Characterizing the impact of sarcopenia on treatment response and survival in previously treated recurrent or metastatic nasopharyngeal carcinoma: Insights from a secondary analysis of the KL-A167 randomized trial.

person Zheran Liu Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China info_outline Zheran Liu, Dou Meng, Huilin Li, Dong Li, Zhihui Li, Lei Cai, Jitao Zhou, Xingchen Peng

Authors person Zheran Liu Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China info_outline Zheran Liu, Dou Meng, Huilin Li, Dong Li, Zhihui Li, Lei Cai, Jitao Zhou, Xingchen Peng Organizations Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China, Chengdu Institute of Computer Application, Chinese Academy of Sciences; University of Chinese Academy of Sciences, Chengdu, China, Department of Oncology, The General Hospital of Western Theater Command, Chengdu, China, Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, Chongqing University, Chongqing, China, Division of Abdominal Tumor Multimodality Treatment, Department of Radiation Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China Abstract Disclosures Research Funding No funding sources reported Background: The relationship between sarcopenia and adverse outcomes among patients with recurrent and metastatic nasopharyngeal carcinoma (R/M NPC) undergoing immunotherapy remains underexplored. This secondary analysis of the KL-A167 clinical trial data aims to elucidate the impact of sarcopenia on treatment efficacy and prognosis in this cohort, while also identifying potential mediating hematological biomarkers. Methods: A cohort of 148 patients enrolled in the KL-A167 clinical trial was analyzed. Logistic and Cox regression models were applied to assess the association between sarcopenia and treatment response, overall survival (OS), and progression-free survival (PFS), with adjustment for clinical prognostic factors. Counterfactual causal mediation analysis was conducted to identify hematological biomarkers potentially mediating the relationship between sarcopenia and prognosis in R/M NPC patients. Results: The presence of sarcopenia was significantly associated with reduced objective response rate (ORR: OR = 0.25, 95% CI = 0.08–0.81, p = 0.020) and disease control rate (DCR: OR = 0.23, 95% CI = 0.07–0.70, p = 0.010). Furthermore, sarcopenia was linked to inferior OS (HR = 2.07, 95% CI = 1.12–3.81, p = 0.020) and PFS (HR = 2.59, 95% CI = 1.48–4.54, p = 0.001). Notably, sarcopenia was characterized by elevated levels of neutrophil count, fibrinogen, and white blood cell count, alongside decreased creatine kinase levels. Fibrinogen emerged as the sole elevated biomarker significantly associated with both OS and PFS. Causal mediation analysis indicated that fibrinogen accounted for 23.5% of the association between sarcopenia and OS and 15.7% of PFS. Conclusions: Sarcopenia significantly correlates with poor treatment response and survival outcomes in patients with R/M NPC receiving immunotherapy. Targeting fibrinogen may offer a novel strategy to mitigate the negative impact of sarcopenia on patient survival.