Abstract: Status and countermeasures of hyperprogressive disease in immunotherapy for hepatocellular carcinoma                         YANG Xin，DAI Chao-liu， XU Feng.  Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang110004, China
Corresponding authors：DAI Chao-liu，E-mail：18793198756@163.com；XU Feng, E-mail：fxu@cmu.edu.cn
Abstract    In recent years, immune checkpoint inhibitors（ICIs）show extraordinary talents in the treatment of middle-advanced 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 the susceptibility factors and biomarkers of HPD to evaluate whether patients can benefit from ICIs treatment, monitor the treatment response in real-time during treatment, to strengthen the identification of pseudo-progression, and to prolong the patient's OS as the ultimate goal. In addition, most HPDs occur within 8 weeks, and the optimal time node for disease assessment should be explored to identify the occurrence of HPD early. At the same time, since there is no unified standard for the definition of HPD and the dependence of evaluation criteria on pre-baseline imaging makes it difficult to achieve clinical stratified management of patients, establishing a common and easy-to-use standard is crucial for the prospective identification of HPD patients in clinical practice.

Key words: hepatocellular carcinoma, immune checkpoint inhibitors, hyperprogressive disease, pseudoprogression

摘要： 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。

关键词: 肝细胞癌, 免疫检查点抑制剂, 超进展疾病, 假性进展