Phase II Evaluation of Stereotactic Ablative Radiotherapy (SABR) and Immunity in 11C-Choline-PET/CT–Identified Oligometastatic Castration-Resistant Prostate Cancer

Abstract Purpose: Outcomes for resistant metastatic castration-resistant prostate cancer (CRPC) are poor. Stereotactic ablative radiotherapy (SABR) induces antitumor immunity in clinical and preclinical studies, but immunologic biomarkers are lacking. Patients and Methods: Eighty-nine patients with...

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Published in:Clinical cancer research 2021-12, Vol.27 (23), p.6376-6383
Main Authors: Zhang, Henan, Orme, Jacob J., Abraha, Feven, Stish, B.J., Lowe, Val J., Lucien, Fabrice, Tryggestad, Erik J., Bold, Michael S., Pagliaro, Lance C., Choo, C. Richard, Brinkmann, Debra H., Iott, Matthew J., Davis, Brian J., Quevedo, J. Fernando, Harmsen, William S., Costello, Brian A., Johnson, Geoffrey B., Nathan, Mark A., Olivier, Kenneth R., Pisansky, Thomas M., Kwon, Eugene D., Dong, Haidong, Park, Sean S.
Format: Article
Language:English
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Summary:Abstract Purpose: Outcomes for resistant metastatic castration-resistant prostate cancer (CRPC) are poor. Stereotactic ablative radiotherapy (SABR) induces antitumor immunity in clinical and preclinical studies, but immunologic biomarkers are lacking. Patients and Methods: Eighty-nine patients with oligometastatic CRPC were identified by 11C-Choline-PET (Choline-PET) from August 2016 to December 2019 and treated with SABR. Prespecified coprimary endpoints were 2-year overall survival (OS) and PSA progression. Secondary endpoints included 2-year SABR-treated local failure and 6-month adverse events. Correlative studies included peripheral blood T-cell subpopulations before and after SABR. Results: 128 lesions in 89 patients were included in this analysis. Median OS was 29.3 months, and 1- and 2-year OS were 96% and 80%, respectively. PSA PFS was 40% at 1 year and 21% at 2 years. Local PFS was 84.4% and 75.3% at 1 and 2 years, respectively, and no grade ≥3 AEs were observed. Baseline high levels of tumor-reactive T cells (TTR; CD8+CD11ahigh) predicted superior local, PSA, and distant PFS. Baseline high levels of effector memory T cells (TEM; CCR7−CD45RA−) were associated with improved PSA PFS. An increase in TTR at day 14 from baseline was associated with superior OS. Conclusions: This is the first comprehensive effector T-cell immunophenotype analysis in a phase II trial before and after SABR in CRPC. Results are favorable and support the incorporation of immune-based markers in the design of future randomized trials in patients with oligometastatic CRPC treated with SABR.
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.CCR-21-2510