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

Henan Zhang; Jacob J. Orme; Feven Abraha; B. J. Stish; Val J. Lowe; Fabrice Lucien; Erik J. Tryggestad; Michael S. Bold; Lance C. Pagliaro; C. Richard Choo; Debra H. Brinkmann; Matthew J. Iott; Brian J. Davis; J. Fernando Quevedo; William S. Harmsen; Brian A. Costello; Geoffrey B. Johnson; Mark A. Nathan; Kenneth R. Olivier; Thomas M. Pisansky; Eugene D. Kwon; Haidong Dong; Sean S. Park

doi:10.1158/1078-0432.CCR-21-2510

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

Henan Zhang, Jacob J. Orme, Feven Abraha, B. J. Stish, Val J. Lowe, Fabrice Lucien, Erik J. Tryggestad, Michael S. Bold, Lance C. Pagliaro, C. Richard Choo, Debra H. Brinkmann, Matthew J. Iott, Brian J. Davis, J. Fernando Quevedo, William S. Harmsen, Brian A. Costello, Geoffrey B. Johnson, Mark A. Nathan, Kenneth R. Olivier, Thomas M. PisanskyEugene D. Kwon, Haidong Dong, Sean S. Park

Research output: Contribution to journal › Article › peer-review

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; CD8þCD11ahigh) 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.

Original language	English (US)
Pages (from-to)	6376-6383
Number of pages	8
Journal	Clinical Cancer Research
Volume	27
Issue number	23
DOIs	https://doi.org/10.1158/1078-0432.CCR-21-2510
State	Published - Dec 1 2021

ASJC Scopus subject areas

General Medicine

Access to Document

10.1158/1078-0432.CCR-21-2510

Cite this

Zhang, H., Orme, J. J., Abraha, F., Stish, B. J., Lowe, V. J., Lucien, F., Tryggestad, E. J., Bold, M. S., Pagliaro, L. C., Choo, C. R., Brinkmann, D. H., Iott, M. J., Davis, B. J., Quevedo, J. F., Harmsen, W. S., Costello, B. A., Johnson, G. B., Nathan, M. A., Olivier, K. R., ... Park, S. S. (2021). Phase II Evaluation of Stereotactic Ablative Radiotherapy (SABR) and Immunity in 11C-Choline-PET/CT-Identified Oligometastatic Castration-Resistant Prostate Cancer. Clinical Cancer Research, 27(23), 6376-6383. https://doi.org/10.1158/1078-0432.CCR-21-2510

Zhang, H, Orme, JJ, Abraha, F, Stish, BJ, Lowe, VJ , Lucien, F, Tryggestad, EJ, Bold, MS, Pagliaro, LC, Choo, CR, Brinkmann, DH, Iott, MJ, Davis, BJ, Quevedo, JF, Harmsen, WS, Costello, BA, Johnson, GB, Nathan, MA, Olivier, KR, Pisansky, TM, Kwon, ED, Dong, H & Park, SS 2021, 'Phase II Evaluation of Stereotactic Ablative Radiotherapy (SABR) and Immunity in 11C-Choline-PET/CT-Identified Oligometastatic Castration-Resistant Prostate Cancer', Clinical Cancer Research, vol. 27, no. 23, pp. 6376-6383. https://doi.org/10.1158/1078-0432.CCR-21-2510

@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.}",

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",

}

TY - JOUR

T1 - Phase II Evaluation of Stereotactic Ablative Radiotherapy (SABR) and Immunity in 11C-Choline-PET/CT-Identified Oligometastatic Castration-Resistant Prostate Cancer

AU - Zhang, Henan

AU - Orme, Jacob J.

AU - Abraha, Feven

AU - Stish, B. J.

AU - Lowe, Val J.

AU - Lucien, Fabrice

AU - Tryggestad, Erik J.

AU - Bold, Michael S.

AU - Pagliaro, Lance C.

AU - Choo, C. Richard

AU - Brinkmann, Debra H.

AU - Iott, Matthew J.

AU - Davis, Brian J.

AU - Quevedo, J. Fernando

AU - Harmsen, William S.

AU - Costello, Brian A.

AU - Johnson, Geoffrey B.

AU - Nathan, Mark A.

AU - Olivier, Kenneth R.

AU - Pisansky, Thomas M.

AU - Kwon, Eugene D.

AU - Dong, Haidong

AU - Park, Sean S.

PY - 2021/12/1

Y1 - 2021/12/1

N2 - 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; CD8þCD11ahigh) 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.

AB - 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; CD8þCD11ahigh) 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.

UR - http://www.scopus.com/inward/record.url?scp=85120466855&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85120466855&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-21-2510

DO - 10.1158/1078-0432.CCR-21-2510

M3 - Article

C2 - 34593526

AN - SCOPUS:85120466855

SN - 1078-0432

VL - 27

SP - 6376

EP - 6383

JO - Clinical Cancer Research

JF - Clinical Cancer Research

IS - 23

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this