Radioactive
iodine is well established as a successful treatment for differentiated
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 treatment, based on the absorbed radiation doses delivered and using treatments to enhance RAI uptake, has not yet been developed. Methods: We performed a multicenter clinical trial to investigate the role of
selumetinib, which modulates the expression of the
sodium iodide symporter, 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 personalized 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 delivered 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 = 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
therapy, 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.