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

Abstract

Background and purpose: 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 and methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Head-and-neck cancer; Hypothyroidism; Mixture model; Normal tissue complication probability; Radiotherapy; Thyroid gland constraint.