Radiobiological Research Articles

Molecular mechanisms of sensitivity and resistance to radiotherapy.

The molecular mechanisms underlying sensitivity and resistance to radiotherapy is an area of active investigation and discovery as its clinical applications have the potential to improve cancer patients' outcomes. In addition to the traditional pathways of radiation biology, our knowledge now includes molecular pathways of radiation sensitivity and resistance which have provided insights into potential targets for enhancing radiotherapy efficacy. Sensitivity to radiotherapy is influenced by the intricate interplay of various molecular mechanisms involved in DNA damage repair, apoptosis, cellular senescence, and epigenetics. Translationally, there have been several successful applications of this new knowledge into the clinic, such as biomarkers for improved response to chemo-radiation. New therapies to modify radiation response, such as the poly (ADP-ribose) polymerase (PARP) inhibitors, derived from research on DNA repair pathways leading to radiotherapy resistance, are being used clinically. In addition, p53-mediated pathways are critical for DNA damage related apoptosis, cellular senescence, and cell cycle arrest. As the understanding of genetic markers, molecular profiling, molecular imaging, and functional assays improve, these advances once translated clinically, will help propel modern radiation therapy towards more precise and individualized practices.

An Overview of the Development of Stereotactic Body Radiation Therapy

Stereotactic body radiation therapy (SBRT) refers to focusing high-energy rays in three-dimensional space on the tumor lesion area, reducing the dose received by surrounding normal tissues, which can effectively improve the local control rate of the tumor and reduce the probability of complications.With the comprehensive development of medical imaging, radiation biology and other disciplines, this less-fractional, high-dose radiotherapy method has been increasingly developed and applied in clinical practice. The background, radio-biological basis, key technologies and main equipment of SBRT are discussed, and its future development direction is prospected.

Overview of FLASHlab@PITZ: the new R&D platform for FLASH radiation therapy and radiation biology

An R&D platform for electron FLASH radiation therapy and radiation biology is being prepared at the Photo Injector Test facility at DESY in Zeuthen (FLASHlab@PITZ). This platform is based on the unique beam parameters available at PITZ: ps scale electron bunches of up to 22 MeV with up to 5 nC bunch charge at MHz bunch repetition rate in bunch trains of up to 1 ms in length repeating at 1 to 10 Hz. It works together with the Technical University of Applied Sciences Wildau (TH Wildau) as partner in close vicinity for the biological resources.A startup beamline has been installed to allow dosimetry studies and irradiation experiments on chemical, biochemical and biological samples after a 60-degree dispersive arm. The measured dose and dose rates under different beam conditions and first experimental results will be reported in this paper. In addition, a dedicated beamline for FLASHlab@PITZhas been designed for better control of the high brightness electron beams. This includes a dogleg to translate the beam and a 2D kicker system to scan the tiny beam focused by quadrupoles across the samples within less than 1 ms. Simulation studies will be presented to demonstrate the extremely flexible dose parameters with various irradiation options for electron FLASH radiation therapy and radiation biology studies.

Comparison of measurements and simulation results of dose for the flash radiation therapy beamline at PITZ

The high-brightness electron beam at the Photo Injector Test facility at DESY in Zeuthen (PITZ) is now also used for FLASHlab@PITZ: an R.&D platform for studying radiation biology and the FLASH effect in radiation therapy. The available parameter space of the electron beam with a momentum of 22 MeV/c allows bunch charges from 1 pC up to 5 nC, bunch durations of 0.160 ps and bunch train lengths up to 1 ms. The number of bunches in the single train can currently be varied between 1 and 1000 bunches, with an upgrade to 4500 foreseen in 2023. Radiation biology studies require accurate dose predic-tion, therefore Monte Carlo simulations based on the FLUKA code were performed. According to estimations, dose delivery of 0.002 Gy (low charge case 1 pC) and 10 Gy (high charge case 5 nC) is possible, if the beam is confined to a circular area with a radius of 5 mm with a lead collimator. For the Monte Carlo simulations, the experimental setup was accurately modelled, including the exit window, lead collimator, etc. Dose measurements were used to compare simulations with experiments. Dose profiles were experimentally measured with Gafchromic films and then compared with Monte Carlo simulations. The first experiments at FLASHlab@PITZ in 2023 have demonstrated flexible dose options for studying the FLASH effect and radiation biology studies.

Remote focusing optical tweezers for 3D imaging.

We present a remote focusing optical tweezer utilizing a 4f symmetrical optical system to compensate the high-order aberration during annular light refocusing. The position of the optical trap can be adjusted beyond the range of one hundred micrometers in the axial direction by means of tuning the position of the mirror placed in the focal region of the illumination objective lens. This optical tweezer can be combined with a sectioning microscope to realize three-dimensional (3D) imaging, e.g., a confocal microscope using a single water immersion objective lens. All optical elements are placed in one side of the sample, which is very useful for application in fields such as radiation biology, where radiation or magnetism disturbance must be introduced on the other side of the sample. In the experiment, a 10 µm diameter silicon dioxide microsphere and pollen cells immersed in the water are translated along the axis using the optical tweezer and, meanwhile, the sectioning images are obtained using the confocal microscope.

Theranostic digital twins: Concept, framework and roadmap towards personalized radiopharmaceutical therapies.

Radiopharmaceutical therapy (RPT) is a rapidly developing field of nuclear medicine, with several RPTs already well established in the treatment of several different types of cancers. However, the current approaches to RPTs often follow a somewhat inflexible "one size fits all" paradigm, where patients are administered the same amount of radioactivity per cycle regardless of their individual characteristics and features. This approach fails to consider inter-patient variations in radiopharmacokinetics, radiation biology, and immunological factors, which can significantly impact treatment outcomes. To address this limitation, we propose the development of theranostic digital twins (TDTs) to personalize RPTs based on actual patient data. Our proposed roadmap outlines the steps needed to create and refine TDTs that can optimize radiation dose to tumors while minimizing toxicity to organs at risk. The TDT models incorporate physiologically-based radiopharmacokinetic (PBRPK) models, which are additionally linked to a radiobiological optimizer and an immunological modulator, taking into account factors that influence RPT response. By using TDT models, we envisage the ability to perform virtual clinical trials, selecting therapies towards improved treatment outcomes while minimizing risks associated with secondary effects. This framework could empower practitioners to ultimately develop tailored RPT solutions for subgroups and individual patients, thus improving the precision, accuracy, and efficacy of treatments while minimizing risks to patients. By incorporating TDT models into RPTs, we can pave the way for a new era of precision medicine in cancer treatment.

Production and measurement of MeV proton microbeams in atmospheric environment based on glass capillary

<sec>Traditionally, ion microbeam is produced by focusing or/and collimating to reduce the beam size to submicron level. The traditional setup for producing the microbeam consists of an expensive focusing and collimating system with a large space, based on electromagnetic fields. Meanwhile, the microbeam obtained through pure collimation of metal micro-tubes is limited by the fabrication processing, i.e. the size of beam spot is largely limited to a few microns and its manufacture is not as simple as that of a glass capillary. Inspired by early studies of the guiding effect, the use of inexpensive and easy-to-make glass capillaries as the tool for ion external microbeam production has become a new direction.</sec><sec>In this work, we use a glass capillary with an open outlet (108 μm in diameter), which serves as a vacuum differential and collimating component, to produce a 2.5 MeV-proton microbeam directly from the linear accelerator into the atmosphere for measurements. We measure the beam spot diameter and energy distribution of the microbeam as a function of the tilt angle of the capillary. We also conduct calculations and ion trajectory analysis on the scattering process of 2.5 MeV protons on the inner walls.</sec><sec>The measurement results show that when the tilt angle is around 0°, there are a direct transmission part that maintains the initial incident energy, and a scattering part with the energy loss in the microbeam. It is found that the proportion of directly transmitted protons and the beam spot size are highest near zero tilt angle. As the tilt angle increases, the beam spot diameter decreases; when the tilt angle is greater than the geometric angle, all the microbeams come from the scattering with the energy loss. The simulation combined with the ion trajectory analysis based on the scattering process can explain the experimental results. It is found that the large angle scattering determines the entire external microbeam spot, and the central region of the beam spot is composed of directly penetrating ions, whose size is determined by the geometric shape of the glass capillary, i.e. the outlet diameter and aspect ratio.</sec><sec>The natural advantage of producing external micobeames easily and inexpensively through glass capillaries is their relative safety and stable operation, and the last but not least point is to simply locate the microbeams on the sample without complex diagnostic tools. The microbeams are expected to be widely used in fields such as radiation biology, medicine, and materials.</sec>

Overview of PHITS Ver.3.34 with particular focus on track-structure calculation

This paper presents the latest updates on PHITS, a versatile radiation transport code, focusing specifically on track-structure models. Track structure calculations are methods used to simulate the movement of charged particles while explicitly considering each atomic reaction. Initially developed for radiation biology, these calculation methods aimed to analyze the radiation-induced damage to DNA and chromosomes. Several track-structure calculation models, including PHITS-ETS, PHITS-ETS for Si, PHITS-KURBUC, ETSART, and ITSART, have been developed and implemented for PHITS. These models allow users to study the behavior of various particles at the nano-scale across a wide range of materials. Furthermore, potential applications of track-structure calculations have also been proposed so far. This collection of track-structure calculation models, which encompasses diverse conditions, opens up new avenues for research in the field of radiation effects.

Synthesis and characterization of high-sensitivity Dy,Eu co-doped CaSO4 thermoluminescent phosphor using coprecipitation technique.

In this work, (99 - x)CaSO4 -Dy2 O3 -xEu2 O3 , (where x = 0, 0.05, 0.1, 0.2, 0.3, 0.4, 0.5) thermoluminescence phosphors were prepared using a coprecipitation method. The thermoluminescence (TL) dosimetry (TLD) characteristics such as TL sensitivity, dose-response, minimum detectable dose, thermal fading, and the effect of sunlight on the prepared phosphors were investigated. The obtained results indicated that the most sensitive phosphor was obtained at x = 0.05. Large thermal fading of 6% after 1 h and 26% after 24 h from irradiation followed by 71% after 1 month with no additional fading was observed within a time frame exceeding 2 months throughout the remaining duration of the investigation, which also spanned over 2 months. Despite the phosphor's high fading rate, the relative sensitivity of the prepared samples was ~90% compared with TLD-100. The marked effect of day sunlight was also determined. High dose-response within the low-dose range from 0.01 to 5 Gy was observed. The obtained results suggested that the synthesized phosphor is well suited for applications involving radiation biology and radiotherapy dosimetry.

Юрій Дуброва (1955–2023) — біолог з України, якого чув світ: нотатки до біографії

The future famous geneticist Prof. Yuri Dubrova (1955–2023) was born in Kyiv (Ukraine), where he received excellent secondary and higher education and was awarded with a gold medal upon graduating from school. Eventually, he became one of the best graduates of the Department of Vertebrate Zoology at the Faculty of Biology of Taras Shevchenko National University of Kyiv. His interests included theoretical biology, evolutionary theory, genetics, biometrics, and bionics (for some time he studied the lateral lineage of cyprinid fishes). In his last years at the university, he focused on the study of spontaneous mutations. At the Vavilov Institute of General Genetics in Moscow, Y. Dubrova continued his post-graduate studies and successfully defended his PhD thesis. After the collapse of the USSR, he moved to the UK in search of better scientific and technical opportunities, where he became a professor at the University of Leicester. The scientist lived and worked in Leicester until the end of his life. He devoted himself fully to science, especially to radiation, medical and population genetics, and to teaching, and tried to participate in the study of highly complex medical and genetic issues related, in particular, to the consequences of man-made disasters—Chornobyl (Ukraine, Belarus), Semipalatinsk (Kazakhstan)—and other cases of large-scale radiation effects on life. Dr. Dubrova is the author and co-author of more than 150 scientific articles published in leading journals, including the American Journal of Human Genetics, International Journal of Radiation Biology, Radiation Research, Molecular Biology and Evolution, International Journal of Cancer, British Journal of Cancer, Science, and Nature. He co-operated with many of the world’s leading geneticists and gave lectures in Ukraine, Russia, the USA, Canada, Japan, etc. The article uses fragments of the author’s long correspondence with Y. Dubrova, which may be of interest to biographers of F. Dobrzhansky, M. Tymofeiev-Resovsky, O. Sozinov, O. Yablokov, O. Kistiakowsky, as well as to students, teachers, and historians of Kyiv National University, Kaniv Nature Reserve, and the University of Leicester.

Salivary Organotypic Tissue Culture: An Ex-vivo 3D Model for Studying Radiation-Induced Injury of Human Salivary Glands.

An organotypic tissue culture model canmaintain the cellular and molecular interactions, as well as the extracellular components of a tissue ex vivo. Thus, this 3D modelbiologically mimics in vivo conditions betterthan commonly used 2D culture in vitro models. Here, we provide a detailed workflow for generating live 3Dorganotypic tissue slices from patient-derived freshly resected salivaryglandular tissues. We also cover the processing of these tissues for various downstream applications like live-dead viability/cytotoxicity assay, FFPE sectioning and immunostaining, and RNA and protein extraction with a focus on the salivary gland radiation injury model. These procedures can be applied extensively to various solid organs and used for disease modeling for cancer research, radiation biology, and regenerative medicine.

Dual Nucleosomal Double-Strand Breaks Are the Key Effectors of Curative Radiation Therapy

Most ionizing radiation produces δ-rays of ≈1 keV that can impart MGy doses to 100 nm3 volumes of DNA. These events can produce severe dual double-strand breaks (DDSBs) on nucleosomes, particularly in dense heterochromatic DNA. This is the most common multiply damaged site, and their probabilities determine the biological effectiveness of different types of radiation. We discuss their frequency, effect on cell survival, DNA repair, and imaging by gold nanoparticle tracers and electron microscopy. This new and valuable nanometer resolution information can be used for determining the optimal tumor cure by maximizing therapeutic effects on tumors and minimizing therapeutic effects on normal tissues. The production of DDSBs makes it important to deliver a rather high dose and LET to the tumor (>2.5 Gy/Fr) and at the same time reach approximately 1.8–2.3 Gy of the lowest possible LET per fraction in TP53 intact normal tissues at risk. Therefore, their intrinsic low-dose hyper-sensitivity (LDHS)-related optimal daily fractionation window is utilized. Before full p53 activation of NHEJ and HR repair at ≈½ Gy, the low-dose apoptosis (LDA) and LDHS minimize normal tissue mutation probabilities. Ion therapy should thus ideally produce the lowest possible LET in normal tissues to avoid elevated DDSBs. Helium to boron ions can achieve this with higher-LET Bragg peaks, producing increased tumor DDSB densities. Interestingly, the highest probability of complication-free cure with boron or heavier ions requires a low LET round-up for the last 10–15 GyE, thereby steepening the dose response and further minimizing normal tissue damage. In conclusion, the new high-resolution DSB and DDSB diagnostic methods, and the new more accurate DNA-repair-based radiation biology, have been combined to increase our understanding of what is clinically important in curative radiation therapy. In fact, we must understand that we already passed the region of optimal LET and need to go back one step rather than forward, with oxygen being contemplated. As seen by the high overkill and severely high LET in the distal tumor and the increased LET to normal tissues (reminding of neutrons or neon ions), it is therefore preferable to use lithium–boron ions or combine carbon with an optimal 10–15 GyE photon, electron, or perhaps even a proton round-up, thus allowing optimized, fractionated, curative, almost complication-free treatments with photons, electrons, and light ions, introducing a real paradigm shift in curative radiation therapy with a potential 5 GyE tumor boost, 25% increase in complication-free cure and apoptotic–senescent Bragg Peak molecular light ion radiation therapy.

Radiological protection in human research ethics using a case study: toward update of the ICRP Publication 62

The benefits of biomedical research involving humans are well recognised, along with the need for conformity to international standards of science and ethics. When human research involves radiation imaging procedures or radiotherapy, an extra level of expert review should be provided from the point of view of radiological protection. The relevant publication of the International Commission for Radiological Protection (ICRP) is now three decades old and is currently undergoing an update. This paper aims to provoke discussions on how the risks of radiation dose and the benefits of research should be assessed, using a case study of diagnostic radiology involving volunteers for whom there is no direct benefit. Further, the paper provides the current understanding of key concepts being considered for review and revision—such as the dose constraint and the novel research methods on the horizon, including radiation biology and epidemiology. The analysis revisits the perspectives described in the ICRP Publication 62, and considers the recent progress in both radiological protection ethics and medical research ethics.

Commissioning and Initial Validation of Commercial Treatment Planning System for the Electron FLASH Research Extension

The aim of this study was to investigate the feasibility of commissioning the 16 MeV electron FLASH beam in a commercial treatment planning system (TPS) for pre-clinical research purposes. The delivery system consisted of a new commercial solution for which a linear accelerator was modified into a FLASH Research Extension platform. Additionally, preliminary radiation biology results were highlighted to showcase the future use of this system. To commission a commercial electron Monte Carlo (MC) for dose calculation of a 16 MeV FLASH beam in the TPS, radiochromic film was used to measure the vendor-required beam data, e.g., profiles and percent depth dose (PDD) curves for cone sizes of 6 × 6 cm2, 10 × 10 cm2, and 15 × 15 cm2 as well as an in-air profile for a 40 × 40 cm2 open field (no cone). Once the electron MC beam model was generated, additional measurements were collected for validation and compared against the calculated dose from the TPS. A treatment planning comparison between the newly commissioned FLASH beam and the conventional electron beam was conducted. Specifically, the dose-volume histograms (DVHs) for target volumes and organs at risk were investigated for skin cancer cases previously treated with conventional electron beams. Lastly, the FLASH dose distribution predicted by the electron MC for an in vitro cell study setup was validated with radiochromic film measurements, and initial radiobiology tests were conducted using FLASH and conventional dose-rate electron beams. The electron MC calculated dose for the 16 MeV electron FLASH beam agreed with measured PDDs within 1% for all field sizes. The beam profile characteristics, such as penumbra, shape, and full width at half maximum, demonstrated good agreement with less than 0.5 mm difference between the TPS and measurements. There were noticeable differences in the profiles of large fields between the FLASH and conventional dose-rate beam models due to the more forward-peaked FLASH beam. For treatment planning, Regarding DVH, the FLASH dose-rate plan provided comparable plan quality to the conventional dose-rate plan, achieving adequate coverage for the target volumes and sparing the healthy organs and tissues. The electron MC dose prediction for the FLASH beam was also found to be in good agreement with the film measurements of the in vitro cell study setup. Furthermore, the FLASH beam was observed to be more effective with a 20 % increase in killing pancreatic cancer cells compared to the conventional dose rate. The study successfully incorporated the 16 MeV electron FLASH Research Extension into the commercial TPS using electron Monte Carlo for dose calculation. This will be valuable for pre-clinical cell and animal studies. This research also enables FLASH treatment planning studies, a key component for the future implementation of FLASH into clinical care. Further research is necessary to incorporate the radiation biology effect of FLASH into the treatment planning system.

All that Glitters is Not Gold: Examining Cost Effectiveness Analyses in Radiation Oncology

Cost effectiveness analyses (CEA) provide data for health policy decisions in resource constrained environments. These are important in Radiation Oncology as infrastructure and delivery costs increase and indications expand. The purpose of this study was to systematically review methodologic quality and trends in CEAs involving radiotherapy (RT). A systematic review was performed on cost effectiveness/utility studies involving RT, querying PubMed and Embase from inception to September 2020. Non-English, reviews, abstracts and cost-only studies were excluded. Independent reviewers screened and abstracted study demographics, economic parameters and methodological details. After screening 1652 abstracts, 214 met criteria. The first publication was in 1995, and more than half (n = 113, 53%) were published after 2014. Author institutions were from North America (n = 128, 60%), Europe (n = 49, 23%) and Asia (n = 30, 14%) with most reporting in US$ (n = 143, 67%). A majority utilized a decision model (n = 164, 77%), healthcare payer perspective (n = 171, 80%) and a finite time horizon (n = 108, 50%). Publications spanned 96 unique journals, most commonly International Journal of Radiation and Oncological Biology and Physics (n = 35, 16%). Treatment intent was curative in 171 studies. Disease sites included breast (n = 34, 16%), genitourinary (n = 31, 14%), and gastrointestinal (n = 31, 14%). RT was mostly used as primary treatment (n = 144, 67%), followed by adjuvant (n = 70, 33%) and neoadjuvant (n = 10, 5%). Emerging topics included stereotactic RT (n = 45, 21%), immunotherapy (n = 6, 3%), oligometastasis (n = 4, 2%), and heavy particles (n = 23, 11%). RT was compared to other RT (n = 136, 64%), surgery (n = 43, 20%), drugs (n = 14, 7%) and observation (n = 31, 17%). Incomplete reporting was common. Missing elements included analysis perspective (n = 13, 6%), time horizon (n = 38, 18%), discounting of utilities (n = 71, 33%) or costs (n = 54, 25%), and willingness-to-pay threshold (n = 59, 28%). Furthermore, 27 studies did not perform sensitivity analyses, 36 did not evaluate incremental cost-effectiveness ratio and only 60 explicitly utilized recognized reporting guidelines. Conflict of interest statements were found in 63%, with sponsor statements in 59%; 25% were industry sponsors. Outcome parameters were obtained from primary (author institution/trial data) sources in 33%, including randomized trials (RCTs) (n = 20, 9%), retrospective data (n = 20, 9%) and population data (n = 9, 4%). The remainder utilized secondary sources including RCTs (n = 71, 33%), retrospective data (n = 35, 16%) or meta-analyses (n = 11, 5%). Outcomes included quality adjusted life years (n = 158, 74%), life-years (n = 30, 14%) or toxicity (n = 26,12%). 31% utilized author generated utilities; of literature derived only 49% were matched to disease and clinical context. While CEAs are increasingly common in RT, reporting and methodologic rigor must improve. Greater use of published guidelines will improve data quality for decision makers.

Commissioning and Assessment of Radiation Field and Dose Inhomogeneity for a Dual X-Ray Tube Cabinet Irradiator: To Ensure Accurate Dosimetry in Radiation Biology Experiments

Standardization of X-ray cabinet irradiators calibration and dose reporting is an ongoing process. Multi-tube designs have been introduced and provide theoretical benefit but have not been assessed for pre-clinical irradiation conditions. This study was to report our experience commissioning a dual x-ray tube cabinet irradiator and assess dose distribution for various conditions. Homogeneity and percent depth dose (PDD) of various tube designs in single-tube setting have been previously reported, however multi-tube designs can overcome field asymmetry caused by the heel effect and improve dose fall-off at depth. Profile measurements and output calibration were performed with a calibrated ion chamber. We measured the percent-depth-dose (PDD) with film for each tube individually (PDDind) and both tubes simultaneously (PDDsim). To replicate conditions similar to petri dishes, we evaluated the range of attenuation and scatter under variable solid water thickness up to 9 mm with 3 mm build-up below (i.e., 1.2 cm total backscatter) under several geometries. The films were placed at a fixed position with variable amount of solid water placed above the film. We measured the output with variable water volumes with a 6 cm petri dish to simulate variable solution volumes that are frequently used during in vitro experiments. Film was also placed in a 3D printed mouse phantom with dimensions of (9.5 × 3.6 × 3.0 cm) and constructed to be roughly cylindrical. The dose in the 20 × 20 cm2 tray was within 8.4% of the central axis dose with both tubes. Dose rates decreased at the furthest points on the tray, but remained within 5% within the 15 × 15 cm2 central area. PDDsim with total 7.9 cm backscatter shows that the output is within 95% of the maximum dose at 4 cm depth. PDDsim with 1.2 cm backscatter is also within 95% of the maximum. The PDDind was less than 90% at 1.8 cm, which is similar to other single-tube systems. Slight increase in dose was seen with increasing solution; however, the doses were within 7% of the measured max dose at 6.3 mm depth. This agrees well with the solid water measurements. The results for both solid water and petri dish with variable medium is shown in Table 1. The 3D printed mouse phantom profiles for each plane showed results consistent with the ion chamber measurements. X-ray cell culture irradiation with dual-tube cabinet irradiation is robust when utilizing established dosimetric tools to confirm output and homogeneity. The conditions assumed for calibrations are often not maintained during experiments. We have confirmed that inhomogeneities are present for single tube use, however they are reduced with simultaneous tube use. Additional monitoring should be performed for each unique irradiation setup.

DNA as the main target in radiotherapy-ahistorical overview from first isolation to anti-tumour immune response.

DNA damage is one of the foremost mechanisms of irradiation at the biological level. After the first isolation of DNA by Friedrich Miescher in the 19th century, the structure of DNA was described by Watson and Crick. Several Nobel Prizes have been awarded for DNA-related discoveries. This review aims to describe the historical perspective of DNA in radiation biology. Over the decades, DNA damage has been identified and quantified after irradiation. Depending on the type of sensing, different proteins are involved in sensing DNA damage and repairing the damage, if possible. For double-strand breaks, the main repair mechanisms are non-homologous end joining and homologous recombination. Additional mechanisms are the Fanconi anaemia pathway and base excision repair. Different methods have been developed for the detection of DNA double-strand breaks. Several drugs have been developed that interfere with different DNA repair mechanisms, e.g., PARP inhibitors. These drugs have been established in the standard treatment of different tumour entities and are being applied in several clinical trials in combination with radiotherapy. Over the past decades, it has become apparent that DNA damage mechanisms are also directly linked to the immune response in tumours. For example, cytosolic DNA fragments activate the innate immune system via the cGAS STING pathway.

Assessment of Medical Student Research Mentorship in Radiation Oncology

Mentored medical student (MS) research opportunities in radiation oncology (RO) provide in-depth exposure to the specialty and may promote greater interest in a career in RO. Many radiation oncologists conduct research; however, the extent to which they directly engage MSs in their research is unknown. The purpose of this study was to characterize MS authorship in American Society for Radiation Oncology (ASTRO) journals. The byline and abstract of all scientific articles (ie, clinical, basic science, training/education) and case reports published from 2019 to 2021 in the International Journal of Radiation Oncology, Biology, and Physics; Practical Radiation Oncology; and Advances in Radiation Oncology were reviewed. Characteristics of MSs and senior authors are reported. A total of 105 of 1785 articles (5.8%) included an MS author, among which 72 (68.6%) were clinical, 13 training/education (12.4%), 12 case reports (11.4%), and 8 basic science (7.6%). MS authors were more common for publications in Advances in Radiation Oncology (9.0%) than Practical Radiation Oncology (6.4%) or the International Journal of Radiation Oncology, Biology, and Physics (4.2%; P=.002). There were 125 unique MS authors from 72 institutions, among which 40 were first author (32.0%), 28 second author (22.4%), and 57 third (or higher) author (45.6%). There were 88 unique senior authors from 55 institutions, among which 10 (11.3%) were on 2 or more MS publications, and 57 (64.7%) shared the same institution as the MS. The median number of articles per mentor institution was 1 (interquartile range, 1-2), and the mentor institutions in the upper quartile in terms of number of MS publications accounted for 53 (50.5%) of all MS publications. Few publications in American Society for Radiation Oncology journals include MS authors with mentorship disproportionately from a small number of academic faculty at select institutions. These findings suggest that there is great potential for radiation oncologists to proactively engage more students in their work.

Companion Animals as a Key to Success for Translating Radiation Therapy Research into the Clinic.

Many successful preclinical findings fail to be replicated during translation to human studies. This leads to significant resources being spent on large clinical trials, and in some cases, promising therapeutics not being pursued due to the high costs of clinical translation. These translational failures emphasize the need for improved preclinical models of human cancer so that there is a higher probability of successful clinical translation. Companion-animal cancers offer a potential solution. These cancers are more similar to human cancer than other preclinical models, with a natural evolution over time, genetic alterations, intact immune system, and a permanent adaptation to the microenvironment. These advantages have led pioneers in veterinary radiation oncology to aid human medicine by elucidating basic principles of radiation biology. More recently, the veterinary and human radiation oncology fields have increasingly collaborated to achieve advancements in education, radiotherapy techniques, and trial networks. This review describes these advancements, including significant prior research findings and the evolution of the veterinary radiation oncology discipline. It concludes by describing how companion-animal models can help shape the future of human radiotherapy. Taken as a whole, this review suggests companion-animal cancers may become widely used for preclinical radiotherapy research.

Comprehensive radiological parameterizations of proton and alpha particle interactions for some selected biomolecules: theoretical computation

Investigation of the interaction of radiations with biomolecules has several applications in the fields of radiation biophysics, radiation protection, medical biology, and medical physics. In this study, a comprehensive radiological parameterization of proton and alpha particles interactions at the energy range of (1 keV–10 GeV) and (1 keV–1 GeV), respectively for nucleotide bases (adenine, guanine, cytosine, uracil, thymine), carbohydrates (glucose, sucrose, raffinose), lipids (cholesterol, retinol, progesterone, cortisone, and phylloquinone), and fatty acids (lauric, myristic, palmitic, stearic, oleic, linoleic, linolenic, arachidonic, and arachidic) biomolecules have been carried out using PAGEX computer software. The radiological parameters calculated are the mass stopping power (S(E)/ρ), mass stopping cross-section (S c), effective atomic number (Z eff), and effective electron density (N eff). The highest values of S(E)/ρ and S c of proton and alpha particle interactions with the biomolecules occurred at the kinetic energy of about 0.1 and 0.5 MeV, respectively while that of the Z eff and N eff occurred at 0.1 MeV and 1 MeV, respectively. The S(E)/ρ and S c similarly vary with the kinetic energy due to their relations. As expected, the dependence of the Z eff and N eff of the biomolecules on the incidence energy was found to be similar. The comparisons of the Z eff and N eff calculated in this study, using PAGEX software with some studies in the literature that used the interpolation method showed variations that account for differences between the two methods.