Multimodality curative-intent treatment in NSCLC: an unprecedented era of change 2017-2025.

Curative-intent multimodality treatment-combining local treatments such as surgery or radiotherapy with systemic therapy-is the cornerstone of care in stage II-III non-small cell lung cancer (NSCLC). Since 2017, the systemic therapy backbones with multimodality treatment have undergone a dramatic transformation, driven by a series of pivotal, practice-changing clinical trials. Immunotherapy and targeted therapies, previously confined to the advanced/metastatic setting, are now firmly embedded in curative-intent regimens.

Preclinical characterisation of changes in cardiac function and circulating biomarkers following differential irradiation of thoracic volumes.

Introduction: The heart and lungs are critical organs at risk in patients receiving radiotherapy for thoracic tumours. Preclinical studies in rat models have provided evidence indicating consequential effects of lung radiation on the heart through vascular remodelling which leads to pulmonary arterial hypertension. In this study, we aimed to assess the impact of lung irradiation on a long-term model of cardiac base irradiation that recapitulates clinical observations of the heart base as a radiosensitive region and to understand relationships between cardiopulmonary irradiation and circulating cytokines profiles.

Consolidation thoracic radiotherapy after chemoimmunotherapy in ES-SCLC: A multicentric retrospective analysis.

Background: The CREST trial established the benefit of consolidative thoracic radiotherapy (TRT) following first line (1L) chemotherapy in extensive-stage small cell lung cancer (ES-SCLC), demonstrating improved 2-year overall survival (OS). However, the role of TRT in the chemoimmunotherapy (CT-IO) era remains unclear, as TRT was excluded from registrational trials.

Methods: This retrospective study analysed consecutive patients (pts) with ES-SCLC treated with 1L CT-IO between January 2020 and January 2024 across 4 centres.

Should Radiation Dose Be Personalized in Patients With Localized NSCLC and Actionable Genetic Alterations? Insight From a Multicenter Real-World Study.

Objectives: Radiation therapy (RT) is central to the management of unresectable stage I to III NSCLC. However, the impact of actionable genetic driver alterations (AGAs) on locoregional control (LRC) from RT remains uncertain. A retrospective, multicenter real-world study was undertaken to determine if common AGAs impact LRC after RT.

Circulating tumor DNA kinetics: A future tool for radiation therapy personalization in lung cancer?

Locally advanced non-small cell lung cancer (NSCLC) is a highly diverse disease in terms of its histology, staging and molecular biology, yet chemoradiation treatment paradigms are currently not individualized for these factors. Circulating tumor DNA (ctDNA) in the plasma has clinical utility for several systemic therapies in advanced NSCLC, before, during and after treatment. However, in radiation oncology, the evidence for ctDNA in locally advanced NSCLC is largely limited to minimal residual disease (MRD) detection after treatment.

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.

Long-Term Outcomes After Concurrent Once- or Twice-Daily Chemoradiation in Limited-Stage Small Cell Lung Cancer: A Brief Report From the CONVERT Trial.

Purpose: CONVERT was a phase 3 international randomized clinical trial comparing once-daily (OD) and twice-daily (BD) radiation therapy (RT). This updated analysis describes the 6.5-year outcomes of these regimens delivered with conformal techniques.

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.

Cardiac radiation improves ventricular function in mice and humans with cardiomyopathy.

Background: Rapidly dividing cells are more sensitive to radiation therapy (RT) than quiescent cells. In the failing myocardium, macrophages and fibroblasts mediate collateral tissue injury, leading to progressive myocardial remodeling, fibrosis, and pump failure. Because these cells divide more rapidly than cardiomyocytes, we hypothesized that macrophages and fibroblasts would be more susceptible to lower doses of radiation and that cardiac radiation could therefore attenuate myocardial remodeling.

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 tumour motion and internal/external correlation in lung SABR.

Objective: This study aims to analyse lung tumour motion and to investigate the correlation between the internal tumour motion acquired from four-dimensional computed tomography (4DCT) and the motion of an external surrogate.

Methods: A data set of 363 4DCT images was analysed. Tumours were classified based on their anatomical lobes.

Clinicoradiological outcomes after radical radiotherapy for lung cancer in patients with interstitial lung disease.

Objective: Interstitial lung disease (ILD) is relatively common in patients with lung cancer with an incidence of 7.5%. Historically pre-existing ILD was a contraindication to radical radiotherapy owing to increased radiation pneumonitis rates, worsened fibrosis and poorer survival compared with non-ILD cohorts.

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.