Prediction of radiation-induced hypothyroidism after proton-based supraclavicular nodal irradiation in breast cancer.

Authors

Jiayao Sun, Ping Li, Yongkuan Hao, Yinxiangzi Sheng, Weiwei Wang, Qing Zhang, Xiaomao Guo

Published in

Medical physics. Volume 53. Issue 10. Pages e70703.

Abstract

The thyroid gland lies adjacent to the supraclavicular target and is highly radiosensitive, placing patients at risk for radiation-induced hypothyroidism (RIHT). While RIHT incidence and predictive models have been well described after photon-based irradiation, evidence in the proton therapy setting remains limited.
To evaluate the incidence of RIHT in breast cancer patients undergoing proton-based supraclavicular nodal irradiation and to develop proton-specific normal tissue complication probability (NTCP) models incorporating dose-volume, dose-averaged linear energy transfer (LETd)-volume, and dose-LETd-volume histogram (DLVH) metrics.
A total of 113 breast cancer patients treated with proton supraclavicular irradiation were retrospectively analyzed. Dose-volume, LETd-volume, and DLVH metrics were extracted for the thyroid gland and individual thyroid lobes. After exclusion of non-informative variables, univariable logistic regression models were developed for all retained candidate predictors. Internal validation and model selection were performed using 1000 bootstrap resamples, and the final bootstrap-selected predictor was defined as the variable with the highest selection frequency. Model performance was assessed using apparent and optimism-corrected area under the receiver operating characteristic curve (AUC). Biological dose metrics were additionally generated using six published LET-dependent relative biological effectiveness (RBE) models and compared with the fixed-RBE model using paired DeLong tests.
Seventeen patients (15.0%) developed RIHT after a median follow-up of 25 months (range, 9-80 months). Under the fixed-RBE framework, the final bootstrap-selected predictors were complementary DLVH metrics: CD10L2 (cc), denoting the absolute volume not simultaneously receiving dose ≥ 10 Gy(RBE) and LETd ≥ 2 keV/µm, CD35L3 (cc), and CD5L4 (cc) for the thyroid gland, ipsilateral lobe, and contralateral lobe, respectively. The corresponding apparent AUCs were 0.794, 0.763, and 0.817, with optimism-corrected AUCs of 0.738, 0.708, and 0.766, respectively. Among the LET-dependent RBE models, the Wedenberg model based on contralateral lobe CD10L4 (cc) yielded the numerically highest optimism-corrected AUC of 0.772. Although LET-dependent RBE models showed slightly higher apparent AUCs than the fixed-RBE model in some analyses, paired DeLong tests did not demonstrate statistically significant differences.
RIHT is a clinically relevant toxicity after proton-based supraclavicular irradiation. Under the fixed-RBE framework, the optimal cutoff values for the final bootstrap-selected complementary DLVH predictors were 5.6 cc for thyroid gland CD10L2 (cc), 2.9 cc for ipsilateral lobe CD35L3(cc), and 4.3 cc for contralateral lobe CD5L4 (cc). Complementary DLVH metrics may be informative for RIHT risk prediction and support thyroid-aware optimization strategies in proton treatment planning, pending further validation.

PMID:
42875928
Bibliographic data and abstract were imported from PubMed on 15 Oct 2026.

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