免疫检查点抑制剂治疗恶性肿瘤引起的超进展现象分析

Hyperprogressive disease triggered by immune checkpoint inhibitors in cancer treatment

免疫检查点抑制剂为部分癌症患者带来显著生存获益,但是部分患者在治疗早期阶段却出现了肿瘤加速生长现象,称为超进展。超进展是一种全新的肿瘤进展方式,预后极差,常伴有患者生存质量的明显下降。超进展的评估大部分以肿瘤生长速率为基础,并使用自然对数进行校正获得。超进展分子机制尚未明确,与肿瘤细胞基因异常表达、肿瘤微环境及淋巴细胞亚型的改变相关。超进展的预测因素尚未清楚,部分临床病理特征、分子标志物和超进展体现出一定的相关性。本文总结了免疫检查点抑制剂引起超进展的定义、评估、发病情况及预测因子,并对发病机制进行初步探讨。

Immune checkpoint inhibitors(ICIs) have substantially improved the long-term survival in a subset of patients with multiple tumor types. However, some patients may develop a hyperprogressive disease(HPD) when they first start taking ICIs. The presence of HPD is always associated with deleterious outcomes and a poor quality of life. The evaluation of HPD is mostly based on a tumor growth ratio that is defined as the log-scale calibrated change in the sum of the longest diameters of the target lesions per month according to Response Evaluation Criteria in Solid Tumors(RECIST 1.1). Several hypotheses have been proposed to elucidate the underlying mechanisms of HPD. Aberrant alterations in driver gene expressions, cancer microenvironments, or T-cell phenotypes may be the cause of HPD. Distinguishing between HPD and a naturally progressive disease remains a major enigma. Some clinicopathological characteristics and molecular biomarkers may have predictive values for HPD. In this review, we aimed to summarize the definition, evaluation, prevalence, potential predictors, and underlying mechanisms of HPD.