Difference In Relative Biological Effectiveness Research Articles

Brain Necrosis in Adult Proton Therapy Patients. Do Necrotic Regions Have Elevated Linear Energy Transfer?

To investigate if brain necrosis induction correlates with regions of high linear energy transfer (LET) for proton radiation therapy treatments with partial brain involvement for central nervous system (CNS) and head and neck (H&N) patients. Fifty patients irradiated between 2004-2016 with CT image changes indicative of brain necrosis after irradiation were collected. For each patient, the necrotic region was contoured using MRI imaging. To obtain the LET distributions in the patients, treatment plans were recalculated using Monte Carlo simulations with TOPAS version 3.0.1. For each patient, voxels in the necrotic region were dose-matched with randomly selected voxels in the non-necrotic region of the brain and analyzed for a correlation of LET and occurrence of necrosis. In addition, a simplified relative biological effectiveness (RBE) model assuming a linear increase of RBE with LET was applied. A multilevel mixed-effects logistic regression was used to assess the impact of LET, dose, and tumor site on voxel-based necrosis. The probability of voxel necrosis was statistically significantly associated with increasing dose (p<0.0001) and tumor site (i.e., for the same dose H&N voxels are significantly more likely than CNS voxels to develop necrosis, p<0.0001). The LET was not associated with necrosis when adjusted for dose and tumor site, p=0.7. However, there are significant differences between patients (I2 statistics = 99.4%, p<0.0001) with some patients having significantly higher mean LET values in the necrotic regions (e.g., average LET 5.0 keV/μm vs 3.4 keV/μm, p<0.0001) while others having no difference or even lower LET values in the necrotic regions (e.g., 3.3 keV/μm vs 3.7 keV/μm, p<0.0001). The average difference in LET for dose-matched voxels was less than 0.2 keV/μm for the CNS and H&N cohorts as well as the average over the entire patient cohort. Selecting only high dose voxels (> 50 Gy) or the hottest 20 or 100 voxels also did not reveal any correlation between LET and onset of necrosis. The largest difference in LET was 1.8 keV/μm. The average difference in RBE over the patient cohort was less than 0.5 Gy(RBE), however, 13 patients had over 1 Gy(RBE) higher biological dose in the necrotic region and two patients showed a difference of over 4 Gy(RBE). Overall, we did not find any evidence for higher LET in necrotic voxels compared to non-necrotic voxels with the same dose (p=0.7). The LET (or RBE) variation alone cannot explain the induction of brain necrosis and there are other risk factors that need to be accounted for. Nevertheless, for some patients, high LET regions correlated with the necrotic region. These patients may benefit from LET optimization.

Relative biological effectiveness of pulsed and continuous 20 MeV protons for micronucleus induction in 3D human reconstructed skin tissue

Background and purpose Laser accelerated radiotherapy is a prospect for cancer treatment with proton and/or carbon ion beams that is currently under fast development. In principal, ultra fast, high-energy laser pulses will lead to a “pulsed” delivery of the induced ion beam with pulse durations of 1 ns and below, whereas conventional proton beams deriving from a cyclotron or synchrotron apply the dose within 100 ms (“continuous”). Materials and methods A simulation of both irradiation modes could be established at the Munich tandem accelerator with a 20 MeV proton beam, and a wide-field fast scanning system was implemented that allowed for application of up to 5 Gy per tissue voxel in a single pulse. The relative biological effectiveness (RBE) of pulsed and continuous modes of irradiation with 20 MeV protons relative to the reference radiation 70 kV X-rays was examined in a human tissue model (3D human reconstructed skin, EpiDermFT™) which preserves the three-dimensional geometric arrangement and communication of cells present in tissues in vivo. Using the induction of micronuclei (MN) in keratinocytes as the biological endpoint, the RBE was calculated as the ratio between the dose of 70 kV X-rays and 3 Gy of 20 MeV protons (pulsed or continuous) which produced equal response. Results For pulsed and continuous 20 MV proton exposures of the human skin model, RBE values of 1.08 ± 0.20 and 1.22 ± 0.15 versus 70 kV X-rays were obtained in a first experiment and 1.00 ± 0.14 and 1.13 ± 0.14 in a second experiment during distinct beam access times, respectively. The ∼10% difference in RBE between the respective irradiation modes in both experiments was associated with large uncertainties which were not statistically significant ( p ≈ 0.5). Conclusion These findings represent an important step on the way towards application of laser-accelerated protons for clinical radiotherapy. Further clinically relevant endpoints in normal and tumor tissue have to be evaluated.

Relative biological effectiveness of boron ions on human melanoma cells

Purpose : To compare the difference in relative biological effectiveness (RBE) between 10 B ions and a 60 Co γ-ray beam for human melanoma cells using in vitro cell survival based on a clonogenic assay. Materials and methods : Cells were irradiated in vitro under aerobic conditions with 60 Co and 10 B ions with different linear energy transfer (LET) (40, 80 and 160 eV nm -1) . The dose to the cells was determined using ferrous sulphate dosimetry and an ionisation chamber. The standard linear-quadratic model and the newly proposed repairable conditionally repairable damage (RCR) model were used to calculate the RBE. Results : The RBE at 10% cell survival for 40, 80 and 160eV nm -1 boron ions compared with 60 Co were 1.98 (1.83-2.22), 2.85 (2.64-3.11) and 3.37 (3.17-3.58), respectively, of almost independence of the model used in the calculation. Conclusions : Different cell survival models may generate different RBE, especially at low doses and high cell survival levels.

Distinct difference in relative biological effectiveness of 252Cf neutrons for the induction of mitotic crossing over and intragenic reversion of the white-ivory allele in Drosophila melanogaster

The relative biological effectiveness (RBE) of 252Cf neutrons was determined for two different types of somatic mutations, i.e., loss of heterozygosity for wing-hair mutations and reversion of the mutant white-ivory eye-color, in Drosophila melanogaster. Loss of heterozygosity for wing-hair mutations results predominantly from mitotic crossing over induced in wing anlage cells of larvae, while the reverse mutation of eye-color is due to an intragenic structural change in the white locus on the X-chromosome. For a quantitative comparison of RBE values for these events, we have constructed a combined mutation assay system so that induced mutant wing-hair clones as well as revertant eye-color clones can be detected simultaneously in the same individuals. Larvae were irradiated at the age of 80 ± 4 h post-oviposition with 252Cf neutrons or 137Cs γ-rays, and male adult flies were examined under the microscope for the presence of the two types of clonal mosaic spots appearing. The induction of wing-hair spots per dose unit was much greater for 252Cf neutrons than for 137Cs γ-rays, whereas the frequencies of eye-color reversion were similar for neutrons and γ-rays. The estimated RBE values of neutrons were 8.5 and 1.2 for the induction of mutant wing-hair spots and revertant eye-color spots, respectively. These results indicate that the RBE of neutrons is much greater for mitotic crossing over in comparison to the intragenic white-ivory reversion events. Possible causes for the difference in RBE are discussed.

Relative Biological Effectiveness of 50-MV X Rays on Jejunal Crypt Survival in Vivo

Earlier in vitro studies of relative biological effectiveness (RBE) of 50-MV X rays show an RBE of approximately 1.1 compared to 4 MV. No difference in RBE has been found for 20-MV X rays or 50-MeV electrons. The higher RBE for 50 MV can be explained to some extent by the small high linear energy transfer contribution from photonuclear reactions at high X-ray energies. To investigate the validity of the results in vitro, a study of the RBE of 50-MV X rays has been performed in vivo using the jejunal crypt microcolony assay in mice. The reference radiation used in this case was 20-MV X rays. The results confirm the earlier in vitro studies. The RBE for 50-MV X rays was estimated to be 1.06, calculated as the ratio between the slopes of the response curves.

Relative Biological Effectiveness of High-Energy Photons (up to 50 MV) and Electrons (50 MeV)

In vitro studies of the relative biological effectiveness (RBE) of 50-MV X rays have shown an RBE of 1.1 relative to 4-MV X rays. This will be important in clinical radiotherapy. The aim of this study was to verify these results and to investigate whether photonuclear processes might cause the difference in RBE. To do so, 50- and 20-MV X rays and 50-MeV electrons were investigated with respect to RBE. Chinese hamster V79 cells were irradiated in a specially designed system which allows for a high reproducibility of geometry and dosimetry. Fractionation experiments were also carried out to establish the RBE at the clinically relevant dose level, 2 Gy. Fricke dosimetry was used, and the results were confirmed with ionization chamber measurements. The RBE for 50-MV X rays was estimated to be 1.14 at a surviving fraction of 0.1 and 1.12 at a surviving fraction of 0.01. The RBEs for the other qualities were equal to one. The RBE calculated for the 2 Gy/fraction experiments was 1.17.

Biological Response In Vitro to Pulsed High Dose Rate Electrons from a Clinical Accelerator

Several studies of biological response to ionizing radiation of high absorbed dose rates have been performed, often with conflicting results. The aim of this study was to establish whether a difference between irradiation at high dose rates and at more conventional dose rates could be verified. Pulsed 50 MeV electrons from a clinical accelerator were used both for the high dose rate experiments (mean dose rate: 3.8 x 10(2) Gy/s) and the reference experiments (mean dose rate: 9.6 x 10(-2) Gy/s). In this study V-79 cells were irradiated in vitro. The experiments were carried out under both oxic and anoxic conditions. No significant difference in relative biological effectiveness (RBE) or oxygen enhancement ratio (OER) was observed at the different dose rates investigated.

Characteristics of Mg/Ar ionisation chambers used as gamma-ray dosemeters in mixed neutron-photon fields

Neutron fields are always accompanied by photons. Because of the difference in relative biological effectiveness of these two radiation components, it is necessary to determine neutron and photon absorbed dose in the mixed field separately. The use of Mg/Ar or Al/Ar ionisation chambers for determination of the photon component of the total absorbed dose could provide specific advantages related to the energies of the photons in the mixed field. Therefore information is presented to enable the greatest accuracy to be obtained in the use of these chambers. The gas flow characteristics of an Mg/Ar ionisation chamber show a complex behaviour most likely due to the Jesse effect in Ar. The dependence of the reading on the wall thickness of the chamber might be influenced by the irradiation geometry. The presence in the beam of charged particles created in hydrogen-rich materials could be important, as well as the contribution of low-energy photons produced by charged particles in the target construction. In Ar, the phenomenon that only positive ions and electrons are produced by ionising particles determines the ion collection. A polarity effect is often observed. The relative neutron sensitivities of different chambers of the same design irradiated under similar conditions show considerable variations.

The mutagenic effectiveness of 8.5 and 24.5 keV neutrons in Barley

The mutagenic effects of intermediate energy neutrons of 8.5 and 24.5 keV are compared with those of of higher energies (100 and 200 keV and fission neutrons). Due to the low dose-rate of intermediate neutrons and the small space available for irradiation, embryos of resting seeds of Bonus barley were used for the study. The relative biological effectiveness (RBE) of these neutrons was obtained by comparison with the effectiveness of 180 kV X-rays in inducing chlorophyll mutations. The following RBE values of mutagenic effectiveness of neutrons of different energies were found (with 80% confidence intervals); 8.5 keV: 0 (neg.−3.3); 24.5 keV: 21 (12–33); 100 keV: 204 (120–330); 200 keV: 102 (49–190); fision neutrons, ∼ 1MeV: 37 (29–47). However, the difference in RBE between 100 and 200 keV neutrons was not significant in the present case. The low mutagenic effectiveness of low-energy neutrons can be ascribed mainly to the short range of the charged particles. According to the two-hit theory for the induction of chromosomal aberrations by ionizing radiation, this would mean that mutations induced with the high RBE of high-LET radiations are mainly chromosomal aberrations (multi-locus deletions).

Repair of Potentially Lethal Radiation Damage: Comparison of Neutron and X-Ray RBE and Implications for Radiation Therapy

Experiments with Chinese hamster cells have shown that neutron irradiation does not result in repair of potentially lethal damage (PLD), i.e., that which can be influenced by changes in environmental conditions following irradiation. Since PLD is presumed to be repaired in tumors but not in normal tissues, this absence of differential sparing of tumor cells relative to normal tissues--a feature characteristic of irradiation with x rays--represents an advantage of neutrons in addition to their reduced oxygen effect. At a given dose, the difference in relative biological effectiveness (RBE) between tumors and normal tissues corresponds to a 5% increase in tumor dose with no concomitant increase in dose to normal tissues, which could be significant in cancer therapy.

Introduction

This subject of relative biological effectiveness (RBE) can have either a broad interpretation or a restricted, more specific one. In the broad sense, for those who are interested in protection primarily, the important thing is to know the relative effectiveness of the end-result, the mechanism being of a lesser importance. But those of us concerned with the more fundamental aspects of the problem are interested in the specific action, and we hope ultimately to learn something more about the biologic effect of radiations. We are interested in the action also because of what we can learn about the particular biologic unit that may respond differently to one type of radiation than to another. And so, if we are talking about the RBE in the restricted sense, we demand that everything be constant except the quality of the radiation, the density of ion pairs along the track of an ionizing particle. Lately, we use “energy transfer,” whatever the type of transfer of energy may be. It is the density of this per micron of path that we think accounts for the difference in RBE. Of course, our unit (for dosage purposes) is a gram of tissue, and within a gram of tissue there can be a lot of variation, but we are thinking in terms of density changes per micron along the path of an ionizing particle. So you will see the different interpretations in the papers that are to follow. None of us, of course, is able to say exactly that we are comparing two radiations in which the intensity is the same and the depth dose is the same, and that the volume of tissue that is irradiated is the same. We make an effort, to be sure, to get all these factors under control, but to control them all at the same time is very difficult.