title: Relationship between radiation-induced apoptosis of T lymphocytes and chronic toxicity in patients with prostate cancer treated by radiation therapy: a prospective study.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: Department of Radiation Oncology, Parc de Salut Mar, Barcelona, Spain; Universitat Pompeu Fabra, Barcelona, Spain. Electronic address: pforo@parcdesalutmar.cat.
authors.forename: Palmira
authors.initials: P
authors.lastname: Foro
authors.affiliation: Department of Radiation Oncology, Parc de Salut Mar, Barcelona, Spain; Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Algara
authors.affiliation: Department of Radiation Oncology, Parc de Salut Mar, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Lozano
authors.affiliation: Department of Radiation Oncology, Parc de Salut Mar, Barcelona, Spain; Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Rodriguez
authors.affiliation: Department of Radiation Oncology, Parc de Salut Mar, Barcelona, Spain; Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Sanz
authors.affiliation: Pathology Department, Parc de Salut Mar, Barcelona, Spain.
authors.forename: Erica
authors.initials: E
authors.lastname: Torres
authors.affiliation: Universitat Autonoma de Barcelona, Barcelona, Spain; Department of Oncology, Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Carles
authors.affiliation: Department of Radiation Oncology, Parc de Salut Mar, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Reig
authors.affiliation: Department of Radiation Oncology, Parc de Salut Mar, Barcelona, Spain.
authors.forename: Ismael
authors.initials: I
authors.lastname: Membrive
authors.affiliation: Department of Radiation Oncology, Parc de Salut Mar, Barcelona, Spain; Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Quera
authors.affiliation: Department of Radiation Oncology, Parc de Salut Mar, Barcelona, Spain.
authors.forename: Enric
authors.initials: E
authors.lastname: Fernandez-Velilla
authors.affiliation: Department of Radiation Oncology, Parc de Salut Mar, Barcelona, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Pera
authors.affiliation: Universitat Pompeu Fabra, Barcelona, Spain; Radiation Protection Department, Parc de Salut Mar, Barcelona, Spain.
authors.forename: Marti
authors.initials: M
authors.lastname: Lacruz
authors.affiliation: Universitat Pompeu Fabra, Barcelona, Spain; Pathology Department, Parc de Salut Mar, Barcelona, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Bellosillo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000528:radiation effects*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000528:radiation effects*; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000209:etiology; D011874:Radiometry; D011878:Radiotherapy / Q000009:adverse effects*; D011879:Radiotherapy Dosage; D013997:Time Factors; D001743:Urinary Bladder / Q000528:radiation effects
chemical_list: D017430:Prostate-Specific Antigen