Dose-volume predictors of post-radiation primary hypothyroidism in head and neck cancer: A systematic review

Abstract

Background and purpose: This systematic review aims to identify radiation dose-volume predictors of primary hypothyroidism after radiotherapy in patients with head and neck cancer (HNC).

Materials and methods: We performed a systematic literature search of Medline, EMBASE and Web of Science from database inception to July 1, 2021 for articles that discuss radiation dose-volume predictors of post-radiation primary hypothyroidism in patients with HNC. Data on the incidence, clinical risk factors and radiation dose-volume parameters were extracted. A meta-analysis was performed using the random-effects model to estimate the pooled odds ratio (OR) of thyroid volume as a predictor of the risk of post-radiation hypothyroidism, adjusted for thyroid radiation dosimetry.

Results: Our search identified 29 observational studies involving 4,530 patients. With median follow-up durations ranging from 1.0 to 5.3 years, the average crude incidence of post-radiation primary hypothyroidism was 41.4 % (range, 10 %-57 %). Multiple radiation dose-volume parameters were associated with post-radiation primary hypothyroidism, including the thyroid mean dose (Dmean), minimum dose, V25, V30, V35, V45, V50, V30-60, VS45 and VS60. Thyroid Dmean and V50 were the most frequently proposed dosimetric predictors. The pooled adjusted OR of thyroid volume on the risk of post-radiation primary hypothyroidism was 0.89 (95 % confidence interval, 0.85-0.93; p < 0.001) per 1 cc increment.

Conclusion: Post-radiation primary hypothyroidism is a common late complication after radiotherapy for HNC. Minimizing inadvertent exposure of the thyroid gland to radiation is crucial to prevent this late complication. Radiation dose-volume constraints individualized for thyroid volume should be considered in HNC radiotherapy planning.

Keywords: 3DRT, dimensional radiotherapy; CI, confidence interval; CT, computer tomography; Dmean, mean dose; Dmin, minimum dose; HNC, head and neck cancer; Head and neck neoplasms; Hypothyroidism; IMRT, intensity modulated radiotherapy; NPC, nasopharyngeal cancer; NTCP, normal tissue complication probability; OPC, oropharyngeal cancer; OR, odds ratio; PRIMSA, Preferred Reporting Items for Systematic Reviews and meta-Analyses; QUANTEC, Quantitative Analysis of The Normal Tissue Effects in the Clinic; ROC, receiver operating curve; Radiotherapy; Survivorship; TSH, thyroid stimulating hormone; ULN, upper limit of normal; VSx, thyroid volume that is spared from x Gy of radiation dose; Vx, thyroid volume that receives x Gy of radiation dose.