High-Accuracy Relative Biological Effectiveness Values Following Low-Dose Thermal Neutron Exposures Support Bimodal Quality Factor Response with Neutron Energy

Theoretical evaluations indicate the radiation weighting factor for thermal neutrons differs from the current International Commission on Radiological Protection (ICRP) recommended value of 2.5, which has radiation protection implications for high-energy radiotherapy, inside spacecraft, on the lunar or Martian surface, and in nuclear reactor workplaces. We examined the relative biological effectiveness (RBE) of DNA damage generated by thermal neutrons compared to gamma radiation. Whole blood was irradiated by 64 meV thermal neutrons from the National Research Universal reactor. DNA damage and erroneous DNA double-strand break repair was evaluated by dicentric chromosome assay (DCA) and cytokinesis-block micronucleus (CBMN) assay with low doses ranging 6–85 mGy. Linear dose responses were observed. Significant DNA aberration clustering was found indicative of high ionizing density radiation. When the dose contribution of both the 14N(n,p)14C and 1H(n,γ)2H capture reactions were considered, the DCA and the CBMN assays generated similar maximum RBE values of 11.3 ± 1.6 and 9.0 ± 1.1, respectively. Consequently, thermal neutron RBE is approximately four times higher than the current ICRP radiation weighting factor value of 2.5. This lends support to bimodal peaks in the quality factor for RBE neutron energy response, underlining the importance of radiological protection against thermal neutron exposures.

A Mechanistic DNA Repair and Survival Model (Medras): Applications to Intrinsic Radiosensitivity, Relative Biological Effectiveness and Dose-Rate

Variations in the intrinsic radiosensitivity of different cells to ionizing radiation is now widely believed to be a significant driver in differences in response to radiotherapy. While the mechanisms of radiosensitivity have been extensively studied in the laboratory, there are a lack of models which integrate this knowledge into a predictive framework. This paper presents an overview of the Medras model, which has been developed to provide a mechanistic framework in which different radiation responses can be modelled and individual responses predicted. This model simulates the repair of radiation-induced DNA damage, incorporating the overall kinetics of repair and its fidelity, to predict a range of biological endpoints including residual DNA damage, mutation, chromosome aberration, and cell death. Validation of this model against a range of exposure types is presented, including considerations of varying radiation qualities and dose-rates. This approach has the potential to inform new tools to deliver mechanistic predictions of radiation sensitivity, and support future developments in treatment personalization.

Impact of Hypoxia on Relative Biological Effectiveness and Oxygen Enhancement Ratio for a 62-MeV Therapeutic Proton Beam

This study uses the yields of double-strand breaks (DSBs) to determine the relative biological effectiveness (RBE) of proton beams, using cell survival as a biological endpoint. DSB induction is determined when cells locate at different depths (6 positions) along the track of 62 MeV proton beams. The DNA damage yields are estimated using Monte Carlo Damage Simulation (MCDS) software. The repair outcomes are estimated using Monte Carlo excision repair (MCER) simulations. The RBE for cell survival at different oxygen concentrations is calculated using the repair-misrepair-fixation (RMF) model. Using 60Co γ-rays (linear energy transfer (LET) = 2.4 keV/μm) as the reference radiation, the RBE for DSB induction and enzymatic DSB under aerobic condition (21% O2) are in the range 1.0–1.5 and 1.0–1.6 along the track depth, respectively. In accord with RBE obtained from experimental data, RMF model-derived RBE values for cell survival are in the range of 1.0–3.0. The oxygen enhancement ratio (OER) for cell survival (10%) decreases from 3.0 to 2.5 as LET increases from 1.1 to 22.6 keV/μm. The RBE values for severe hypoxia (0.1% O2) are in the range of 1.1–4.4 as LET increases, indicating greater contributions of direct effects for protons. Compared with photon therapy, the overall effect of 62 MeV proton beams results in greater cell death and is further intensified under hypoxic conditions.

Multi-Institutional Retrospective Analysis of Carbon-Ion Radiotherapy for Patients with Locally Advanced Adenocarcinoma of the Uterine Cervix

The clinical significance of carbon-ion radiotherapy (CIRT) for adenocarcinoma (AC) of the uterine cervix has been assessed in several single-institutional studies. To validate the significance, we conducted a multi-institutional survey of CIRT for locally advanced AC (LAAC) of the uterine cervix. We retrospectively analyzed the clinical outcomes of patients with stage IIB–IVA LAAC of the uterine cervix who underwent chemo-CIRT or CIRT alone between April 2010 and April 2016. Patients received 74.4 Gy (relative biological effectiveness [RBE]) in 20 fractions of CIRT or 55.2 Gy (RBE) in 16 fractions of CIRT plus three sessions of brachytherapy. Patients aged ≤ 70 years with adequate bone marrow and organ function were administered cisplatin weekly (40 mg/m2 per week for up to 5 weeks). Fifty-five patients were enrolled in this study. The median follow-up period was 67.5 months. The 5-year overall survival (OS) and local control (LC) rates were 68.6% and 65.2%, respectively. Multivariate analysis showed that the initial tumor response within 6 months was significantly associated with LC and OS. The present study represents promising outcomes of CIRT or chemo-CIRT for LAAC of the uterine cervix, especially in the cases showing initial rapid regression of the tumor.