORR分别达到47.7%和52.3%。对于肿瘤血栓，根据mRECIST标准的2年控制率为93.1%。未观察到5级不良事件，而血小板减少症（22.1%）和白细胞减少症（14.0%）是主要的3级不良事件。
索拉非尼与放疗联合应用对于伴有门静脉或肝静脉肿瘤血栓形成的HCC患者是一种有效且耐受性良好的治疗方法。
肝细胞癌（HCC）合并血管肿瘤血栓患者的治疗选择有限。索拉非尼与放疗联合应用于伴有门静脉或肝静脉肿瘤血栓形成的HCC的疗效和安全性尚未阐明。本II期试验表明，索拉非尼与放疗联合应用在治疗伴有门静脉或肝静脉肿瘤血栓形成的晚期HCC中有效且耐受性良好。
本研究在ClinicalTrials.gov（NCT03535259）注册。
