To study the effects of metastasis-directed stereotactic body radiation therapy (mdSBRT) on CD8+ T-cell subpopulations and to correlate post-mdSBRT immunophenotypic responses with clinical outcomes in patients with oligometastatic prostate cancer (OPCa).
Peripheral blood mononuclear cells (PBMCs) were prospectively isolated from 37 patients with OPCa (≤3 metastases) treated with mdSBRT. Immunophenotyping identified circulating CD8+ T-cell subpopulations including: Tumor-Reactive (TTR), Effector Memory (TEM), Central Memory (TCM), Effector (TEF), and Naïve (TN) 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. Kaplan-Meier method was used for survival. Cumulative incidence for progression and new distant metastasis was estimated considering death as a competing risk.
Median follow-up was 39 months (IQR 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 (HR 1.22 [95%CI, 1.02-1.47]; P=0.033), and an increase in the TTR cell subpopulation was protective against the risk of local progression (HR 0.80 [95%CI, 0.65-0.98]; P=0.032).
An increase in the TTR cell subpopulation was protective against the risk of disease progression while 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 anti-tumor effect.
International journal of radiation oncology, biology, physics. 2018 Sep 08 [Epub ahead of print]
Jaden D Evans, Lindsay K Morris, Henan Zhang, Siyu Cao, Xin Liu, Kristin C Mara, Bradley J Stish, Brian J Davis, Aaron S Mansfield, Roxana S Dronca, Matthew J Iott Cnp, Eugene D Kwon, Robert L Foote, Kenneth R Olivier, Haidong Dong, Sean S Park
Department of Radiation Oncology, Mayo Clinic, Rochester, MN., Department of Immunology, Mayo Clinic, Rochester, MN., Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN., Division of Medical Oncology, Mayo Clinic, Rochester, MN., Division of Medical Oncology, Mayo Clinic, Rochester, MN; Division of Medical Oncology, Mayo Clinic, Jacksonville, FL., Department of Urology, Mayo Clinic, Rochester, MN., Department of Immunology, Mayo Clinic, Rochester, MN; Department of Urology, Mayo Clinic, Rochester, MN.