晚期肝细胞癌转化治疗的挑战与思考

Challenges and reflections on conversion therapy for advanced hepatocellular carcinoma

近年伴随生物治疗药物不断涌现,晚期肝癌系统治疗取得了巨大进展。免疫阻断点抑制剂抗体联合抗血管生成靶向药物已成为晚期肝癌治疗的一线推荐方案并取得明确的肿瘤学获益与生存获益;免疫靶向联合局部治疗研究方案不断涌现,明确提高了客观反应率;靶免转化序贯外科治疗方案正在重塑晚期肝癌治疗格局,最终提高了根治性手术切除率与远期生存率。这场由免疫治疗±靶向治疗为基本架构引导的治疗新变局中,注定挑战不断,思考亦须随行。以免疫靶向联合转化序贯外科方案探索为例来看,任一适用方案在被广泛、成熟地应用于常规诊疗之前,均应包括药物联用方案的选择、疗效的评估、毒副反应的处理、手术标准与时机、术后辅助治疗方案、长期生存获益验证、原发与继发耐药的后线治疗方案的选择等一系列新问题与挑战。本文将择其部分要点提供一些建议与思考。

With the continuous emergence of biotherapy drugs in recent years,great progress has been made in the systemic therapy for advanced liver cancer.Immune checkpoint inhibitors combined with anti-angiogenic targeted drugs has become the first-line regimen recommended for the treatment of advanced liver cancer and has achieved clear oncology benefits and survival benefits.The regimens for immunotherapy combined with local treatment continue to emerge and have clearly improved objective response rate,and targeted and immune therapeutic regimens combined with sequential surgical treatment are reshaping the treatment pattern of advanced liver cancer and have finally improved radical surgical resection rate and long-term survival rate.Such changes in treatment guided by immunotherapy with or without targeted therapy have brought great challenges and thus require meticulous thoughts.With exploration of immune and targeted therapies combined with sequential surgical regimen as an example,there is a series of new problems and challenges before they are widely applied in routine diagnosis and treatment,including the selection of drug combination regimens,the evaluation of therapeutic efficacy,the treatment of toxic and side effects,surgical standards and timing,postoperative adjuvant treatment regimens,the validation of long-term survival benefits,and the selection of second-line treatment regimens for primary and secondary drug resistance.This article puts forward some suggestions and thoughts for several key aspects.