{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T15:24:01Z","timestamp":1765812241171,"version":"3.48.0"},"reference-count":27,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Radiotherapy (RT) combined with immune checkpoint inhibitors (ICIs) has shown therapeutic benefits, and the potential for enhanced immune activation has raised concerns about increased immune-related adverse events (irAEs). The immunological implications of mediastinal RT combined with ICI therapy remain unclear. Methods: We conducted an exploratory retrospective review of 58 patients with esophageal oresophagogastric junction cancer who received ICIs between 2021 and 2024. Patients were categorized into RT (+) and RT (-) groups based on whether they underwent mediastinal RT. The incidence and severity of irAEs were compared using chi-square testing. Subgroup analyses included treatment sequence (RT before vs. after ICI), interval between RT and ICI (&lt;90 vs. \u226590 days), and ICI regimen (nivolumab [N], pembrolizumab [P], or nivolumab plus ipilimumab [NI]). Results: irAEs occurred in 28.6% of RT (+) and 39.1% of RT (-) (p = 0.42). Severe irAEs were uncommon in both groups. Treatment sequence and RT-ICI interval did not significantly influence irAE incidence. irAEs were more frequent in the NI group (85.7%) than in N (22.9%) or P (31.2%) (p = 0.01). Mediastinal RT itself did not increase irAE risk. Conclusions: Although RT combined with ICIs has been hypothesized to elevate irAEs through enhanced immune activation, mediastinal RT did not increase irAEs in this cohort. However, given the exploratory and small patient cohort, these findings suggest, with caution, that mediastinal irradiation may attenuate systemic immune activation through lymphocyte depletion, potentially balancing ICI-induced immune responses.<\/jats:p>","DOI":"10.3390\/cancers17243992","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T15:15:08Z","timestamp":1765811708000},"page":"3992","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An Exploratory Retrospective Study on the Association of Radiotherapy with the Risk of Immune-Related Adverse Events in Esophageal and Esophagogastric Junction Cancer Patients Receiving Immunotherapy"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9717-7464","authenticated-orcid":false,"given":"Nobukazu","family":"Hokamura","sequence":"first","affiliation":[{"name":"Department of Surgery, Teikyo University School of Medicine, Tokyo 173-0003, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeo","family":"Fukagawa","sequence":"additional","affiliation":[{"name":"Department of Surgery, Teikyo University School of Medicine, Tokyo 173-0003, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4464-664X","authenticated-orcid":false,"given":"Ryoji","family":"Fukushima","sequence":"additional","affiliation":[{"name":"Department of Surgery, Teikyo University School of Medicine, Tokyo 173-0003, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Kiyokawa","sequence":"additional","affiliation":[{"name":"Department of Surgery, Teikyo University School of Medicine, Tokyo 173-0003, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2522-0961","authenticated-orcid":false,"given":"Masahiro","family":"Horikawa","sequence":"additional","affiliation":[{"name":"Department of Surgery, Teikyo University School of Medicine, Tokyo 173-0003, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuichi","family":"Igarashi","sequence":"additional","affiliation":[{"name":"Department of Surgery, Teikyo University School of Medicine, Tokyo 173-0003, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hironori","family":"Midorikawa","sequence":"additional","affiliation":[{"name":"Department of Surgery, Teikyo University School of Medicine, Tokyo 173-0003, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinya","family":"Kaneshiro","sequence":"additional","affiliation":[{"name":"Department of Surgery, Teikyo University School of Medicine, Tokyo 173-0003, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2295-517X","authenticated-orcid":false,"given":"Kenshiro","family":"Shiraishi","sequence":"additional","affiliation":[{"name":"Department of Radiology, Teikyo University School of Medicine, Tokyo 173-0003, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1158\/1078-0432.CCR-16-0037","article-title":"Toward Precision Radiotherapy for Use with Immune Checkpoint Blockers","volume":"24","author":"Formenti","year":"2018","journal-title":"Clin. 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