{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T06:00:53Z","timestamp":1785477653808,"version":"3.56.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"\n Background<\/jats:title>\n The addition of immunotherapy to definitive chemoradiotherapy has improved outcomes for patients with unresectable advanced esophageal squamous-cell carcinoma (ESCC). However, treatment-related hematologic toxicity, particularly radiation-induced lymphopenia, may impair systemic antitumor immunity and compromise the efficacy of immunotherapy. Because vertebral bodies (VB) contain a substantial proportion of active bone marrow, irradiation of this region may contribute to immune cell depletion. This study evaluated the association between VB dose\u2013volume parameters and grade \u22653 hematologic toxicities (HT3+) in ESCC patients treated with chemoradiotherapy and immunotherapy.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n All radiation doses were converted to equivalent doses in 2 Gy fractions (EQD\n 2<\/jats:sub>\n ). Vertebral bodies were contoured, and VB dose\u2013volume parameters (V5\n EQD2<\/jats:sub>\n \u2013V50\n EQD2<\/jats:sub>\n , Dmean\n EQD2<\/jats:sub>\n , and Dmax\n EQD2<\/jats:sub>\n ) were extracted. Logistic regression was used to evaluate factors associated with HT3\u00a0+. Receiver operating characteristic (ROC) analysis was performed to determine optimal VB dose thresholds. These thresholds were subsequently evaluated for associations with post-radiotherapy absolute lymphocyte count (ALC), immunotherapy response, progression-free survival (PFS), and overall survival (OS). Survival outcomes were analyzed using the Kaplan\u2013Meier method.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Among 157 ESCC patients, 141 (89.8%) developed HT3\u00a0+. Low-dose VB irradiation parameters (V5\n EQD2<\/jats:sub>\n \u2013V20\n EQD2<\/jats:sub>\n ) were significantly associated with HT3+, predominantly driven by lymphocyte depletion. ROC analysis demonstrated moderate discriminative ability, with AUCs of 0.704, 0.709, and 0.699 for V5\n EQD2<\/jats:sub>\n , V10\n EQD2<\/jats:sub>\n , and V20\n EQD2<\/jats:sub>\n , respectively. The corresponding optimal thresholds of V5\n EQD2<\/jats:sub>\n = 60.1%, V10\n EQD2<\/jats:sub>\n = 53.9%, and V20\n EQD2<\/jats:sub>\n = 51.9%, which effectively stratified HT3+ risk. Patients meeting these VB dose constraints exhibited higher post-radiotherapy ALC, improved immunotherapy response, and favorable survival outcomes, particularly OS.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Low-dose VB irradiation is strongly associated with severe hematologic toxicity in ESCC patients receiving chemoradiotherapy and immunotherapy. Minimizing VB exposure during treatment planning may help preserve lymphocyte counts, mitigate radiation-induced immune suppression, and support immune-mediated treatment efficacy.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1832306","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T05:39:22Z","timestamp":1785476362000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Vertebral body dosimetry associated with hematologic toxicities and survival in esophageal squamous-cell carcinoma treated with chemoradiotherapy plus immunotherapy"],"prefix":"10.3389","volume":"17","author":[{"given":"Shijie","family":"Shang","sequence":"first","affiliation":[{"name":"Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong 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