Purpose/Objective(s): 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 tumour control. We applied radiobiological modeling to evaluate the dosimetric feasibility and benefit of dominant intra-prostatic lesion simultaneous in-field boosts (DIL-SIB) to GTVs defined using a novel molecular PET probe (18F-DCFPyL) directed against prostate specific membrane antigen (PSMA).

Materials/Methods: As part of a prospective clinical trial, IGPC-2, patients with clinically localized, biopsy-proven PCa underwent preoperative 18F-DCFPyL PET/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 that generated a biologically plausible volume (GTV comprised of contiguous voxels without gaps; range 23%SUVmax to 40%SUVmax). 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 (NCT01168479), PROFIT (NCT00304759), PACE (NCT01584258), and hypoFLAME (NCT02853110) protocols were compared.

Results: Comparative DIL-SIB plans for 6 men were generated from the pre-operative 18F-DCFPyL PET/CT. Median boost GTV volume was 1.015 cm³ (0.42 – 1.83 cm³). Two cases were high-risk by NCCN criteria, four were intermediate risk (all generated plans were to prostate only). In two patients with DIL-SIB volumes close to the rectal wall, minor compromise in the SIB-DIL boost dose was necessary to maintain trial specified organ at risk dose constraints. Dosimetric and radiobiologic comparison of the four fractionation schemes are presented in Table 1. Overall, DIL-SIB plans yielded higher uncomplicated tumor control probability (90-94%) compared to standard dose plans (83-85%).

Conclusion: PSMA PET provides a novel approach to define GTV volumes for SIB-DIL dose escalation. Work is ongoing to validate PSMA PET-delineated GTV volumes through correlation to co-registered post-prostatectomy digitized histopathology. Table 1. Dosimetric quantities for standard and PSMA PET-delineated boost for four fractionation schemes. *TCP(1-NTCP) is probability of uncomplicated tumor control.

	FLAME		PROFIT		PACE		HYPO-FLAME
Parameter	Standard	Boost	Standard	Boost	Standard	Boost	Standard	Boost
PTV Boost (Gy)
D95%	77.0	95.0	60.7	79.0	35.5	45.5	35.5	48.7
PTV Pros (Gy)
D95%	75.0	75.5	60.0	60.6	35.0	35.4	35.0	35.3
Rectum (Gy)
D1cc	77.1	79.4	62.7	66.4	35.9	37.9	35.9	38.1
TCP(1-NTCP)*	85.2	92.0	82.8	92.5	83.0	93.8	83.0	90.3