Serum cytokines predict response and survival in esophageal squamous cell carcinoma receiving chemoradiotherapy plus toripalimab

Chemoradiotherapy (CRT) combined with anti-PD-1 for locally advanced esophageal squamous cell carcinoma (LA ESCC) has shown promising efficacy. There is a need for predictive biomarkers to identify patients who could benefit from this therapy. Analysis of 142 patients form three phase 2 trials resulted in development of the CYTOscore of cytokine-based biomarkers for treatment response and survival in this setting. The exploration cohort consisted of 81 participants from two phase 2 trials, and the validation cohort consisted of 61 participants of a third phase 2 trial. Nineteen serum cytokines were assessed at baseline, during, and post CRT plus toripalimab. Cox analyses identified IL-8, CCL3, and CCL4 as potential biomarkers. These biomarkers were used to construct CYTOscore. Patients stratified by baseline CYTOscore showed significantly longer overall survival (HR 0.31; p=0.00045), progression-free survival (HR 0.33; p=0.00036), and higher complete response rate (66% versus 35%; p=0.014) in the low-risk group compared to the high-risk group. These results were confirmed in the validation cohort. A nomogram incorporating baseline CYTOscore and clinical characteristics showed promising predictive accuracy for 1-, 2-, and 3-year OS (AUC 0.77, 0.78, and 0.76, respectively). The authors conclude that the CYTOscore effectively predicts treatment response and survival in LA ESCC patients receiving CRT plus toripalimab.