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Research Article: Local control after stereotactic radiation for thyroid cancer: a histology risk-stratified analysis

Date Published: 2026-09-30

Abstract:
Recurrent and metastatic non-anaplastic thyroid cancer has traditionally been considered relatively radioresistant. We evaluated whether anatomic site or histology risk group better predicts local control (LC) following stereotactic radiation therapy (SBRT/SRS). We retrospectively reviewed 32 patients with 66 treated lesions (42 skeletal, 24 non-skeletal) treated between 2012 and 2025. Histology was dichotomized into low-risk (papillary, follicular, medullary, Hürthle cell; n=61) and high-risk (poorly differentiated and squamous cell carcinoma; n=5). BED 10 was calculated using ?/? = 10 Gy. LC was defined per RECIST 1.1. Kaplan–Meier and log-rank tests were used. Intra-patient correlation was addressed via generalized estimating equations (GEE) and Cox shared frailty models. A multivariable GEE model included histology risk, site, BED 10 , PTV volume, prior surgery, and age. Median follow-up was 15.0 months. Six local failures occurred (crude LC 90.9%); 1- and 2-year LC were 96.5% and 87.1%. Histology risk was the dominant determinant: low-risk histology achieved 95.1% crude LC versus 40.0% for high-risk (log-rank p=0.002). In multivariable GEE analysis, low-risk histology was independently associated with LC (OR 158.0, 95% CI 1.72–14,479.7; p=0.028), whereas skeletal site was not (OR 1.07, 95% CI 0.02–51.8; p=0.974). BED 10 was not associated with LC after adjustment (p=0.752). Skeletal and non-skeletal LC were similar after histology stratification (95.0% vs 95.2% among low-risk). Treatment was well tolerated; no Grade ?3 radiation toxicity, myelopathy, or fractures occurred. In stereotactic radiation for metastatic non-anaplastic thyroid cancer, histology risk grouping—not anatomic site or dose escalation—is the dominant predictor of local control. These findings support histology-based risk stratification for SRT patient selection.

Introduction:
Recurrent and metastatic non-anaplastic thyroid cancer has historically been regarded as relatively radioresistant, particularly when treated with conventional fractionation. However, the advent of stereotactic radiation therapy (SRT) has challenged this paradigm by enabling the delivery of highly conformal, ablative doses that may overcome intrinsic tumor resistance. Accumulating clinical experience indicates that high-dose hypofractionated radiation can achieve durable local control, especially in patients with…

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