Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Liver Int. 2021 Jun;41(6):1398-1408. doi: 10.1111/liv.14813. Epub 2021 Mar 11.
BACKGROUND & AIMS: The optimal systemic chemotherapy for combined hepatocellular-cholangiocarcinoma (cHCC-CCA) has not yet been defined. The definition and classification of cHCC-CCA has changed recently in the 5th edition of WHO classification. We reviewed the pathological findings with the new classification and analysed the efficacy of systemic chemotherapy in patients with unresectable/metastatic cHCC-CCA.
Among 254 patients with histologically confirmed cHCC-CCA from 1999 to 2015 in Asan Medical Center, Seoul, Korea, 99 patients who received systemic chemotherapy for unresectable/metastatic disease were included. Overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were retrospectively evaluated.
Sorafenib (n = 62) and cytotoxic chemotherapy (n = 37) were administered as first-line chemotherapies; the ORR was 14.1%, and the median PFS and OS were 3.8 and 10.6 months, respectively, with a median follow-up duration of 39.6 months. The efficacy outcomes were not significantly different between patients who received sorafenib and those who received cytotoxic chemotherapy (ORR, 9.7% vs 21.6%, P = .14; median PFS, 4.2 vs 2.9 months, P = .52; median OS, 10.7 vs 10.6 months, P = .34). In multivariate analysis, large intrahepatic tumour burden (≥30% of liver volume), elevated serum bilirubin and non-platinum containing first-line chemotherapy remained as significant prognostic factors for poorer OS.
The efficacy outcomes according to first-line treatment were not significantly different between sorafenib and cytotoxic chemotherapy, and pathological findings were not found to help for determining appropriate therapeutic agent or assessing the prognosis. To overcome the poor treatment outcomes, further studies are needed to find proper treatment targets, biomarkers and the best treatment strategies.
联合肝细胞癌-胆管癌（cHCC-CCA）的最佳全身化疗尚未确定。最近在世界卫生组织（WHO）第 5 版分类中，cHCC-CCA 的定义和分类已经发生了变化。我们回顾了新分类的病理发现，并分析了不可切除/转移性 cHCC-CCA 患者接受全身化疗的疗效。
在韩国首尔 Asan 医疗中心 1999 年至 2015 年间经组织学证实的 254 例 cHCC-CCA 患者中，纳入了 99 例接受不可切除/转移性疾病全身化疗的患者。回顾性评估总缓解率（ORR）、无进展生存期（PFS）和总生存期（OS）。
索拉非尼（n=62）和细胞毒性化疗（n=37）分别作为一线化疗药物；ORR 为 14.1%，中位 PFS 和 OS 分别为 3.8 和 10.6 个月，中位随访时间为 39.6 个月。接受索拉非尼和接受细胞毒性化疗的患者的疗效结果无显著差异（ORR，9.7% vs 21.6%，P=0.14；中位 PFS，4.2 与 2.9 个月，P=0.52；中位 OS，10.7 与 10.6 个月，P=0.34）。多因素分析显示，较大的肝内肿瘤负荷（≥肝体积的 30%）、血清胆红素升高和非铂类一线化疗是 OS 较差的显著预后因素。
索拉非尼和细胞毒性化疗的一线治疗疗效无显著差异，且病理发现无助于确定合适的治疗药物或评估预后。为了克服治疗效果不佳的问题，需要进一步研究以找到合适的治疗靶点、生物标志物和最佳治疗策略。
