TSH Suppression During Radiotherapy on Thyroid Site to Prevent Iatrogenic Hypothyroidism in Pediatric Cancer Patients (WIN-HYPO2021)

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Status and phase: Enrolling; Phase 3

Conditions: Hypothyroidism; Irradiation

Treatments: Drug: Levothyroxine

Study type: Interventional

Funder types: Other

Identifiers

NCT05316922

INT122/21

Details and patient eligibility

About

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.

Full description

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).

Enrollment: 68 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Any patient with medulloblastoma, Hodgkin/non-Hodgkin Lymphoma before radiotherapy (RT) planning including thyroid parenchyma without previous primary or secondary hypothyroidism;
2. Written informed consent prior to any study-specific analysis and/or data collection.

Exclusion criteria

1. Any patient with medulloblastoma, Hodgkin/non-Hodgkin Lymphoma after radiotherapy including thyroid parenchyma;
2. Not signed consent.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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68 participants in 2 patient groups

TSH suppression during irradiation

Experimental group

Description:

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.

Treatment:

Drug: Levothyroxine

Any TSH suppression during irradiation

No Intervention group

Description:

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.