Search

Background and Purpose: Symptomatic arrhythmia is common following radiotherapy for non-small cell lung cancer (NSCLC), frequently resulting in morbidity and hospitalization. Modern treatment planning technology theoretically allows sparing of cardiac substructures. Atrial fibrillation (AF) comprises the majority of post-radiotherapy arrhythmias, but efforts to prevent this cardiotoxicity have been limited as the causative cardiac substructure is not known. In this study we investigated if incidental radiation dose to the pulmonary veins (PVs) is associated with AF., Material and Methods: A single-centre study of patients completing contemporary (chemo)radiation for NSCLC, with modern planning techniques. Oncology, cardiology and death records were examined, and AF events were verified by a cardiologist. Cardiac substructures were contoured on planning scans for retrospective dose analysis., Results: In 420 eligible patients with NSCLC treated with intensity-modulated (70%) or 3D-conformal (30%) radiotherapy with a median OS of 21.8 months (IQR 10.8-35.1), there were 26 cases of new AF (6%). All cases were grade 3 except two cases of grade 4. Dose metrics for both the left (V55) and right (V10) PVs were associated with the incidence of new AF. Metrics remained statistically significant after accounting for the competing risk of death and cardiovascular covariables for both the left (HR 1.02, 95%CI 1.00-1.03, p = 0.005) and right (HR 1.01 (95%CI 1.00-1.02, p = 0.033) PVs., Conclusion: Radiation dose to the PVs during treatment of NSCLC was associated with the onset of AF. Actively sparing the PVs during treatment planning could reduce the incidence of AF during follow-up, and screening for AF may be warranted for select cases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

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. Clinical notes were interrogated for baseline patient, tumor and cardiac details, and both follow-up cancer control and cardiac events. Three cardiologists verified cardiac events. Radiotherapy planning scans were retrieved for application of validated deep learning-based autosegmentation. Pre-specified Cox regression analyses were generated with varying degrees of adjustment for overall survival. Fine and Gray regression for the risk of cardiac events, accounting for the competing risk of death and cardiac covariables was undertaken., Results: Statin therapy was prescribed to 59% of the 478 included patients. The majority (88%) of patients not prescribed a statin had at least one indication for statin therapy according to cardiovascular guidelines. In total, 340 patients (71%) died and 79 patients (17%) experienced a cardiac event. High-intensity (HR 0.68, 95%CI 0.50-0.91, p = 0.012) and medium-intensity (HR 0.70, 95%CI 0.51-0.97, p = 0.033) statin therapy were associated with improved overall survival after adjustment for patient, cancer, treatment, response and cardiovascular clinical factors. There were no consistent differences in the rate or grade of cardiac events according to statin intensity., Conclusions: Statin therapy is associated with improved overall survival in patients receiving curative-intent radiotherapy for NSCLC, and there is evidence of a dose-response relationship. This study highlights the importance of a pre-treatment cardiovascular risk assessment in this cohort. Further studies are needed to examine if statin therapy is cardioprotective in patients undergoing treatment for NSCLC with considerable incidental cardiac radiation dose and a low baseline cardiac risk., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

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., Materials and Methods: The gross and radiological anatomy relevant to atrial fibrillation was derived from cardiology and radiology literature by a multidisciplinary team. A region of interest and contouring instructions for radiotherapy computed tomography scans were iteratively developed and subsequently evaluated. Radiation oncologists (n = 5) and radiation technologists (n = 2) contoured the PVs on the four-dimensional planning datasets of five patients with locally advanced lung cancer treated with 1.8-2.75 Gy fractions. Contours were compared to reference contours agreed by the researchers using geometric and dosimetric parameters., Results: The mean dose to the PVs was 35% prescription dose. Geometric and dosimetric similarity of the observer contours with reference contours was fair, with an overall mean Dice of 0.80 ± 0.02. The right superior PV (mean DSC 0.83 ± 0.02) had better overlap than the left (mean DSC 0.80 ± 0.03), but the inferior PVs were equivalent (mean DSC of 0.78). The mean difference in mean dose was 0.79 Gy ± 0.71 (1.46% ± 1.25)., Conclusion: A PV atlas with multidisciplinary approval led to reproducible delineation for radiotherapy planning, supporting the utility of the atlas in future clinical radiotherapy cardiotoxicity research encompassing arrhythmia endpoints., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Standard of care radiotherapy in LA-NSCLC is 60-66 Gy in 30-33 fractions. However outcomes for these patients are poor with 5-year survival in the range of 10-20%. Randomised controlled trials have shown that dose escalation in a linear fashion does not improve outcomes for all patients, thus there is a need to tailor the prescription to the individual patient. This review assesses the strategies published to personalise the radiation therapy dose prescription in LA-NSCLC. A systematic and scoping search of the literature was performed to identify studies that met the inclusion criteria. 19 relevant studies were identified ranging from prospective clinical trials to mathematically modelled concept studies. Heterogeneity existed between all clinical studies. Nine heterogeneous publications proposed methodology to adapt the dose prescription to the individual patient. A number of encouraging strategies have been identified but fall short of the evidence level required to influence clinical practice., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background and Purpose: To evaluate the impact of ATR inhibition using AZD6738 in combination with radiotherapy on the response of non-small cell lung cancer (NSCLC) tumour models and a murine model of radiation induced fibrosis., Materials and Methods: AZD6738 was evaluated as a monotherapy and in combination with radiation in vitro and in vivo using A549 and H460 NSCLC models. Radiation induced pulmonary fibrosis was evaluated by cone beam computed tomography (CBCT) and histological staining., Results: AZD6738 specifically inhibits ATR kinase and enhanced radiobiological response in NSCLC models but not in human bronchial epithelial cells (HBECs) in vitro. Significant tumour growth delay was observed in cell line derived xenografts (CDXs) of H460 cells (p<0.05) which were less significant in A549 cells. Combination of AZD6738 with radiotherapy showed no significant change in lung tissue density by CBCT (p>0.5) and histological scoring of radiation induced fibrosis (p>0.5)., Conclusion: Inhibition of ATR with AZD6738 in combination with radiotherapy increases tumour growth delay without observable augmentation of late radiation induced toxicity further underpinning translation towards clinical evaluation in NSCLC., (Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: To assess the impact of a standardized delineation protocol and training interventions on PET/CT-based target volume delineation (TVD) in NSCLC in a multicenter setting., Material and Methods: Over a one-year period, 11 pairs, comprised each of a radiation oncologist and nuclear medicine physician with limited experience in PET/CT-based TVD for NSCLC from nine different countries took part in a training program through an International Atomic Energy Agency (IAEA) study (NCT02247713). Teams delineated gross tumor volume of the primary tumor, during and after training interventions, according to a provided delineation protocol. In-house developed software recorded the performed delineations, to allow visual inspection of strategies and to assess delineation accuracy., Results: Following the first training, overall concordance indices for 3 repetitive cases increased from 0.57±0.07 to 0.66±0.07. The overall mean surface distance between observer and expert contours decreased from -0.40±0.03cm to -0.01±0.33cm. After further training overall concordance indices for another 3 repetitive cases further increased from 0.64±0.06 to 0.80±0.05 (p=0.01). Mean surface distances decreased from -0.34±0.16cm to -0.05±0.20cm (p=0.01)., Conclusion: Multiple training interventions improve PET/CT-based TVD delineation accuracy in NSCLC and reduce interobserver variation., (Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

This document describes best practice and evidence based recommendations for the use of FDG-PET/CT for the purposes of radiotherapy target volume delineation (TVD) for curative intent treatment of non-small cell lung cancer (NSCLC). These recommendations have been written by an expert advisory group, convened by the International Atomic Energy Agency (IAEA) to facilitate a Coordinated Research Project (CRP) aiming to improve the applications of PET based radiation treatment planning (RTP) in low and middle income countries. These guidelines can be applied in routine clinical practice of radiotherapy TVD, for NSCLC patients treated with concurrent chemoradiation or radiotherapy alone, where FDG is used, and where a calibrated PET camera system equipped for RTP patient positioning is available. Recommendations are provided for PET and CT image visualization and interpretation, and for tumor delineation using planning CT with and without breathing motion compensation., (Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Introduction: Correct target definition is crucial in stereotactic radiotherapy for lung tumors. We evaluated use of deformable registration (DR) for target contouring on 4-dimensional (4D) CT scans., Materials and Methods: Three clinicians contoured gross tumor volume (GTV) in an end-inspiration phase of 4DCT of 6 patients on two occasions. Two clinicians contoured GTVs in all phases of 4DCT and on maximum intensity projections (MIP). The initial GTV was auto-propagated to 9 other phases using a B-spline algorithm (VelocityAI). Internal target volumes (ITVs) generated were (i) ITV(10manual) encompassing all physician-contoured GTVs, (ii) ITV-MIP(optimized) from MIP after review of individual 4DCT phases, (iii) ITV(10deformed) encompassing auto-propagated GTVs using DR, and (iv) ITV(10deformed-optimized), from an ITV(10deformed) target that was modified to form a 'clinically optimal' ITV. Volume-overlaps were scored using Dice's Similarity Coefficients (DSCs)., Results: Intra-clinician GTV reproducibility was greater than inter-clinician reproducibility (mean DSC 0.93 vs. 0.88, p<0.0004). In five of 6 patients, ITV-MIP(optimized) differed from the ITV(10deformed-optimized). In all patients, the DSC between ITV(10deformed-optimized) and ITV(10deformed) was higher than that between ITV(10deformed-optimized) and ITV-MIP(optimized) (p<0.02 T-test)., Conclusion: ITVs created in stage I tumors using DR were closer to 'clinically optimal' ITVs than was the case with a MIP-modified approach., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)