TP53 and the Ultimate Biological Optimization Steps of Curative Radiation Oncology.

The new biological interaction cross-section-based repairable-homologically repairable (RHR) damage formulation for radiation-induced cellular inactivation, repair, misrepair, and apoptosis was applied to optimize radiation therapy. This new formulation implies renewed thinking about biologically optimized radiation therapy, suggesting that most TP53 intact normal tissues are low-dose hypersensitive (LDHS) and low-dose apoptotic (LDA). This generates a fractionation window in LDHS normal tissues, indicating that the maximum dose to organs at risk should be ≤2.

Comparative evaluation of advanced oxidation processes (AOPs) for reducing SARS-CoV-2 viral load from campus sewage water.

Presence of SARS-CoV-2 in wastewater is a major concern as the wastewater meets rivers and other water bodies and is used by the population for various purposes. Hence it is very important to treat sewage water in an efficient manner in order to reduce the public health risk. In the present work, various advanced oxidation processes (AOPs) have been evaluated for disinfection of SARS-CoV-2 from sewage water collected from STP inlet of academic institutional residential.

Quantifying Cellular Repair, Misrepair and Apoptosis Induced by Boron Ions, Gamma Rays and PRIMA-1 Using the RHR Formulation.

The recent interaction cross-section-based formulation for radiation-induced direct cellular inactivation, mild and severe sublethal damage, DNA-repair and cell survival have been developed to accurately describe cellular repair, misrepair and apoptosis in TP53 wild-type and mutant cells. The principal idea of this new non-homologous repairable-homologous repairable (RHR) damage formulation is to separately describe the mild damage that can be rapidly handled by the most basic repair processes including the non-homologous end joining (NHEJ), and more complex damage requiring longer repair times and high-fidelity homologous recombination (HR) repair. Taking the interaction between these two key mammalian DNA repair processes more accurately into account has significantly improved the method as indicated in the original publication.

A DNA Repair-Based Model of Cell Survival with Important Clinical Consequences.

This work provides a description of a new interaction, cross-section-based model for radiation-induced cellular inactivation, sublethal damage, DNA repair and cell survival, with the ability to more accurately elucidate different radiation-response phenomena. The principal goal of this work is to describe the damage-induction cross sections, as well as repair and survival, as Poisson processes with two main types of damage: mild damage that can be rapidly handled by the most basic repair processes; and more complex damage requiring longer repair times and the high-fidelity homologous recombination (HR) repair process to ensure accuracy and safety in the survival. This work is unique in its use of Poisson statistics to quantify the main repairable cell compartments that are exposed to simple and more complex sublethal hits, the cross section of which determines what is homologically and non-homologically repairable.

Radiation-Induced Chromosomal Breaks may be DNA Repair Fragile Sites with Larger-scale Correlations to Eight Double-Strand-Break Related Data Sets over the Human Genome.

In this work, we compared the genomic distribution of common radiation-induced chromosomal breaks to eight different data sets covering the whole human genome. Sites with a high probability of chromatid breakage after exposure to low and high ionization density radiations were often located inside common and rare fragile sites, indicating that they may be a new and more local type of DNA repair-related fragility. Breaks in specific chromosome bands after acute exposure to oil and benzene also showed strong correlation with these sites and fragile sites.

Systemic Immuno-metabolic alterations in chronic obstructive pulmonary disease (COPD).

Background: Metabolic adaptation in immune cells is necessary to modulate immune cell function as it is intricately coupled with intracellular metabolism. We aimed to characterize the metabolic state of human peripheral blood mononuclear cells (PBMCs) after long-term exposure to tobacco smoke in smokers with preserved lung function and COPD subjects.

Methods: PBMCs were isolated from healthy non-smokers (HNS), healthy smokers (HS) and COPD subjects, cultured and the mitochondrial respiration while utilizing glucose (glycolysis), fatty acids (β-oxidation) or pyruvate (direct Krebs' cycle substrate) was measured using the XFp Extracellular Flux Analyzer.

Clinical application of in vivo treatment delivery verification based on PET/CT imaging of positron activity induced at high energy photon therapy.

The purpose of this study was to investigate in vivo verification of radiation treatment with high energy photon beams using PET/CT to image the induced positron activity. The measurements of the positron activation induced in a preoperative rectal cancer patient and a prostate cancer patient following 50 MV photon treatments are presented. A total dose of 5 and 8 Gy, respectively, were delivered to the tumors.

A comparative analysis of radiobiological models for cell surviving fractions at high doses.

For many years the linear-quadratic (LQ) model has been widely used to describe the effects of total dose and dose per fraction at low-to-intermediate doses in conventional fractionated radiotherapy. Recent advances in stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) have increased the interest in finding a reliable cell survival model, which will be accurate at high doses, as well. Different models have been proposed for improving descriptions of high dose survival responses, such as the Universal Survival Curve (USC), the Kavanagh-Newman (KN) and several generalizations of the LQ model, e.

Radiobiological description of the LET dependence of the cell survival of oxic and anoxic cells irradiated by carbon ions.

Light-ion radiation therapy against hypoxic tumors is highly curative due to reduced dependence on the presence of oxygen in the tumor at elevated linear energy transfer (LET) towards the Bragg peak. Clinical ion beams using spread-out Bragg peak (SOBP) are characterized by a wide spectrum of LET values. Accurate treatment optimization requires a method that can account for influence of the variation in response for a broad range of tumor hypoxia, absorbed doses and LETs.

Evaluation of nuclear reaction cross-sections and fragment yields in carbon beams using the SHIELD-HIT Monte Carlo code. Comparison with experiments.

In light ion therapy, the knowledge of the spectra of both primary and secondary particles in the target volume is needed in order to accurately describe the treatment. The transport of ions in matter is complex and comprises both atomic and nuclear processes involving primary and secondary ions produced in the cascade of events. One of the critical issues in the simulation of ion transport is the modeling of inelastic nuclear reaction processes, in which projectile nuclei interact with target nuclei and give rise to nuclear fragments.

Fast IMRT with narrow high energy scanned photon beams.

Purpose: Since the first publications on intensity modulated radiation therapy (IMRT) in the early 1980s almost all efforts have been focused on fairly time consuming dynamic or segmental multileaf collimation. With narrow fast scanned photon beams, the flexibility and accuracy in beam shaping increases, not least in combination with fast penumbra trimming multileaf collimators. Previously, experiments have been performed with full range targets, generating a broad bremsstrahlung beam, in combination with multileaf collimators or material compensators.

Dose prescription and treatment planning based on FMISO-PET hypoxia.

Purpose: The study presents the implementation of a novel method for incorporating hypoxia information from PET-CT imaging into treatment planning and estimates the efficiency of various optimization approaches. Its focuses on the feasibility of optimizing treatment plans based on the non-linear conversion of PET hypoxia images into radiosensitivity maps from the uptake properties of the tracers used.

Material And Methods: PET hypoxia images of seven head-and-neck cancer patients were used to determine optimal dose distributions needed to counteract the radiation resistance associated with tumor hypoxia assuming various scenarios regarding the evolution of the hypoxic compartment during the treatment.

Accurate description of the cell survival and biological effect at low and high doses and LET's.

To accurately describe the radiation response over a wide dose and ionization density range Binomial and Poisson statistics have been combined with the recently developed potentially Repairable-Conditionally-Repairable (RCR) damage response model and the combination is shown to have several advantages for the accurate description of the cell survival at both low and very high doses and LET's, especially when compared with the classical Linear and Linear Quadratic cell survival models. Interestingly, the potentially and conditionally repairable damage types of the RCR model may also be linked to the two major radiation damage repair pathways of eukaryotic cells namely Non Homologous End Joining (NHEJ) and Homologous Recombination (HR) respectively. In addition it describes the damage interaction of low and high LET damage in different dose fractions more accurately than any other model (cf.

Production of clinically useful positron emitter beams during carbon ion deceleration.

In external beam radiation therapy, radioactive beams offer the best clinical solution to simultaneously treat and in vivo monitor the dose delivery and tumor response using PET or PET-CT imaging. However, difficulties mainly linked to the low production efficiency have so far limited their use. This study is devoted to the analysis of the production of high energy (11)C fragments, preferably by projectile fragmentation of a stable monodirectional and monoenergetic primary (12)C beam in different absorbing materials (decelerators) in order to identify the optimal elemental composition.

Comparison of dose response models for predicting normal tissue complications from cancer radiotherapy: application in rat spinal cord.

Seven different radiobiological dose-response models have been compared with regard to their ability to describe experimental data. The first four models, namely the critical volume, the relative seriality, the inverse tumor and the critical element models are mainly based on cell survival biology. The other three models: the Lyman (Gaussian distribution), the parallel architecture and the Weibull distribution models are semi-empirical and rather based on statistical distributions.

Analytical description of the LET dependence of cell survival using the repairable-conditionally repairable damage model.

In light-ion radiation therapy, both the dose and the local energy spectrum, which is often characterized with the linear energy transfer (LET), must be considered. In treatment optimization, it is advantageous to use a radiobiological model that analytically accounts for both dose and LET for the ion type of interest. With such a model the biological effect can also be estimated for dose and LET combinations for which there are no observations in the underlying experimental data.

Vascular structure and binomial statistics for response modeling in radiosurgery of cerebral arteriovenous malformations.

Radiation treatment of arteriovenous malformations (AVMs) has a slow and progressive vaso-occlusive effect. Some studies suggested the possible role of vascular structure in this process. A detailed biomathematical model has been used, where the morphological, biophysical and hemodynamic characteristics of intracranial AVM vessels are faithfully reproduced.

A systems biology approach to radiation therapy optimization.

During the last 20 years, the field of cellular and not least molecular radiation biology has been developed substantially and can today describe the response of heterogeneous tumors and organized normal tissues to radiation therapy quite well. An increased understanding of the sub-cellular and molecular response is leading to a more general systems biological approach to radiation therapy and treatment optimization. It is interesting that most of the characteristics of the tissue infrastructure, such as the vascular system and the degree of hypoxia, have to be considered to get an accurate description of tumor and normal tissue responses to ionizing radiation.

Development of high-resolution molecular phase-contrast stereoscopic X-ray imaging for accurate cancer diagnostics.

A new high-resolution molecular phase-contrast stereoscopic X-ray imaging (PSXI) modality is under development. It is aimed at offering oncologists and radiologists a system solution to discover and locate early-stage cancers and to assess tumour characteristics and therapeutic responses. The method is primarily developed for clinical implementation of biologically optimised target-specific cancer therapy to maximise cure and improve quality of life of cancer patients.

Dose prescription and optimisation based on tumour hypoxia.

INTRODUCTION. Tumour hypoxia is an important factor that confers radioresistance to the affected cells and could thus decrease the tumour response to radiotherapy. The development of advanced imaging methods that quantify both the extent and the spatial distribution of the hypoxic regions has created the premises to devise therapies that target the hypoxic regions in the tumour.

Clinical and radiobiological advantages of single-dose stereotactic light-ion radiation therapy for large intracranial arteriovenous malformations. Technical note.

Object: Radiation treatment of large arteriovenous malformations (AVMs) remains difficult and not very effective, even though seemingly promising methods such as staged volume treatments have been proposed by some radiation treatment centers. In symptomatic patients harboring large intracranial AVMs not amenable to embolization or resection, single-session high-dose stereotactic radiation therapy is a viable option, and the special characteristics of high-ionization-density light-ion beams offer several treatment advantages over photon and proton beams. These advantages include a more favorable depth-dose distribution in tissue, an almost negligible lateral scatter of the beam, a sharper penumbra, a steep dose falloff beyond the Bragg peak, and a higher probability of vascular response due to high ionization density and associated induction of endothelial cell proliferation and/or apoptosis.

Analytical theory for the fluence, planar fluence, energy fluence, planar energy fluence and absorbed dose of primary particles and their fragments in broad therapeutic light ion beams.

The purpose of the present work is to develop analytical expressions for the depth variation of the fluence, planar fluence, the energy fluence, planar energy fluence, the mean energy and absorbed dose of primary ions and their associated fragments in tissue-like media with ranges of clinical interest. The analytical expressions of the primary ions and associated fragments take into account nuclear interactions, energy losses, range straggling and multiple scattering. The analytical models of the radiation field quantities were compared with the results of the modified Monte Carlo (MC) code SHIELD-HIT(+).

Quantifying tumour hypoxia by PET imaging--a theoretical analysis.

Information on tumour oxygenation could be obtained from various imaging methods, but the success of incorporating it into treatment planning depends on the accuracy of quantifying it. This study presents a theoretical analysis of the efficiency of measuring tumour hypoxia by PET imaging. Tissue oxygenations were calculated for ranges of biologically relevant physiological parameters and were then used to simulate PET images for markers with different uptake characteristics.

The dose--response relation for rat spinal cord paralysis analyzed in terms of the effective size of the functional subunit.

Radiobiological models for estimating normal tissue complication probability (NTCP) are increasingly used in order to quantify or optimize the clinical outcome of radiation therapy. A good NTCP model should fulfill at least the following two requirements: (a) it should predict the sigmoid shape of the corresponding dose-response curve and (b) it should accurately describe the probability of a specified response for arbitrary non-uniform dose delivery for a given endpoint as accurately as possible, i.e.

Development of phase-contrast X-ray imaging techniques and potential medical applications.

A significant improvement over conventional attenuation-based X-ray imaging, which lacks contrast in small objects and soft biological tissues, is obtained by introducing phase-contrast imaging. As recently demonstrated, phase-contrast imaging is characterized by its extraordinary image quality, greatly enhanced contrast, and good soft tissue discrimination with very high spatial resolution down to the micron and even the sub-micron region. The rapid development of compact X-ray sources of high brightness, tuneability, and monochromaticity as well as high-resolution X-ray detectors with high quantum efficiency and improved computational methods is stimulating the development of a new generation of X-ray imaging systems for medical applications.