CD4 and CD8 T-lymphocyte apoptosis can predict radiation-induced late toxicity: a prospective study in 399 patients

Clin Cancer Res. 2005 Oct 15;11(20):7426-33. doi: 10.1158/1078-0432.CCR-04-2634.

Abstract

Purpose: 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.

Experimental design: 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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis / radiation effects*
  • CD4-Positive T-Lymphocytes / pathology
  • CD4-Positive T-Lymphocytes / radiation effects*
  • CD8-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / radiation effects
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / blood
  • Neoplasms / pathology
  • Neoplasms / radiotherapy*
  • Predictive Value of Tests
  • Prospective Studies
  • Survival Analysis
  • Treatment Outcome