Radiation-induced lymphocyte apoptosis and chromosomic aberrations for prediction of toxicities in patients undergoing radical radiotherapy for breast or prostate cancers

Abstract

Objectives: Radiation-induced lymphocyte apoptosis (RILA) and chromosomal damage assays (CDA) are proposed predictors of radiotherapy (RT) adverse events (RTAE). This study evaluated RILA and CDA in patients undergoing different RT dose regimens for early breast (FAST trial) or prostate (CHHiP trial) cancer.

Methods: Consecutive patients were recruited from each trial. Fresh heparinized blood samples were analysed for RILA and CDA. The primary endpoint was time to first change in photographic breast appearance (FAST) or time to first grade ≥2 RTOG bladder or bowel toxicity (CHHiP). The secondary endpoint in FAST was breast fibrosis.

Results: The dataset included 103 FAST and 297 CHHiP trial patients. No significant association of RILA with the primary endpoint was observed in the FAST trial. However, the risk of grade ≥2 breast fibrosis was lower in patients with RILA ≥24% compared to those with RILA ≤16% (P = .012). In the CHHiP trial, no significant associations were found between CDA after prostate RT outcomes. However, higher levels of micronuclei per cell were associated with a lower risk of grade ≥2 RTOG pelvic toxicities. The relative risk of developing grade ≥2 RTAE decreased for patients with RILA ≥ 24% but was not statistically significant.

Conclusions: No association was found between RILA and photographic breast appearance. High RILA values were statistically associated with a lower risk of grade ≥2 breast fibrosis. In the CHHiP trial, most assays showed no association with pelvic toxicities.

Advances in knowledge: RILA is confirmed as a potential predictor of breast fibrosis regarding fraction sizes.

Keywords: apoptosis; breast fibrosis; chromosomic aberrations; lymphocyte; pelvic toxicities; radiotherapy adverse effects.