Hypothyroidism is associated with radiation-induced pulmonary fibrosis

Radiation-induced pulmonary fibrosis (RIPF) is a common late complication for breast cancer patients after radiation therapy (RT). Breast cancer patients are often accompanied by hypothyroidism. We therefore sought to evaluate the association between hypothyroidism and RIPF susceptibility.

We retrospectively analyzed 781 breast cancer patients who underwent postoperative intensity-modulated radiation therapy (IMRT) between 2020 and 2021. Univariate and multivariate Cox regression analyses were used to evaluate the prevalence of hypothyroidism between patients with or without RIPF. Propensity score matching (PSM) was employed to balance baseline characteristics between the two groups. Analysis of the occurrence time of RIPF was performed using the Kaplan-Meier Survival estimator.

Hypothyroidism was found to be significantly associated with RIPF susceptibility using univariate analysis (OR = 5.51; 95 % CI: 2.55-11.90; P = 0.001). When considering age, body mass index (BMI), diabetes, smoking, and surgical modality, multivariate analysis further confirmed the significant association of hypothyroidism with RIPF susceptibility (OR = 5.85; 95 % CI: 2.58-13.26; P = 0.001). Even after PSM, hypothyroidism remained significantly associated with RIPF susceptibility using both univariate (OR = 65.29; 95 % CI: 1.95-2181.19; P = 0.02) and multivariate analyses (OR = 6.03; 95 % CI: 2.69-13.50; P = 0.001), respectively. The occurrence time of RIPF was comparable between patients with or without hypothyroidism analyzed by data after PSM (Median occurrence time = 6 months in both groups, P = 0.055).

Hypothyroidism is significantly associated with RIPF susceptibility in breast cancer patients treated with postoperative IMRT. These results highlight the potential of thyroid function as a modifiable risk factor in RIPF and underscore the need for further mechanistic and interventional studies.