Immune checkpoint inhibitors combined with radiotherapy/chemoradiotherapy in treating locally advanced or recurrent/metastatic esophageal squamous cell carcinoma: A real-world study

Abstract

Objective: This study was designed to investigate the prognostic factors for immune checkpoint inhibitors (ICIs) combined utilization with radiotherapy (RT)/chemoradiotherapy (CRT) and to evaluate their toxicity in locally advanced or recurrent/metastatic esophageal squamous cell carcinoma (LA/RM ESCC). Methods: In this study, 198 LA/RM ESCC patients who received ICIs combined with RT/CRT in the Department of Radiotherapy of the Fourth Hospital of Hebei Medical University were retrospectively analyzed. Univariate and multivariate analyses were performed to determine the prognostic factors for overall survival (OS) and progression-free survival (PFS). Subgroup analysis was utilized to explore the prognostic factors, the treatment respond and treatment-related adverse events (trAEs) were analyzed. Results: The median OS and PFS were 30.4 months (95% confidence interval [CI]: 15.1–45.7 months) and 15.3 months (95% CI: 12.8–17.8 months), respectively. The median OS and PFS for patients achieving objective respond (ORR group, including complete response and partial response) were 50.8 months (95% CI: 25.8–75.7 months) and 20.5 months (95% CI: 14.1–27.0), respectively, which were higher than those in non-ORR group (OSnon-ORR:17.5 months, 95% CI: 14.0–21.0; χ2 = 13.881, P < 0.001; PFSnon-ORR: 12.1 months, 95% CI: 10.1–14.1, χ2 = 10.676, P = 0.001). Results from subgroup analysis illustrated combined ICIs with radiotherapy could improve the treatment respond (χ2 = 47.725, P = 0.000). The OS rate (χ2 = 18.836, P < 0.001) and PFS rate (χ2 = 6.881, P = 0.009) were significantly higher in the whole-lesion radiotherapy group than in the partial-lesion radiotherapy group. Multivariate analysis showed that the number of immune cycles, the coverage of radiotherapy target, the modality of ICIs-combination therapy and treatment response were independent prognosis factors for OS (hazard ratio [HR] = 0.512, 2.043, 1.889, and 1.912, respectively; P = 0.001, 0.001, 0.013, and 0.002, respectively). Radiotherapy coverage and treatment response were independent factors for PFS (HR = 1.478 and 1.597, respectively; P = 0.032 and 0.012, respectively). In the entire study population, 83 patients (41.9%) had ≥ grade 2 trAEs. Conclusions: ICIs combined with radiotherapy/chemoradiotherapy are safe and effective in LA/RM ESCC patients. The addition of radiotherapy could improve the treatment respond and whole-lesion radiotherapy improve prognosis compared with partial-lesion radiotherapy group. The number of immunotherapy cycles and treatment response are the main factors affecting prognosis.