Radiation and Cancer Biology

SS 05 - Biology 2 - Radiation and Immune Response Session I

46 - SABR Produces Systemic Adaptive Immune Responses in Castration-Sensitive Oligometastatic Prostate Cancer Patients

Sunday, October 21
4:55 PM - 5:05 PM
Location: Room 007 C/D

SABR Produces Systemic Adaptive Immune Responses in Castration-Sensitive Oligometastatic Prostate Cancer Patients
P. T. Tran1, R. Phillips2, N. Radwan2, T. Hether3, M. Vignali3, I. Kaplan3, A. E. Ross2, C. Deville Jr2, S. C. Greco2, D. Song2, H. Wang2, K. Pienta2, T. L. DeWeese1, A. P. Dicker4, and M. Eisenberger2; 1Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 2Johns Hopkins Medicine, Baltimore, MD, 3Adaptive Biotechnologies, Seattle, WA, 4Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA

Purpose/Objective(s): Local ablative treatment to oligometastatic (OM) patients can result in long term disease-free survival in colorectal, sarcoma and lung cancer patients. The importance of consolidating all macroscopic tumor deposits in prostate cancer in the modern era is an area of active investigation. Stereotactic ablative radiation (SABR) is highly focused, high-dose radiation and exciting pre-clinical studies suggest that SABR can activate the immune system against cancer cells resulting in a systemic anti-tumor immune response that can be accentuated with proper immunotherapy. Here we report on interim immunological outcomes of our Phase II randomized trial of SABR to men with recurrent low volume (1-3 metastases) metastatic hormone sensitive prostate cancer (HSPC).

Materials/Methods: Patients are randomized 2:1 to SABR:observation with minimization to balance assignment by primary intervention, prior hormonal therapy, and PSA doubling time. Progression after 6 months will be compared using Fisher's exact test based on an intention-to-treat. Local control will be assessed using RECIST 1.1 criteria. Adverse events will be summarized by type and grade. Quality of life pre- and post- SABR will be measured by Brief Pain Inventory. Further fundamental analysis of the OM state will be achieved through correlation with deep sequencing of circulating T-cell receptor (TCR) clonotypes.

Results: Since April 2016 we have randomized 49/54. 25 men had whole blood (8 observation and 17 SABR) drawn at day 1 and day 90 that was purified for genomic DNA and deep sequenced for the TCR-beta gene. Samples were sequenced at a deep resolution with average unique TCR rearrangements at day 1 and day 90 of >70,336 and >61,339 per sample, respectively. Examining samples for TCR clonality and Daley-Smith Richness, two global measures of TCR repertoires, did not demonstrate any changes over time or between groups (p>0.20). Differential TCR clonotype abundance analysis of individual patients demonstrated that patients treated with SABR had an average of 12 expanded and 10 contracted clones compared to an average of 1 expanded and <1 contracted clone for the observation arm at Day 90 (p <0.024).

Conclusion: This trial is the first randomized Phase II study in the Western Hemisphere evaluating the safety and efficacy of SABR in OM HSPC. Our leading-edge laboratory and imaging correlates allow an unprecedented opportunity to characterize, in isolation, the effects of SABR on the dynamics of the immunologic response on the OM state. Our interim data suggest, for the first time to our knowledge, that SABR alone can produce a systemic adaptive immune response in humans even with a poorly immunogenic tumor type such as prostate cancer. Future translational studies should be leveraged to optimize SABR-immunotherapy combinations for maximal anti-tumor effect.

Author Disclosure: P.T. Tran: Research Grant; NIH-NCI, ACS, Kimmel Foundation, Astellas-Medivation, American Lung Association, Movember-PCF, PCORI. Honoraria; Dendreon. Consultant; RefleXion Medical. Advisory Board; Astellas-Medivation, Dendreon. Travel Expenses; Dendreon, RefleXion Medical. Patent/License Fees/Copyright; Compounds and Methods of Use in Ablative RT, Natsar Pharmaceuticals. Chair of Radiation Oncology Study Section; RSNA R&E Foundation. Senior Editor; Cancer Research. R. Phillips: None. N. Radwan: None. T. Hether: Stock Options; Adaptive Biotechnologies. M. Vignali: Stock Options; Adaptive Biotechnologies. A.E. Ross: Consultant agreement ended 2014, currently conducting collaborative research; GenomeDx. Consultant; GenomeDx. C. Deville: None. D. Song: Stock; Roche. H. Wang: None. T.L. DeWeese: None. A.P. Dicker: Research Grant; Radiation Therapy Oncology Group. Travel Expenses; Prostate Cancer Foundation. Chair; Department of Defense.

Phuoc Tran, MD, PhD

Johns Hopkins Medicine

Disclosure:
Employment
Johns Hopkins Medical Institutions: Associate Professor: Employee

Compensation
ACS: Research Grants; American Lung Association: Research Grants; Astellas-Medivation: Advisory Board, Research Grants; Dendreon: Advisory Board, Honoraria, Travel Expenses; Kimmel Foundation: Research Grants; Movember-PCF: Research Grants; NIH-NCI: Research Grants; PCORI: Research Grants; RefleXion Medical: Consultant, Research Grants, Travel Expenses

Ownership
Compounds and Methods of Use in Ablative RT: Patent/License Fees/Copyright; Natsar Pharmaceuticals: Patent/License Fees/Copyright

Leadership
Cancer Research: Senior Editor; Journal of Clinical Oncology: Editorial Board; RSNA R&E Foundation: Chair of Radiation Oncology Study Section

Presentation(s):

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