Radiation-induced Hypothyroidism Research Articles

Hypothyroidism in patients treated with radiotherapy for head and neck carcinoma: standardised long-term follow-up study.

Hypothyroidism is a common complication when radiotherapy is part of the treatment for head and neck tumours. This study aimed to show the incidence of hypothyroidism and possible risk factors in these patients. Factors related to the population, tumour, treatment and occurrence of hypothyroidism were analysed in 241 patients diagnosed with head and neck carcinoma. Approximately 53 per cent of patients were diagnosed with radiation-induced hypothyroidism. Its occurrence was related to: tumour location, laryngeal surgery type, neck dissection type, post-operative complications, cervical radiotherapy and radiotherapy unit type (linear particle accelerator or telecobalt therapy technology). Control of thyroid function should be standardised for several years after treatment, particularly in patients with risk factors, such as those treated with telecobalt therapy, those with post-operative complications and for whom the thyroid parenchyma is included in the irradiated area (laryngeal or pharyngeal location and bilateral cervical radiation).

A prospective study on hypopituitarism after radiotherapy in non pituitary brain tumors

Objective: Pituitary function and hypopituitarism have not been well evaluated in adult patients with non-pituitary brain cancer. Methods: Thirty-one (31) patients treated with primary or postoperative radiotherapy (RT) for various cancers in the brain region without pre-existing hypothalamic pituitary (HP) disorder from other causes were prospectively evaluated. Serum samples were obtained from the patients to determine levels of growth hormone (GH), thyroid-stimulating hormone (TSH), and free thyroxine (FT4). Serum samples were measured before treatment, 3 and 6 months after completion of radiation therapy (RT). The hypothalamus-pituitary axis (HPA) and dose volume histograms (DVH) of the patients were derived from their computed tomography-based treatment plans. Results: Clinical hypopituitarism was not observed, but 83% of patients who tested for hypopituitarism demonstrated subclinical hypopituitarism after a median interval of 6 months. Subclinical GH and TSH deficiency were observed in 17 (54%) and 9 (29%) participants, respectively. Significant declines in TSH (p Conclusion: Radiation-induced hypopituitarism and central hypothyroidism are regarded as primary damage to the pituitary gland. Time after therapy is critical and so with time the incidence of growth hormone deficiency and thyroid stimulating hormone deficiency is likely to significantly increase and to no longer be subclinical. Neuronal cell death and degeneration because of the direct effects of radiation seem to play basic roles.

Radiation-Induced Hypothyroidism in Squamous Cell Carcinoma of the Head and Neck: A Dose-Volume Histogram Analysis

Radiation-Induced Hypothyroidism in Squamous Cell Carcinoma of the Head and Neck: A Dose-Volume Histogram Analysis

External validation of a normal tissue complication probability model for radiation-induced hypothyroidism in an independent cohort

ABSTRACTBackground. A normal tissue complication probability (NTCP) model for radiation-induced hypothyroidism (RIHT) was previously derived in patients with squamous cell carcinoma of the head and neck (HNSCC) discerning thyroid volume (Vthyroid), mean thyroid dose (Dmean), and latency as predictive factors. The purpose of this study was to test the performance of this model in an independent cohort of patients receiving primary radiotherapy (RT) for HNSCC.Material and methods. A validation cohort of 198 patients with HNSCC was included after plasma thyrotropin (TSH) assessment. RIHT was defined as TSH > 4.0 mU/l from blood samples obtained during follow-up. A new mixture NTCP model was developed from the validation cohort after multivariable analysis. Due to only one follow-up TSH assessment in the validation cohort, the time factor derived from the original cohort was fixed in a mixture model and applied for the NTCP validation. Association between model predictions of the initial model and observed clinical outcome in the validation cohort was investigated by applying the previous model (Vthyroid, Dmean and time) on the new cohort and comparing it to the clinical outcome.Results. Both Dmean and Vthyroid were confirmed as significant risk factors for RIHT in the validation cohort, odds ratio (OR) 1.19 (1.1–1.37) and OR 0.75 (0.57–0.9), respectively. A small difference in overall probability of RIHT was observed between the cohorts, further analysis indicated this to be related to less frequent blood tests in the validation cohort relative to the original cohort. However, Pearson's correlation coefficients between model and clinical outcome were high: r = 0.97 estimated by the original model versus the original cohort, and r = 0.97 estimated by the original model versus the new cohort.Conclusion. Dmean and Vthyroid were significant predictors of RIHT in both cohorts. The original NTCP model demonstrated external validity owing to high Pearson's correlation coefficients between estimated and observed incidence rates of RIHT in the original as well as in the validation cohort. This model may facilitate clinically relevant estimations of RIHT after RT to the neck.

Variation of normal tissue complication probability (NTCP) estimates of radiation-induced hypothyroidism in relation to changes in delineation of the thyroid gland

Background. To examine the variations of risk-estimates of radiation-induced hypothyroidism (HT) from our previously developed normal tissue complication probability (NTCP) model in patients with head and neck squamous cell carcinoma (HNSCC) in relation to variability of delineation of the thyroid gland.Patients and methods. In a previous study for development of an NTCP model for HT, the thyroid gland was delineated in 246 treatment plans of patients with HNSCC. Fifty of these plans were randomly chosen for re-delineation for a study of the intra- and inter-observer variability of thyroid volume, Dmean and estimated risk of HT. Bland-Altman plots were used for assessment of the systematic (mean) and random [standard deviation (SD)] variability of the three parameters, and a method for displaying the spatial variation in delineation differences was developed.Results. Intra-observer variability resulted in a mean difference in thyroid volume and Dmean of 0.4 cm3 (SD ± 1.6) and -0.5 Gy (SD ± 1.0), respectively, and 0.3 cm3 (SD ± 1.8) and 0.0 Gy (SD ± 1.3) for inter-observer variability. The corresponding mean differences of NTCP values for radiation-induced HT due to intra- and inter-observer variations were insignificantly small, -0.4% (SD ± 6.0) and -0.7% (SD ± 4.8), respectively, but as the SDs show, for some patients the difference in estimated NTCP was large.Conclusion. For the entire study population, the variation in predicted risk of radiation-induced HT in head and neck cancer was small and our NTCP model was robust against observer variations in delineation of the thyroid gland. However, for the individual patient, there may be large differences in estimated risk which calls for precise delineation of the thyroid gland to obtain correct dose and NTCP estimates for optimized treatment planning in the individual patient.

A Dose-Effect Relationship and Estimated Parameters for the Lyman-Kutcher-Burman (LKB) Model of Normal Tissue Complication Probability (NTCP) for Radiation-Induced Hypothyroidism

Radiation-induced hypothyroidism is a known complication of radiation therapy to the head and neck region. However, the dose-volumetric threshold had not been definitively determined. With the advent of IMRT providing insight on fine-grained dose-volume information, we can now develop models that more accurately portray the physiology of the thyroid, in hope of improving previous models that were mostly based on data from the 3D-CRT era. This study attempts to use the Lyman-Kutcher-Burman (LKB) model to assess the relationship between the dose-volume histogram and radiation-induced hypothyroidism, and to estimate parameters of the model.

Radiation-Induced Hypothyroidism and Related Dosimetric Parameters in Breast Cancer Patients

To investigate the incidence of RT induced hypothyroidism based on the dose and volume characteristics in breast cancer patients who were treated with lymphatic irradiation in addition to chest wall or breast.

A Validation Study of Normal Tissue Complication Probability (NTCP) Models for Radiation-Induced Hypothyroidism (HT)

A Validation Study of Normal Tissue Complication Probability (NTCP) Models for Radiation-Induced Hypothyroidism (HT)

V30 as a predictor for radiation-induced hypothyroidism: a dosimetric analysis in patients who received radiotherapy to the neck

IntroductionThe purpose of this study is to evaluate the possible predictors of thyroid disorders after neck radiotherapy, with a focus on radiation dose-volume factors.MethodsThyroid function was measured in 100 patients who had received radiotherapy to the neck, including the thyroid. All radiation-induced thyroid dysfunctions were determined with an endpoint of abnormal thyroid stimulating hormone (TSH), free triiodothyronine (fT3) and thyroxine (fT4) and thyroid peroxidase antibodies and (TPA). The total volume of the thyroid, mean radiation dose to the thyroid (Dmean) and thyroid volume percentage that received radiation doses of 10–50 Gy (V10-V50) were calculated in all patients. The evaluated risk factors for thyroid dysfunction included dose-volume parameters, sex, age, previous surgery, chemotherapy and comorbidity.ResultsThere were 52 patients with hypothyroidism and V30 (p = 0.03), thyroid volume (p = 0.01) and Dmean (p = 0.03) appeared to be correlated with hypothyroidism in univariate analysis. However, there was not association found in multivariate analysis for these factors.ConclusionsThyroid disorders after radiation therapy to the neck still represent a clinically underestimated problem. V30 may be a useful tool for evaluating the risk of hypothyroidism when determining an individual patient’s treatment.

Volumetric modulated arc radiotherapy sparing the thyroid gland for early-stage glottic cancer: A dosimetrical analysis

Previous studies on advanced radiotherapy (RT) techniques for early stage glottic cancer have focused on sparing the carotid artery. However, the aim of the present study was to evaluate the dosimetric advantages of volumetric modulated arc therapy (VMAT) in terms of sparing the thyroid gland in early-stage glottic cancer patients. In total, 15 cT1N0M0 glottic cancer patients treated with definitive RT using VMAT were selected, and for dosimetric comparison, a conventional RT plan comprising opposed-lateral wedged fields was generated for each patient. The carotid artery, thyroid gland and spinal cord were considered organs at risk. The prescription dose was 63 Gy at 2.25 Gy per fraction. For the thyroid gland and carotid artery, all compared parameters were significantly lower with VMAT compared with conventional RT. For the thyroid gland, the median reduction rates of the mean dose (Dmean), the volume receiving ≥30% of the prescription dose (V30) and the V50 were 32.6, 40.9 and 46.0%, respectively. The Dmean was 14.7±2.6 Gy when using VMAT compared with 22.2±3.9 Gy when using conventional RT. The differences between the techniques in terms of planning target volume coverage and dose homogeneity were not significant. When considering a recent normal tissue complication probability model, which indicated the mean thyroid gland dose as the most significant predictor of radiation-induced hypothyroidism, the dosimetric advantage shown in this study may be valuable in reducing hypothyroidism following RT for early stage glottic cancer patients.

Dose-volumetric Parameters for Predicting Hypothyroidism after Radiotherapy for Head and Neck Cancer

To investigate predictors affecting the development of hypothyroidism after radiotherapy for head and neck cancer, focusing on radiation dose-volumetric parameters, and to determine the appropriate radiation dose-volumetric threshold of radiation-induced hypothyroidism. A total of 114 patients with head and neck cancer whose radiotherapy fields included the thyroid gland were analysed. The purpose of the radiotherapy was either definitive (n = 81) or post-operative (n = 33). Thyroid function was monitored before starting radiotherapy and after completion of radiotherapy at 1 month, 6 months, 1 year and 2 years. A diagnosis of hypothyroidism was based on a thyroid stimulating hormone value greater than the maximum value of laboratory range, regardless of symptoms. In all patients, dose volumetric parameters were analysed. Median follow-up duration was 25 months (range; 6-38). Forty-six percent of the patients were diagnosed as hypothyroidism after a median time of 8 months (range; 1-24). There were no significant differences in the distribution of age, gender, surgery, radiotherapy technique and chemotherapy between the euthyroid group and the hypothyroid group. In univariate analysis, the mean dose and V35-V50 results were significantly associated with hypothyroidism. The V45 is the only variable that independently contributes to the prediction of hypothyroidism in multivariate analysis and V45 of 50% was a threshold value. If V45 was <50%, the cumulative incidence of hypothyroidism at 1 year was 22.8%, whereas the incidence was 56.1% if V45 was ≥50% (P = 0.034). The V45 may predict risk of developing hypothyroidism after radiotherapy for head and neck cancer, and a V45 of 50% can be a useful dose-volumetric threshold of radiation-induced hypothyroidism.

Relationship of Gender and Smoking History in the Development of Hypothyroidism From Exposure to External Beam Radiation for Head and Neck Cancers.

BackgroundPatients with head and neck cancers (HNCs) are often treated with external beam radiation therapy (XRT). Unfortunately this therapy is not without its unintended consequences. One of these side effects includes the development of radiation-induced hypothyroidism. Our study is designed to pay special attention to variables like gender and smoking history and analyze their relationship with the development of hypothyroidism.MethodsPatients’ charts were reviewed over a period of 13 years from January 1, 2000 to November 30, 2013 to gather information on patients who had previously received XRTs for HNCs. We used the Tumor Registry Database at the University of Florida, College of Medicine in Jacksonville for this retrospective review. Patient characteristics were examined including age, gender, race/ethnicity and smoking history. Special attention was paid to the development of hypothyroidism (thyroid stimulating hormones > 5.0 with appropriate decrease in free serum T4) levels after exposure to XRT for HNCs. Results were then analyzed using the univariate statistical analysis which was done using the SAS software using a 0.05 alpha level of significance expressed in terms of odds ratio (OR) with 95% confidence intervals (CIs).ResultsWe found a total of 1,116 patients in our database who have received XRTs for HNCs. Out of these 72 (6.45%) patients developed hypothyroidism. Out of 263 African American patients 20 (7.6%) had hypothyroidism, whereas 49 (6%) out of 819 white people had this outcome. As for gender 32 out of 341 females (9.4%) and 40 out of 775 males had hypothyroidism. Thirty-five out of 544 (6.4%) with no family history and 19 (2.4%) out of 205 (9.3%) with positive family history for cancer had the outcome too. Finally 43 (6.5%) out of 664 smokers and 17 (8.3%) out of 206 non-smokers were found to develop hypothyroid as well. Both groups were found to have homogenous average age at diagnosis. When the univariate analysis was conducted, the strongest predicting variable was gender as hypothyroid patients were 1.90 (95% CI 1.17 - 3.09) times more likely to be females, and these results were statistically significant with P value of 0.008. More patients tended to be African Americans with OR 1.21 (CI 0.822 - 1.78), had positive family history of cancer (negative family history had OR 0.67 (CI 0.38 - 1.21), and less likely to be smokers (OR 0.77 (0.43 - 1.38). However, race, family history of cancer and smoking history did not achieve any statistical significance as evident by the P values.ConclusionIn our patient population, females were more likely to develop radiation-induced hypothyroidism.

Radiation-Induced Hypothyroidism in Squamous Cell Carcinoma of the Head and Neck: Comparison Between Concurrent Chemoradiation Therapy and Radiation Therapy Alone

Radiation-Induced Hypothyroidism in Squamous Cell Carcinoma of the Head and Neck: Comparison Between Concurrent Chemoradiation Therapy and Radiation Therapy Alone

Longitudinal study on the correlations of thyroid antibody and thyroid hormone levels after radiotherapy in patients with nasopharyngeal carcinoma with radiation‐induced hypothyroidism

The purpose of this study was to evaluate the correlations of thyroid antibody and thyroid hormone in postradiotherapy (post-RT) patients with nasopharyngeal carcinoma (NPC). Serum thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), thyroperoxidase antibody (anti-TPO), and thyroglobulin antibody (anti-TG) levels of 55 patients with NPC were taken before RT and at 3, 6, 12, and 18 months after RT. Patients with hypothyroidism at 18 months after RT and those with normal thyroid function were categorized into the hypo and normal groups, respectively. The thyroid antibody levels were compared between the 2 groups, and the correlations of thyroid antibody and thyroid hormone were evaluated for the hypo group. The anti-TPO and anti-TG of the hypo group were higher than the normal group. In the hypo group, there was a positive correlation (r = 0.51) between TSH and anti-TG and a negative correlation between fT4 and anti-TPO (r = -0.55). There were correlations of the thyroid antibody and thyroid hormone levels in patients with radiation-induced hypothyroidism.

Radiation-induced primary hypothyroidism in patients with head and neck cancer

Radiation-induced primary hypothyroidism in patients with head and neck cancer

PD-0189: Multivariate NTCP models for radiation-induced hypothyroidism

PD-0189: Multivariate NTCP models for radiation-induced hypothyroidism

PD-0451: IMRT increases the incidence of radiation-induced hypothyroidism in patients with nasopharyngeal carcinoma

PD-0451: IMRT increases the incidence of radiation-induced hypothyroidism in patients with nasopharyngeal carcinoma

Development of multivariate NTCP models for radiation-induced hypothyroidism: a comparative analysis

BackgroundHypothyroidism is a frequent late side effect of radiation therapy of the cervical region. Purpose of this work is to develop multivariate normal tissue complication probability (NTCP) models for radiation-induced hypothyroidism (RHT) and to compare them with already existing NTCP models for RHT.MethodsFifty-three patients treated with sequential chemo-radiotherapy for Hodgkin’s lymphoma (HL) were retrospectively reviewed for RHT events. Clinical information along with thyroid gland dose distribution parameters were collected and their correlation to RHT was analyzed by Spearman’s rank correlation coefficient (Rs). Multivariate logistic regression method using resampling methods (bootstrapping) was applied to select model order and parameters for NTCP modeling. Model performance was evaluated through the area under the receiver operating characteristic curve (AUC). Models were tested against external published data on RHT and compared with other published NTCP models.ResultsIf we express the thyroid volume exceeding X Gy as a percentage (Vx(%)), a two-variable NTCP model including V30(%) and gender resulted to be the optimal predictive model for RHT (Rs = 0.615, p < 0.001. AUC = 0.87). Conversely, if absolute thyroid volume exceeding X Gy (Vx(cc)) was analyzed, an NTCP model based on 3 variables including V30(cc), thyroid gland volume and gender was selected as the most predictive model (Rs = 0.630, p < 0.001. AUC = 0.85). The three-variable model performs better when tested on an external cohort characterized by large inter-individuals variation in thyroid volumes (AUC = 0.914, 95% CI 0.760–0.984). A comparable performance was found between our model and that proposed in the literature based on thyroid gland mean dose and volume (p = 0.264).ConclusionsThe absolute volume of thyroid gland exceeding 30 Gy in combination with thyroid gland volume and gender provide an NTCP model for RHT with improved prediction capability not only within our patient population but also in an external cohort.

A Prospective Cohort Study on Radiation-induced Hypothyroidism: Development of an NTCP Model

To establish a multivariate normal tissue complication probability (NTCP) model for radiation-induced hypothyroidism. The thyroid-stimulating hormone (TSH) level of 105 patients treated with (chemo-) radiation therapy for head-and-neck cancer was prospectively measured during a median follow-up of 2.5 years. Hypothyroidism was defined as elevated serum TSH with decreased or normal free thyroxin (T4). A multivariate logistic regression model with bootstrapping was used to determine the most important prognostic variables for radiation-induced hypothyroidism. Thirty-five patients (33%) developed primary hypothyroidism within 2 years after radiation therapy. An NTCP model based on 2 variables, including the mean thyroid gland dose and the thyroid gland volume, was most predictive for radiation-induced hypothyroidism. NTCP values increased with higher mean thyroid gland dose (odds ratio [OR]: 1.064/Gy) and decreased with higher thyroid gland volume (OR: 0.826/cm(3)). Model performance was good with an area under the curve (AUC) of 0.85. This is the first prospective study resulting in an NTCP model for radiation-induced hypothyroidism. The probability of hypothyroidism rises with increasing dose to the thyroid gland, whereas it reduces with increasing thyroid gland volume.

Normal Tissue Complication Probability Modeling of Radiation-Induced Hypothyroidism After Head-and-Neck Radiation Therapy

To determine the dose-response relationship of the thyroid for radiation-induced hypothyroidism in head-and-neck radiation therapy, according to 6 normal tissue complication probability models, and to find the best-fit parameters of the models. Sixty-five patients treated with primary or postoperative radiation therapy for various cancers in the head-and-neck region were prospectively evaluated. Patient serum samples (tri-iodothyronine, thyroxine, thyroid-stimulating hormone [TSH], free tri-iodothyronine, and free thyroxine) were measured before and at regular time intervals until 1 year after the completion of radiation therapy. Dose-volume histograms (DVHs) of the patients' thyroid gland were derived from their computed tomography (CT)-based treatment planning data. Hypothyroidism was defined as increased TSH (subclinical hypothyroidism) or increased TSH in combination with decreased free thyroxine and thyroxine (clinical hypothyroidism). Thyroid DVHs were converted to 2 Gy/fraction equivalent doses using the linear-quadratic formula with α/β = 3 Gy. The evaluated models included the following: Lyman with the DVH reduced to the equivalent uniform dose (EUD), known as LEUD; Logit-EUD; mean dose; relative seriality; individual critical volume; and population critical volume models. The parameters of the models were obtained by fitting the patients' data using a maximum likelihood analysis method. The goodness of fit of the models was determined by the 2-sample Kolmogorov-Smirnov test. Ranking of the models was made according to Akaike's information criterion. Twenty-nine patients (44.6%) experienced hypothyroidism. None of the models was rejected according to the evaluation of the goodness of fit. The mean dose model was ranked as the best model on the basis of its Akaike's information criterion value. The D(50) estimated from the models was approximately 44 Gy. The implemented normal tissue complication probability models showed a parallel architecture for the thyroid. The mean dose model can be used as the best model to describe the dose-response relationship for hypothyroidism complication.