Li Yaoqi, Wang You, Shen Rui, Liu Weijun, Zhu Chenglou
Department of Surgical Oncology, Gansu Provincial Hospital, Lanzhou, China.
The First School of Clinical Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, China.
Front Oncol. 2025 Jun 12;15:1494007. doi: 10.3389/fonc.2025.1494007. eCollection 2025.
To investigate the risk factors, underlying mechanisms, and preventive strategies associated with hyperprogressive disease (HPD) induced by immunotherapy.
We analyzed the clinical data of a patient who developed HPD following palliative gastrectomy and received a combination therapy of Sintilimab, S-1 (tegafur, gimeracil, and oteracil potassium), and Oxaliplatin (SOX). Additionally, a literature review on tumor immunotherapy was conducted to further explore the risk factors and mechanisms of HPD.
In this case, the development of HPD was associated with a high postoperative tumor burden, elevated PD-1 expression, and aberrant activation of signaling pathways mediated by EGFR, MET, and FGFR1 amplifications. In addition, a TP53 p.F270V mutation led to inactivation of tumor suppressor function.
Although immune checkpoint inhibitors (ICIs) have demonstrated significant efficacy in cancer treatment, HPD induced by ICIs can drastically shorten patients' OS, warranting cautious use in populations with high-risk factors. Effective prevention of HPD involves screening for risk factors, monitoring predictive biomarkers such as circulating-free DNA (cfDNA) via liquid biopsy, and identifying high-risk populations through gene mutation analysis.
探讨免疫治疗诱导的超进展性疾病（HPD）相关的危险因素、潜在机制及预防策略。
我们分析了1例姑息性胃切除术后发生HPD并接受信迪利单抗、S-1（替吉奥，即替加氟、吉美嘧啶和奥替拉西钾）及奥沙利铂（SOX）联合治疗患者的临床资料。此外，对肿瘤免疫治疗进行文献回顾，以进一步探究HPD的危险因素及机制。
在此病例中，HPD的发生与术后肿瘤负荷高、PD-1表达升高以及由表皮生长因子受体（EGFR）、间质-上皮转化因子（MET）和纤维母细胞生长因子受体1（FGFR1）扩增介导的信号通路异常激活有关。此外，TP53基因p.F270V突变导致肿瘤抑制功能失活。
尽管免疫检查点抑制剂（ICIs）在癌症治疗中已显示出显著疗效，但ICIs诱导的HPD可大幅缩短患者的总生存期（OS），因此在具有高危因素的人群中应谨慎使用。有效预防HPD包括筛查危险因素、通过液体活检监测循环游离DNA（cfDNA）等预测生物标志物以及通过基因突变分析识别高危人群。
