Department of Drug Development and Innovation (D3i), Institut Curie, Saint-Cloud, Paris, France.
INSERM U900 Research Unit, Saint-Cloud, France.
BioDrugs. 2020 Aug;34(4):463-476. doi: 10.1007/s40259-020-00425-y.
Indications of immunotherapy in oncology are continuously expanding, and unconventional types of response have been observed with these new treatments. These include transient progressive disease followed by a partial response, described as pseudoprogression, that raises the question of treatment beyond progression; and rapid disease progression associated with clinical decline, reported as hyperprogression. However, there are currently no consensual definitions of these phenomena and their impact on daily practice remains unclear. We reviewed existing data on pseudoprogression and hyperprogression with a focus on the definitions, incidence, predictive factors, potential biological mechanisms, and methods published to help distinguish pseudoprogression from progression and hyperprogression. The incidence of pseudoprogression ranged from 0 to 15%, with some authors also including disease stabilization after a first progression. For hyperprogression, incidence ranged from 4 to 29% with various definitions, and several authors reported a correlation with worse survival. Both phenomena were observed in a large panel of cancer types. Several radiological and biological methods have been reported to help distinguish pseudoprogression from progression and hyperprogression, such as analysis of radiomics, and circulating-tumor DNA or cell-free DNA, but these need to be confirmed in larger prospective cohorts. In conclusion, pseudoprogression and hyperprogression are both frequent types of responses under immunotherapy, and there is a need to better characterize these to improve the management of cancer patients. Treatment beyond progression should always be considered with caution and necessitates close clinical monitoring. In case of suspected hyperprogression, immunotherapy should be stopped early.
肿瘤免疫治疗的适应证不断扩大，这些新疗法出现了非常规类型的反应。这些反应包括短暂的疾病进展后出现部分缓解，被描述为假性进展，这引发了一个问题，即是否应该在疾病进展后继续治疗；还有与临床恶化相关的快速疾病进展，被称为超进展。然而，目前对于这些现象尚无共识定义，其对日常实践的影响也不明确。我们回顾了假性进展和超进展的现有数据，重点关注这些现象的定义、发生率、预测因素、潜在生物学机制以及已发表的有助于区分假性进展和进展、超进展的方法。假性进展的发生率为 0 至 15%，一些作者还包括首次进展后的疾病稳定。对于超进展，不同定义的发生率为 4%至 29%，有几位作者报告称其与生存率更差相关。这两种现象均在大量癌症类型中观察到。已经报道了几种影像学和生物学方法来帮助区分假性进展和进展、超进展，例如放射组学分析、循环肿瘤 DNA 或游离肿瘤 DNA，但这些方法需要在更大的前瞻性队列中得到验证。总之，假性进展和超进展都是免疫治疗下常见的反应类型，需要更好地对其进行特征描述，以改善癌症患者的管理。在进展后继续治疗应始终谨慎考虑，并需要密切的临床监测。如果怀疑出现超进展，应尽早停止免疫治疗。
