Background and purpose: Chromosomal aberrations in peripheral blood lymphocytes are a biomarker for radiation exposure and are associated with an increased risk for malignancies. To determine the long-term cytogenetic effect of radiotherapy, we analyzed the persistence of different aberration types up to 2.5 years after the treatment.
Materials and methods: Cytogenetic damage was analyzed in lymphocytes from 14 patients that had undergone C-ion boost + IMRT treatment for prostate cancer. Samples were taken immediately, 1 year and 2.5 years after therapy. Aberrations were scored using the multiplex fluorescence in situ hybridization technique and grouped according to their transmissibility to daughter cells.
Results: Dicentric chromosomes (non-transmissible) and translocations (transmissible) were induced with equal frequencies. In the follow-up period, the translocation yield remained unchanged while the yield of dicentrics decreased to ≈40% of the initial value (p = 0.011 and p = 0.001 for 1 and 2.5 years after compared to end of therapy). In 2 patients clonal aberrations were observed; however they were also found in samples taken before therapy and thus were not radiotherapy induced.
Conclusion: The shift in the aberrations spectrum towards a higher fraction of translocations indicates the exposure of hematopoietic stem and progenitor cells underlining the importance of a careful sparing of bone marrow during radiotherapy to minimize the risk for secondary cancers.
Keywords: BM, bone marrow; Bone marrow; BrdU, Bromodeoxyuridine; Carbon ion therapy; Chromosomal translocations; FISH, Fluorescence in situ hybridization; FPG, fluorescence plus Giemsa staining; GTV, gross tumor volume; HSPCs, hematopoietic stem/progenitor cells; Hematopoietic stem cells; PBLs, peripheral blood lymphocytes; Prostate cancer; Risk assessment; mFISH, multiplex fluorescence in situ hybridization.