PURPOSE: To assess the correlation of radiation-induced apoptosis in vitro of CD4 and CD8 T lymphocytes with late toxicity of prostate cancer patients treated with radiation therapy.
METHODS AND MATERIALS: 214 patients were prospectively included in the study. Peripheral blood was drawn from patients before treatment and irradiated with 8 Gy. The percentage of CD4+ and CD8+ T lymphocytes that underwent radiation-induced apoptosis was assessed by flow cytometry. Toxicity and mortality were correlated in 198 cases with pretreatment apoptosis and clinical and biological variables by use of a Cox proportional hazards model.
RESULTS: The mean percentage of CD4+ and CD8+ T lymphocyte radiation-induced apoptosis was 28.58% (±14.23) and 50.76% (±18.9), respectively. Genitourinary (GU) toxicity was experienced by 39.9% of patients, while gastrointestinal (GI) toxicity was experienced by 19.7%. The probability of development of GU toxicity was nearly doubled (hazard ratio [HR] 1.99, P=.014) in those patients in whom the percentage of in vitro radiation-induced apoptosis of CD4+ T-lymphocytes was ≤ 28.58%. It was also almost double in patients who received doses ≥50 Gy in 65% of the bladder volume (V65 ≥50) (HR 1.92, P=.048). No correlation was found between GI toxicity and any of the variables studied. The probability of death during follow-up, after adjustment for different variables, was 2.7 times higher in patients with a percentage of CD8+ T lymphocyte apoptosis ≤ 50.76% (P=.022).
CONCLUSIONS: In conclusion, our study shows, in the largest prospective cohort of prostate cancer patients undergoing radiation therapy, that in vitro radiation-induced apoptosis of CD4+ T lymphocytes assessed before radiation therapy was associated with the probability of developing chronic GU toxicity. In addition, the radiation dose received in the urinary bladder (V65 ≥50) affected the occurrence of GU toxicity. Finally, we also demonstrate that radiation-induced apoptosis of CD8+ T lymphocytes was associated with overall survival, although larger series are needed to confirm this finding.
Written by:
Foro P, Algara M, Lozano J, Rodriguez N, Sanz X, Torres E, Carles J, Reig A, Membrive I, Quera J, Fernandez-Velilla E, Pera O, Lacruz M, Bellosillo B. Are you the author?
Department of Radiation Oncology, Parc de Salut Mar, Barcelona, Spain; Universitat Pompeu Fabra, Barcelona, Spain; Pathology Department, Parc de Salut Mar, Barcelona, Spain; Universitat Autonoma de Barcelona, Barcelona, Spain; Department of Oncology, Hospital Vall d'Hebron, Barcelona, Spain; Universitat Pompeu Fabra, Barcelona, Spain; Radiation Protection Department, Parc de Salut Mar, Barcelona, Spain; Universitat Pompeu Fabra, Barcelona, Spain; Pathology Department, Parc de Salut Mar, Barcelona, Spain.
Reference: Int J Radiat Oncol Biol Phys. 2014 Apr 1;88(5):1057-63.
doi: 10.1016/j.ijrobp.2014.01.002
PubMed Abstract
PMID: 24661659
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