A Retrospective Study On Clinical And Dosimetric Factors Of Early Primary Hypothyroidism After Intensity Modulated Radiation Therapy For Nasopharyngeal Carcinoma

Objective:This study aim to investigate the rate and risk factors for early Radiation-induced hypothyroidism（RHT）in nasopharyngeal carcinoma（NPC）patients treated with intensity-modulated radiotherapy（IMRT）,and establish a multivariate normal tissue complication probability model for hypothyroidism.Materials and methods:144 NPC patients treated with IMRT for NPC at Jiangxi Cancer Hospital from December 2018 to January 2020 were retrospectively reviewed.thyroid function assessments before and after IMRT were periodically monitored.RHT was defined as an elevated TSH serum level（>4.78u IU/L）,with or without low serum FT4concentration.In order to clarify the related factors of radioactive hypothyroidism,the clinical characteristics and dosimetry parameters of the patients were statistically analyzed.The count data should be tested usingχ2 test or Fisher’s exact method.The K-S method is used to test the normality of measurement data,the independent sample T test is used for the measurement data that conforms to the normal distribution,and the Mann-Whitney U test is used for the measurement data that does not conform to the normal distribution.The optimal cut-off was determined using a receiver operating characteristics（ROC）analysis.Youden’s index was performed on pretreatment TSH,thyroid volume and dosimetric parameters to identify the cut-off values.Cox proportional hazard models with univariate were performed to identify the predictors for RHT,freedom from RHT was analyzed using the Kaplan–Meier method and the log-rank test.Factors with a P-value of 0.1 in the univariate analysis were enrolled into the multivariate Cox regression model with backward selection.All tests were two-sided,and a p-value of<0.05 was considered statistically signification.Results:A total of 144 patients were included in the analyses,with a median follow up of17 months（3.0-26.0 month）.Of the 144 patients,36 developed HT within 2 years,and the 6-month and 1-year incidence rates were 14.6%and 24.3%,respectively.In the patients with radiation-induced hypothyroidism in thisstudy,the median onset time was 6.0 months（0-13.0 months）.ROC analysis results showed that the area under the curve of thyroid volume,V₃₀,V₅₀,V_50,60,D_50%and Dmean were 0.633,0.628,0.591,0.585,0.584 and 0.621,respectively and the best cut-off values were 15cm³,0.99,0.6,0.55,52Gy and 50Gy.Univariate analysis found that the thyroid volume<15cm³（HR=4.05,95%CI=1.57-10.41,p=0.004）,chemotherapy cycles<3 times（HR=0.38,95%CI=0.17-0.71,p=0.032）,V₃₀<0.99（HR=0.51,95%CI=0.26-0.98,p=0.045）,V₅₀<0.6（HR=0.42,95%CI=0.21-0.83,p=0.013）,V_50,60<0.55（HR=0.46,95%CI=0.23-0.93,p=0.030）,D_50%<52Gy（HR=0.41,95%CI=0.21-0.80,p=0.010）and Dmean<50Gy（HR=0.51,95%CI=0.26-0.99,P=0.047）is the influencing factor of radiation-induced hypothyroidism.COX multivariate analysis showed that thyroid volume<15cm³（HR=4.05,95%CI=1.57-10.41,p=0.006）and thyroid D_50%≥52Gy（HR=2.43,95%CI=1.24-4.75,p=0.015）are independent predictors of radiation-induced hypothyroidism.According to combinational model of thyroid volume and thyroid D50%to predictearly radiation-induced hypothyroidism,the patients in this study were divided into low-risk groups（thyroid volume≥15cm³）,intermediate-risk group(thyroid volume<15cm³,thyroid D_50%<52Gy)and high-risk group(thyroid volume<15cm³,thyroid D_50%≥52Gy).The 1-year incidence rate of the three groups is9.4%,24.7%,and 58.3%,respectively.Conclusion:Thyroid volume and D_50%could be reliable predictors of HT after IMRT for NPC.The combination of thyroid volume and thyroid D50%can better predict the risk of radioactive hypothyroidism.For patients with thyroid volume≤15cm³,D_50%≤52Gy might be a useful restricted dose to adopt during IMRT planning.