Hepatobiliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
Okinaka Memorial Institute for Medical Disease, Tokyo, Japan.
J Gastrointest Surg. 2022 Aug;26(8):1637-1646. doi: 10.1007/s11605-022-05388-9. Epub 2022 Jun 17.
Increasing number of patients with advanced hepatocellular carcinoma (HCC) has recently achieved salvage interventions after introduction of new biologic agents, while there are insufficient data to determine if such additional intervention(s) after treatment with newer biologic agents are truly advantageous for patients with advanced HCC.
The clinical records of 107 consecutive patients who underwent lenvatinib treatment for advanced HCC were extensively reviewed and the prognostic advantages of individual additional treatments after lenvatinib treatment were investigated through a regression analysis considering time-dependent covariates.
Multivariate analysis revealed that R0 resection or curative-intent radiofrequency ablation (RFA) (hazard ratio [HR], 0.07; 95% CI, 0.01-0.32), transarterial chemoembolization or transarterial infusion therapy (HR, 0.39; 95% CI, 0.19-0.81), and subsequent line of systemic therapy (HR, 0.25; 95% CI, 0.10-0.63) were associated with improved disease-specific survival (DSS), while R2 resection or palliative-intent RFA showed no correlation with DSS. The best response during lenvatinib therapy, nutritional status, plasma des-gamma-carboxyprothrombin level, a baseline CT enhancement pattern, and BCLC stage were also selected as independent predictors for DSS. Among the various treatments performed after lenvatinib therapy, R0 resection also showed clear prognostic advantage in both progression-free survival (HR, 0.30; 95% CI, 0.16-0.58) and time-to-treatment failure (HR, 0.08; 95% CI, 0.02-0.39), suggesting that successful conversion to surgery may prolong survival outcomes through prolonged cancer-free interval in advanced HCC.
Additional intervention(s)/treatment(s) after lenvatinib therapy for advanced HCC may have prognostic advantage in strictly selected populations. Successful conversion to curative resection may offer survival benefit with acceptable clinical outcomes.
随着新型生物制剂的引入，越来越多的晚期肝细胞癌（HCC）患者在接受新的治疗方案后获得了挽救性干预，但目前尚无足够的数据来确定在接受新型生物制剂治疗后进行额外的干预是否对晚期 HCC 患者真正有利。
对 107 例接受仑伐替尼治疗的晚期 HCC 患者的临床资料进行了详细回顾，并通过考虑时间依赖性协变量的回归分析，研究了仑伐替尼治疗后单独进行额外治疗的预后优势。
多因素分析显示，R0 切除或根治性射频消融术（RFA）（风险比 [HR]，0.07；95%CI，0.01-0.32）、经动脉化疗栓塞术或经动脉灌注治疗（HR，0.39；95%CI，0.19-0.81）和后续系统治疗（HR，0.25；95%CI，0.10-0.63）与疾病特异性生存（DSS）改善相关，而 R2 切除或姑息性 RFA 与 DSS 无相关性。仑伐替尼治疗期间的最佳反应、营养状况、血浆去γ-羧基凝血酶原水平、基线 CT 增强模式和 BCLC 分期也被选为 DSS 的独立预测因素。在仑伐替尼治疗后进行的各种治疗中，R0 切除在无进展生存期（HR，0.30；95%CI，0.16-0.58）和治疗失败时间（HR，0.08；95%CI，0.02-0.39）方面也表现出明显的预后优势，这表明在晚期 HCC 中，成功转为手术可能通过延长无癌间期来延长生存结局。
在严格选择的人群中，晚期 HCC 患者在接受仑伐替尼治疗后进行额外的干预/治疗可能具有预后优势。成功转为根治性切除可能会带来生存获益，同时具有可接受的临床结局。
