Radiation-induced Hypothyroidism Research Articles

Analysis of correlative risk factors for radiation-induced hypothyroidism in head and neck tumors

ObjectiveThe aim of the study is to identify clinical and dosimetric factors that could predict the risk of radiation-induced hypothyroidism(RIHT) in head and neck cancer(HNC) patients following intensity-modulated radiotherapy(IMRT).MethodsA total of 103 HNC patients were included in our study. General clinical characteristic and dosimetric data of all recruited patients were analyzed, respectively. The univariate and multivariate logistic regression anlalysis were successively conducted to identify optimal predictors, which aim to construct the nomogram. And the joint prediction was performed.ResultsThe incidence of patients with HNC was 36.9% (38/103). Among the clinical factors, gender, N stage, chemotherapy, frequency of chemotherapy and surgery involving the thyroid were related to RIHT. Logistic regression analysis showed that thyroid volume, Dmean, VS45, VS50, VS60 and V30,60 were independent predictors of RIHT, which were also incorporated in the nomogram. An AUC of 0.937 (95%CI, 0.888–0.958) also was showed outstanding resolving ability of the nomogram. When the volume of the thyroid was greater than 10.6 cm3, the incidence of RIHT was 14.8%, and when the volume of the thyroid was equal to or smaller than 10.6 cm3, the incidence was 72.5%. The incidence rates of RIHT in the group with VS60≦8.4cm3 and VS60 > 8.4cm3 were 61.4% and 19.3%, respectively.ConclusionsThyroid volume and thyroid VS60 are independent predictors of RIHT in patients with HNC. Moreover, more attention should be paid to patients with thyroid volume ≤ 10.6cm3. Thyroid VS60 > 8.4cm3 may be a useful threshold for predicting the development of RIHT. The nomogram conducted by the research may become a potential and valuable tool that could individually predict the risk of RIHT for HNC patients.

Risk Factors Causing Hypothyroidism in Patients With Head and Neck Cancer After Radiotherapy Using SIB-VMAT.

We evaluated the incidence of radiation-induced hypothyroidism and its risk factors in patients with head and neck cancer who underwent radiotherapy using simultaneous integrated boost-volumetric-modulated arc therapy (SIB-VMAT). This retrospective study included 86 patients who received definitive radiotherapy using SIB-VMAT for head and neck cancer. The incidence of ≥ grade 2 hypothyroidism was evaluated. We also evaluated the relationships between hypothyroidism development and clinical factors and thyroid dose-volume parameters. During a median follow-up period of 17 months (range=3-65 months), 31 patients (36.0%, 31/86) developed grade 2 hypothyroidism requiring hormone replacement therapy. No patients experienced ≥ grade 3 hypothyroidism. The cumulative incidences of hypothyroidism at 1 and 2 years after radiation therapy were 24.5% and 38.7%, respectively, with a median onset time of 10.0 months (range=3.0-35.0 months). Thyroid volume (p=0.003), volume of the thyroid spared at 60 Gy (VS60; cut-off value, 5.16 ml; p=0.009), VS70 (cut-off value, 8.0 ml; p=0.007), VS60 equivalent dose in 2 Gy fraction (EQD2; cut-off value, 7.78 ml; p=0.001), and VS70EQD2 (cut-off value, 10.59 ml; p=0.008) were significantly associated with the development of radiation-induced hypothyroidism. Radiation-induced hypothyroidism is not rare in patients with head and neck cancer undergoing radiotherapy using SIB-VMAT. Radiation dose-volume parameters detected in this study may be useful indicators to prevent this complication.

A multivariable normal tissue complication probability model for predicting radiation-induced hypothyroidism in nasopharyngeal carcinoma patients in the modern radiotherapy era.

Radiation-induced hypothyroidism (RHT) is a common long-term complication for nasopharyngeal carcinoma (NPC) survivors. A model using clinical and dosimetric factors for predicting risk of RHT could suggest a proper dose-volume parameters for the treatment planning in an individual level. We aim to develop a multivariable normal tissue complication probability (NTCP) model for RHT in NPC patients after intensity-modulated radiotherapy or volumetric modulated arc therapy. The model was developed using retrospective clinical data and dose-volume data of the thyroid and pituitary gland based on a standard backward stepwise multivariable logistic regression analysis and was then internally validated using 10-fold cross-validation. The final NTCP model consisted of age, pretreatment thyroid-stimulating hormone and mean thyroid dose. The model performance was good with an area under the receiver operating characteristic curve of 0.749 on an internal (200 patients) and 0.812 on an external (25 patients) validation. The mean thyroid dose at ≤45Gy was suggested for treatment plan, owing to an RHT incidence of 2% versus 61% in the >45Gy group.

Radiomics and dosiomics for predicting radiation-induced hypothyroidism and guiding intensity-modulated radiotherapy

To guide individualized intensity-modulated radiotherapy (IMRT), we developed and prospectively validated a multiview radiomics risk model for predicting radiation-induced hypothyroidism in patients with nasopharyngeal carcinoma. And simulated radiotherapy plans with same dose-volume-histogram (DVH) but different dose distributions were redesigned to explore the clinical application of the multiview radiomics risk model. The radiomics and dosiomics were built based on selected radiomics and dosiomics features from planning computed tomography and dose distribution, respectively. The multiview radiomics risk model that integrated radiomics, dosiomics, DVH parameters, and clinical factors had better performance than traditional normal tissue complication probability models. And multiview radiomics risk model could identify differences of patient hypothyroidism-free survival that cannot be stratified by traditional models. Besides, two redesigned simulated plans further verified the clinical application and advantage of the multiview radiomics risk model. The multiview radiomics risk model was a promising method to predict radiation-induced hypothyroidism and guide individualized IMRT.

An Analytical Study to Determine Dose-Volume Threshold for Radiation Induced Hypothyroidism.

Objective: To determine radiation dose volume threshold in predicting the development of hypothyroidism in cancer patients following neck irradiation. Methods: This is a cross sectional follow up study for patients who had been previously irradiated, prior to enrolment in the study. We have done thyroid dose-volumetric analysis on 120 histologically proven cancer patients in the age group of 18-75 years who received neck irradiation as a part of their definitive or adjuvant radiotherapy with three-dimensional conformal or intensity-modulated radiotherapy technique (3D -CRT or IMRT) and completed at least six months post-radiotherapy. Primary tumor sites included carcinoma or lymphoma of the head and neck, breast, cervical, and upper thoracic esophagus, requiring neck irradiation. Results: The proportion of patients who tested positive for Radiation induced hypothyroidism (RIHT) was found to be 40%, with clinical hypothyroidism and subclinical hypothyroidism being 25.8% and 14.2%, respectively. Time to develop hypothyroidism peaks around two years. Mean thyroid gland dose (Dmean) >28 Gy, thyroid gland volume receiving 40 Gy dose (i.e. V40) >49% and age <50 years were found to be significant risk factors for the development of RIHT on binary logistic regression. RT dose >50 Gy and thyroid gland volume spared from 40 Gy (i.e. VS40) < 2.12cm3 were statistically significant predictors for RIHT on chi-square and (Receiver operating characteristic) ROC curve analysis respectively but not on regression analysis. Conclusion: Dose-volume threshold for the thyroid gland as Dmean <28 Gy and V40 <49% may prevent the development of RIHT.

Improved prediction of radiation-induced hypothyroidism in nasopharyngeal carcinoma using pre-treatment CT radiomics

When planning radiation therapy, late effects due to the treatment should be considered. One of the most common complications of head and neck radiation therapy is hypothyroidism. Although clinical and dosimetric data are routinely used to assess the risk of hypothyroidism after radiation, the outcome is still unsatisfactory. Medical imaging can provide additional information that improves the prediction of hypothyroidism. In this study, pre-treatment computed tomography (CT) radiomics features of the thyroid gland were combined with clinical and dosimetric data from 220 participants to predict the occurrence of hypothyroidism within 2 years after radiation therapy. The findings demonstrated that the addition of CT radiomics consistently and significantly improves upon conventional model, achieving the highest area under the receiver operating characteristic curve (AUCs) of 0.81 ± 0.06 with a random forest model. Hence, pre-treatment thyroid CT imaging provides useful information that have the potential to improve the ability to predict hypothyroidism after nasopharyngeal radiation therapy.

Development and Validation of CT-Based Dose-Volume-Radiomics Nomogram for Radiation Induced Hypothyroidism in Nasopharyngeal Carcinoma

Several studies reported hypothyroidism occurred in 40-50% of patients who were treated with neck irradiation. Post-radiation hypothyroidism impairs quality of life, increases the risk of cardiac complications, and requires lifelong thyroxine replacement in affected patients. At present, radiation dose-volume constraints of thyroid gland are used to predict thyroid function outcomes in patients with nasopharyngeal carcinoma (NPC). However, it is limited by (a) inferior predictive power, (b) a lack of analyzing individualized thyroid characteristics as a categoriad to predict radiation induced hypothyroidism (RIHT). In this study, we firstly developed and validated CT-based dose-volume-radiomics nomogram to predict RIHT in patients with NPC. A total of 451 NPC patients who underwent definitive radiotherapy were randomly assigned into the training (n = 338) and validation set (n = 113) in a 3:1 ratio. Dose-volume parameters, including the thyroid volume, mean dose (Dmean), percentage of the volume that received xGy of radiation (Vx), and the absolute volume that was spared from xGy of radiation (Vsx), were collected from radiotherapy planning databases. We defined primary hypothyroidism as an elevated TSH serum level (> 4.94 mIU/L) in combination with a normal or low serum FT4 level, regardless of symptoms. 1316 CT radiomic features were extracted and selected to construct the radiomics signature (RS). A CT-based nomogram was established by integrating clinical factors, dose-volume parameters and radiomics signature in training set and was tested in validation set. With a median follow-up period of 68 months, 301 (66.7%) patients developed RIHT. Compared with other dose-volume parameters including thyroid volume, V30, V50, Dmean, Vs45, Vs50, the thyroid volume spared from 60Gy (Vs60) had best power to predict RIHT. The radiomics signature constructed by 8 selected radiomic features showed better prognostic performance than Vs60 for predicting RIHT in training set (RIHT vs. Vs60, C-index: 0.69 vs. 0.58) and internal validation set (C-index: 0.65 vs. 0.55). Patients were stratified into high- and low-risk groups by median radiomic signature. Patients in high-risk group had higher rate of RIHT than patients in low-risk group (training set:61% vs.39%, P<0.05; validation set: 73% vs.32%, P<0.05). The nomogram established by integrating radiomics signature with Vs60 showed optimal prognostic performance with C-index of 0.71 in training, 0.66 in validation set. Calibration curves showed good agreement. CT-based dose-volume-radiomics nomogram provided an excellent prognostic tool for predict incidence rate of RITH in patients with NPC received definitive radiotherapy.

Correlation between Thyroid Radiation Dose and Thyroid Function after Adjuvant Hypofractionated Locoregional Radiotherapy in Breast Cancer Patients

Radiotherapy (RT) is used quite often among breast cancer patients, and because these patients now live longer than they used to, long-term treatment-related adverse effects, such as hypothyroidism, are becoming increasingly relevant. Radiation-induced hypothyroidism is a late side effect of radiation to the thyroid gland, which could develop months to years after radiotherapy. However, there is no sufficient data on hypothyroidism in patients with breast cancer who receive locoregional RT, which usually affects a portion of the thyroid gland. In this prospective study, we tried to correlate between the radiation dose received by the thyroid gland and the incidence of thyroid dysfunction in breast cancer patients treated with hypofractionated locoregional radiotherapy, as well as establishing potential planning objectives that could help in sparing the thyroid gland. Our study included 109 women who received 3-D conformal loco-regional breast radiotherapy, these patients had normal thyroid function prior to start of radiotherapy. Patients had follow-up thyroid function tests 6 months after finishing radiotherapy. Based on dose volume histograms (DVH), the percentages of the thyroid volume, and ipsilateral thyroid lobe, receiving 5, 10, 15, 20, 25, 30, 35, and 40 Gy (V5, V10, V15, V20, V25, V30, V35, and V40 respectively), in addition to the mean and maximum thyroid doses, were estimated. Follow-up assessment of thyroid function and statistical analysis unveiled incidence of radiotherapy induced hypothyroidism to be 8.3%. Possible risk factors included high maximum radiation dose and V40 to the thyroid gland and the ipsilateral thyroid lobe, as well as high mean dose and smaller volume of the ipsilateral thyroid lobe. The likelihood of hypothyroidism was significantly increased with V40 of >5% of the thyroid gland, and V40 of >11% of the ipsilateral thyroid lobe. Further study is recommended for larger populations and longer follow-up periods.

Development and validation of a machine learning model of radiation-induced hypothyroidism with clinical and dose–volume features

Background and purposeRadiation-induced hypothyroidism (RIHT) is a common but underestimated late effect in head and neck cancers. However, no consensus exists regarding risk prediction or dose constraints in RIHT. We aimed to develop a machine learning model for the accurate risk prediction of RIHT based on clinical and dose–volume features and to evaluate its performance internally and externally. Materials and methodsWe retrospectively searched two institutions for patients aged >20 years treated with definitive radiotherapy for nasopharyngeal or oropharyngeal cancer, and extracted their clinical information and dose–volume features. One was designated the developmental cohort, the other as the external validation cohort. We compared the performances of machine learning models with those of published normal tissue complication probability (NTCP) models. ResultsThe developmental and external validation cohorts consisted of 378 and 49 patients, respectively. The estimated cumulative incidence rates of grade ≥1 hypothyroidism were 53.5% and 61.3% in the developmental and external validation cohorts, respectively. Machine learning models outperformed traditional NTCP models by having lower Brier scores at every time point and a lower integrated Brier score, while demonstrating a comparable calibration index and mean area under the curve. Even simplified machine learning models using only thyroid features performed better than did traditional NTCP algorithms. The machine learning models showed consistent performance between folds. The performance in a previously unseen external validation cohort was comparable to that of the cross-validation. ConclusionsOur model outperformed traditional NTCP models, with additional capabilities of predicting the RIHT risk at individual time points. A simplified model using only thyroid dose–volume features still outperforms traditional NTCP models and can be incorporated into future treatment planning systems for biological optimization.

Risk factors of early thyroid dysfunction after definitive radiotherapy in nasopharyngeal carcinoma patients.

To explore the patterns and risk factors of early thyroid dysfunction in nasopharyngeal carcinoma (NPC) patients within 1 year after intensity-modulated radiation therapy (IMRT). Patients with NPC who received definitive IMRT between April 2016 and April 2020 were included. All patients had normal thyroid function before definitive IMRT. The chi-square test, Student's T-test, Mann-Whitney U test, Kaplan-Meier method, receiver operating characteristics curve, and Cox proportional hazard analysis were used for statistical analysis. A total of 132 NPC patients were identified. Of these patients, 56 (42.4%) had hypothyroidism and 17 (12.9%) had hyperthyroidism. The median time to hypothyroidism and hyperthyroidism was 9 months (range, 1-12 months) and 1 month (range, 1-6 months) after definitive IMRT, respectively. In patients with hypothyroidism, 41 (73.2%) had subclinical hypothyroidism and 15 (26.8%) had clinical hypothyroidism. In those with hyperthyroidism, 12 patients (70.6%) had subclinical hyperthyroidism, and five patients (29.4%) had clinical hyperthyroidism. Age, clinical stage, thyroid volume, and V45 were independent risk factors for early radiation-induced hypothyroidism within 1 year after IMRT. Patients aged <47 years, stage III/IV disease, or pre-irradiation thyroid volume < 14 cm3 had higher risks of developing hypothyroidism. Primary subclinical hypothyroidism was the most common subtype of early thyroid dysfunction in NPC patients within 1 year after IMRT. Age, clinical stage, thyroid volume, and V45 were independent risk factors for early radiation-induced hypothyroidism in NPC patients.

Radiation-Induced Hypothyroidism in Patients with Breast Cancer after Hypofractionated Radiotherapy: A Prospective Cohort Study

<h3>Purpose/Objective(s)</h3> To assess the incidence and risk factors of radiation-induced hypothyroidism (RHT) after adjuvant hypofractionated radiotherapy (RT) in patients with breast cancer, and identify the dose constraint for the thyroid gland. The trends of RHT over time were also evaluated to determine the optimal timing of screening for RHT in breast cancer patients treated with hypofractionated RT. <h3>Materials/Methods</h3> Consecutive eligible breast cancer patients who were treated with hypofractionated RT were prospectively evaluated. Thyroid function tests were performed before and at regular times following RT (every 3-4 months during the first two years, then every six months until five years). RHT was defined as twice elevated serum thyroid-stimulating hormone (TSH) with decreased or normal free thyroxin after RT. The patient, tumor, and treatment factors were evaluated for possible associations with the risk of RHT. The incidence of RHT was calculated from the end of RT using the Kaplan–Meier method, and the differences between groups were compared with the log-rank test. Multivariate analysis was performed using Cox logistic regression analysis. A multivariate Cox proportional hazards regression model with penalized spline (P-spline) was used to examine the relationship between thyroid mean dose (Dmean) and RHT. A two-sided test of P < 0.05 was considered statistically significant. <h3>Results</h3> A total of 500 patients treated between 2017 and 2020 were analyzed. All patients underwent chest wall/breast ± regional nodal irradiation with a prescription dose of 43.5Gy in 15 fractions. Among them, 369 (73.8%) patients received supraclavicular nodal radiation (SCRT). Eighty-two (16.4%) patients had elevated TSH before RT. At a median follow-up of 21.9 months, 131 (26.2%) patients developed RHT, and 59 (11.8%) patients received thyroid hormone-replacement therapy. The 2-year cumulative incidence of RHT was 26.0%. Patients with SCRT had a significantly increased 2-year cumulative incidence of RHT compared with patients without SCRT (31.5% and 11.4%, p<0.001). The median time to the onset of RHT was 9.3 months (range, 1.0-42.4) after RT. The peak incidence of RHT occurred around 6-12 months after RT. Multivariate analysis revealed that elevated baseline TSH and increased thyroid Dmean as a continuous variable were independent risk factors for developing RHT. After adjusted for baseline TSH, there was a nonlinear relationship between Dmean and the risk of RHT. Dmean > 21 Gy was identified as the threshold value for predicting RHT (HR=2.2, p<0.001). Dmean > 21 Gy compared with Dmean ≤ 21 Gy was associated with a significantly higher incidence of RHT at two years after RT (17.0% vs. 32.2%, P<0.001). <h3>Conclusion</h3> The incidence of RHT was high in breast cancer patients. Thyroid function test should be started no later than six months following RT. We recommend that the Dmean of the thyroid should be kept lower than 21Gy for hypofractionated RT.

Radiation-Induced Hypothyroidism in Patients With Breast Cancer After Hypofractionated Radiation Therapy: A Prospective Cohort Study

Our objective was to assess the incidence and risk factors of radiation-induced hypothyroidism (RHT) after adjuvant hypofractionated radiation therapy (RT) in patients with breast cancer. Eligible patients with breast cancer who were treated with hypofractionated RT were prospectively evaluated. Thyroid function tests were performed before and at regular times after RT. RHT was defined as twice elevated serum thyroid-stimulating hormone (TSH) with decreased or normal free thyroxin after RT. The patient, tumor, and treatment factors were evaluated for possible associations with the risk of RHT. Five hundred patients were analyzed. All patients underwent chest wall/breast with or without regional nodal irradiation. Among them, 369 (73.8%) patients received supraclavicular nodal radiation (SCRT). Eighty-two (16.4%) patients had elevated TSH before RT. At a median follow-up of 21.9 months, 131 (26.2%) patients developed RHT, and 59 (11.8%) patients received thyroid hormone-replacement therapy. Patients with SCRT had a significantly increased 2-year cumulative incidence of RHT compared with patients without SCRT (31.5% and 11.4%, P<.001). The peak incidence of RHT occurred around 6 to 12 months after RT. Multivariate analysis revealed that elevated baseline TSH and increased thyroid mean dose (Dmean) were independent risk factors for developing RHT. After adjusted for baseline TSH, there was a nonlinear relationship between thyroid Dmean and the risk of RHT. Dmean >21 Gy was the threshold value for predicting RHT (hazard ratio, 2.2; P<.001). The incidence of RHT was high in patients with breast cancer. Thyroid function test should be started no later than 6 months after RT. We recommend that the Dmean of the thyroid should be kept lower than 21 Gy for hypofractionated RT.

Early post-treatment 18F-FDG PET/CT for predicting radiation-induced hypothyroidism in head and neck cancer

BackgroundRadiation-induced hypothyroidism (RIHT) is a common, but underestimated, late adverse effect in head and neck cancer. We investigated the value of early post-treatment 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for predicting RIHT.MethodsWe searched our institutional database for patients aged ≥ 20 years who had undergone definitive radiotherapy for nasopharyngeal or oropharyngeal cancer between 2005 and 2017, followed by 18F-FDG PET/CT within 180 days of radiotherapy completion. We visually assessed and compared PET/CT and baseline characteristics in patients with and without RIHT using the chi-square test for categorical variables and the t-test for continuous variables. Variable predictive ability was evaluated by measuring the area under receiver operating characteristic curves.ResultsFifty-two patients were included; 22 (42%) developed RIHT and 30 (58%) did not. Two patients presented with diffuse thyroid uptake on PET/CT via visual assessment, and both developed RIHT later. Among the PET/CT variables, thyroid functioning volume was significantly higher in patients without RIHT than in patients with RIHT (16.30 ± 6.03 cm3 vs. 10.61 ± 3.81 cm3, p < 0.001). The maximum standard uptake values of the thyroid and pituitary glands did not differ significantly between the groups. Two patient characteristics, pretreatment thyroid volume and mean radiotherapy dose to the thyroid, also showed significant differences between the groups. An algorithmic approach combining visual grading of thyroid 18F-FDG uptake and thyroid functioning volume cutoff of 14.01 yielded an area under curve of 0.89 (95% confidence interval, 0.80–0.98); the sensitivity, specificity, positive predictive value, and negative predictive value were 87.0%, 82.3%, 80.0%, and 88.9%, respectively.ConclusionEarly post-treatment PET/CT-derived thyroid functioning volume was a good predictor of RIHT development. Diffusely increased thyroid 18F-FDG uptake on PET/CT may indicate impending RIHT. Routine surveillance of thyroid function is warranted in patients at high risk of developing RIHT.

Thyroid function following radiation therapy in breast cancer patients: risk of radiation-induced hypothyroidism.

BackgroundRadiation exposure to the thyroid gland seems unavoidable in breast cancer (BC) patients receiving radiation therapy (RT) to the supraclavicular (SC) region. Hence, this study aimed to evaluate the effects of SC region RT on thyroid function and the prevalence of radiation-induced hypothyroidism (RIHT) in BC patients at regular intervals post-treatment.Materials and methodsTwenty-one patients with BC were enrolled in this analytical cross-sectional study by simple and convenient sampling, from March 2019 to March 2020. Thyroid function and the prevalence of RIHT were evaluated and compared by measuring the serum of thyroid-stimulating hormone (TSH) and free thyroxine hormone (fT4) levels before radiation therapy (pre-RT) and 3 and 6 months after radiation therapy (post-RT). The patients underwent 3 dimensional conformal. radiation therapy (3D CRT) of breast/chest wall, axillary, and supraclavicular lymph nodes with 50 Gy/25 fractions/5 weeks. The collected data were analyzed using SPSS software (version 20).ResultsSerum levels of TSH increased at 3 and 6 months post-RT, this increase was not statistically significant (p > 0.05). Nevertheless, serum levels of fT4 were significantly elevated at 3 and 6 months post-RT (p < 0.01). A correlation was observed between the follow-up period and the incidence of RIHT, where it was 0% at 3 months and 9.5% at 6 months post-RT. RIHT was not significantly associated with any factors, including patient’s age, type of surgery, thyroid gland dose, and thyroid gland volume.ConclusionsIt seems that SC region RT does not have a significant adverse effect on the thyroid function among BC patients at 3 and 6 months post-treatment. Hence, a long-term follow-up with a larger sample size is suggested.

Evaluation of the Radiobiological Models Predicting the Radiation-Induced Hypothyroidism in the Partially Irradiated Thyroid Gland of Patients with Breast Cancer

Background: Radiation-induced hypothyroidism (RHT) is one of the side effects that might have an impact on the quality of life of patients with breast cancer treated with radiotherapy. Objectives: The aim of the current study was to evaluate the performances of the Lyman-Kutcher-Burman (LKB) and Log-Logistic models in the prediction of hypothyroidism (HT) as well as the estimation of the model parameters for the incidence of RHT among patients with breast cancer. Methods: Fifty-two patients treated with radiation therapy (RT) for breast cancer were prospectively evaluated. Patients' serum samples [tri-iodothyronine, thyroxine, thyroid-stimulating hormone (TSH), free triiodothyronine, and free thyroxine] were measured before RT and also at a regular time interval until 1 year after the completion of RT. For each patient, dose-volume histograms (DVHs) of the thyroid gland were derived from their treatment planning dataset. Patients whose TSH levels were higher than normal with a decrease in FT4 levels were considered as cases with RHT. The LKB and Log-Logistic radiobiological models were evaluated by comparing them with the resultant follow-up data. The parameters for radiobiological models have been deduced by fitting the models to the follow-up data. The models were fitted in a Bayesian setting and compared according to the widely applicable information criterion (WAIC). Results: Twenty-one (40%) patients developed RHT at a follow-up of 1 year after the end of radiation treatment. The fitted values of D50 for the LKB and Log-Logistic models were 37.71 and 25.50 Gy, respectively for the partially irradiated thyroid of patients with breast cancer. The mean time to the incidence of RHT was obtained at 6.7 months in the studied group. Conclusions: A volumetric effect was found for the thyroid gland in the implemented normal tissue complication probability models. Compared to the follow-up data, the Log-Logistic model was ranked as the best model for predicting the rate of RHT in patients with breast cancer.

RONC-10. Radiation-induced hypothyroidism in pediatric brain tumour survivors: radiation dose-volume predictors of its onset

Abstract BACKGROUND: Central hypothyroidism is a well-known late effect of radiotherapy in children treated for brain tumours. AIM: To determine the risk of central hypothyroidism (CH) and the radiation dose-volume predictors of its onset. METHODS: We retrospectively analyzed 64 patients who received radiotherapy for brain tumours, with at least a 2-year-long serological follow-up, determined CH incidence and radiation predictive factors of its onset. To estimate the risk of CH according to the site of the tumour inside the central nervous system (CNS) we considered the sellar-suprasellar region, anterior cranial region, and others. For the same purpose, a further analysis was conducted comparing craniospinal radiotherapy (CSI) versus involved-field radiotherapy (IF-RT). Dose constraints for CH were determined using the Receiver Operating Characteristic to identify the pituitary mean dose cut-off and the probability of CH over time was assessed with the Cox model. RESULTS: 18 cases were excluded due to the presence of CH before RT; 17 of remaining 46 (37%) patients presented CH during follow-up: 14 of 17 (82%) patients received CSI, 3 (18%) IF-RT sellar-suprasellar region and anterior cranial region. A median dose higher than 30.5 Gy to the pituitary gland results in a 4-fold increased risk of central hypothyroidism (HR=3.9; 95% CI 1.1, 13.4; p=0.03). Almost 90% of events occurred within 5 years after treatment ended. 29 of 46 (63%) patients did not manifest CH and were in the "other regions”. However, 14 of these (48%) underwent CSI. CONCLUSIONS: Our data confirm the relationship between central hypothyroidism and mean pituitary radiation dose, and suggest a minimum of 5 years follow up in children brain tumor survivors. Tumours outside the sellar-suprasellar region, treated with radiotherapy, are not associated with CH onset. A significant association between CSI and risk of CH, highlighted with our analysis, warrants further investigations and a longer follow up

Incidence of radiation-induced hypothyroidism following head and neck irradiation: a single-center analysis.

BackgroundThe purpose of this study was to investigate the incidence of primary hypothyroidism (HT), as well as any correlation between dosimetric parameters and thyroid dysfunctions after neck radiotherapy (RT) in head and neck cancer (HNC) patients.Materials and methodsThis study retrospectively reviewed HNC patients who finished neck RT for at least 12 months and who had available back-up treatment information. Eligible patients further received a single thyroid function test (TFT). Dosimetric parameters of the thyroid glands were retrospectively evaluated in order to detect any correlation between dose-volume parameters and primary HT.ResultsWe reviewed 1,102 HNC patients. Accordingly, 64 patients were deemed eligible and were included in this study. The median time interval between RT completion and TFT was 21 months (interquartile range, 14–34 months), while 26 patients (40.6%) were diagnosed with HT. The thyroid volume spared from a dose of 50 Gy (VS50Gy) was found to be statistically significant and considered an associated factor for developing HT (p = 0.047). Furthermore, there was an observable trend indicating a reduction in the risk of HT when VS50Gy was more than 5 cm3 (p = 0.052).ConclusionIn our study, VS50Gy was determined to be a significant predictive parameter of radiation-induced HT.

Predictors of radiation-induced hypothyroidism in nasopharyngeal carcinoma survivors after intensity-modulated radiotherapy

BackgroundThe aim of the study is to identify clinical and dosimetric factors that could predict the risk of hypothyroidism in nasopharyngeal carcinoma (NPC) patients following intensity-modulated radiotherapy (IMRT).MethodsA total of 404 non-metastatic NPC patients were included in our study. All patients were treated with IMRT. The thyroid function were performed for all patients before and after radiation at regular intervals. The time onset for developing hypothyroidism was defined as the time interval between the completion of RT and the first recorded abnormal thyroid hormone test. The cumulative incidence rates of hypothyroidism were estimated using Kaplan–Meier method. Univariate and multivariate Cox regression analyses were performed to detect the most promising factors that were associated with hypothyroidism.ResultsMedian follow up was 60.6 months. The 3-, 5- and 7- year cumulative incidence rate of hypothyroidism was 39.4%, 49.1% and 54.7%, respectively. The median time to primary hypothyroidism and central hypothyroidism were 15.4 months (range 2.9–83.8 months) and 29.9 months (range 19.8–93.6 months), respectively. Univariate and multivariate analyses revealed that younger age, female gender and small thyroid volume were the most important factors in predicting the risk of hypothyroidism. Dtmean (mean dose of thyroid), V30-V50 (percentage of thyroid volume receiving a certain dose level) and VS45-VS60 (the absolute volumes of thyroid spared from various dose levels) remained statistically significant in multivariate analyses. Cutoff points of 45 Gy (Dtmean), 80% (Vt40) and 5 cm3 (VS45Gy) were identified to classify patients as high-risk or low-risk group.ConclusionThyroid Vt40 highly predicted the risk of hypothyroidism after IMRT for NPC patients. We recommended plan optimization objectives to reduce thyroid Vt40 to 80%.Trial registration: Retrospectively registered.

Association between Cervical Lymph Node Metastasis and the Incidence of Radiation-Induced Hypothyroidism in Nasopharyngeal Carcinoma.

Background It is controversial and unclear how N-stage would increase the risk of incidence of hypothyroidism (HT) for patients with nasopharyngeal carcinoma (NPC) after radiotherapy. Our study aimed to explore the correlation between cervical lymph node metastasis and the incidence of HT in NPC. Materials and Methods A total of 206 patients with NPC treated at the Cancer Hospital of University of Chinese Academy of Sciences, and their clinical information were retrospectively collected. A series of univariate logistic regression models were performed to explore the association of clinical and lymph node indices with the development of HT. Significant features in univariate analysis were then used to construct three prediction models, for HT prediction using multivariate logistic regression based on Bayesian information criterion. Prediction performance of those models was measured by area under the receiver operating characteristic curve (AUC) using 10-fold cross-validation. Results A total of 111 patients developed HT, and the incidence of HT in N2–3 and N0–1 patients was 58.82% and 44.29%, respectively. Compared to Model 1 (consisted of pretreatment TSH concentration, thyroid volume, and N-stage) whose AUCs were 0.801 and 0.766 in training and validation sets, with N-stage be replaced by shortest distance from thyroid, Model 2 achieved more stable AUCs of 0.824 and 0.801. While with numbers of positive lymph nodes in Level IIb additionally added, Model 3 improved its AUCs to 0.841 and 0.813. Conclusion The shortest distance between the lymph nodes and thyroid gland and the number of lymph nodes in IIb are better predictors of radiation-induced HT than the N-stage.

Dysphagia, hypothyroidism, and osteoradionecrosis after radiation therapy for head and neck cancer.

ObjectivesTo analyze the long‐term side effects of radiation therapy (RT) for head and neck cancer (HNC).MethodsRetrospective chart analysis of all 688 HNC patients treated during 2010–2015 at Turku University Hospital, Finland. All patients who survived for more than a year after RT/chemoRT were included (n = 233). Intensity modulated RT (IMRT) with standard fractionation was applied in each case.ResultsOne hundred and six patients (45%) reported persisting dysphagia, for which neck RT increased risk. Definitive neck RT to high‐risk volume did not increase late toxicity risks compared to elective neck RT. Radiation‐induced hypothyroidism (29%, n = 67) was more common among younger patients and females. Osteoradionecrosis (12%, n = 29) was more common in the oral cavity cancer group (20.7%, n = 92) compared to all other subsites.ConclusionsLate toxicities of RT for HNC are common. Age, gender, tumor subsite, and neck RT affect susceptibility to long‐term side effects.Level of evidence4.