Radiation-Induced Lymphocyte Apoptosis to Predict Radiation Therapy Late Toxicity in Prostate Cancer Patients

Purpose: 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 and Materials: 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 DiOC6/7AAD 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.