3348 - Early Detection of Prostate Cancer Immune Response to Radiation and Androgen Deprivation Therapy: Unleashing the Power of HRS Mpmri Imaging, Molecular Biomarkers and Digital Pathology

12:45pm - 02:00pm PT

Hall F

Screen: 25

Presenter(s)

Benjamin Spieler, MD - Department of Radiation Oncology, Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL

S. M. Gaston¹, R. Stoyanova², O. N. Kryvenko³, M. C. Abramowitz¹, A. L. Breto², E. J. Hernandez³, V. T. Clonch³, C. P. Anderson³, A. Galvez³, A. Bartley³, L. Salcedo³, J. Saltz⁴, Y. Zhang⁴, R. Gupta⁴, T. Kurc⁴, B. A. Mahal¹, A. Dal Pra¹, I. B. Mihaylov¹, A. Pollack¹, and B. Spieler¹; ¹Department of Radiation Oncology, University of Miami/Sylvester Comprehensive Cancer Center, Miami, FL, ²Department of Radiation Oncology, Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, ³University of Miami Miller School of Medicine, Miami, FL, ⁴Stony Brook University, Stony Brook, NY

Purpose/Objective(s): The emergence and progression of prostate cancer (PCa) are associated with mechanisms of immune escape creating a tumor microenvironment (TME) resistant to available immune-based interventions. While PCa radiation therapy (RT) and androgen deprivation therapies (ADT) can induce intra-tumoral immune cell infiltration, the dose and timing of RT/ADT that best achieve cancer control while recruiting anti-tumor immune cell populations have not been established. Ultra-high dose RT interventions such as stereotactic body radiotherapy (SBRT) are common treatment approaches; however, little is known mechanistically about the tumoral and peri-tumoral changes induced by ultra-high dose RT in PCa, as well as the modulatory effects of ADT on the tumor and TME. The UAdapt clinical trial (NCT06111313, PI: Spieler) is designed to characterize changes in both tumor tissue and circulating immune cell populations induced by ultra-high dose RT and ADT therapies.

Materials/Methods: UAdapt investigates in-treatment immune response to focal, ultra-high dose RT (=12 Gy single fraction RT targeting mpMRI-defined intraprostatic lesions) ± ADT. We are characterizing immune cell populations in and around PCa foci that are sampled longitudinally using a quantitative multi-parametric MRI (mpMRI) fusion biopsy system called HRS. This study includes early post-treatment biopsies 2-3 weeks after RT or RT+ADT to capture “first responder” lymphoid and macrophage cell infiltration at the center and edge of mpMRI tumor and in adjacent benign prostate tissue. We are using digital pathology to map tumor-infiltrating and peri-tumoral lymphocytes (TILs) to obtain quantitative indices of immune infiltrate response to RT ± ADT. These infiltrates include both immune-activating and immunosuppressive cell populations; we are using CyTOF Imaging Mass Cytometry (CyTOF IMC) to map different immune infiltrate populations in UAdapt biopsy tissues. Additional correlative studies are supported by longitudinal mpMRI, PSMA PET/CT imaging and blood and urine research samples obtained at baseline and at early (2-3 weeks) and later (3 months, 9 months, 2-2.5 years) post-treatment intervals. Enrollment is underway, and we have demonstrated the technical feasibility of our longitudinal biopsy, imaging, and biospecimen collection. We have also started our digital pathology, CyTOF IMC, and circulating immune biomarker analyses. The UAdapt PCa clinical trial offers the unique opportunity to characterize in-treatment immune response to ultra-high dose RT ± ADT. The key innovation of UAdapt is a trial structure designed to address key clinical questions while facilitating highly relevant tumor and TME analyses using quantitative imaging and molecular markers of both tumor response and normal tissue effects.

Results: TBD

Conclusion: TBD