肝细胞癌免疫治疗超进展的现状与应对策略

Status and countermeasures of hyperprogressive disease in immunotherapy for hepatocellular carcinoma

近年来,免疫检查点抑制剂(ICIs)在中晚期肝细胞癌治疗中大放异彩。随着ICIs应用日益广泛,部分病人接受ICIs治疗后出现了肿瘤超进展(HPD),导致生存期显著缩短。HPD已然成为中晚期肝细胞癌病人ICIs治疗不可忽视的问题。对于部分病人而言,HPD的临床结局是毁灭性的。因此,临床上需要结合HPD的易感因素及生物标记物评估病人能否从ICIs治疗中获益,并且在治疗过程中实时监测治疗反应,加强对假性进展的鉴别,将延长病人的总生存期(OS)作为最终目标。此外,大多数HPD发生时间在8周内,应探索最佳的疾病评估时间节点以早期识别HPD的发生。同时,由于HPD定义尚无统一标准且评估标准对基线前成像的依赖性导致临床上病人的分层管理难以实现,建立通用且简便易行的标准对临床前瞻性识别HPD病人至关重要。

In recent years,immune checkpoint inhibitors(ICIs)show extraordinary talents in the treatment of middleadvanced hepatocellular carcinoma.With the increasing application of ICIs,some patients suffer from hyper progressive disease after receiving ICIs which causes significantly shortened survival.HPD has become a problem that cannot be ignored in the treatment of ICIs.For some patients,the clinical outcome of HPD is devastating.Therefore, clinically, it is necessary to combine thesusceptibility factors and biomarkers of HPD to evaluatewhether patients can benefit from ICIs treatment, monitor thetreatment response in real- time during treatment, tostrengthen the identification of pseudo- progression, and toprolong the patient's OS as the ultimate goal. In addition, mostHPDs occur within 8 weeks, and the optimal time node fordisease assessment should be explored to identify theoccurrence of HPD early. At the same time, since there is nounified standard for the definition of HPD and the dependenceof evaluation criteria on pre- baseline imaging makes itdifficult to achieve clinical stratified management of patients,establishing a common and easy-to-use standard is crucial forthe prospective identification of HPD patients in clinicalpractice.