SELIMETRY—a multicentre I-131 dosimetry trial: a clinical perspective

Abstract

Treatment options for patients with thyroid cancer that is no longer sensitive to iodine therapy are limited. Those treatments which currently exist are associated with significant toxicity. The SELIMETRY trial (EudraCT No 2015-002269-47) aims to investigate the role of the MEK inhibitor Selumetinib in resensitizing advanced iodine refractory differentiated thyroid cancer to radioiodine therapy. Patients deemed to have sufficient iodine uptake in previously iodine refractory lesions after 4 weeks of Selumetinib therapy will be given an empirical activity of 5.5 GBq I-131, and response to therapy will be assessed. The trial presents an opportunity to investigate the dosimetric aspects of radioiodine therapy for advanced thyroid cancer. Patients will undergo serial I-123 single-photon emission CT (SPECT)/CT scans following Selumetinib therapy to determine whether there has been a change in the degree of iodine uptake to justify further I-131 therapy, and to allow dosimetric calculations to predict absorbed dose to target lesions following therapy. Patients receiving I-131 therapy will undergo a further series of post-therapy SPECT/CT scans to allow dosimetric calculations. We describe the challenges in setting up a multicentre trial in a relatively underinvestigated field, describing the work that has been carried out to calibrate and validate measurements to ensure that standardized image data are collected at each site. We hope that this trial will lead to individualization and optimization of therapy for patients with advanced thyroid cancer and that the ground work carried out in setting up a network of centres capable of standardized molecular radiotherapy dosimetry will lead to further clinical trials in this field.

Radiotheragnostics Paradigm for Radioactive Iodine (Iodide) Management of Differentiated Thyroid Cancer

“…While ESTRADA epitomizes RTGs, it is the most technically challenging method for guiding towards optimal RAI AA. It is available on a research basis in a very few facilities that have access to radiation physicists with the skill-set for either 123 I SPECT/CT [ 23 , 24 ] and/or 124 I PET/CT [ 17 , 19 ] dosimetry calculations. On the other hand, MTA could be more readily operationalized at any center that has a standard gamma-camera with high-energy collimator (a thyroid uptake probe is optional).…”

Clinical trials in molecular radiotherapy—Tribulations and Triumphs Report of the NCRI CTRad meeting held at the Lift Islington, 8 June 2018

“…Dr Jon Wadsley, Consultant Clinical Oncologist at Weston Park Hospital and the Clinical Lead for the North Trent Cancer Research Network, opened this session with a summary of the challenges in setting up the SELIMETRY trial. 12 The primary end point of this Phase 2 trial is to assess Selumetinib-enhanced radioiodine therapy in DTC patients that are refractory to radioiodine. Selumetinib is a MEK kinase inhibitor believed to allow re-expression of sodium iodide symporters and therefore allow the patient a further option of radioiodine treatment.…”

Factors Associated with Dose Determination of Radioactive Iodine Therapy for Differentiated Thyroid Cancer

“…Maxon et al considered the target absorbed dose to thyroid remnants as 300 Gy and to metastatic disease as 80 Gy [34]. To calculate the delivered dose to target tissue, serial imaging acquisition was performed for generating time-activity curve [35,36], and sometimes assumption of biologic half-life was also used [37]. To obtain activity of target tissue, the lesions should be visualized for several days on imaging.…”

“…Pretreatment I-124 positron emission tomography-computed tomography (PET/CT) scans shows excellent correlation with I-131 uptake during RAI treatment [36,38], and PET/ magnetic resonance (MR) imaging also shows similar results to those of PET/CT [39]. As I-124 is not easily available in many countries, SPECT/CT using I-123 or I-131 is also applied for lesion-based analysis [29,35,40].…”