Schütte Kerstin, Schinner Regina, Fabritius Mathias P, Möller Melina, Kuhl Christiane, Iezzi Roberto, Öcal Osman, Pech Maciej, Peynircioglu Bora, Seidensticker Max, Sharma Rohini, Palmer Daniel, Bronowicki Jean-Pierre, Reimer Peter, Malfertheiner Peter, Ricke Jens
Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany.
Department of Internal Medicine and Gastroenterology, Niels-Stensen-Kliniken Marienhospital, Osnabrück, Germany.
Liver Cancer. 2020 Dec;9(6):771-786. doi: 10.1159/000510798. Epub 2020 Nov 11.
Extrahepatic spread is reported as a prognostic factor in patients with advanced hepatocellular carcinoma (HCC) receiving systemic therapy. However, clinical studies have reported conflicting results for the clinical impact of the pattern of tumor progression during treatment and the role of new extrahepatic metastases in length of survival.
To evaluate the impact of extrahepatic metastases on survival in patients with HCC treated with sorafenib or with a combination of sorafenib and selective internal radiation treatment (SIRT).
SORAMIC is a randomized, controlled trial comprising diagnostic, local ablation, and palliative cohorts. In the palliative cohort, patients not eligible for transarterial chemoembolization (TACE) were randomized 11:10 to SIRT plus sorafenib (SIRT + sorafenib) or sorafenib alone. This exploratory subanalysis evaluated the impact of extrahepatic metastases on survival.
In the intent-to-treat cohort, 216 patients were randomized to SIRT + sorafenib and 208 to sorafenib alone. Seventeen patients with distant organ metastases (bone, = 11; adrenal glands, = 5; peritoneum, = 1) and 262 without distant metastases at study entry were analyzed in this substudy. Patients with (Group A) and without (Group B) distant organ metastases at study entry presented with a median survival of 11.3 and 14.8 months, respectively ( = 0.2807). During follow-up of patients with no organ metastases at baseline, extrahepatic disease progression occurred in 50 patients (19.1%). No statistically significant difference in survival was observed between patients without extrahepatic progression and those with new extrahepatic disease during treatment (14.8 vs. 14.9 months; = 0.6483). Development of new pulmonary metastases during treatment significantly shortened median survival (7.6 vs. 15.0 months, = 0.0060).
This subanalysis of the SORAMIC trial suggests that in patients with liver-dominant advanced HCC, metastases to distant organs with the exception of pulmonary metastases do not in general exert a negative impact on patient prognosis. The choice of palliative treatment should incorporate a personalized analysis of the pattern of tumor distribution.
肝外扩散被报道为接受全身治疗的晚期肝细胞癌（HCC）患者的一个预后因素。然而，临床研究对于治疗期间肿瘤进展模式的临床影响以及新的肝外转移灶在生存时长方面的作用报告了相互矛盾的结果。
评估肝外转移对接受索拉非尼或索拉非尼与选择性内放射治疗（SIRT）联合治疗的HCC患者生存的影响。
SORAMIC是一项随机对照试验，包括诊断、局部消融和姑息治疗队列。在姑息治疗队列中，不符合经动脉化疗栓塞（TACE）条件的患者按11:10随机分组接受SIRT联合索拉非尼（SIRT + 索拉非尼）或单独索拉非尼治疗。这项探索性亚组分析评估了肝外转移对生存的影响。
在意向性治疗队列中，216例患者被随机分配接受SIRT + 索拉非尼治疗，208例接受单独索拉非尼治疗。本亚组研究分析了17例有远处器官转移（骨转移11例；肾上腺转移5例；腹膜转移1例）的患者以及262例研究入组时无远处转移的患者。研究入组时伴有（A组）和不伴有（B组）远处器官转移的患者的中位生存期分别为11.3个月和14.8个月（P = 0.2807）。在基线时无器官转移的患者随访期间，50例患者（19.1%）出现肝外疾病进展。在无肝外进展的患者与治疗期间出现新的肝外疾病的患者之间未观察到生存方面的统计学显著差异（14.8个月对14.9个月；P = 0.6483）。治疗期间新出现肺转移显著缩短了中位生存期（7.6个月对15.0个月，P = 0.0060）。
SORAMIC试验的这项亚组分析表明，在以肝脏为主的晚期HCC患者中，除肺转移外，远处器官转移一般不会对患者预后产生负面影响。姑息治疗的选择应纳入对肿瘤分布模式的个体化分析。
