3074 - Chromosomal Aberrations in Peripheral Blood Lymphocytes as Predictive Biomarkers for Severe Adverse Events in Thoracic Definitive Chemoradiotherapy

Purpose/Objective(s):

This prospective observational study evaluated whether chromosomal aberrations (CAs) in peripheral blood lymphocytes (PBLs) during radiotherapy (RT) could predict radiation-induced toxicities in lung and esophageal cancer patients receiving definitive RT.

Materials/Methods: Eleven lung cancer and eighteen esophageal cancer patients receiving definitive chemoradiotherapy (CRT) were enrolled. The planned RT dose was 60–66 Gy for lung cancer and 50–60 Gy for esophageal cancer. All patients were planned to receive 2 Gy RT five days a week with platinum-based chemotherapy. PBLs were planned to be obtained during treatment on the day when the cumulative dose reached 20 Gy and on the last day of RT. Dicentric and ring chromosomes in PBLs were counted to evaluate the number of CAs. For the evaluation of radiation-induced toxicities, radiation pneumonitis and radiation esophagitis were assessed using the Common Terminology Criteria for Adverse Events version 5.0. Toxicity assessments were conducted for at least six months after RT, and the onset and progression of toxicities were closely monitored. Symptomatic pneumonitis (= Grade 2) was defined as severe due to its impact on clinical decisions. For esophagitis, Grade = 3 toxicity, which requires tube feeding or causes severe pain, was defined as severe esophagitis. Patients developing these toxicities were classified as overreactors (OR), while others were non-overreactors (NOR). The analysis of CA numbers and toxicity assessment was conducted by independent researchers. The Mann-Whitney U test was used to analyze the association between CA numbers and CRT-induced adverse events. A P-value of < 0.05 was considered statistically significant.

Results:

All patients received planned CRT. The median numbers of CAs per cell showed inter-individual variability and increased with cumulative dose. In lung cancer patients, the median CA numbers at 20 Gy and at the final dose (60–66 Gy) were 0.27 (0.04–0.56) and 0.75 (0.11–1.42), respectively. In esophageal cancer patients, the median CA numbers were 0.32 (0.22–1.10) at 20 Gy and 0.95 (0.52–2.30) at the final dose. In total, five patients developed grade =2 pneumonitis, and four patients developed grade =3 esophagitis during or after CRT (OR, n=9), while eleven patients had grade = 1 pneumonitis and grade = 2 esophagitis (NOR, n=20). The number of CAs was significantly higher in the OR group than in the NOR group at a cumulative dose of 20 Gy (median: 0.45 vs. 0.29, P=0.002) and on the last day of RT (median: 1.31 vs. 0.78, P < 0.001). All adverse events occurred after reaching 20 Gy.

Conclusion:

The number of CAs in PBLs at a cumulative dose of 20 Gy could be a useful biomarker for predicting acute CRT toxicities in thoracic malignancies.