Okan Cakir Muharrem, Kirca Onder, Gunduz Seyda, Ozdogan Mustafa
Applied Health Sciences, Edinburgh Napier University, EH11 4BN Scotland, United Kingdom
J BUON. 2019 Nov-Dec;24(6):2232-2241.
Immune checkpoint inhibitors have revolutionized cancer treatment with patient improved survival, quality of life, and a longer response. However, up to 30% of patients experience paradoxical accelerated tumor progression early after immune-checkpoint blockade therapy. This phenomenon is also known as hyperprogression (HP). Unlike other responses, such as pseudoprogression or natural progression, HP causes worse survival outcomes in patients. Older age, higher metastatic burden, and previous radiation have been independently associated with HP. Even though the exact molecular mechanism underlying HP after immune-checkpoint blockade therapy remains unknown, oncogenic signaling activation including MDM2 amplification or EGFR alterations, the modification of tumor microenvironment by radiotherapy with immune checkpoint inhibitors, and alterations in immune landscape of tumors have been hypothesized as the biological mechanisms behind HP. Patients with HP have been presented with poor prognosis and increased deleterious mutations in cancer genes, along with alterations in the tumor microenvironment. As immune checkpoint inhibitors have been more widely accepted by oncologists, proper assessment of this unique tumor response remains challenging in clinical practice. This work documents the recent findings on epidemiology, biological and clinicopathological factors of HP after immunotherapy.
免疫检查点抑制剂彻底改变了癌症治疗方式，提高了患者的生存率、生活质量，并延长了缓解期。然而，高达30%的患者在免疫检查点阻断治疗后早期出现矛盾的肿瘤加速进展。这种现象也被称为超进展（HP）。与其他反应（如假性进展或自然进展）不同，HP会导致患者的生存结果更差。年龄较大、转移负担较高和既往接受过放疗与HP独立相关。尽管免疫检查点阻断治疗后HP的确切分子机制仍不清楚，但致癌信号激活（包括MDM2扩增或EGFR改变）、放疗联合免疫检查点抑制剂对肿瘤微环境的改变以及肿瘤免疫格局的改变被认为是HP背后的生物学机制。HP患者预后较差，癌症基因中有害突变增加，同时肿瘤微环境也发生改变。随着免疫检查点抑制剂越来越被肿瘤学家广泛接受，在临床实践中对这种独特的肿瘤反应进行恰当评估仍然具有挑战性。这项工作记录了免疫治疗后HP的流行病学、生物学和临床病理因素的最新研究结果。
