title: CD4 and CD8 T-lymphocyte apoptosis can predict radiation-induced late toxicity: a prospective study in 399 patients.
abstract: OBJECTIVE
  Predicting late effects in patients treated with radiation therapy by assessing in vitro radiation-induced CD4 and CD8 T-lymphocyte apoptosis can be useful in individualizing treatment.
  
  
  METHODS
  In a prospective study, 399 curatively irradiated patients were tested using a rapid assay where fresh blood samples were in vitro irradiated with 8 Gy X-rays. Lymphocytes were collected and prepared for flow cytometric analysis. Apoptosis was assessed by associated condensation of DNA. The incidences of late toxicities were compared for CD4 and CD8 T-lymphocyte apoptoses using receiver-operating characteristic curves and cumulative incidence.
  
  
  RESULTS
  No association was found between early toxicity and T-lymphocyte apoptosis. Grade 2 and 3 late toxicities were observed in 31% and 7% of patients, respectively. More radiation-induced T-lymphocyte apoptosis was significantly associated with less grade 2 and 3 late toxicity (Gray's test, P < 0.0001). CD8 (area under the curve = 0.83) was more sensitive and specific than CD4. No grade 3 late toxicity was observed for patients with CD4 and CD8 values greater than 15% and 24%, respectively. The 2-year cumulative incidence for grade 2 or 3 late toxicity was 70%, 32%, and 12% for patients with absolute change in CD8 T-lymphocyte apoptosis of < or =16, 16 to 24, and >24, respectively.
  
  
  CONCLUSIONS
  Radiation-induced T-lymphocyte apoptosis can significantly predict differences in late toxicity between individuals. It could be used as a rapid screen for hypersensitive patients to radiotherapy. In future dose escalation studies, patients could be selected using the apoptosis assay.
authors.affiliation: Authors' Affiliations: Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Mahmut
authors.initials: M
authors.lastname: Ozsahin
authors.forename: Nigel E A
authors.initials: NE
authors.lastname: Crompton
authors.forename: Sophie
authors.initials: S
authors.lastname: Gourgou
authors.forename: Andrew
authors.initials: A
authors.lastname: Kramar
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: YuQuan
authors.initials: Y
authors.lastname: Shi
authors.forename: Wendy Jeanneret
authors.initials: WJ
authors.lastname: Sozzi
authors.forename: Abderrahim
authors.initials: A
authors.lastname: Zouhair
authors.forename: René O
authors.initials: RO
authors.lastname: Mirimanoff
authors.forename: David
authors.initials: D
authors.lastname: Azria
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000528:radiation effects*; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology / Q000528:radiation effects*; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology / Q000528:radiation effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000473:pathology / Q000532:radiotherapy*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome