@article{75edbc97728446ccb82a85c83c6c67dc,
title = "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 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{\th}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. _2021 American Association for Cancer Research.",
author = "Henan Zhang and Orme, {Jacob J.} and Feven Abraha and Stish, {B. J.} and Lowe, {Val J.} and Fabrice Lucien and Tryggestad, {Erik J.} and Bold, {Michael S.} and Pagliaro, {Lance C.} and Choo, {C. Richard} and Brinkmann, {Debra H.} and Iott, {Matthew J.} and Davis, {Brian J.} and Quevedo, {J. Fernando} and Harmsen, {William S.} and Costello, {Brian A.} and Johnson, {Geoffrey B.} and Nathan, {Mark A.} and Olivier, {Kenneth R.} and Pisansky, {Thomas M.} and Kwon, {Eugene D.} and Haidong Dong and Park, {Sean S.}",
note = "Funding Information: V.J. Lowe reports personal fees from Eisai Inc, AVID Radiopharmaceuticals, and Merck Research and grants from General Electric, Siemens Molecular Imaging, and NIH during the conduct of the study as well as grants from AVID Radiopharmaceuticals outside the submitted work. E.J. Tryggestad reports grants from NCI/NIH during the conduct of the study. L.C. Pagliaro reports other support from Merck, Astellas, Pfizer, Exelixis, and Roche/Genentech outside the submitted work. M.J. Iott reports grants from NIH/NCI during the conduct of the study. B.A. Costello reports other support from Exelixis and Clinical Care Options outside the submitted work. G. B. Johnson reports other support from Curium; grants from MedTrace and Blue Earth; and grants and other support from Novartis, Pfizer, Clarity, and ViewPoint outside the submitted work; in addition, G.B. Johnson has a patent for radionuclide imaging and therapy pending. E.D. Kwon reports a patent for B7-H1 issued, licensed, and with royalties paid from BMS. S.S. Park reports grants from NIH/NCI during the conduct of the study as well as grants from MacroGenics and other support from AstraZeneca outside the submitted work; in addition, S.S. Park has a patent for Assessing and Treating Prostate Cancer issued. No disclosures were reported by the other authors. Funding Information: We thank Ms. Christina C. Todd (research coordinator), Ms. Brianna N. Tranby (assistance in manuscript preparation), and our patients who participated in this study. This research was supported by NCI R01 CA200551 (to S.S. Park, V.J. Lowe, D.H. Brinkmann, E.D. Kwon, and H. Dong). Publisher Copyright: {\textcopyright} 2021 American Association for Cancer Research Inc.. All rights reserved.",
year = "2021",
month = dec,
day = "1",
doi = "10.1158/1078-0432.CCR-21-2510",
language = "English (US)",
volume = "27",
pages = "6376--6383",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "23",
}