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Advances in Radiation Oncology





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Purpose: Prostate cancer is multifocal. However, there often exists a single dominant focus in the gland responsible for driving the biology of the disease. Dose escalation to the dominant lesion is a proposed strategy to increase tumor control. We applied radiobiological modeling to evaluate the dosimetric feasibility and benefit of dominant intraprostatic lesion simultaneous in-field boosts (DIL-SIB) to the gross tumor volume (GTV), defined using a novel molecular positron emission tomography (PET) probe (18F-DCFPyL) directed against prostate specific membrane antigen (PSMA). Methods and Materials: Patients with clinically localized, biopsy-proven prostate cancer underwent preoperative [ F]-DCFPyL PET/computed tomography (CT). DIL-SIB plans were generated by importing the PET/CT into the RayStation treatment planning system. GTV-PET for the DIL-SIB was defined by the highest %SUVmax (percentage of maximum standardized uptake value) that generated a biologically plausible volume. Volumetric arc–based plans incorporating prostate plus DIL-SIB treatment were generated. Tumor control probability (TCP) and normal tissue complication probability (NTCP) with fractionation schemes and boost doses specified in the FLAME (Investigate the Benefit of a Focal Lesion Ablative Microboost in Prostate Cancer; NCT01168479), PROFIT (Prostate Fractionated Irradiation Trial; NCT00304759), PACE (Prostate Advances in Comparative Evidence; NCT01584258), and hypoFLAME (Hypofractionated Focal Lesion Ablative Microboost in prostatE Cancer 2.0; NCT02853110) protocols were compared. Results: Comparative DIL-SIB plans for 6 men were generated from preoperative [ F]-DCFPyL PET/CT. Median boost GTV volume was 1.015 cm (0.42-1.83 cm ). Median minimum (D99%) DIL-SIB dose for F35 , F20 , F5 , and F5 were 97.3 Gy, 80.8 Gy, 46.5 Gy, and 51.5Gy. TCP within the GTV ranged from 84% to 88% for the standard plan and 95% to 96% for the DIL-SIB plans. Within the rest of the prostate, TCP ranged from 89% to 91% for the standard plans and 90% to 92% for the DIL-SIB plans. NTCP for the rectum NTCP was similar for the DIL-SIB plans (0.3%-2.7%) compared with standard plans (0.7%-2.6%). Overall, DIL-SIB plans yielded higher uncomplicated TCP (NTCP, 90%-94%) versus standard plans (NTCP, 83%-85%). Conclusions: PSMA PET provides a novel approach to define GTV for SIB-DIL dose escalation. Work is ongoing to validate PSMA PET-delineated GTV through correlation to coregistered postprostatectomy digitized histopathology. 18 18 3 3 BS BS BS BSH