Voxel-Level Dosimetry for Combined Iodine 131 Radiopharmaceutical Therapy and External Beam Radiation Therapy Treatment Paradigms for Head and Neck Cancer.

PURPOSE: Targeted radiopharmaceutical therapy (RPT) in combination with external beam radiation therapy (EBRT) shows promise as a method to increase tumor 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 combines Monte Carlo-based dosimetry from the 2 radiation modalities at the voxel level using deformable image registration (DIR) and radiobiological constructs for patients enrolled in a phase 1 clinical trial combining EBRT and RPT. METHODS AND MATERIALS: Serial single-photon emission computed tomography (SPECT)/computed tomography (CT) patient scans were performed at approximately 24, 48, 72, and 168 hours postinjection of 577.2 MBq/m2 (15.6 mCi/m2) CLR 131, an iodine 131-containing RPT agent. Using RayStation, clinical EBRT treatment plans were created with a treatment planning CT (TPCT). SPECT/CT images were deformably registered to the TPCT using the Elastix DIR module in 3D Slicer software and assessed by measuring mean activity concentrations and absorbed doses. Monte Carlo EBRT dosimetry was computed using EGSnrc. RPT dosimetry was conducted using RAPID, a GEANT4-based RPT dosimetry platform. Radiobiological metrics (biologically effective dose and equivalent dose in 2-Gy fractions) were used to combine the 2 radiation modalities. RESULTS: The DIR method provided good agreement for the activity concentrations and calculated absorbed dose in the tumor volumes for the SPECT/CT and TPCT images, with a maximum mean absorbed dose difference of -11.2%. Based on the RPT absorbed dose calculations, 2 to 4 EBRT fractions were removed from patient EBRT treatments. For the combined treatment, the absorbed dose to target volumes ranged from 57.14 to 75.02 Gy. When partial volume corrections were included, the mean equivalent dose in 2-Gy fractions to the planning target volume from EBRT + RPT differed -3.11% to 1.40% compared with EBRT alone. CONCLUSIONS: This work demonstrates the clinical feasibility of performing combined EBRT + RPT dosimetry on TPCT scans. Dosimetry guides treatment decisions for EBRT, and this work provides a bridge for the same paradigm to be implemented within the rapidly emerging clinical RPT space.

Prior injury accelerates subsequent wound closure in a mouse model of regeneration.

Tissue regeneration and scarless healing involves the complete replacement and functional restoration of damaged organs and tissues. In this study of the "scarless healing" MRL mouse model, we demonstrate that 2-mm diameter through-and-through holes made in the cartilaginous part of previously injured MRL mouse ears are closed more efficiently, and that the regenerative repair response is significantly accelerated compared with unprimed MRL and control "nonhealer" strains of mice. Accelerated healing was detected both locally and distally from the original site of injury indicating the involvement of systemic components such as circulating cell types or soluble factors. Histologically, we observed early differences during the wound repair process (before Day 4 post injury) with accelerated formation of blastema-like structures, epidermal downgrowths, and enhanced epithelium thickening in wound border zones in primed MRL mice versus unprimed MRL mice. Although the mechanism of tissue regeneration remains unclear, the results from this study justify the use of the MRL model for further experimentation directed toward the identification of proteins and cell types capable of stimulating scarless tissue regeneration.