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Title: Free Thyroid Transfer: A Novel Procedure to Prevent Radiation-induced Hypothyroidism

Abstract

Purpose: The incidence of hypothyroidism after radiation therapy for head and neck cancer (HNC) has been found to be ≤53%. Medical treatment of hypothyroidism can be costly and difficult to titrate. The aim of the present study was to assess the feasibility of free thyroid transfer as a strategy for the prevention of radiation-induced damage to the thyroid gland during radiation therapy for HNC. Methods and Materials: A prospective feasibility study was performed involving 10 patients with a new diagnosis of advanced HNC undergoing ablative surgery, radial forearm free-tissue transfer reconstruction, and postoperative adjuvant radiation therapy. During the neck dissection, hemithyroid dissection was completed with preservation of the thyroid arterial and venous supply for implantation into the donor forearm site. All patients underwent a diagnostic thyroid technetium scan 6 weeks and 12 months postoperatively to examine the functional integrity of the transferred thyroid tissue. Results: Free thyroid transfer was executed in 9 of the 10 recruited patients with advanced HNC. The postoperative technetium scans demonstrated strong uptake of technetium at the forearm donor site at 6 weeks and 12 months for all 9 of the transplanted patients. Conclusions: The thyroid gland can be transferred as a microvascular free transfer with maintenance of function. Thismore » technique could represent a novel strategy for maintenance of thyroid function after head and neck irradiation.« less

Authors:
 [1];  [1];  [2];  [1];  [3];  [4];  [1];  [5];  [1]
  1. Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Alberta, Edmonton, Alberta (Canada)
  2. (Saudi Arabia)
  3. Division of Radiation Oncology, Department of Oncology, University of Alberta, Edmonton, Alberta (Canada)
  4. Division of Endocrinology and Metabolism, Department of Medicine, University of Alberta, Edmonton, Alberta (Canada)
  5. Institute for Head and Neck and Thyroid Cancers, Icahn School of Medicine, Mount Sinai Hospital, New York, New York (United States)
Publication Date:
OSTI Identifier:
22648778
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 96; Journal Issue: 1; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; FEASIBILITY STUDIES; HYPOTHYROIDISM; NECK; PATIENTS; RADIOTHERAPY; TECHNETIUM; THYROID

Citation Formats

Harris, Jeffrey, Almarzouki, Hani, Department of Otolaryngology-Head and Neck Surgery, King Abdulaziz University, Jeddah, Barber, Brittany, E-mail: brittanybarber0@gmail.com, Scrimger, Rufus, Romney, Jacques, O'Connell, Daniel, Urken, Mark, and Seikaly, Hadi. Free Thyroid Transfer: A Novel Procedure to Prevent Radiation-induced Hypothyroidism. United States: N. p., 2016. Web. doi:10.1016/J.IJROBP.2016.04.004.
Harris, Jeffrey, Almarzouki, Hani, Department of Otolaryngology-Head and Neck Surgery, King Abdulaziz University, Jeddah, Barber, Brittany, E-mail: brittanybarber0@gmail.com, Scrimger, Rufus, Romney, Jacques, O'Connell, Daniel, Urken, Mark, & Seikaly, Hadi. Free Thyroid Transfer: A Novel Procedure to Prevent Radiation-induced Hypothyroidism. United States. doi:10.1016/J.IJROBP.2016.04.004.
Harris, Jeffrey, Almarzouki, Hani, Department of Otolaryngology-Head and Neck Surgery, King Abdulaziz University, Jeddah, Barber, Brittany, E-mail: brittanybarber0@gmail.com, Scrimger, Rufus, Romney, Jacques, O'Connell, Daniel, Urken, Mark, and Seikaly, Hadi. 2016. "Free Thyroid Transfer: A Novel Procedure to Prevent Radiation-induced Hypothyroidism". United States. doi:10.1016/J.IJROBP.2016.04.004.
@article{osti_22648778,
title = {Free Thyroid Transfer: A Novel Procedure to Prevent Radiation-induced Hypothyroidism},
author = {Harris, Jeffrey and Almarzouki, Hani and Department of Otolaryngology-Head and Neck Surgery, King Abdulaziz University, Jeddah and Barber, Brittany, E-mail: brittanybarber0@gmail.com and Scrimger, Rufus and Romney, Jacques and O'Connell, Daniel and Urken, Mark and Seikaly, Hadi},
abstractNote = {Purpose: The incidence of hypothyroidism after radiation therapy for head and neck cancer (HNC) has been found to be ≤53%. Medical treatment of hypothyroidism can be costly and difficult to titrate. The aim of the present study was to assess the feasibility of free thyroid transfer as a strategy for the prevention of radiation-induced damage to the thyroid gland during radiation therapy for HNC. Methods and Materials: A prospective feasibility study was performed involving 10 patients with a new diagnosis of advanced HNC undergoing ablative surgery, radial forearm free-tissue transfer reconstruction, and postoperative adjuvant radiation therapy. During the neck dissection, hemithyroid dissection was completed with preservation of the thyroid arterial and venous supply for implantation into the donor forearm site. All patients underwent a diagnostic thyroid technetium scan 6 weeks and 12 months postoperatively to examine the functional integrity of the transferred thyroid tissue. Results: Free thyroid transfer was executed in 9 of the 10 recruited patients with advanced HNC. The postoperative technetium scans demonstrated strong uptake of technetium at the forearm donor site at 6 weeks and 12 months for all 9 of the transplanted patients. Conclusions: The thyroid gland can be transferred as a microvascular free transfer with maintenance of function. This technique could represent a novel strategy for maintenance of thyroid function after head and neck irradiation.},
doi = {10.1016/J.IJROBP.2016.04.004},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 1,
volume = 96,
place = {United States},
year = 2016,
month = 9
}
  • Purpose: Hypothyroidism (HT) is a frequent late side effect of Hodgkin's lymphoma (HL) therapy. The purpose of this study is to determine dose-volume constraints that correlate with functional impairment of the thyroid gland in HL patients treated with three-dimensional radiotherapy. Methods and Materials: A total of 61 consecutive patients undergoing antiblastic chemotherapy and involved field radiation treatment (median dose, 32 Gy; range, 30-36 Gy) for HL were retrospectively considered. Their median age was 28 years (range, 14-70 years). Blood levels of thyroid-stimulating hormone (TSH), free triiodo-thyronine (FT3), free thyroxine (FT4), and thyroglobulin antibody (ATG) were recorded basally and at differentmore » times after the end of therapy. For the thyroid gland, normal tissue complication probability (NTCP), dosimetric parameters, and the percentage of thyroid volume exceeding 10, 20, and 30 Gy (V10, V20, and V30) were calculated in all patients. To evaluate clinical and dosimetric factors possibly associated with HT, univariate and multivariate logistic regression analyses were performed. Results: Eight of 61 (13.1%) patients had HT before treatment and were excluded from further evaluation. At a median follow-up of 32 months (range, 6-99 months), 41.5% (22/53) of patients developed HT after treatment. Univariate analyses showed that all dosimetric factors were associated with HT (p < 0.05). On multivariate analysis, the thyroid V30 value was the single independent predictor associated with HT (p = 0.001). This parameter divided the patients into low- vs. high-risk groups: if V30 was {<=} 62.5%, the risk of developing HT was 11.5%, and if V30 was >62.5%, the risk was 70.8% (p < 0.0001). A Cox regression curve stratified by two levels of V30 value was created (odds ratio, 12.6). Conclusions: The thyroid V30 predicts the risk of developing HT after sequential chemo-radiotherapy and defines a useful constraint to consider for more accurate HL treatment planning.« less
  • Purpose: 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. Methods and Materials: 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)-basedmore » 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 {alpha}/{beta} = 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. Results: 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{sub 50} estimated from the models was approximately 44 Gy. Conclusions: 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.« less
  • In an attempt to reduce the incidence of hypothyroidism following irradiation of the neck, we administered oral L-thyroxine in doses sufficient to suppress serum TSH to 20 patients receiving radiation therapy for Hodgkin's disease or other lymphomas. L-thyroxine was discontinued when radiation therapy was completed. Twenty similar patients who did not receive L-thyroxine during radiation therapy served as a control group. After a mean follow-up period of 33 months, seven patients (35%) in the L-thyroxine group developed elevation of serum TSH and were started on chronic L-thyroxine therapy. In the control group, after mean follow-up of 19 months, five patientsmore » (25%) developed elevation of TSH and were started on chronic L-thyroxine. We conclude that suppression of serum TSH during neck irradiation does not prevent subsequent thyroid dysfunction.« less
  • Purpose: To establish a multivariate normal tissue complication probability (NTCP) model for radiation-induced hypothyroidism. Methods and Materials: 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. Results: Thirty-five patients (33%) developed primary hypothyroidism within 2 years after radiation therapy. An NTCP model based on 2 variables, including the mean thyroidmore » 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{sup 3}). Model performance was good with an area under the curve (AUC) of 0.85. Conclusions: 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.« less
  • The risk of developing thyroid cancer and other thyroid neoplasms after radiation exposure is well known, but specific modifiers of the dose-response relationship are not. The authors have identified 4,296 subjects who received treatment before their sixteenth birthday with orthovoltage radiation for benign conditions in the head and neck area. Individual thyroid dose estimates were calculated for 3,843 subjects. Of the 2,634 subjects who have been found, 1,043 have developed thyroid nodules of all types, and 309 have developed thyroid cancer. The radiation dose-response relationship was consistent with a linear excess relative risk model for thyroid cancer and thyroid nodulesmore » within the range of observed doses. Women developed thyroid cancer and thyroid nodules at a higher rate, but the slopes of the dose-response curves were the same for men and women. Age at radiation exposure was a significant factor of the risk, with a lower age at exposure associated with a higher risk. To determine the effect of the wide publicity and the screening program, which began in 1974, the authors compared the dose-response relationship for cases diagnosed before and after 1974. The overall rates increased dramatically after 1974, but the estimates of the slopes of the dose-response curves were not statistically different. The slope of the dose-response curve for thyroid neoplasms appears to have reached a maximum 25-29 yr after radiation exposure, but the dose response continued to be elevated at the end of follow-up. These data are consistent with the tumorigenic effects of radiation lasting at least 40 yr.« less