Prospective Immunophenotyping of CD8+ T Cells and Associated Clinical Outcomes of Patients With Oligometastatic Prostate Cancer Treated With Metastasis-Directed SBRT

Jaden D. Evans, Lindsay K. Morris, Henan Zhang, Siyu Cao, Xin Liu, Kristin C. Mara, Bradley J. Stish, Brian J. Davis, Aaron Mansfield, Roxana S Dronca, Matthew J. Iott, Eugene D Kwon, Robert L. Foote, Kenneth R. Olivier, Haidong M Dong, Sean S Park

Research output: Contribution to journalArticle

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Abstract

Purpose: This study examined the effects of metastasis-directed stereotactic body radiation therapy (mdSBRT) on CD8+ T-cell subpopulations and correlated post-mdSBRT immunophenotypic responses with clinical outcomes in patients with oligometastatic prostate cancer (OPCa). Methods and Materials: Peripheral blood mononuclear cells were prospectively isolated from 37 patients with OPCa (≤3 metastases) who were treated with mdSBRT. Immunophenotyping identified circulating CD8+ T-cell subpopulations, including tumor-reactive (TTR), effector memory, central memory (TCM), effector, and naïve T cells from samples collected before and after mdSBRT. Univariate Cox proportional hazards regression was used to assess whether changes in these T-cell subpopulations were potential risk factors for death and/or progression. The Kaplan-Meier method was used for survival. Cumulative incidence for progression and new distant metastasis weas estimated, considering death as a competing risk. Results: Median follow-up was 39 months (interquartile range, 34-43). Overall survival at 3 years was 78.2%. Cumulative incidence for local progression and new distant metastasis at 3 years was 16.5% and 67.6%, respectively. Between baseline and day 14 after mdSBRT, an increase in the TCM cell subpopulation was associated with the risk of death (hazard ratio, 1.22 [95% confidence interval, 1.02-1.47]; P =.033), and an increase in the TTR cell subpopulation was protective against the risk of local progression (hazard ratio, 0.80 [95% confidence interval, 0.65-0.98]; P =.032). Conclusions: An increase in the TTR cell subpopulation was protective against the risk of disease progression, and an increase in the TCM cell subpopulation was associated with the risk of death in patients with OPCa treated with mdSBRT. Disease control may be further improved by better understanding the CD8+ T-cell subpopulations and by enhancing their antitumor effect.

Original languageEnglish (US)
Pages (from-to)229-240
Number of pages12
JournalInternational Journal of Radiation Oncology Biology Physics
Volume103
Issue number1
DOIs
StatePublished - Jan 1 2019

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Immunophenotyping
metastasis
Prostatic Neoplasms
cancer
Neoplasm Metastasis
T-Lymphocytes
radiation therapy
progressions
Radiotherapy
death
hazards
effectors
cells
confidence
incidence
Confidence Intervals
intervals
blood cells
Survival
Incidence

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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Prospective Immunophenotyping of CD8+ T Cells and Associated Clinical Outcomes of Patients With Oligometastatic Prostate Cancer Treated With Metastasis-Directed SBRT. / Evans, Jaden D.; Morris, Lindsay K.; Zhang, Henan; Cao, Siyu; Liu, Xin; Mara, Kristin C.; Stish, Bradley J.; Davis, Brian J.; Mansfield, Aaron; Dronca, Roxana S; Iott, Matthew J.; Kwon, Eugene D; Foote, Robert L.; Olivier, Kenneth R.; Dong, Haidong M; Park, Sean S.

In: International Journal of Radiation Oncology Biology Physics, Vol. 103, No. 1, 01.01.2019, p. 229-240.

Research output: Contribution to journalArticle

Evans, Jaden D. ; Morris, Lindsay K. ; Zhang, Henan ; Cao, Siyu ; Liu, Xin ; Mara, Kristin C. ; Stish, Bradley J. ; Davis, Brian J. ; Mansfield, Aaron ; Dronca, Roxana S ; Iott, Matthew J. ; Kwon, Eugene D ; Foote, Robert L. ; Olivier, Kenneth R. ; Dong, Haidong M ; Park, Sean S. / Prospective Immunophenotyping of CD8+ T Cells and Associated Clinical Outcomes of Patients With Oligometastatic Prostate Cancer Treated With Metastasis-Directed SBRT. In: International Journal of Radiation Oncology Biology Physics. 2019 ; Vol. 103, No. 1. pp. 229-240.
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abstract = "Purpose: This study examined the effects of metastasis-directed stereotactic body radiation therapy (mdSBRT) on CD8+ T-cell subpopulations and correlated post-mdSBRT immunophenotypic responses with clinical outcomes in patients with oligometastatic prostate cancer (OPCa). Methods and Materials: Peripheral blood mononuclear cells were prospectively isolated from 37 patients with OPCa (≤3 metastases) who were treated with mdSBRT. Immunophenotyping identified circulating CD8+ T-cell subpopulations, including tumor-reactive (TTR), effector memory, central memory (TCM), effector, and na{\"i}ve T cells from samples collected before and after mdSBRT. Univariate Cox proportional hazards regression was used to assess whether changes in these T-cell subpopulations were potential risk factors for death and/or progression. The Kaplan-Meier method was used for survival. Cumulative incidence for progression and new distant metastasis weas estimated, considering death as a competing risk. Results: Median follow-up was 39 months (interquartile range, 34-43). Overall survival at 3 years was 78.2{\%}. Cumulative incidence for local progression and new distant metastasis at 3 years was 16.5{\%} and 67.6{\%}, respectively. Between baseline and day 14 after mdSBRT, an increase in the TCM cell subpopulation was associated with the risk of death (hazard ratio, 1.22 [95{\%} confidence interval, 1.02-1.47]; P =.033), and an increase in the TTR cell subpopulation was protective against the risk of local progression (hazard ratio, 0.80 [95{\%} confidence interval, 0.65-0.98]; P =.032). Conclusions: An increase in the TTR cell subpopulation was protective against the risk of disease progression, and an increase in the TCM cell subpopulation was associated with the risk of death in patients with OPCa treated with mdSBRT. Disease control may be further improved by better understanding the CD8+ T-cell subpopulations and by enhancing their antitumor effect.",
author = "Evans, {Jaden D.} and Morris, {Lindsay K.} and Henan Zhang and Siyu Cao and Xin Liu and Mara, {Kristin C.} and Stish, {Bradley J.} and Davis, {Brian J.} and Aaron Mansfield and Dronca, {Roxana S} and Iott, {Matthew J.} and Kwon, {Eugene D} and Foote, {Robert L.} and Olivier, {Kenneth R.} and Dong, {Haidong M} and Park, {Sean S}",
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T1 - Prospective Immunophenotyping of CD8+ T Cells and Associated Clinical Outcomes of Patients With Oligometastatic Prostate Cancer Treated With Metastasis-Directed SBRT

AU - Evans, Jaden D.

AU - Morris, Lindsay K.

AU - Zhang, Henan

AU - Cao, Siyu

AU - Liu, Xin

AU - Mara, Kristin C.

AU - Stish, Bradley J.

AU - Davis, Brian J.

AU - Mansfield, Aaron

AU - Dronca, Roxana S

AU - Iott, Matthew J.

AU - Kwon, Eugene D

AU - Foote, Robert L.

AU - Olivier, Kenneth R.

AU - Dong, Haidong M

AU - Park, Sean S

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Purpose: This study examined the effects of metastasis-directed stereotactic body radiation therapy (mdSBRT) on CD8+ T-cell subpopulations and correlated post-mdSBRT immunophenotypic responses with clinical outcomes in patients with oligometastatic prostate cancer (OPCa). Methods and Materials: Peripheral blood mononuclear cells were prospectively isolated from 37 patients with OPCa (≤3 metastases) who were treated with mdSBRT. Immunophenotyping identified circulating CD8+ T-cell subpopulations, including tumor-reactive (TTR), effector memory, central memory (TCM), effector, and naïve T cells from samples collected before and after mdSBRT. Univariate Cox proportional hazards regression was used to assess whether changes in these T-cell subpopulations were potential risk factors for death and/or progression. The Kaplan-Meier method was used for survival. Cumulative incidence for progression and new distant metastasis weas estimated, considering death as a competing risk. Results: Median follow-up was 39 months (interquartile range, 34-43). Overall survival at 3 years was 78.2%. Cumulative incidence for local progression and new distant metastasis at 3 years was 16.5% and 67.6%, respectively. Between baseline and day 14 after mdSBRT, an increase in the TCM cell subpopulation was associated with the risk of death (hazard ratio, 1.22 [95% confidence interval, 1.02-1.47]; P =.033), and an increase in the TTR cell subpopulation was protective against the risk of local progression (hazard ratio, 0.80 [95% confidence interval, 0.65-0.98]; P =.032). Conclusions: An increase in the TTR cell subpopulation was protective against the risk of disease progression, and an increase in the TCM cell subpopulation was associated with the risk of death in patients with OPCa treated with mdSBRT. Disease control may be further improved by better understanding the CD8+ T-cell subpopulations and by enhancing their antitumor effect.

AB - Purpose: This study examined the effects of metastasis-directed stereotactic body radiation therapy (mdSBRT) on CD8+ T-cell subpopulations and correlated post-mdSBRT immunophenotypic responses with clinical outcomes in patients with oligometastatic prostate cancer (OPCa). Methods and Materials: Peripheral blood mononuclear cells were prospectively isolated from 37 patients with OPCa (≤3 metastases) who were treated with mdSBRT. Immunophenotyping identified circulating CD8+ T-cell subpopulations, including tumor-reactive (TTR), effector memory, central memory (TCM), effector, and naïve T cells from samples collected before and after mdSBRT. Univariate Cox proportional hazards regression was used to assess whether changes in these T-cell subpopulations were potential risk factors for death and/or progression. The Kaplan-Meier method was used for survival. Cumulative incidence for progression and new distant metastasis weas estimated, considering death as a competing risk. Results: Median follow-up was 39 months (interquartile range, 34-43). Overall survival at 3 years was 78.2%. Cumulative incidence for local progression and new distant metastasis at 3 years was 16.5% and 67.6%, respectively. Between baseline and day 14 after mdSBRT, an increase in the TCM cell subpopulation was associated with the risk of death (hazard ratio, 1.22 [95% confidence interval, 1.02-1.47]; P =.033), and an increase in the TTR cell subpopulation was protective against the risk of local progression (hazard ratio, 0.80 [95% confidence interval, 0.65-0.98]; P =.032). Conclusions: An increase in the TTR cell subpopulation was protective against the risk of disease progression, and an increase in the TCM cell subpopulation was associated with the risk of death in patients with OPCa treated with mdSBRT. Disease control may be further improved by better understanding the CD8+ T-cell subpopulations and by enhancing their antitumor effect.

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