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Research Article: Normal tissue complication probability model of temporal lobe injury following re-irradiation of CIRT for local recurrent nasopharyngeal carcinoma

Date Published: 2026-06-26

Abstract:
Temporal lobe injury (TLI) is a significant complication after carbon-ion re-irradiation (reRT-CIRT) for locally recurrent nasopharyngeal carcinoma (rNPC). This study established normal tissue complication probability (NTCP) models for TLI based on (1) the second-course CIRT dose alone and (2) the cumulative dose of both radiotherapy courses, with the goal of defining clinically applicable, modality-specific dose constraints. Eighty-nine rNPC patients who underwent reRT-CIRT between 2016 and 2020 were retrospectively analyzed. Deformable image registration transferred initial IMRT dose distributions onto CIRT planning scans, and voxel-wise cumulative equivalent doses in 2-Gy fractions (EQD 2 , ?/? = 3 Gy) were calculated. Patients were stratified into training (n = 52) and validation (n = 37) cohorts. Multivariate logistic regression identified TLI predictors under two scenarios—second-course dose only versus cumulative two-course dose—and model performance was evaluated by ROC analysis. TLI occurred in 27 patients (30.3%), predominantly unilateral (24/27); 14 were Grade 1 (asymptomatic, MRI-detected only), 7 Grade 2, 5 Grade 3, and 1 Grade 4. The second-course D 0.5 cc model [TD 5 34.27 Gy (RBE); TD 50 78.53 Gy (RBE); AUC 0.8450, 95% CI 0.7571–0.9329] and the cumulative D 5 cc model (TD 5 41.60 Gy; TD 50 124.31 Gy; AUC 0.8225, 95% CI 0.7228–0.9222) yielded equivalent and concordant risk stratification, with the inter-group dose difference primarily driven by the re-irradiation course. Compared with our previous photon-based reRT model, the CIRT-derived TD 50 for D 0.5 cc and D 1 cc were ~20% higher (78.5 vs. 65.4 Gy; 76.8 vs. 62.9 Gy), indicating that photon-based constraints systematically overestimate TLI risk under CIRT. A CIRT-specific NTCP model based on the second-course D 0.5 cc achieves predictive performance equivalent to cumulative two-course dose summation, obviating prior-course dose reconstruction. This simplified, modality-specific tool offers practical guidance for individualized risk assessment and dose-constraint optimization in carbon-ion re-irradiation for rNPC.

Introduction:
Locally recurrent nasopharyngeal carcinoma (NPC) represents one of the primary modes of treatment failure following initial radiotherapy ( 1 , 2 ). Carbon ion radiotherapy (CIRT) has shown dosimetric and clinical advantages over intensity-modulated radiotherapy (IMRT) in the re-irradiation of rNPC, offering improved dose conformity and potentially reduced toxicity ( 3 , 4 ). However, temporal lobe injury (TLI) remains a significant complication after re-irradiation, particularly when the recurrent lesion is in…

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