Baseline Cardiac Parameters as Biomarkers of Radiation Cardiotoxicity in Lung Cancer: An NI-HEART Analysis.

Background: Radiation-induced cardiotoxicity poses a significant challenge in lung cancer management because of the close anatomical proximity of the heart to the lungs, compounded by a high prevalence of cardiovascular risk factors among patients.

Objectives: The aim of this study was to assess the predictive value of routinely available clinical and imaging-based cardiac parameters in identifying "high risk" patients for major adverse cardiac events (MACE) and mortality following radiation therapy (RT).

Methods: The medical records of patients who underwent definitive RT for non-small cell lung cancer using modern planning techniques at a single center between 2015 and 2020 were retrospectively reviewed.

A comparative analysis of preclinical computed tomography radiomics using cone-beam and micro-computed tomography scanners.

Background And Purpose: Radiomics analysis extracts quantitative data (features) from medical images. These features could potentially reflect biological characteristics and act as imaging biomarkers within precision medicine. However, there is a lack of cross-comparison and validation of radiomics outputs which is paramount for clinical implementation.

Feasibility and guidelines for the use of an injectable fiducial marker (BioXmark ) to improve target delineation in preclinical radiotherapy studies using mouse models.

Background: Preclinical models of radiotherapy (RT) response are vital for the continued success and evolution of RT in the treatment of cancer. The irradiation of tissues in mouse models necessitates high levels of precision and accuracy to recapitulate clinical exposures and limit adverse effects on animal welfare. This requirement has been met by technological advances in preclinical RT platforms established over the past decade.

Dose-dependent changes in cardiac function, strain and remodelling in a preclinical model of heart base irradiation.

Background And Purpose: Radiation induced cardiotoxicity (RICT) is as an important sequela of radiotherapy to the thorax for patients. In this study, we aim to investigate the dose and fractionation response of RICT. We propose global longitudinal strain (GLS) as an early indicator of RICT and investigate myocardial deformation following irradiation.

Characterisation of quantitative imaging biomarkers for inflammatory and fibrotic radiation-induced lung injuries using preclinical radiomics.

Background And Purpose: Radiomics is a rapidly evolving area of research that uses medical images to develop prognostic and predictive imaging biomarkers. In this study, we aimed to identify radiomics features correlated with longitudinal biomarkers in preclinical models of acute inflammatory and late fibrotic phenotypes following irradiation.

Materials And Methods: Female C3H/HeN and C57BL6 mice were irradiated with 20 Gy targeting the upper lobe of the right lung under cone-beam computed tomography (CBCT) image-guidance.

The Association of Incidental Radiation Dose to the Heart Base with Overall Survival and Cardiac Events after Curative-intent Radiotherapy for Non-small Cell Lung Cancer: Results from the NI-HEART Study.

Aims: Cardiac disease is a dose-limiting toxicity in non-small cell lung cancer radiotherapy. The dose to the heart base has been associated with poor survival in multiple institutional and clinical trial datasets using unsupervised, voxel-based analysis. Validation has not been undertaken in a cohort with individual patient delineations of the cardiac base or for the endpoint of cardiac events.

A multimodality assessment of the protective capacity of statin therapy in a mouse model of radiation cardiotoxicity.

Purpose: Despite technological advances in radiotherapy (RT), cardiotoxicity remains a common complication in patients with lung, oesophageal and breast cancers. Statin therapy has been shown to have pleiotropic properties beyond its lipid-lowering effects. Previous murine models have shown statin therapy can reduce short-term functional effects of whole-heart irradiation.

Evaluation of Radiosensitization and Cytokine Modulation by Differentially PEGylated Gold Nanoparticles in Glioblastoma Cells.

Glioblastoma (GBM) is known as the most aggressive type of malignant brain tumour, with an extremely poor prognosis of approximately 12 months following standard-of-care treatment with surgical resection, radiotherapy (RT), and temozolomide treatment. Novel RT-drug combinations are urgently needed to improve patient outcomes. Gold nanoparticles (GNPs) have demonstrated significant preclinical potential as radiosensitizers due to their unique physicochemical properties and their ability to pass the blood-brain barrier.

Association between statin therapy dose intensity and radiation cardiotoxicity in non-small cell lung cancer: Results from the NI-HEART study.

Introduction: Radiation cardiotoxicity is a dose-limiting toxicity and major survivorship issue for patients with non-small cell lung cancer (NSCLC) completing curative-intent radiotherapy, however patients' cardiovascular baseline is not routinely optimised prior to treatment. In this study we examined the impact of statin therapy on overall survival and post-radiotherapy cardiac events.

Methods: Patients treated between 2015-2020 at a regional center were identified.

Assessment of Variabilities in Lung-Contouring Methods on CBCT Preclinical Radiomics Outputs.

Radiomics image analysis has the potential to uncover disease characteristics for the development of predictive signatures and personalised radiotherapy treatment. Inter-observer and inter-software delineation variabilities are known to have downstream effects on radiomics features, reducing the reliability of the analysis. The purpose of this study was to investigate the impact of these variabilities on radiomics outputs from preclinical cone-beam computed tomography (CBCT) scans.

Development and optimisation of a preclinical cone beam computed tomography-based radiomics workflow for radiation oncology research.

Background And Purpose: Radiomics features derived from medical images have the potential to act as imaging biomarkers to improve diagnosis and predict treatment response in oncology. However, the complex relationships between radiomics features and the biological characteristics of tumours are yet to be fully determined. In this study, we developed a preclinical cone beam computed tomography (CBCT) radiomics workflow with the aim to use models to further develop radiomics signatures.

A pulmonary vein atlas for radiotherapy planning.

Background And Purpose: Cardiac arrhythmia is a recognised potential complication of thoracic radiotherapy, but the responsible cardiac substructures for arrhythmogenesis have not been identified. Arrhythmogenic tissue is commonly located in the pulmonary veins (PVs) of cardiology patients with arrhythmia, however these structures are not currently considered organs-at-risk during radiotherapy planning. A standardised approach to their delineation was developed and evaluated.

Modelling oxygen effects on the in- and out-of-field radiosensitivity of cells exposed to intensity-modulated radiation fields.

. The delivery of intensity-modulated radiation fields has improved the conformity of dose to tumour targets during radiotherapy (RT). Previously, it has been shown that intercellular communication between cells positioned in- and outside of the radiation field impacts cellular radiosensitivity under hypoxic and normoxic conditions.

Roadmap for precision preclinical x-ray radiation studies.

This Roadmap paper covers the field of precision preclinical x-ray radiation studies in animal models. It is mostly focused on models for cancer and normal tissue response to radiation, but also discusses other disease models. The recent technological evolution in imaging, irradiation, dosimetry and monitoring that have empowered these kinds of studies is discussed, and many developments in the near future are outlined.

Spatial Gene Expression Changes in the Mouse Heart After Base-Targeted Irradiation.

Purpose: Radiation cardiotoxicity (RC) is a clinically significant adverse effect of treatment for patients with thoracic malignancies. Clinical studies in lung cancer have indicated that heart substructures are not uniformly radiosensitive, and that dose to the heart base drives RC. In this study, we aimed to characterize late changes in gene expression using spatial transcriptomics in a mouse model of base regional radiosensitivity.

Validation of an established deep learning auto-segmentation tool for cardiac substructures in 4D radiotherapy planning scans.

Background: Emerging data suggest that dose-sparing several key cardiac regions is prognostically beneficial in lung cancer radiotherapy. The cardiac substructures are challenging to contour due to their complex geometry, poor soft tissue definition on computed tomography (CT) and cardiorespiratory motion artefact. A neural network was previously trained to generate the cardiac substructures using three-dimensional radiotherapy planning CT scans (3D-CT).

Murine models of radiation cardiotoxicity: A systematic review and recommendations for future studies.

Background And Purpose: The effects of radiation on the heart are dependent on dose, fractionation, overall treatment time, and pre-existing cardiovascular pathology. Murine models have played a central role in improving our understanding of the radiation response of the heart yet a wide range of exposure parameters have been used. We evaluated the study design of published murine cardiac irradiation experiments to assess gaps in the literature and to suggest guidance for the harmonisation of future study reporting.

A scoping review of small animal image-guided radiotherapy research: Advances, impact and future opportunities in translational radiobiology.

Background And Purpose: To provide a scoping review of published studies using small animal irradiators and highlight the progress in preclinical radiotherapy (RT) studies enabled by these platforms since their development and commercialization in 2007.

Materials And Methods: PubMed searches and manufacturer records were used to identify 907 studies that were screened with 359 small animal RT studies included in the analyses. These articles were classified as biology or physics contributions and into subgroups based on research aims, experimental models and other parameters to identify trends in the preclinical RT research landscape.

Radiomics for Predicting Lung Cancer Outcomes Following Radiotherapy: A Systematic Review.

Lung cancer's radiomic phenotype may potentially inform clinical decision-making with respect to radical radiotherapy. At present there are no validated biomarkers available for the individualisation of radical radiotherapy in lung cancer and the mortality rate of this disease remains the highest of all other solid tumours. MEDLINE was searched using the terms 'radiomics' and 'lung cancer' according to the Preferred Reporting Items for Systematic Reviews and Met-Analyses (PRISMA) guidance.

A Brief Overview of the Preclinical and Clinical Radiobiology of Microbeam Radiotherapy.

Microbeam radiotherapy (MRT) is the delivery of spatially fractionated beams that have the potential to offer significant improvements in the therapeutic ratio due to the delivery of micron-sized high dose and dose rate beams. They build on longstanding clinical experience of GRID radiotherapy and more recently lattice-based approaches. Here we briefly overview the preclinical evidence for MRT efficacy and highlight the challenges for bringing this to clinical utility.

Radiobiology of the FLASH effect.

Radiation exposures at ultrahigh dose rates (UHDRs) at several orders of magnitude greater than in current clinical radiotherapy (RT) have been shown to manifest differential radiobiological responses compared to conventional (CONV) dose rates. This has led to studies investigating the application of UHDR for therapeutic advantage (FLASH-RT) that have gained significant interest since the initial discovery in 2014 that demonstrated reduced lung toxicity with equivalent levels of tumor control compared with conventional dose-rate RT. Many subsequent studies have demonstrated the potential protective role of FLASH-RT in normal tissues, yet the underlying molecular and cellular mechanisms of the FLASH effect remain to be fully elucidated.

Cancer Cells Can Exhibit a Sparing FLASH Effect at Low Doses Under Normoxic Conditions.

Background: Irradiation with ultra-high dose rate (FLASH) has been shown to spare normal tissue without hampering tumor control in several studies. Few cell lines have been investigated , and previous results are inconsistent. Assuming that oxygen depletion accounts for the FLASH sparing effect, no sparing should appear for cells irradiated with low doses in normoxia.