The Use of 124-I-PET/CT Whole Body and Lesional Dosimetry in Differentiated Thyroid Cancer

Study Description:

Each study participant will undergo rhTSH and THW-aided 124IPET/ CT dosimetric evaluations and will be subsequently treated with THW-aided RAI activity based on dosimetric calculations enabling maximum safe dosage.

Objectives:

Primary objective: To compare the 124I -PET/CT lesional and whole body dosimetry in each individual patient with metastatic radioiodine (RAI)-avid thyroid cancer under preparation with rhTSH and THW.

Secondary objective: To evaluate the predicted by PET/CT lesional uptake with the early response to therapy.

Endpoints:

Primary Endpoint: The predicted radiation dose measured as rads per lesion compared per each measurable lesion between the dose calculated under rhTSH and under THW.

Secondary Endpoints: Area under the curve analyzing the association of dose per lesion measured in rads and objective response to treatment at 1, 2, 3, 4, 5 years landmarks.

• INCLUSION CRITERIA:
• Patients with established thyroid cancer diagnosis based on the pathology report reviewed at the National Institutes of Health, who:

• underwent total thyroidectomy plus or minus neck lymph node dissection as clinically indicated,
• are presenting with known per structural imaging (US neck, CT or MRI neck/chest/abdomen/pelvis) persistent/recurrent disease either locally advanced or presenting with distant metastases; or
• are presenting with suspected persistent/recurrent locoregional or distant metastases based on the high risk features such as advanced tumor per pathology report (tumor size >4 cm, exrathyroidal extension, higher risk pathology such as tall cell, columnar cell, poorly differentiated variant, follicular thyroid cancer with gross vascular invasion, positive margins after the surgery, bulky lymphadenopathy in the central and/or lateral neck), detectable/increasing baseline/suppressed thyroglobulin (Tg) level or detectable/increasing anti-Tg antibody titers if anti-Tg antibodies are present.
• are either RAI -naive or requiring repeated RAI therapy for locally advanced disease or distant metastases or underwent therapy with BRAF inhibitor (dabrafenib or vemurafenib*) or selumetinib** for at least 4 weeks that may re-induce RAI uptake.
• Underwent imaging with either a CT or MRI of the brain and spine with gadolinium contrast to screen for the brain/spine metastases.

• Age greater than or equal to 18 years of age.
• 24 hour urine iodine excretion of less than or equal to 150 micro grams/24 hour.

• BRAF inhibitors are recommended by 2021 NCCN guidelines as one of the management options for BRAF mutant tumors(13,14)

• Selumetinib has an FDA orphan drug designation for adjuvant treatment of metastatic thyroid cancer to re-induce RAI uptake

Exclusion criteria

-Patients with RAI-non avid disease documented by negative post-therapy whole body scans performed after previous RAI treatments and not subjected to re-differentiation therapy.

• Serious underlying medical conditions that restrict diagnostic testing or therapy such as renal failure, congestive cardiac failure or active coexisting non-thyroid carcinoma, severe depression which might be exacerbated by thyroid hormone withdrawal.
• Patients with spinal or brain metastases as they are at risk of TSH-stimulation induced swelling of metastatic lesions leading to potentially detrimental side effects. These patients will be evaluated per the standard of care protocol 77-DK-0096.

• Pregnant or lactating women per self report.
• Adults who are incapable of providing informed consent.