The Role of Pretherapy Quantitative Imaging and Dosimetry in Radioiodine Therapy for Advanced Thyroid Cancer

Radioactive iodine is well established as a successful treatment for dif-ferentiated thyroid cancer (DTC), although around 15% of patients have local recurrence or develop distant metastases and may become refractory to radioactive iodine (RAI). A personalized approach to treat-ment, based on the absorbed radiation doses delivered and using treat-ments to enhance RAI uptake, has not yet been developed. Methods: We performed a multicenter clinical trial to investigate the role of selu-metinib, which modulates the expression of the sodium iodide sympor-ter, and hence iodine uptake, in the treatment of RAI-refractory DTC. The iodine uptake before and after selumetinib was quantified to assess the effect of selumetinib. The range of absorbed doses delivered to metastatic disease was calculated from pre-and posttherapy imaging, and the predictive accuracy of a theranostic approach to enable per-sonalized treatment planning was investigated. Results: Significant inter-and intrapatient variability was observed with respect to the uptake of RAI and the effect of selumetinib. The absorbed doses deliv-ered to metastatic lesions ranged from less than 1 Gy to 1,170 Gy. A strong positive correlation was found between the absorbed doses predicted from pretherapy imaging and those measured after therapy (r 5 0.93, P , 0.001). Conclusion: The variation in outcomes from RAI therapy of DTC may be explained, among other factors, by the range of absorbed doses delivered. The ability to assess the effect of treatments that modulate RAI uptake, and to estimate the absorbed doses at ther-apy, introduces the potential for patient stratification using a theranostic approach. Patient-specific absorbed dose planning might be the key to more successful treatment of advanced DTC.