Longitudinal Monitoring of Radiation-Induced Chromosomal Aberrations during Proton Therapy
Abstract
Purpose
Cytogenetic biodosimetry provides a biological measure of radiation-induced DNA damage; however, its application in clinical proton therapy patients remains limited. The purpose of this study was to establish a longitudinal framework for assessing chromosomal damage in a proton therapy patient using serial blood sampling at key treatment time points.
Methods
Peripheral blood samples were collected from a proton therapy patient at three predefined clinical time points: pre-treatment baseline, mid-treatment, and post-treatment. Blood collection was performed using standard venipuncture techniques, and samples were processed according to established cytogenetic biodosimetry protocols. Peripheral blood lymphocytes were cultured, harvested, and prepared for chromosome aberration analysis using conventional metaphase preparation methods. Cytogenetic dosimetry was conducted by scoring chromosome aberrations, with dicentric chromosomes serving as the primary biomarker of radiation-induced DNA damage. Metaphase spreads meeting established quality criteria were analyzed to ensure reliable aberration identification. Dicentric chromosome frequency was quantified for each time point and used to assess temporal changes in cytogenetic damage associated with proton therapy exposure.
Results
Baseline measurements demonstrated low background levels of chromosomal aberrations, consistent with expected spontaneous dicentric frequencies in unirradiated peripheral blood lymphocytes. At mid-treatment, an increase in dicentric chromosome frequency was observed relative to baseline, indicating treatment-associated DNA damage accumulation. Following treatment completion, additional changes in dicentric frequency were measured, demonstrating a continued temporal response to proton irradiation. The observed trends reflect the dynamic nature of chromosomal damage during the course of therapy.
Conclusion
This study demonstrates the feasibility of longitudinal cytogenetic dosimetry in a proton therapy patient and provides a proof-of-concept framework for monitoring treatment-induced DNA damage in vivo. These findings establish a foundation for future studies involving larger patient cohorts, patient-specific biological response assessment, and integration with automated cytogenetic scoring methodologies.