title: Radio-induced apoptosis of peripheral blood CD8 T lymphocytes is a novel prognostic factor for survival in cervical carcinoma patients.
abstract: OBJECTIVE
  A close relationship exists between immune response and tumor behavior. This study aimed to explore the associations between radiation-induced apoptosis (RIA) in peripheral blood lymphocytes (PBL) and clinical pathological variables. Furthermore, it assessed the role of RIA as a prognostic factor for survival in cervical carcinoma patients.
  
  
  METHODS
  Between February 1998 and October 2003, 58 consecutive patients with nonmetastatic, localized stage I-II cervical carcinoma who had been treated with radiotherapy (RT) ± chemotherapy were included in this study. Follow-up ended in January 2013. PBL subpopulations were isolated and irradiated with 0, 1, 2 and 8 Gy then incubated for 24, 48 and 72 h. Apoptosis was measured by flow cytometry and the β value, a parameter defining RIA of lymphocytes, was calculated.
  
  
  RESULTS
  Mean follow-up duration was 111.92 ± 40.31 months. Patients with lower CD8 T lymphocyte β values were at a higher risk of local relapse: Exp(B) = 5.137, confidence interval (CI) 95 % = 1.044-25.268, p = 0.044. Similar results were observed for regional relapse: Exp(B) = 8.008, CI 95 % = 1.702-37.679, p = 0.008 and disease relapse: Exp(B) = 6.766, CI 95 % = 1.889-24.238, p = 0.003. In multivariate analysis, only the CD8 T lymphocyte β values were found to be of prognostic significance for local disease-free survival (LDFS, p = 0.049), regional disease-free survival (RDFS, p = 0.002), metastasis-free survival (MFS, p = 0.042), disease-free survival (DFS, p = 0.001) and cause-specific survival (CSS p = 0.028).
  
  
  CONCLUSIONS
  For the first time, RIA in CD8 T lymphocytes was demonstrated to be a predictive factor for survival in cervical carcinoma patients.
authors.affiliation: Radiation Oncology Department, Hospital Universitario de Gran Canaria Dr. Negrín, C/ Barranco de La Ballena s/n, 35016, Las Palmas de Gran Canaria, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Ordoñez
authors.forename: L A
authors.initials: LA
authors.lastname: Henríquez-Hernández
authors.forename: M
authors.initials: M
authors.lastname: Federico
authors.forename: A
authors.initials: A
authors.lastname: Valenciano
authors.forename: B
authors.initials: B
authors.lastname: Pinar
authors.forename: M
authors.initials: M
authors.lastname: Lloret
authors.forename: E
authors.initials: E
authors.lastname: Bordón
authors.forename: C
authors.initials: C
authors.lastname: Rodríguez-Gallego
authors.forename: P C
authors.initials: PC
authors.lastname: Lara
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects*; D001918:Brachytherapy; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects*; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011879:Radiotherapy Dosage; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*
chemical_list: D002945:Cisplatin