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Magnetic resonance imaging (MRI) offers superior soft tissue contrast to computed tomography (CT), the current standard imaging modality for planning radiotherapy treatment. Improved soft tissue contrast could reduce uncertainties in identifying tumour and surrounding healthy tissues, potentially leading to improved outcomes in patients with lung cancer. This study explored patient experience of MR treatment planning scans in addition to a CT scan. Participants were recruited to the 'Magnetic Resonance Imaging for the Delineation of Organs At Risk and Target Volumes in Lung Cancer Patients (MR-Lung)' study at a UK specialist cancer centre. Participants completed their standard of care radiotherapy planning CT scan and two additional MRI scans. Baseline and post-scan questionnaires were completed assessing anxiety and claustrophobia. Motion artefact during MRI was assessed by a modified visual grading analysis. Sixteen participants completed semi-structured interviews; transcripts were analysed thematically. 29 people (66% female; aged 54–89 years) participated. Nineteen participants completed all imaging and 10 participants withdrew before completion. There was minimal adverse impact on state and scan-specific anxiety levels from completing the MRI scans. Completers experienced significantly less scan-specific anxiety during MRI 1 compared to non-completers (U = 33, z = −1.98, p < 0.05). 78% of those who withdrew during or post MRI 1 were positioned 'arms up'. Motion artefact negatively impacted image quality in 34% of scans. Participants commonly reported concerns during MRI; noise, claustrophobia and pain in upper limbs. Two thirds of participants tolerated two additional MR scans with minimal adverse impact on anxiety levels. Patient arm positioning and comfort ought to be considered when introducing MR-Linac systems. A screening tool to identify those at high risk of non-completion should be developed. [ABSTRACT FROM AUTHOR]

Patients treated with curative-intent lung radiotherapy are in the group at highest risk of severe complications and death from COVID-19. There is therefore an urgent need to reduce the risks associated with multiple hospital visits and their anti-cancer treatment. One recommendation is to consider alternative dose-fractionation schedules or radiotherapy techniques. This would also increase radiotherapy service capacity for operable patients with stage I-III lung cancer, who might be unable to have surgery during the pandemic. Here we identify reduced-fractionation for curative-intent radiotherapy regimes in lung cancer, from a literature search carried out between 20/03/2020 and 30/03/2020 as well as published and unpublished audits of hypofractionated regimes from UK centres. Evidence, practical considerations and limitations are discussed for early-stage NSCLC, stage III NSCLC, early-stage and locally advanced SCLC. We recommend discussion of this guidance document with other specialist lung MDT members to disseminate the potential changes to radiotherapy practices that could be made to reduce pressure on other departments such as thoracic surgery. It is also a crucial part of the consent process to ensure that the risks and benefits of undergoing cancer treatment during the COVID-19 pandemic and the uncertainties surrounding toxicity from reduced fractionation have been adequately discussed with patients. Furthermore, centres should document all deviations from standard protocols, and we urge all colleagues, where possible, to join national/international data collection initiatives (such as COVID-RT Lung) aimed at recording the impact of the COVID-19 pandemic on lung cancer treatment and outcomes. [ABSTRACT FROM AUTHOR]

Concurrent chemotherapy and radiotherapy (CCRT) followed by durvalumab immune therapy in appropriate patients is considered to be the standard of care in most fit stage III non-small-cell lung cancer (NSCLC) patients. However, CCRT is a toxic treatment that affects all organ systems and may cause acute and permanent side effects, some of which may be lethal. Supportive care is therefore of utmost importance in this clinical setting. A group of experts from the European Society for Therapeutic Radiology and Oncology (ESTRO) and the European Society of Medical Oncology (ESMO) identified the following items of importance for further improvement of supportive care: smoking cessation; nutrition before and during CCRT (including treatment and prevention of anorexia); physical exercise before and during CCRT; prevention and treatment of acute esophagitis and dysphagia; treatment of cough and dyspnea; treatment of skin reactions; treatment of fatigue; prophylaxis of nausea and emesis; prevention, diagnosis, and treatment of cardiac disease and damage; and optimization of radiotherapy techniques and chemotherapy adjustments to reduce toxicity in the era of immune therapy. The resulting recommendations are summarized in this manuscript and knowledge gaps identified, in which future investments are needed to improve supportive care and hence quality of life and survival for our stage III NSCLC patients. • Supportive care is an integral part of CCRT. • All aspects are important. • A multi-disciplinary approach is mandatory. [ABSTRACT FROM AUTHOR]

Proffered Papers: Proffered papers 13: Lung OC-0226: Pre-existing cardiac disease and cardiopulmonary RT dose associate with cardiac death in lung cancer A. Abravan, C. Faivre-Finn, K. Banfill, A. McWilliam, M. Van Herk. [Extracted from the article]

Radiotherapy has been shown to play a key role in the management of small cell lung cancer. There are well-established data in the literature for the use of concurrent chemoradiotherapy for stage I–III disease, although key questions remain over the timing of radiation, the optimal dose/fractionation and particularly once versus twice daily treatment, the use of elective nodal irradiation and drug combinations. Data for the use of thoracic radiation in stage IV disease, after chemotherapy, have recently become available and are leading to a change in practice. Prophylactic cranial irradiation has been shown to be of use in both stage I–III and stage IV disease, although uncertainties surround its use in the elderly population and the use of brain imaging before treatment. This overview will address the current available evidence and focus on areas for future research. [ABSTRACT FROM AUTHOR]

The European Society for Medical Oncology (ESMO) held a virtual consensus-building process on epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer in 2021. The consensus included a multidisciplinary panel of 34 leading experts in the management of lung cancer. The aim of the consensus was to develop recommendations on topics that are not covered in detail in the current ESMO Clinical Practice Guideline and where the available evidence is either limited or conflicting. The main topics identified for discussion were: (i) tissue and biomarkers analyses; (ii) early and locally advanced disease; (iii) metastatic disease and (iv) clinical trial design, patient's perspective and miscellaneous. The expert panel was divided into four working groups to address questions relating to one of the four topics outlined above. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This manuscript presents the recommendations developed, including findings from the expert panel discussions, consensus recommendations and a summary of evidence supporting each recommendation. • A virtual consensus on the management of EGFR-mutant NSCLC was organized by the ESMO, including 34 experts from 18 countries. • The experts compiled recommendations with supporting evidence on controversial topics about the EGFR-mutant lung cancer. • Recommendations were formulated for tissue and biomarkers analyses; early, locally advanced and metastatic disease; miscellaneous. [ABSTRACT FROM AUTHOR]

So far, the impact of intra-thoracic anatomical changes (ITACs) on patients treated with stereotactic ablative radiotherapy (SABR) for early-stage non-small cell lung cancer is unknown. Studying these is important, as ITACs have the potential to impact the workflow and reduce treatment quality. The aim of this study was to assess and categorise ITACs, as detected on cone beam computed tomography scans (CBCT), and their subsequent impact upon treatment in lung cancer patients treated with SABR. CBCTs from 100 patients treated with SABR for early non-small cell lung cancer were retrospectively reviewed. The presence of the following ITACs was assessed: atelectasis, infiltrative change, pleural effusion, baseline shift and gross tumour volume (GTV) increase and decrease. ITACs were graded using a traffic light protocol. This was adapted from a tool previously developed to assesses potential target undercoverage or organ at risk overdose. The frequency of physics or clinician review was noted. A linear mixed effects model was used to assess the relationship between ITAC grade and set-up time (time from first CBCT to beam delivery). ITACs were observed in 22% of patients. Twenty-one per cent of these were categorised as 'red', implying a risk of underdosage to the GTV. Most were 'yellow' (51%), indicating little impact upon planning target volume coverage of the GTV. Physics or clinician review was required in 10% of all treatment fractions overall. Three patients needed their treatment replanned. The mixed effect model analysis showed that ITACs cause a significant prolongation of set-up time (Χ 2(3) = 9.22, P = 0.02). Most ITACs were minor, but associated with unplanned physics or clinician review, representing a potentially significant resource burden. ITACs also had a significant impact upon set-up time, with consequences for the wider workflow and intra-fraction motion. Detailed guidance on the management of ITACs is needed to provide support for therapeutic radiographers delivering lung SABR. • ITACs occur not infrequently during the delivery of stereotactic ablative radiotherapy for lung cancer. • The development of ITACs represents a resource burden due to the unscheduled clinician and physics involvement. • Intra-thoracic anatomical changes have the potential to prolong treatment set-up time. [ABSTRACT FROM AUTHOR]

Choosing the optimal palliative lung radiotherapy regimen is challenging. Guidance from The Royal College of Radiologists recommends treatment stratification based on performance status, but evidence suggests that higher radiotherapy doses may be associated with survival benefits. The aim of this study was to investigate the effects of fractionation regimen and additional factors on the survival of palliative lung cancer radiotherapy patients. A retrospective univariable (n = 925) and multivariable (n = 422) survival analysis of the prognostic significance of baseline patient characteristics and treatment prescription was carried out on patients with non-small cell and small cell lung cancer treated with palliative lung radiotherapy. The covariates investigated included: gender, age, performance status, histology, comorbidities, stage, tumour location, tumour side, smoking status, pack year history, primary radiotherapy technique and fractionation scheme. The overall mortality rate at 30 and 90 days of treatment was calculated. Univariable analysis revealed that performance status (P < 0.001), fractionation scheme (P < 0.001), comorbidities (P = 0.02), small cell histology (P = 0.02), 'lifelong never' smoking status (P = 0.01) and gender (P = 0.06) were associated with survival. Upon multivariable analysis, only better performance status (P = 0.01) and increased dose/fractionation regimens of up to 30 Gy/10 fractions (P < 0.001) were associated with increased survival. Eighty-five (9.2%) and 316 patients (34%) died within 30 and 90 days of treatment, respectively. In this retrospective single-centre analysis of palliative lung radiotherapy, increased total dose (up to and including 30 Gy/10 fractions) was associated with better survival regardless of performance status. • Larger doses of palliative lung radiotherapy are associated with increased survival. • Performance status is independently linked to survival. • Palliative lung radiotherapy dose is independently linked to survival. [ABSTRACT FROM AUTHOR]

• Cardiac toxicity from lung cancer radiotherapy is a recognised side effect. • Cardiac death is under-reported in patients who received lung cancer radiotherapy. • This adds to the difficulty of investigating radiotherapy related cardiac damage. Lung cancer is the most common malignancy worldwide. Radical radiotherapy is an essential treatment in the management of early and locally advanced lung cancer. Cardiac events are known to occur following radical radiotherapy for lung cancer. This study examines the burden of cardiac events post radiotherapy, and estimates the accuracy of death certification in patients who received radical radiotherapy for lung cancer. We conducted a retrospective observational cohort study for all patients receiving radical radiotherapy for non-small cell lung cancer (NSCLC) at a large cancer centre between 01/01/2010 to 31/12/2016. Baseline cardiovascular disease and cancer status and treatment data were collected, along with hospital admission data and documented cause of death from the national registry for a median follow-up period of 34 months. Of 1224 patients included in the analysis, 378 (30.9%) patients had cardiovascular disease at baseline, including 140 (11.4%) with prior myocardial infarction. In the 846 patients without known cardiovascular disease, 451 (53.3%) had a QRISK2 predicted 10-year cardiovascular risk >20% over 10 years. During follow-up, 215 hospitalisations occurred (Incidence rate 6.2 per hundred patient years) which were classified as primarily cardiac, and 622 patients died (18 per 100 patient-years). However, death certificates stated a primary cardiac cause of death in only 33 cases (5.3% of deaths). Notably, 29% of patients dying out of hospital and certified as cancer death did not have documented cancer relapse prior to death, and 61% had no community palliative care input prior to death, implying these events may have been sudden and unexpected. There is a high prevalence of baseline cardiovascular disease in people undergoing radiotherapy for NSCLC, accompanied by significant rates of post-radiotherapy cardiovascular hospitalisation. However, only a small proportion of deaths are attributed to cardiovascular disease, together with the large amount of sudden deaths observed, this suggests that cardiovascular death is greatly under-reported in official statistics. [ABSTRACT FROM AUTHOR]

Background The clinical significance of circulating tumour cells (CTCs) in limited-stage small-cell lung cancer (LS-SCLC) is not well defined. We report a planned exploratory analysis of the prevalence and prognostic value of CTCs in LS-SCLC patients enrolled within the phase III randomised CONVERT (concurrent once-daily versus twice-daily chemoradiotherapy) trial. Patients and methods Baseline blood samples were enumerated for CTCs using CellSearch in 75 patients with LS-SCLC who were enrolled in the CONVERT trial and randomised between twice- and once-daily concurrent chemoradiation. Standard statistical methods were used for correlations of CTCs with clinical factors. Log-rank test and Cox regression analyses were applied to establish the associations of 2, 15 and 50 CTC thresholds with progression-free survival (PFS) and overall survival (OS). An optimal CTC count threshold for LS-SCLC was established. Results CTCs were detected in 60% (45/75) of patients (range 0–3750). CTC count thresholds of 2, 15 and 50 CTCs all significantly correlate with PFS and OS. An optimal CTC count threshold in LS-SCLC was established at 15 CTCs, defining 'favourable' and 'unfavourable' prognostic risk groups. The median OS in <15 versus ≥15 CTCs was 26.7 versus 5.9 m (P  = 0.001). The presence of ≥15 CTCs at baseline independently predicted ≤1 year survival in 70% and ≤2 years survival in 100% of patients. Conclusion We report the prognostic value of baseline CTC count in an exclusive LS-SCLC population at thresholds of 2, 15 and 50 CTCs. Specific to LS-SCLC, ≥15 CTCs was associated with worse PFS and OS independent of all other factors and predicted ≤2 years survival. These results may improve disease stratification in future clinical trial designs and aid clinical decision making. Trial registration ClinicalTrials.gov identifier: NCT00433563. [ABSTRACT FROM AUTHOR]

Background and purpose In lung cancer patients, accuracy in contouring is hampered by image artefacts introduced by respiratory motion. With the widespread introduction of 4DCT there is additional uncertainty caused by the use of different reconstruction techniques which will influence contour definition. This work aims to assess both inter- and intra-observer contour variation on average and motion compensated (mid-position) reconstructions. Material and methods Eight early stage non-small cell lung cancer patients that received 4DCT were selected and these scans were reconstructed as average and motion compensated datasets. 5 observers contoured the organs at risk (trachea, oesophagus, proximal bronchial tree, heart and brachial plexus) for each patient and each reconstruction. Contours were compared against a STAPLE volume with distance to agreement metrics. Intra-observer variation was assessed by redelineation after 4 months. Results The inter-observer variation was significantly smaller using the motion compensated datasets for the trachea ( p  = 0.006) and proximal bronchial tree ( p  = 0.004). For intra-observer variation, a reduction in contour variation was seen across all organs at risk in using motion compensated reconstructions. Conclusions This work shows that there is benefit in using motion compensated reconstructions for reducing both inter-observer and intra-observer contouring variations for organs at risk in lung cancer patients. [ABSTRACT FROM AUTHOR]

Lung cancer remains the leading cause of cancer-related death worldwide, with non-small cell lung cancer accounting for 85% of the disease. Over 70% of patients present with locally advanced, non-resectable or metastatic disease and despite improvements in chemoradiotherapy regimens and the development of molecularly targeted agents, 5 year survival rates remain poor, with acquired resistance to novel targeted therapies becoming a growing concern. Currently there remains an unmet need in effectively treating and inducing durable responses in advanced disease. Targeting the immune system has, however, recently given hope of improving therapeutic outcomes for these patients. The notion that the immune system is capable of recognising and eliminating cancer cells is now a widely accepted phenomenon and growing evidence suggests lung cancer is an attractive target for such intervention. Recent success targeting the programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) axis of immune checkpoint inhibition suggests a major immunotherapeutic advance in treating lung cancer and unheralded opportunity for such approaches to further improve outcome for patients. Currently there is considerable interest in combining anti-PD-1 or PD-L1 monoclonal antibodies with established standard of care therapies such as radiotherapy. Radiotherapy is known to be immunostimulatory and efforts are underway to combine and augment the efficacy of the immune checkpoint inhibitors further. This review outlines the interaction between lung cancer and the immune system, summarises current evidence supporting the use of monoclonal antibodies targeting the PD-1 axis in lung cancer and explores the potential of combining radiotherapy with immunotherapy to augment anti-tumour immune responses. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Concurrent chemoradiotherapy (CCRT) with etoposide and platinum (carboplatin/cisplatin) plus the anti‒PD-1 antibody pembrolizumab (pembro) has shown antitumor activity and acceptable safety in patients (pts) with limited-stage small-cell lung cancer (LS-SCLC). The poly (ADP-ribose) polymerase (PARP) inhibitor, olaparib, has shown activity in combination with checkpoint inhibitors in SCLC. KEYLYNK-013 (NCT04624204) is a randomized, placebo-controlled, double-blind phase 3 trial of pembro plus CCRT followed by pembro with or without olaparib in pts with newly diagnosed LS-SCLC.Materials/methods: Eligible pts are those aged ≥18 years with previously untreated LS-SCLC, ECOG PS 0/1, and adequate pulmonary function. Pts are randomized 1:1:1 to receive pembro 200 mg Q3W (groups A and B) or pembro placebo (saline) Q3W (group C) during the chemoradiation phase. All pts also receive 4 cycles of chemotherapy (etoposide 100 mg/m2 on days 1, 2, and 3 of each cycle and investigator's choice of carboplatin AUC 5 mg/mL/min or cisplatin 75 mg/m2 on day 1 of each cycle) with definitive thoracic radiotherapy (total dose of 45 Gy in 30 fractions twice daily over 3 weeks or 66 Gy in 33 fractions once daily over 6.5 weeks starting on day 1 of cycle 2). After chemoradiation, prophylactic cranial irradiation is strongly recommended for pts with CR/PR or at investigator's discretion for pts with SD. Postchemoradiation pts receive pembro 400 mg Q6W plus olaparib placebo (group A), or pembro 400 mg Q6W plus olaparib 300 mg BID (group B), or pembro placebo plus olaparib placebo (group C) for 9 cycles/12 months. Randomization is stratified by ECOG PS (0 vs 1), SCLC stage (I/II vs III), radiation fractionation (twice vs once daily), and region (east Asia vs North America/western Europe/UK/Australia vs rest of world). Tumor imaging occurs at baseline, within 12 weeks of cycle 1 day 1, followed by Q9W to the end of year 2, Q12W in year 3, Q16W in year 4, every 6 months in year 5, and annually thereafter. Imaging is assessed per RECIST v1.1 by blinded independent central review. AEs are made per NCI-CTCAE v5.0. Health-related quality of life is assessed using EORTC-QLQ-C30 and QLQ-LC13. Primary endpoints are OS and PFS per RECIST v1.1 by blinded independent central review. OS and PFS are estimated by the Kaplan-Meier method. Between-group differences will be evaluated with stratified log-rank tests and Cox proportional hazard models with Efron's method of tie handling. Secondary endpoints include ORR, duration of response, safety, and pt-reported outcomes. Enrollment began in Dec 2020 and is ongoing at 43 sites in 11 countries as of Feb 24, 2021.Results: TBD CONCLUSION: TBD. [ABSTRACT FROM AUTHOR]

This manuscript provides recommendations for the diagnosis, treatment and follow-up of early stage non-small cell lung cancer developed during the 2nd ESMO Consensus Conference on Lung Cancer in May 2013To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11–12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines in advanced disease, early-stage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on early-stage disease. [ABSTRACT FROM AUTHOR]

Aims: Recent clinical series suggest that treating patients with isotoxic twice-daily radiotherapy may be beneficial. This dosimetric planning study compared the use of intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DRT) to deliver isotoxic treatment for non-small cell lung cancer (NSCLC) patients. Materials and methods: Twenty patients with stage II/III NSCLC were selected. A dose-escalated plan was produced retrospectively for each using three different methods: (i) three to five beams 3DRT; (ii) seven beams inverse-planned conformal radiotherapy; (iii) seven beams IMRT. The starting point for dose escalation was 55.8 Gy in 1.8 Gy per fraction twice-daily. The number of fractions was then increased until one or more organ at risk tolerance dose was exceeded or a maximum dose of 79.2 Gy was reached. Results: The median escalated doses were 70.2, 66.6 and 64.8 Gy for IMRT, 3DRT and inverse-planned conformal radiotherapy, respectively. IMRT allowed a significant dose increase in comparison with the other two methods (P < 0.05), whereas no significant difference was found between 3DRT and inverse-planned conformal radiotherapy. IMRT was more successful at escalating dose in patients where the brachial plexus and spinal canal were close to the planning target volume. IMRT did not allow the escalation of dose beyond 70.2 Gy (82.8 Gy BED10, 69 Gy EQD2) due to the proximity of disease to the great vessels and the proximal bronchial tree. Conclusions: IMRT allows increased dose escalation compared with conformal radiotherapy. However, there is limited opportunity to escalate the prescription dose beyond 70.2 Gy twice-daily in disease close to the central mediastinal structures. [ABSTRACT FROM AUTHOR]

Poster Highlights: Poster highlights 21 PH: Predictive modelling PH-0650: External validation of survival of lung cancer patients due to setup uncertainties towards the heart C. Brink, U. Bernchou, A. Bertelsen, O. Hansen, T. Schytte, L. Holloway, M. Van Herk, C. Johnson-Hart, G.J. Price, M.C. Aznar, A. McWilliam, C. Faivre-Finn, C. Hansen. [Extracted from the article]

Proffered Papers: Proffered papers 1: HSR HERO OC-0074: Impact of early diagnosis and improved access to treatment on lung cancer survival T. Mee, S. Brown, N.F. Kirkby, N.G. Burnet, C. Faivre-Finn, K.J. Kirkby. [Extracted from the article]

Abstract: Accurate radiological staging of small-cell lung cancer (SCLC) is of paramount importance in selection of individual patients with limited stage disease for potentially curative treatment while avoiding toxic treatment in those with distant metastatic disease. [18F] flurodeoxy-d-glucose (FDG) positron emission tomography (PET) is an attractive tool for this purpose but there is limited evidence to support its use in the routine staging of SCLC. Whether therapeutic decisions based on FDG-PET imaging should be made remains uncertain. There is only preliminary evidence for use of FDG-PET as a prognostic biomarker, in the assessment of response to treatment and delineation of disease in conformal radiation planning. [Copyright &y& Elsevier]