Hyperprogression disease induced by Sintilimab combined with Oxaliplatin and S-1 after surgery: a case report and literature review

Yaoqi Li¹Rui Shen²Weijun Liu³Zhu Chenglou^4*

• ¹Gansu Provincial Hospital, Lanzhou, Gansu Province, China
• ²Chengxian People's Hospital, Chengxian, China
• ³Longxi County First People's Hospital, Longxi, China
• ⁴Lanzhou University, Lanzhou, China

Objective: To investigate the risk factors, underlying mechanisms, and preventive strategies associated with hyperprogressive disease (HPD) induced by immunotherapy. Methods: 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. Results: In this case, the development of HPD was associated with a high postoperative tumor burden (Figure 3), elevated PD-1 expression (Figure 2), and aberrant activation of signaling pathways mediated by EGFR, MET, and FGFR1 amplifications (Table 2). In addition, a TP53 p.F270V mutation led to inactivation of tumor suppressor function (Table 2). Conclusion: 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.