Nomogram for radiation-induced hypothyroidism prediction in nasopharyngeal carcinoma after treatment

Abstract

The authors Ren Luo and Mei Li contributed equally to this work.Objective: The aim of this study was to develop a nomogram for radiation-induced hypothyroidism (RHT) prediction. Methods: We collected data from 164 patients with nasopharyngeal carcinoma (NPC) in our previous prospective study. Biochemical hypothyroidism was defined as a serum thyroid-stimulating hormone level greater than the normal value. We collected both clinical and dose-volume factors. A univariate Cox regression analysis was performed to identify RHT risk factors. Optimal predictors were selected according to the least absolute shrinkage and selection operator (LASSO). We then selected the Cox regression models that best balanced the prediction performance and practicability to build a nomogram for RHT prediction. Results: There were 38 (23.2%) patients who developed RHT, and the median follow-up was 24 months. The univariate Cox regression analysis indicated that gender, minimum dose, mean dose (D mean ) and V 25 -V 60 [V x (%), the percentage of thyroid volume receiving .x Gy] of the thyroid were significantly associated with RHT. The variables of gender, receiving chemotherapy or not (chemo), D mean and V 50 were selected using the LASSO analysis. A nomogram based on a three-variable (gender, chemo and V 50 ) Cox regression model was constructed, and its concordance index was 0.72. Good accordance between prediction and observation was showed by calibration curves in the probability of RHT at 18, 24 and 30 months. Conclusion: This study built a nomogram for RHT in NPC survivors by analyzing both clinical and dose-volume parameters using LASSO. Thus, the individual dose constraint could be achieved in a visual format. Advances in knowledge: This study used LASSO to more accurately address the multicollinear problem between variables. The resulting nomogram will help physicians predict RHT. INTRODUCTIONRadiation-induced hypothyroidism (RHT) is a common late complication after irradiation to the neck area. The majority of early RHT cases are silent because subclinical hypothyroidism (HT) can be detected only by thyroid hormone tests [elevated serum thyroid-stimulating hormone (TSH) and normal serum free thyroxine (fT4) and/ or serum free triiodothyronine (fT3)]. However, other cases show overt disease [overt hypothyroidism (overt HT)] that presents with elevated TSH and decreased fT4 and/or fT3. The incidence of subclinical HT is 24-50%, and overt HT develops in 6-20% of patients with head and neck cancer who receive radiotherapy (RT).1 HT has been demonstrated to be correlated with the development of cardiovascular and pulmonary disorders in addition to diabetes mellitus, 2-7 which increases the adverse effects of RHT on patient quality of life.

Development of a normal tissue complication probability (NTCP) model for radiation-induced hypothyroidism in nasopharyngeal carcinoma patients

“…In accordance with the previous studies [ 3 , 8 , 9 , 16 , 19 , 22 ], the female gender and V 50 were identified as risk factors in this study. It remains controversial [ 9 , 29 – 31 ] whether chemotherapy is a predictor of RHT.…”

“…It remains controversial [ 9 , 29 – 31 ] whether chemotherapy is a predictor of RHT. However, in our previous study [ 22 ], chemotherapy plays a major role in the nomogram for biochemical HT prediction in NPC patients. In this study, only one experienced biochemical HT among 19 patients who did not receive chemotherapy, and chemotherapy was identified as an independent predictor in the multivariate analysis.…”

“…The detail information of patient eligibility, radiation therapy, chemotherapy regimen, and thyroid function evaluation was also described in our previous publications [ 4 , 22 ].…”

Validation of previously reported predictors for radiation-induced hypothyroidism in nasopharyngeal cancer patients treated with intensity-modulated radiation therapy, a post hoc analysis from a Phase III randomized trial

“…Other parameters predicting a higher rate of hypothyroidism included younger age [ 5 , 11 , 12 ], female sex [ 13 , 14 ], mean radiation dose to the thyroid [ 6 ] and small thyroid volume [ 5 , 6 , 10 , 12 , 15 ]. The use of chemotherapy, and autoimmune disease, may also be associated with hypothyroidism [ 16 – 18 ].…”

Thyroid V50 is a risk factor for hypothyroidism in patients with nasopharyngeal carcinoma treated with intensity-modulated radiation therapy: a retrospective study

“…Currently, scholars here and abroad hold different opinions on the relationship between thyroid dose-volume and HT. One study suggested that the thyroid minimum dose, mean dose, and V 25 -V 60 are significantly associated with HT [21]. Sommat et al [22] have suggested that the thyroid V 40 is closely related to HT, where the incidence of radiation-induced HT in the thyroid V 40 ≤ 85% and thyroid V 40 > 85% groups was 21.4% (3/14) and 61.4% (54/88), respectively.…”