Modelling of RBE differences in selected points within similar spread-out Bragg-peaks (SOBP) placed at superficial and deep water phantom locations in passively scattered beams but not in scanned pencil beams: A hypothesis.

Purpose: To model relative biological effectiveness (RBE) differences found in two studies which used spread-out Bragg-peaks (SOBP) placed at (a) superficial depth and (b) at the maximum range depth. For pencil beam scanning (PBS), RBE at similar points within the SOBP did not change between the two extreme SOBP placement depths; in passively scattered beams (PSB), high RBE values (typically 1.2-1.

A generalised method for calculating repopulation-corrected tumour EQD2 values in a wide range of clinical situations, including interrupted treatments.

Any radiotherapy schedule can be characterised by its 2 Gy per fraction equivalent dose (EQD2). EQD2s are easily calculated for late-responding normal tissues but for tumours significant errors may arise if no allowance is made for any repopulation which occurs in the reference and/or the derived EQD2 schedule. This article presents a systematic approach to calculating tumour EQD2 values utilising the concept of biologically effective dose (BED) with inclusion of repopulation effects.

Feasibility and safety of shortened hypofractionated high-dose palliative lung radiotherapy - A retrospective planning study.

Objective: Assess the safety and feasibility of shortened hypofractionated high-dose palliative lung radiotherapy in a retrospective planning study.

Methods: Fifteen late stage (III or IV) NSCLC lung radiotherapy patients previously treated with the standard palliative 36 Gy in 12 fractions (12F) schedule were non-randomly selected to achieve a representative distribution of tumour sizes, volumes, and location. Plans were produced using 30 Gy in 5 fractions (5F) and 6 fractions (6F) using a 6MV FFF co-planar VMAT technique.

Improving the Accuracy of Biologically Effective Dose Estimates, from a Previously Published Study, After Radiosurgery for Acoustic Neuromas.

Objective: To recalculate biological effective dose values (BED) for radio-surgical treatments of acoustic neuroma from a previous study. BEDs values were previously overestimated by only using beam-on times in calculations, so excluding the important beam-off-times (when deoxyribonucleic acid repair continues) which contribute to the overall treatment time. Simple BED estimations using a mono-exponential approximation may not always be appropriate but if used should include overall treatment time.

The influence of hypoxia on LET and RBE relationships with implications for ultra-high dose rates and FLASH modelling.

. To investigate relationships between linear energy transfer (LET), fluence rates, changes in radiosensitivity and the oxygen enhancement ratio (OER) in different ion beams and extend these concepts to ultra-high dose rate (UHDR) or FLASH effects.LET values providing maximum relative biological effect (RBE), designated as LET, are found for neon, carbon and helium beams.

Further development of spinal cord retreatment dose estimation: including radiotherapy with protons and light ions.

Purpose: A graphical user interface (GUI) was developed to aid in the assessment of changes in the radiation tolerance of spinal cord/similar central nervous system tissues with time between two individual treatment courses.

Methods: The GUI allows any combination of photons, protons (or ions) to be used as the initial, or retreatment, radiotherapy courses. Allowances for clinical circumstances, of reduced tolerance, can also be made.

Low radiation dose to treat pneumonia and other inflammations.

Infection, the invasion of pathogenic microorganisms and viruses, causes reactive inflammation mediated by endogenous signals, with influx of leucocytes with distinct properties and capable of mounting a cellular or antibody response. Different forms of inflammation may also occur in response to tumours, in allergy and autoimmune disorders. Pneumonia, respiratory tract infection and septic shock for instance can arise as serious complications of the Covid-19 virus.

Fast neutron energy based modelling of biological effectiveness with implications for proton and ion beams.

A practical neutron energy dependent RBE model has been developed, based on the relationship between a mono-energetic neutron energy and its likely recoil proton energy. Essentially, the linear energy transfer (LET) values of the most appropriate recoil proton energies are then used to modify the linear quadratic model radiosensitivities (α and β) from their reference LET radiation values to provide the RBE estimates. Experimental neutron studies published by Hall (including some mono-energetic beams ranging from 0.

The physical separation between the LET associated with the ultimate relative biological effect (RBE) and the maximum LET in a proton or ion beam.

Purpose: To identify the relative positions of the ultimate RBE, at a LET value of LET (where the LET-RBE turnover point occurs independently of dose), and of the maximum LET (LET) for a range of ions from protons to Iron ions.

Methods: For a range of relativistic velocities (β), the kinetic energies, LET values and ranges for each ion are obtained using SRIM software. For protons and helium ions, the LET changes with β are plotted and LET is compared with LET For all the ions studied the residual ranges of particles at LET and LET are subtracted to provide the physical separation (S) between LET and LET.

Clinical and practical considerations in the design of appropriate compensation schedules following treatment interruptions.

Compensatory dose calculations to mitigate the deleterious effect of unscheduled treatment interruptions remain important. They may be increasingly required during and after epidemics, as with the present Covid-19 virus. The information presented to those involved in the actual dose estimations is often limited, thereby increasing the likelihood of confusion, further time delays and possibly incorrect decisions.

Clinical Radiobiology of Fast Neutron Therapy: What Was Learnt?

Neutron therapy was developed from neutron radiobiology experiments, and had identified a higher cell kill per unit dose and an accompanying reduction in oxygen dependency. But experts such as Hal Gray were sceptical about clinical applications, for good reasons. Gray knew that the increase in relative biological effectiveness (RBE) with dose fall-off could produce marked clinical limitations.

The influence of the α/β ratio on treatment time iso-effect relationships in the central nervous system.

To investigate the influence of changes in α/β ratio (range 1.5-3 Gy) on iso-effective doses, with varying treatment time, in spinal cord and central nervous system tissues with comparable radio-sensitivity. It is important to establish if an α/β ratio of 2 Gy, the accepted norm for neuro-oncology iso-effect estimations, can be used.

Physical characteristics at the turnover-points of relative biological effect (RBE) with linear energy transfer (LET).

This paper considers the kinematic physical characteristics of ionic beams for maximum relative bio-effectiveness (RBE). RBE studies, based on heterogenous cell survival studies at different laboratories and linear energy transfer (LET) conditions for proton, helium, carbon, neon and argon ions, have been further analysed to determine the LET values where RBE is maximal and the LET-RBE relationship has a turnover point. The SRIM stopping power software and other classical equations are used to determine the particle velocities, kinetic energies and their effective ionic charges at LET.

Establishment of a Therapeutic Ratio for Gamma Knife Radiosurgery of Trigeminal Neuralgia: The Critical Importance of Biologically Effective Dose Versus Physical Dose.

Objective: How variations of treatment time affect the safety and efficacy of Gamma Knife (GK) radiosurgery is a matter of considerable debate. With the relative simplicity of treatment planning for trigeminal neuralgia (TN), this question has been addressed in a group of these patients. Using the concept of the biologically effective dose (BED), the effect of the two key variables, dose and treatment time, were considered.

Use of radiobiology in medical jurisprudence, with particular reference to delays in diagnosis and therapeutic onset.

Objective: This paper considers aspects of radiobiology and cell and tissue kinetics applicable to legal disputations concerned with diagnostic and treatment onset delays.

Methods: Various models for tumour volume changes with time are reviewed for estimating volume ranges at earlier times, using ranges of kinetic parameters. Statistical cure probability methods, using Poisson statistics with allowances for parameter heterogeneity, are also described to estimate the significance of treatment delays, as well as biological effective dose (BED) estimations of radiation effectiveness.

Effects of variations in overall treatment time on the clonogenic survival of V79-4 cells: Implications for radiosurgery.

The importance of effects related to the repair of sublethal radiation damage as treatment duration varies, partly a function of dose-rate, is a current controversy in clinical radiosurgery. Cell survival studies have been performed to verify the importance of this effect in relation to established models. Mammalian V79-4 cells were irradiated in vitro with γ-rays, either as an acute exposure in a few minutes, where the effects of sublethal irradiation damage repair over the period of exposure can be ignored, or as protracted exposures delivered over 15-120 min.

The radiobiological effects of He, C and Ne ions as a function of LET on various glioblastoma cell lines.

The effects of the charged ion species 4He, 12C and 20Ne on glioblastoma multiforme (GBM) T98G, U87 and LN18 cell lines were compared with the effects of 200 kVp X-rays (1.7 keV/μm). These cell lines have different genetic profiles.

Modeling and multiscale characterization of the quantitative imaging based fibrosis index reveals pathophysiological, transcriptome and proteomic correlates of lung fibrosis induced by fractionated irradiation.

Pulmonary fibrosis represents a leading cause of morbidity and mortality worldwide. Therapy induced lung fibrosis constitutes a pivotal dose-limiting side effect of radiotherapy and other anticancer agents. We aimed to develop objective criteria for assessment of fibrosis and discover pathophysiological and molecular correlates of lung fibrosis as a function of fractionated whole thoracic irradiation.

Determining RBE for development of lung fibrosis induced by fractionated irradiation with carbon ions utilizing fibrosis index and high-LET BED model.

Background And Purposes: Carbon ion radiotherapy (CIRT) with raster scanning technology is a promising treatment for lung cancer and thoracic malignancies. Determining normal tissue tolerance of organs at risk is of utmost importance for the success of CIRT. Here we report the relative biological effectiveness (RBE) of CIRT as a function of dose and fractionation for development of pulmonary fibrosis using well established fibrosis index (FI) model.

Potential lethal damage repair in glioblastoma cells irradiated with ion beams of various types and levels of linear energy transfer.

Glioblastoma (GBM), a Grade IV brain tumour, is a well-known radioresistant cancer. To investigate one of the causes of radioresistance, we studied the capacity for potential lethal damage repair (PLDR) of three altered strains of GBM: T98G, U87 and LN18, irradiated with various ions and various levels of linear energy transfer (LET). The GBM cells were exposed to 12C and 28Si ion beams with LETs of 55, 100 and 200 keV/μm, and with X-ray beams of 1.