Investigating National Solutions for Personalised Iodine-131 Radiation Exposure

Study Overview
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Brief Summary
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This is a single-arm non-interventional prospective observational study to perform quantitative I-131 imaging and patient-specific dosimetry for patients undergoing radioiodine treatment.

Detailed Description
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The hypothesis underlying this study is that treatment outcome in molecular radiotherapy is dependent on the absorbed doses delivered rather than on the radioactivity administered. For up to 50 patients, post treatment dosimetry will be performed to establish the range of absorbed doses and associated uncertainties delivered to thyroid remnants, residual disease, and healthy organs from an ablative administration of I-131 radioiodine. Imaging systems in participating centres will be characterised (system volume sensitivity, partial-volume effect and dead-time) and set up for quantitative imaging to allow for collation of data. Patients will be assigned to one of two dosimetry gamma camera scanning schedules. For scanning schedule 1 (Standard of Care) a single standard-of-care scan (SPECT/CT) will be acquired according to local protocol with regards to time post-radioiodine administration. A minimum of 20 patients will be assigned to scanning schedule 2 (Standard of Care + Additional Imaging), for which a standard-of-care scan and two to four additional SPECT scans will be acquired between 6 - 168 hours post-administration. SPECT imaging datasets will be reconstructed with attenuation and scatter corrections to allow quantitative dosimetry calculations. Time integrated activity will be derived from analysis of the quantitative SPECT data and combined with relevant dose factors to obtain absorbed dose estimates for each target tissue. The subset of patients with additional imaging will be used to establish the pharmacokinetic properties of radioiodine in each tissue type (biological retention half-life) to enable determination of time integrated activity in patients with a single standard-of-care scan. A minimum of 3 whole-body retention measurements will be performed per day during the patient's stay in hospital, approximately every 2-6 hours, according to local standard of care procedures. At each external measurement time point the quantified level of radioactivity in the whole body will be recorded. Patients will be followed-up at their standard-of-care clinic visits to assess the success of treatment as well as for short to mid-term toxicity. Results from standard of care biochemical, radiological and haematological assessments (TSH, thyroglobulin, anti-thyroglobulin antibodies, ultrasound, serum creatinine, haemoglobin, white cell count, neutrophil count and platelet count) will be recorded to assess response to treatment. Statistical analysis of the relationship between the absorbed doses and outcome data will be performed.

Official Title
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Investigating National Solutions for Personalised Iodine-131 Radiation Exposure - Measuring Absorbed Dose to Tumour and Organs at Risk Following Routine Iodine Ablation Therapy

Conditions
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Differentiated Thyroid Cancer

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Histologically proven DTC (pT1b - pT3, any N, any M) Total thyroidectomy performed WHO PS 0-2 (autonomous, self-caring) Exclusion Criteria: External radiotherapy in the last 6 weeks Systematic chemotherapy in the last 6 weeks Pregnancy or breast feeding

Ages Eligible for Study
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Minimum Age: 18 Years

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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Range of absorbed doses and associated uncertainties delivered to thyroid remnants, residual disease, metastatic disease and healthy organs. | To establish the range of absorbed doses and associated uncertainties delivered to thyroid remnants, residual disease, metastatic disease and healthy organs from an administration of I-131 radioiodine. | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with successful treatment. | Investigation into the relationship between quantitative uptake values and/or absorbed doses delivered and treatment success. Treatment success will be defined by a thyroglobulin level of less than 2.0 ng per millilitre at 6-9 months post treatment. | 9 months | 
| Threshold absorbed dose to the thyroid remnant for treatment success. | To establish a threshold absorbed dose to the thyroid remnant required for treatment success. The association between these absorbed doses and the therapy outcome will be investigated, using logistic regression modelling as appropriate, with absorbed dose as a continuous variable. The relationship between the absorbed doses delivered and treatment success will be analysed using ROC analysis to establish a threshold absorbed dose for treatment success. | 9 months | 
| Association of biomarkers with absorbed dose | The association between absorbed doses and biomarkers (routine clinical haematological and biochemistry measurements) will be investigated using univariate logistic regression modelling as appropriate, with haematological and biochemistry measurements as continuous variables. | 9 months | 
| Association of biomarkers with treatment success | The association between treatment success and biomarkers (routine clinical haematological and biochemistry measurements) will be investigated using univariate logistic regression modelling as appropriate with haematological and biochemistry measurements as continuous variables. Treatment success will be defined by a thyroglobulin level of less than 2.0 ng per millilitre at 6-9 months post treatment. | 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radioiodine Therapy, Radiation Dose, Dosimetry