Purpose: Radiopharmaceutical therapy (RPT) in combination with external beam radiotherapy (EBRT) shows promise as a method to offer disease control and mitigate potential high-grade toxicities associated with re-treatment for patients with recurrent head and neck cancer. This work establishes a patient-specific dosimetry framework that uses radiobiological models to combine the dosimetry from RPT and EBRT and applies it to a first-of-a-kind clinical trial where patients are treated with a ¹³¹I-based RPT compound (CLR 131) and reduced fractionation EBRT.
Methods: Serial SPECT/CT patient scans performed at approximately 24-, 48-, 72-, and 168-hours post-injection of 15.6 mCi/m² CLR 131 were used as input to a GEANT4 based RPT dosimetry platform named RAPID. Phantom-based recovery coefficients were applied to physician delineated tumor volumes to account for partial volume effects. Separately, EBRT treatment plans were created using standard of care (SOC) clinical practices (prescribed doses of 60-66 Gy in 2 Gy fractions). For treatment, the total number of EBRT fractions delivered was reduced accordingly to achieve the SOC total dose when including the CLR 131 RPT mean absorbed dose to the PTV. Radiobiological models (BED, EUD, EQD2) were used to compare the two radiation modalities.
Results: The RPT mean absorbed dose to the PTV reduced EBRT treatments by 3-4 fractions. The RPT BED to the PTV was nearly equivalent to the absorbed dose yet the RPT EUD indicated dose heterogeneity in two patients. The EBRT EUD indicated the absorbed dose was largely homogeneous and the EBRT BED was greater than the EBRT absorbed dose.
Conclusion: RPT proffers a method to reduce the EBRT dose from current SOC treatments. Incorporating RPT dose during the optimization of EBRT plans could further reduce normal tissue toxicities. The framework employed here is extendible to other permutations of EBRT and RPT treatments.
Funding Support, Disclosures, and Conflict of Interest: This work is supported by NIH SPORE CA196513-01. BB and JG are co-founders of Voximetry, Inc., a nuclear medicine dosimetry company in Madison, WI.