Lesional dosimetry in 131I refractory metastatic differentiated thyroid cancer with BRAFp.V600E or RAS mutation treated with trametinib +/- dabrafenib followed by radioactive iodine
Abstract
Purpose: In the MERAIODE phase II prospective trial (NCT03244956), patients with radioactive iodine refractory metastatic differentiated thyroid cancer (DTC) were treated with trametinib +/- dabrafenib before the administration of 5.5 GBq of 131I. A post-therapeutic lesional dosimetry study was conducted to assess the correlation between lesion absorbed doses and tumour response.
Methods: Absorbed doses (AD) were calculated from four planar images acquired 1, 2, 3 and 4 days after 131I administration and normalized using a day-4 SPECT/CT. Lesional 131I activity was quantified on SPECT using a single calibration factor and a 50%SUVmax threshold segmentation. Lesion volumes were manually segmented on diagnostic CT scans acquired prior 131I and at 3, 6 and 9 months. Lesions were categorised using a 3D extrapolated RECIST 1.1 classification based on volumetric changes.
Results: Median AD was higher in BRAFp.V600E mutated lesions (n = 19; 393.5 Gy [20.4-2906.3]) than in RAS mutated lesions (n = 6; 35.3 Gy [6.9-76.0]; p = 0.0005). At 6 months, 58% of BRAFp.V600E mutated lesions showed partial/complete response with a higher median AD (896 Gy) than stable/progressive lesions (183 Gy; p = 0.006). Eighty per cent of lesions receiving an AD above 393 Gy were classified as responders, whereas all lesions receiving an AD above 478 Gy were classified as responders.
Conclusion: The median AD was significantly higher in the BRAFp.V600E mutated DTC lesions than in the RAS mutated DTC…
How strong is the evidence?
Evidence Hub reads this as a clinical trial, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 19 participants or records.
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