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In this study, Monte Carlo codes, Geant4 and MCNP6, were used to characterize the fast neutron therapeutic beam produced at iThemba LABS in South Africa. Experimental and simulation results were compared using the latest generation of Silicon on Insulator (SOI) microdosimeters from the Centre for Medical Radiation Physics (CMRP). Geant4 and MCNP6 were able to successfully model the neutron gantry and simulate the expected neutron energy spectrum produced from the reaction by protons bombarding a 9Be target. The neutron beam was simulated in a water phantom and its characteristics recorded by the silicon microdosimeters; bare and covered by a 10B enriched boron carbide converter, at different positions. The microdosimetric quantities calculated using Geant4 and MCNP6 are in agreement with experimental measurements. The thermal neutron sensitivity and production of 10B capture products in the p+ boron-implanted dopant regions of the Bridge microdosimeter is investigated. The obtained results are useful for the future development of dedicated SOI microdosimeters for Boron Neutron Capture Therapy (BNCT). This paper provides a benchmark comparison of Geant4 and MCNP6 capabilities in the context of further applications of these codes for neutron microdosimetry.

Introduction About 5% of cancer patients receiving radiation therapy (RT) exhibit severe normal tissue reactions. The prediction of late toxicity in cancer patients would enable individualized and optimized radiation dose prescription. In this study, four different candidate in vitro cellular radiosensitivity assays for prediction of late normal tissue reactions were evaluated in a retrospective matched case-control set-up of breast cancer patients. Materials and methods Breast cancer patients expressing severe radiation toxicity (12 cases) and no or minimal reactions (12 controls) with a follow-up of at least 3 years were selected for this study. Case and control patients were matched for therapy and patient related variables. After in vitro irradiation of patient blood samples, case and control radiation responses were compared for the following biological end points: radiation-induced CD8+ late apoptosis, residual DNA double strand breaks (DSB), G0 and G2+caf micronucleus assay. Results Despite a substantial overlap in standard deviations, all cellular assays showed a significant difference between cases and controls. Less radiation-induced apoptosis was observed in CD8+ lymphocytes of cases (14.45%) compared to the matched controls (30.64%) (p 0.01). The number of residual DNA DSB was higher in cases (9.92 foci/cell) compared to their matched controls (9.17 foci/cell) (p 0.01). The average dose response curve of the G0 MN assay for cases lies above the average dose response curve of the controls. Finally, a pairwise comparison of the G2+caf MN results showed a higher MN yield for cases (351 MN/1000BN) compared to controls (219 MN/1000BN) (p 0.01). Conclusion Current results suggest that intrinsic radiosensitivity is involved in the development of late radiotoxic effects. Larger prospective studies are warranted to validate the retrospective findings in order to use in vitro cellular assays in the future to predict late normal tissue radiosensitivity in clinical practice.

Introduction Due to their long life span, accumulation of DNA damage in stem cells can compromise their genomic integrity. Hematopoietic stem and progenitor cells (HSPCs), characterized by the cell surface marker CD34, may be a major target for radiation-induced leukemogenesis. Secondary leukemia risks are especially important for childhood cancer survivors treated with radiotherapy, since epidemiological data indicate that the risk for radiation-induced hematological malignancies is 3–5 times higher for children compared to adults. In order to investigate the underlying mechanism of radiation-induced leukemia, an in vitro study of the radiation effects in CD34+ cells was performed. Materials and Methods Human CD34+ HSPCs were isolated from umbilical cord blood by using CD34+ immunomagnetic beads (Miltenyi). Peripheral blood T-lymphocytes were isolated from healthy adults using RosetteSepTM human T-cell enrichment cocktail (Stemcell). Radiation-induced DNA double-strand breaks (DSBs) were assessed by microscopic scoring of γ -H2AX/53BP1 foci 0.5h after low-dose x-ray exposure, while DNA repair was evaluated by scoring residual γ -H2AX/53BP1 foci 24h after 4 Gy x-ray exposure. A micro-culture cytokinesis block micronucleus (MN) assay was developed for CD34+ cells in order to study radiation-induced mutagenic effects after 2 Gy x-ray exposure. Results HSPCs show significantly lower endogenous levels of DNA DSBs and MNi compared to adult T-lymphocytes. No statistical significant difference could be observed in the number of DNA DSBs induced by low-dose x-rays (100 and 200 mGy) between HSPCs and T-lymphocytes. However, the number of residual DNA DSBs 24h post-exposure was significantly lower in HSPCs (3.54 foci/cell) compared to T-lymphocytes (5.77 foci/cell). Furthermore, HSPCs showed a significantly higher number of MNi (371MN/1000BN cells) compared to T-lymphocytes (275MN/1000BN cells). Conclusion The low number of residual DNA DSBs 24h post-exposure and the high number of radiation-induced MN yields in HSPCs indicate fast error-prone DNA repair and mutagenesis after radiation exposure, which could trigger leukemia development.