TSH Suppression During Radiotherapy on Thyroid Site to Prevent Iatrogenic Hypothyroidism in Pediatric Cancer Patients

Study Overview
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Brief Summary
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To offer the possibility of a treatment that could achieve a meaningful reduction in the incidence of post-radiation therapy hypothyroidism. Thyroid dysfunction may develop from a few months to several years after patients have completed their radiation treatment. In children with chronic diseases, or given lengthy anti-neoplastic treatments, recurrent or persistent endocrine disorders may have a negative effect on growth and development into adulthood.

Detailed Description
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Patients will undergo basal thyroid ultrasound and FT3, FT4, TSH assay. Simulations with computed tomography, and computer assisted three-dimensional treatment planning with a dose volume histogram will be used to identify thyroid volumes and corresponding RT isodose distributions. The enrolled patients will be randomly assigned (1:1) to TSH suppression group (experimental group) or non-TSH suppression group (control group). Random allocation will be managed centrally by Clinical epidemiology and Trial organization of the Fondazione IRCCS Istituto Nazionale dei Tumori. The randomization list will be generated by SAS software. Investigators and patients will not be masked to treatment allocation. From 14 days beforehand and throughout their RT, patients in the experimental arm will receive L-thyroxine in the morning on an empty stomach (half an hour before breakfast), starting with 1-2 μg/kg, and adjusting the dose every 3 days to ensure TSH < 0.3 μIU/mL before RT beginning. The 0.3 μIU/mL threshold is just below normal range not causing hyperthyroidism, and is defined as mild TSH suppression. Based on hormone status, L-thyroxine doses will be gradually increased to patients' individual minimum TSH-suppressive dose before starting RT, maintained throughout the treatment, then rapidly tapered off (half dose the next day after RT, 25% the following day and stop).

Official Title
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Protection From Iatrogenic Hypothyroidism Patients With MBL and Pediatric Patients With HL and Non-HL Needing Radiotherapy on Thyroid Site

Conditions
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Hypothyroidism; Irradiation

Intervention / Treatment
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* Drug: Levothyroxine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any patient with medulloblastoma, Hodgkin/non-Hodgkin Lymphoma before radiotherapy (RT) planning including thyroid parenchyma without previous primary or secondary hypothyroidism; Written informed consent prior to any study-specific analysis and/or data collection. Exclusion Criteria: Any patient with medulloblastoma, Hodgkin/non-Hodgkin Lymphoma after radiotherapy including thyroid parenchyma; Not signed consent.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective, non-blinded, randomised two cohorts study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TSH suppression during irradiation<br>From 14 days beforehand and throughout their RT, patients in the experimental arm will receive L-thyroxine in the morning, starting with 1-2 μg/kg, and adjusting the dose every 3 days to ensure TSH < 0.3 μIU/mL before RT beginning. The 0.3 μIU/mL threshold is just below normal range not causing hyperthyroidism, and is defined as mild TSH suppression. Based on hormone status, L-thyroxine doses will be gradually increased to patients' individual minimum TSH-suppressive dose before starting RT, maintained throughout the treatment, then rapidly tapered off and stopped. During radiation treatment course will be checked twice a week for serum FT3, FT4, TSH assays in order to maintain TSH < 0.3 μIU/mL, possibly without exceeding normal levels of FT3 and FT4. Once a week patients will also have a full visit and any other blood examination according to protocol in use and Institutional practice. | Drug: Levothyroxine<br>* Levothyroxine is used to treat hypothyroidism (low thyroid function). This medicine is given when your thyroid does not produce enough of this hormone on its own.<br>* Other names: Thyroid drugs;|
| No Intervention: Any TSH suppression during irradiation<br>Patient in the standard arm will perform radiotherapy treatment without any TSH suppression. At the end of radiation they will do serum FT3, FT4, TSH assay and then, after one year from RT, thyroid ultrasound + serum FT3, FT4, TSH assay. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hypothyroidism-free survival | Hypothyroidism-free survival at 3 years after radiotherapy including part or the whole thyroid parenchyma on the intention-to-treat population will be the main end-point. | 3 years |