Vertebral body dosimetry associated with hematologic toxicities and survival in esophageal squamous-cell carcinoma treated with chemoradiotherapy plus immunotherapy.

BACKGROUND: 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-volume parameters and grade ≥3 hematologic toxicities (HT3+) in ESCC patients treated with chemoradiotherapy and immunotherapy. METHODS: All radiation doses were converted to equivalent doses in 2 Gy fractions (EQD2). Vertebral bodies were contoured, and VB dose-volume parameters (V5EQD2-V50EQD2, DmeanEQD2, and DmaxEQD2) were extracted. Logistic regression was used to evaluate factors associated with HT3 +. 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-Meier method. RESULTS: Among 157 ESCC patients, 141 (89.8%) developed HT3 +. Low-dose VB irradiation parameters (V5EQD2-V20EQD2) 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 V5EQD2, V10EQD2, and V20EQD2, respectively. The corresponding optimal thresholds of V5EQD2 = 60.1%, V10EQD2 = 53.9%, and V20EQD2 = 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. CONCLUSIONS: 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.