Supplementary Material for: Conventional or drug-eluting beads? Randomized study of chemo-embolization for hepatocellular carcinoma: JIVROSG-1302

Introduction With the advent of effective systemic therapy, transarterial chemoembolization (TACE) is established as a highly effective locoregional treatment modality for carefully selected patients of hepatocellular carcinoma (HCC). This randomized controlled trial was conducted to clarify whether selective TACE with drug-eluting beads loaded with epirubicin (DEB-TACE) or selective conventional TACE with epirubicin-ethiodized oil (cTACE) might be more effective for obtaining complete response (CR) in patients with HCC. Methods Between March 2016 and May 2019, Child-Pugh class A or B patients with unresectable HCC who were scheduled to receive selective TACE were randomly assigned at a 1:1 ratio to the DEB-TACE arm or the cTACE arm. The primary endpoint was the CR rate at 3 months, as evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) by an independent review committee, and the secondary endpoints were the CR rate at 1 month and incidences of adverse events. Results A total of 200 patients (DEB-TACE, 99 patients; cTACE, 101 patients) were enrolled in the study. The CR rates at 3 months and 1 month were significantly higher in the cTACE arm (75.2%, 84.2%) as compared with the DEB-TACE arm (27.6%, 35.7%). However, the frequencies of adverse events of any grade, including pyrexia (DEB-TACE vs. cTACE, 19.4% vs. 45.5%, p=0.0001), fatigue (5.1% vs. 15.8%, p=0.0194), malaise (11.1% vs. 25.7%, p=0.0103), appetite loss (12.1% vs. 28.7%, p=0.0048), abdominal pain (12.1% vs. 23.8%, p=0.0423), increased serum bilirubin (22.2% vs. 48.5%, p=0.0002), hypoalbuminemia (43.4% vs. 60.3%, p=0.0154), increased serum aspartate aminotransferase (35.7% vs. 81.2%, p<0.0001), and increased serum alanine aminotransferase (35.7% vs. 77.2%, p<0.0001), were also significantly higher in the cTACE arm than in the DEB-TACE arm. Conclusions Selective cTACE appeared to have higher CR rates for local tumor control as compared to selective DEB-TACE for HCC. However, the frequency of post-embolization syndrome was also significantly higher in the cTACE group than in the DEB-TACE group. Thus, to achieve CR, cTACE may be selected over DEB-TACE in patients who can be expected to tolerate post-embolization syndrome.

引言 随着有效系统治疗的问世，经动脉化疗栓塞术（transarterial chemoembolization, TACE）已成为经严格筛选的肝细胞癌（hepatocellular carcinoma, HCC）患者的高效局部治疗手段。本随机对照试验旨在明确：对于肝细胞癌患者，采用载表柔比星微球的选择性经动脉化疗栓塞术（drug-eluting beads loaded with epirubicin, DEB-TACE）与采用表柔比星-碘化油的常规选择性经动脉化疗栓塞术（epirubicin-ethiodized oil, cTACE），哪种更有助于实现完全缓解（complete response, CR）。
方法 2016年3月至2019年5月期间，拟接受选择性TACE治疗的不可切除肝细胞癌且Child-Pugh分级为A级或B级的患者，以1:1的比例随机分配至DEB-TACE组与cTACE组。本研究的主要终点为独立评审委员会依据实体瘤疗效评价标准改良版（modified Response Evaluation Criteria in Solid Tumors, mRECIST）评估的3个月完全缓解率；次要终点为1个月完全缓解率与不良事件发生率。
结果 本研究共纳入200例患者（DEB-TACE组99例，cTACE组101例）。与DEB-TACE组的27.6%（1个月时为35.7%）相比，cTACE组3个月及1个月的完全缓解率（分别为75.2%、84.2%）显著更高。然而，cTACE组任意级别不良事件的发生率亦显著高于DEB-TACE组，包括发热（DEB-TACE组vs.cTACE组：19.4% vs.45.5%，p=0.0001）、乏力（5.1% vs.15.8%，p=0.0194）、全身不适（11.1% vs.25.7%，p=0.0103）、食欲减退（12.1% vs.28.7%，p=0.0048）、腹痛（12.1% vs.23.8%，p=0.0423）、血清胆红素升高（22.2% vs.48.5%，p=0.0002）、低白蛋白血症（43.4% vs.60.3%，p=0.0154）、血清天门冬氨酸氨基转移酶升高（35.7% vs.81.2%，p<0.0001）以及血清丙氨酸氨基转移酶升高（35.7% vs.77.2%，p<0.0001）。
结论 相较于选择性DEB-TACE，选择性cTACE用于肝细胞癌患者时，其局部肿瘤控制的完全缓解率更高。但cTACE组的栓塞后综合征发生率亦显著高于DEB-TACE组。因此，对于可耐受栓塞后综合征的患者，若以实现完全缓解为治疗目标，可优先选择cTACE而非DEB-TACE。