Radiation-induced lymphocyte apoptosis to predict radiation therapy late toxicity in prostate cancer patients.
OBJECTIVE
To examine a potential correlation between the in vitro apoptotic response of lymphocytes to radiation and the risk of developing late gastrointestinal (GI)/genitourinary (GU) toxicity from radiotherapy for prostate cancer.


METHODS
Prostate cancer patients formerly enrolled in a randomized study were tested for radiosensitivity by using a radiation-induced lymphocyte apoptosis assay. Apoptosis was measured using flow cytometry-based Annexin-FITC/7AAD and DiOC(6)/7AAD assays in subpopulations of lymphocytes (total lymphocytes, CD4+, CD8+ and CD4-/CD8-) after exposure to an in vitro dose of 0, 2, 4, or 8 Gy.


RESULTS
Patients with late toxicity after radiotherapy showed lower lymphocyte apoptotic responses to 8 Gy than patients who had not developed late toxicity (p = 0.01). All patients with late toxicity had apoptosis levels that were at or below the group mean. The negative predictive value in both apoptosis assays ranged from 95% to 100%, with sensitivity values of 83% to 100%. Apoptosis at lower dose points and in lymphocyte subpopulations had a weaker correlation with the occurrence of late toxicity.


CONCLUSIONS
Lymphocyte apoptosis after 8 Gy of radiation has the potential to predict which patients will be spared late toxicity after radiation therapy. Further research should be performed to identify the specific subset of lymphocytes that correlates with late toxicity, followed by a corresponding prospective study.
Schnarr
Kara
K
Department of Medicine, St. George's University, Grenada, WI, USA.
Boreham
Douglas
D
Sathya
Jinka
J
Julian
Jim
J
Dayes
Ian S
IS
D017209:Apoptosis / Q000502:physiology / Q000528:radiation effects*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology / Q000528:radiation effects*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology / Q000528:radiation effects*; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007496:Iridium Radioisotopes / Q000627:therapeutic use; D008297:Male; D011237:Predictive Value of Tests; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011836:Radiation Tolerance / Q000502:physiology*; D011878:Radiotherapy / Q000009:adverse effects; D012044:Regression Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology / Q000528:radiation effects
D007496:Iridium Radioisotopes