Radiotherapy combined with immune checkpoint inhibitors in locally advanced/metastatic esophageal squamous cell carcinoma: clinical trials, efficacy and future directions

Abstract

Esophageal squamous cell carcinoma (ESCC) is a common malignancy worldwide and often diagnosed at advanced stages with poor prognosis. Combination of radiotherapy and immunotherapy seems to be a promising approach for treating ESCC. This comprehensive review article summarizes the current state of combination of radiotherapy and immunotherapy in locally advanced/metastatic ESCC, delineates the clinical trials that merit attention, and outlines unresolved issues and future research directions in this field. The clinical trial findings suggest that radio-immunotherapy combination may improve tumor response and overall survival with manageable side effects, highlighting the importance of patient selection and the necessity for further research to optimize treatment strategies. Issues such as irradiation dosage, fractionation regimen, irradiation site and technique of radiotherapy, as well as the timing, sequence and duration of combination therapy will all affect treatment outcomes, justifying further in-depth investigation.

Advancing Esophageal Cancer Treatment: Immunotherapy in Neoadjuvant and Adjuvant Settings

“…Radiotherapy has also been shown to lead to an abscopal effect. The direct and indirect antitumor effects of radiotherapy may be further augmented by immunotherapy [17]. Immunotherapy may serve as a primer for improved response to subsequent lines of chemoradiation.…”

Current and future on definitive concurrent chemoradiotherapy for inoperable locally advanced esophageal squamous cell carcinoma

“…The most recognized molecular markers are PD-L1, microsatellite instability and tumor mutational load, but they are still some way from being ideal predictive markers. Various external factors, including sample quality, assay conditions, and cutoff values can influence the predictive accuracy of these markers (82)(83)(84).…”

Navigating a Complex Intersection: Immunotherapy and Radiotherapy Synergy in Squamous Cell Carcinoma of the Skin—A Comprehensive Literature Review

“…Several case reports and early clinical trials [27,59,60] have described the use of immunoradiotherapy in metastatic SCC. A recently published manuscript [59] suggested that patients with metastatic SCC who received a combination of immune checkpoint inhibitors and radiotherapy resulted in significant tumor regression and prolonged survival. Similarly, early-phase clinical trials have reported objective responses and disease control in patients with metastatic SCC receiving immunoradiotherapy [27,60].…”

“…These reports highlight the potential of immunoradiotherapy to induce tumor regression and achieve durable responses in metastatic disease. Despite the promising results [27,59,60], challenges exist in the successful implementation of immunoradiotherapy in metastatic SCC.…”