SELIMETRY: resensitising iodine refractory differentiated thyroid cancer to radioiodine


Session type:

Jon Wadsley1, Gemma Ainsworth2, Matthew Beasley3, Sarah Brown2, Amy Coulson2, Yong Du4, Kate Farnell5, Glenn Flux4, Kate Garcez6, Matthew Griffin7, Helen Howard2, Jennifer Marshall8, Laura Moss9, Kate Newbold4, Abigail Pascoe7, Jayne Swain2, Jan Taprogge4, Andrew Weaver10, Katie Wood11
1Sheffield Teaching Hospitals NHS Foundation Trust, 2University of Leeds, 3University Hospitals Bristol NHS Foundation Trust, 4Royal Marsden NHS Foundation Trust, 5Butterfly Thyroid Cancer Trust, 6The Christie NHS Foundation Trust, 7Nottingham University Hospitals NHS Trust, 8University Hospital Southampton NHS Foundation Trust, 9Velindre Cancer Centre, 10Oxford University Hospitals NHS Foundation Trust, 11Royal Surrey NHS Foundation Trust



Radioiodine refractory differentiated thyroid cancer (RRDTC) carries a poor prognosis. Multi-targeted kinase inhibitors (MKIs) can extend progression free survival (PFS) but are associated with significant toxicity. A pilot study demonstrated that a MEK inhibitor, Selumetinib, can reinstate iodine uptake in RRDTC, potentially making further radioiodine therapy of value. SELIMETRY aimed to replicate these findings, to investigate the degree of clinical benefit in terms of PFS and toxicity with this approach, and to investigate the accuracy of pre-therapy dosimetry.


Patients with RRDTC with evidence of progression by RECIST v1.1 criteria within the previous 12 months but no prior therapy for RRDTC were recruited to this multicentre, single arm phase 2 trial. Eligible patients were given Selumetinib 75mg bd for 4 weeks. Pre- and post- treatment [123I]NaI SPECT/CT scans were assessed centrally for evidence of sufficient increase in iodine uptake to warrant further [131I]NaI therapy. Those with sufficient uptake received 5.5GBq [131I]NaI and had post therapy SPECT/CT scans to allow dosimetric calculations. The primary endpoint was 12 month PFS in the iodine-uptake cohort. It was planned to recruit 60 patients. Assuming an iodine-uptake rate of 60% and a 10% drop out rate this would yield 38 patients in the iodine-uptake cohort.


Due to a lower than expected rate of conversion to iodine uptake, and to slow accrual, it was not considered feasible to recruit sufficient patients to meet the primary endpoint. 30 patients were recruited. 28 received at least one dose of Selumetinib. Nine went on to receive radioiodine therapy. In this group, PFS at 12 months was 62.82% (80% CI: 39.79, 81.54) and median PFS time was 12.13 months. Toxicity was greater than previously reported with Selumetinib. A high degree of correlation between predicted and delivered absorbed dose from post-Selumetinib [123I]NaI SPECT/CT and post [131I]NaI SPECT/CT was demonstrated.


Increased iodine uptake was seen in a proportion of patients following Selumetinib, albeit in fewer patients than previously observed. We have demonstrated that it is possible to predict the absorbed dose delivered at therapy from pre-therapy [123I]NaI imaging. 

Impact statement

This study introduces the potential for personalised treatment planning for molecular radiotherapy based on dosimetry.