Hypothyroidism after primary radiotherapy for head and neck squamous cell carcinoma: normal tissue complication probability modeling with latent time correction.

Abstract

To develop a normal tissue complication probability (NTCP) model of radiation-induced biochemical hypothyroidism (HT) after primary radiotherapy for head and neck squamous cell carcinoma (HNSCC) with adjustment for latency and clinical risk factors. Patients with HNSCC receiving definitive radiotherapy with 66-68Gy without surgery were followed up with serial post-treatment thyrotropin (TSH) assessment. HT was defined as TSH >4.0mU/l. Data were analyzed with both a logistic and a mixture model (correcting for latency) to determine risk factors for HT and develop an NTCP model based on mean thyroid dose (MTD) and thyroid volume. 203 patients were included. Median follow-up: 25.1months. Five-year estimated risk of HT was 25.6%. In the mixture model, the only independent risk factors for HT were thyroid volume (cm(3)) (OR=0.75 [95% CI: 0.64-0.85], p<0.001) and MTD (Gy) (OR=1.12 [95% CI: 1.07-1.20], p<0.001). From the mixture NTCP-model individual dose constraints for a 25% risk of HT were 26, 38, 48 and 61Gy for thyroid volumes of 10, 15, 20 and 25cm(3), respectively. Comparing the logistic and mixture models demonstrates the importance of latent-time correction in NTCP-modeling. Thyroid dose constraints in treatment planning should be individualized based on thyroid volume.