Combination Radiopharmaceutical Therapy and Radiotherapy for Thyroid Cancer: Dosimetry-Driven Precision Medicine

Radiopharmaceutical therapy (RPT) of patients with differentiated metastatic thyroid cancer has been standard treatment for more than 80 y. A high and uniform expression of the NaI symporter in malignant thyroid cells results in tumoricidal absorbed doses (ADs) delivered by the β-particle emissions of the radioactive iodine (¹³¹I). Treatment is less effective for patients whose disease exhibits reduced or variable expression of NaI symporter. Methods: We have investigated a treatment strategy that combines radioiodine with external-beam radiotherapy (EBRT) for patients with low ¹³¹I uptake. By combining the AD delivered by the RPT agent with that delivered by EBRT, we achieve the targeted tumoricidal AD (80 Gy 2-Gy equieffective dose) while maintaining safe normal-organ AD. A tracer administration of RPT is used to calculate a patient-specific administered activity (AA) for therapy that yields organ-at-risk ADs below toxicity thresholds. The tumor and relevant organ-at-risk ADs from the therapeutic administration are calculated and provided to the radiation oncology medical physicists for combination therapy planning. We illustrate this precision-medicine approach to treating thyroid cancer patients using data from the first 5 patients in our ongoing clinical trial. Results: A precision-medicine approach gave an AA ranging from 14.3 to 19.5 GBq. Combined RPT-EBRT therapy of the selected lesions yielded doses ranging from 73 to 147 Gy. Conclusion: We have demonstrated the feasibility of combined RPT-EBRT in thyroid cancer patients with reduced radioiodine uptake when a standard AA of 5.55 GBq (150 mCi) would have delivered a much lower AD to lesions, less likely to lead to a response. There is considerable patient variability in clearance kinetics. Clinical benefit assessment in adjusting AA on the basis of a precision methodology would require a multicenter trial.