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Introduction: The international phase II single-arm LungTech trial 22113-08113 of the European Organization for Research and Treatment of Cancer assessed the safety and efficacy of stereotactic body radiotherapy (SBRT) in patients with centrally located early-stage NSCLC., Methods: Patients with inoperable non-metastatic central NSCLC (T1-T3 N0 M0, ≤7cm) were included. After prospective central imaging review and radiation therapy quality assurance for any eligible patient, SBRT (8 × 7.5 Gy) was delivered. The primary endpoint was freedom from local progression probability three years after the start of SBRT., Results: The trial was closed early due to poor accrual related to repeated safety-related pauses in recruitment. Between August 2015 and December 2017, 39 patients from six European countries were included and 31 were treated per protocol and analyzed. Patients were mainly male (58%) with a median age of 75 years. Baseline comorbidities were mainly respiratory (68%) and cardiac (48%). Median tumor size was 2.6 cm (range 1.2-5.5) and most cancers were T1 (51.6%) or T2a (38.7%) N0 M0 and of squamous cell origin (48.4%). Six patients (19.4%) had an ultracentral tumor location. The median follow-up was 3.6 years. The rates of 3-year freedom from local progression and overall survival were 81.5% (90% confidence interval [CI]: 62.7%-91.4%) and 61.1% (90% CI: 44.1%-74.4%), respectively. Cumulative incidence rates of local, regional, and distant progression at three years were 6.7% (90% CI: 1.6%-17.1%), 3.3% (90% CI: 0.4%-12.4%), and 29.8% (90% CI: 16.8%-44.1%), respectively. SBRT-related acute adverse events and late adverse events ≥ G3 were reported in 6.5% (n = 2, including one G5 pneumonitis in a patient with prior interstitial lung disease) and 19.4% (n = 6, including one lethal hemoptysis after a lung biopsy in a patient receiving anticoagulants), respectively., Conclusions: The LungTech trial suggests that SBRT with 8 × 7.5Gy for central lung tumors in inoperable patients is associated with acceptable local control rates. However, late severe adverse events may occur after completion of treatment. This SBRT regimen is a viable treatment option after a thorough risk-benefit discussion with patients. To minimize potentially fatal toxicity, careful management of dose constraints, and post-SBRT interventions is crucial., Competing Interests: Disclosure Dr. Levy reports academic funding from Roche, Beigene, AstraZeneca, and Pharmamar. Dr. Adebahr was supported by the German Cancer Consortium (DKTK) and is now supported by a grant from the Federal Ministry of Education and Research (BMBF). The remaining authors declare no conflict of interest., (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Purpose: Radiation pneumonitis (RP) is a dose-limiting toxicity for patients undergoing radiotherapy (RT) for lung cancer, however, the optimal practice for diagnosis, management, and follow-up for RP remains unclear. We thus sought to establish expert consensus recommendations through a Delphi Consensus study., Methods: In Round 1, open questions were distributed to 31 expert clinicians treating thoracic malignancies. In Round 2, participants rated agreement/disagreement with statements derived from Round 1 answers using a 5-point Likert scale. Consensus was defined as ≥ 75 % agreement. Statements that did not achieve consensus were modified and re-tested in Round 3., Results: Response rate was 74 % in Round 1 (n = 23/31; 17 oncologists, 6 pulmonologists); 82 % in Round 2 (n = 19/23; 15 oncologists, 4 pulmonologists); and 100 % in Round 3 (n = 19/19). Thirty-nine of 65 Round 2 statements achieved consensus; a further 10 of 26 statements achieved consensus in Round 3. In Round 2, there was agreement that risk stratification/mitigation includes patient factors; optimal treatment planning; the basis for diagnosis of RP; and that oncologists and pulmonologists should be involved in treatment. For uncomplicated radiation pneumonitis, an equivalent to 60 mg oral prednisone per day, with consideration of gastroprotection, is a typical initial regimen. However, in this study, no consensus was achieved for dosing recommendation. Initial steroid dose should be administered for a duration of 2 weeks, followed by a gradual, weekly taper (equivalent to 10 mg prednisone decrease per week). For severe pneumonitis, IV methylprednisolone is recommended for 3 days prior to initiating oral corticosteroids. Final consensus statements included that the treatment of RP should be multidisciplinary, the uncertainty of whether pneumonitis is drug versus radiation-induced, and the importance risk stratification, especially in the scenario of interstitial lung disease., Conclusions: This Delphi study achieved consensus recommendations and provides practical guidance on diagnosis and management of RP., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Matthew Evison – Declarations of interest: none; Gregory Videtic – Declarations of interest: none; Corinne Faivre-Finn –Declarations of interest: none; Kevin Franks –Declarations of interest: none; Suresh Senan – Varian Medical Systems: Advisory board, Departmental research support; AstraZeneca: Advisory board, Institutional research support; BMS: Institutional research support; MSD: Advisory board, consultancy; Iain Phillips –Declarations of interest: none; Jacqueline Kruser –Dr. Kruser has received support for unrelated work from the National Institutes of Health/National Heart, Lung, and Blood Institute under grant numbers F32HL140824 and K23HL146890. Dr. Kruser’s spouse receives honoraria for lectures and speakers bureaus from Astra Zeneca. (Found online); David Palma – Dr Palma reports a Clinician-Scientist Grant from the Ontario Institute for Cancer Research, royalties from Uptodate.com, and a consultant role with equity from Need Inc, all unrelated to the current work; Timothy Kruser –Dr. Kruser sits on the speakers bureau and advisory board for AstraZeneca and serves as a Consultant for Radiologica LLC; Clive Peedell – Disclosures: Speaker fees Elekta, Varian; Clifford Robinson – Radialogica: Leadership, Stock and Other Ownership Interests; Quantaras: Stock and Other Ownership Interests, Consulting or Advisory Role; Varian Medical Systems: Consulting or Advisory Role, Research Funding; AstraZeneca: Consulting or Advisory Role; MED Serono: Consulting or Advisory Role; EmpNia: Consulting or Advisory Role; Merck: Research Funding; Noninvasive imaging and treatment system for cardiac arrhythmias WO 2017078757 A1 U.S. Provisional Application No. 62/598,162 Entitled SYSTEM AND METHOD FOR DETERMINING SEGMENTS FOR ABLATION: Patents, Royalties, Other Intellectual Property; Angela Wright – Declarations of interest: none; Lorraine McCleod – Declarations of interest: none; Percy Lee –Declarations: Varian, Viewray, AstraZeneca, Genentech, Johnson & Johnson: Consulting Fees; AstraZeneca, UK: Manuscript support for a different manuscript (“All support for the present manuscript (e.g., funding, provision of study materials, medical writing, article processing charges, etc.) No time limit for this item.”); Varian, Viewray, AstraZeneca: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events; Radiosurgery Society: Support for attending meeting/travel; Genentech, Viewray, AstraZeneca: Participation on a Data Safety Monitoring Board or Advisory Board; Radiosurgery Society board of director: Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid; Houda Bahig –Declarations: Research grants from Varian Medical Systems; Research grant from Astra Zeneca; Advisory boards - Sanofi & Astra Zeneca; Kevin Chua – Declarations: Advisory boards: AstraZeneca, Regeneron, Roche, Seagen, MSD, Takeda; Speaker honoraria: Varian, PeerVoice; Travel: Varian; Shakar Shiva – Declarations of interest: none; Melody Qu – Declarations of interest: none; Nazia Chaudhuri –Declarations of interest: none; Susan Harden –Declarations of interest: none; Cicely Cunningham –Declarations of interest: none; Indu S. Voruganti Maddali – Declarations of interest: none; Alexander V. Louie – Dr. Louie has received honoraria from AstraZeneca, unrelated to this review; Stephen Harrow – Declarations of interest: none., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

Patients with curable non-surgical lung cancer are often current smokers, have co-existing medical comorbidities and are treated with curative radiotherapy. To maximise the benefits of modern radiotherapy, there is an urgent need to optimise the patient's health to improve survival and quality of life., Methods and Analysis: The Yorkshire Cancer Research-funded Prehabilitation Radiotherapy Exercise, smoking Habit cessation and Balanced diet Study (PREHABS) (L426) is a single-centre prospective feasibility study to assess embedding behavioural changes into the radical radiotherapy pathway of patients with lung cancer. Feasibility will be assessed by measuring acceptability, demand and implementation. The duration of the study is 24 months. PREHABS has two workstreams: the intervention study and the theory of change (ToC) study. Intervention study : PREHABS will commence at the R-IDEAL phase 2 trial (exploratory) based on existing evidence and includes support for smoking cessation, increasing activity and dietary well-being. Patients undergoing radical radiotherapy for lung cancer will be recruited from the oncology department at Leeds Teaching Hospitals NHS Trust (LTHT). ToC study : to maximise the acceptability and adherence to the PREHABS, we will use a ToC approach to qualitatively explore the key barriers and enablers of implementing a tailored programme of 'prehabilitation'. The PREHABS ToC study participants will be recruited from patients with lung cancer undergoing radical radiotherapy and staff from the LTHT oncology department., Analysis: The primary endpoint analysis will report the number of participants and adherence to the study interventions. Secondary endpoints include continued engagement with study interventions post-treatment. The analysis will focus on descriptive statistics. Thematic analysis of the qualitative data from the ToC study will identify consensus on intervention optimisation and delivery., Ethics and Dissemination: On 12 May 2021, the Cambridge East Ethics Committee granted ethical approval (21/EE/0048). The study is registered in the National Institute for Health and Care Research (NIHR) portfolio. The results will be disseminated through publication in peer-reviewed scientific journals and presented at conferences., Trial Registration Number: NIHR portfolio 48420., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Patient-reported outcome measures, including satisfaction with treatment decisions, provide important information in addition to clinical outcomes, survival and decision-making in lung cancer surgery. We investigated associations between preoperative clinical and socio-demographic factors and patient-reported satisfaction 6 weeks after radical treatment for early-stage non-small cell lung cancer (NSCLC)., Methods: We conducted a sub-group analysis of the prospective observational longitudinal study of 225 participants in two treatment groups-surgical (VATS) and radiotherapy (SABR). The Patient Satisfaction Questionnaire-18 (PSQ-18) was used to measure patient satisfaction 6 weeks after treatment. Clinical variables, Index of Multiple Deprivation decile and Decision self-efficacy scores were used in regression analysis. Variables with a p level < 0.1 were used as independent predictors in generalised linear logistic regression analyses., Results: As expected, the two groups differed in pre-treatment clinical features. The SABR group experienced more grade 1-2 complications than the VATS group. No differences were found between the groups in any subscale of the PSQ-18 questionnaire. Patients experiencing complications or living in more deprived areas were more satisfied with care. Properative factors independently associated with patient satisfaction were the efficacy in decision-making and age., Conclusion: We showed that efficacy in treatment decision-making and age was the sole predictor of patient satisfaction with their care after radical treatment for early-stage NSCLC. Patients from more deprived areas and patients who suffered complications reported greater subsequent satisfaction. Involving patients in their care may improve satisfaction after treatment for early-stage NSCLC., (© 2021. The Author(s).)

Background: The United Kingdom National Institute for Health and Care Excellence guidelines recommend that patients and professionals make shared decisions between surgery and stereotactic ablative radiotherapy (SABR) when treating early-stage non-small cell lung cancer (NSCLC). Variation by center suggests treatment decisions may be disproportionately influenced by clinician judgment and treatment availability rather than by patient preference. This systematic review critically evaluates studies of patient and clinician preferences for treatment of early-stage NSCLC., Methods: Primary empirical research up to April 30, 2020, was identified from searches of MEDLINE, Embase, PsycInfo, and Web of Science databases. Data extracted included study characteristics and methods, preferences for NSCLC treatment, and involvement in decision making and risk of bias using the Mixed Methods Appraisal Tool. Findings were synthesized using descriptive data and narrative synthesis., Results: Included in the review were 23 studies, of which 18 measured patient preferences, 4 clinician preferences, and 1 both clinician and patient preferences. Patients and clinicians were both most likely to prefer a collaborative role in treatment decisions. Most patients did not recall there being a choice between surgery or SABR options and thus experienced minimal decisional conflict., Conclusions: For professionals to support patients in making informed, value-based decisions about NSCLC treatments, better quality evidence is needed of the clinical and quality of life trade-offs for both surgery and SABR., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: Video-assisted thoracoscopic (VATS) lung resection is the recommended curative treatment for early-stage non-small cell lung cancer (NSCLC). Patients considered at high surgical risk, are treated with stereotactic ablative body radiotherapy (SABR) as a lower morbidity alternative. This study aims to investigate the impact of SABR and VATS resection on patients' quality of life (QoL) over the first year after treatment., Methods: A prospective longitudinal observational study recruiting early-stage NSCLC patients from a single UK centre. QoL was assessed with EORTC QLQ-C30 and Lung Cancer Module LC13 at baseline, 6 weeks and 3, 6 and 12 months post-treatment., Results: From 01.03.2017 till 01.03.2018, 244/281 patients (87%) consented to participate, 225 (95 SABR and 130 VATS) were included in the analysis. SABR patients had significantly worse baseline QoL scores than VATS patients, even after adjusting for preoperative clinical factors (C-30 Global Health mean: SABR = 53.8, VATS = 71.2; Physical Functioning mean: SABR = 57, VATS = 82.2; Fatigue mean: SABR = 43.5, VATS = 23.7; C30 Dyspnea mean: SABR = 49.5, VATS = 26.2). During the 12 months post SABR treatment patients' QoL scores remained stable. In the VATS group, there was a deterioration 6-weeks after treatment in Role, Physical, Social Functions, Global Health, Fatigue, C30/LC13 Dyspnoea, Pain, Appetite loss, Constipation, LC13 Pain in Chest and Arms. The scores improved by 12 months without reaching the preoperative values., Conclusions: Although QoL outcomes for SABR and VATS are not comparable due to different medical selection criteria, the QoL impact of the two treatments during the first year showed different trends which will inform patients and clinicians during decision-making discussions., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Aims: 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., Materials and Methods: 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)., Results: 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)., Conclusion: 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., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

Purpose/objectives: A recent study has shown that tight conformity of lung Stereotactic Ablative Radiotherapy (SABR) plans might worsen loco-regional control and can predict distant metastases. The study aims to report overall survival (OS), progression-free survival (PFS), local recurrence free survival (LRFS), and dosimetry of early-stage lung cancer patients treated with SABR and to try to explore any dosimetric predictor of outcomes., Material and Methods: Patients treated in our institute (May 2009-August 2018) were included. Electronic medical records were reviewed for baseline characteristics, treatment details, and outcomes. Dosimetric data were extracted from Xio and Monaco software. Patients were treated according to the United Kingdom (UK) SABR consortium guidelines. Kaplan-Meier's analysis with log-rank test was used for survival analysis. The univariate and multivariable Cox regression model was used for correlating dosimetric variables and outcomes., Results: We treated 1266 patients with median age of 75 years and 47.4% were male. Median follow up was 56 months. Median OS was 36 months with 1, 2, and 5 years OS of 84.2%, 64.5%, and 31.5%, respectively. Median for PFS and LRFS was not reached. One, 2, and 5 years PFS were 87.4%, 78.4%, and 72.5%, respectively. One, 2, and 5 years LRFS were 98.2%, 95.1%, and 92.5%, respectively. Planning target volume (PTV), dose to 99% volume of PTV (D99), and R50 (volume receiving the 50% dose/volume (PTV)) were significantly associated with OS. PTV, mean lung dose (MLD), V20 (volume of lung minus gross tumour volume (GTV) receiving 20 Gy), V12.5 (volume of lung minus GTV receiving 12.5 Gy), and dose fractionation were significantly associated with PFS. Nothing was associated with LRFS on univariate analysis. R100 of >1.1 was associated with better OS, PFS, and LRFS compared to R100 ≤ 1.1., Conclusion: SABR achieves good clinical outcomes in patients with early-stage lung cancer; even in elderly patients with multiple comorbidities. In the largest UK early lung cancer cohort treated with SABR, we found that dosimetry correlates with clinical outcomes. Further validation of these results is needed to guide future optimisation of SABR delivery.

Purpose: Not all patients with stage III non-small cell lung cancer (NSCLC) are suitable for concurrent chemoradiation therapy (CRT). Local failure rate is high for sequential concurrent CRT. As such, there is a rationale for treatment intensification., Methods and Materials: Isotoxic intensity modulated radiation therapy (IMRT) is a multicenter feasibility study that combines different intensification strategies including hyperfractionation, acceleration, and dose escalation facilitated by IMRT. Patients with unresectable stage III NSCLC, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2, and unsuitable for concurrent CRT were recruited. A minimum of 2 cycles of platinum-based chemotherapy was compulsory before starting radiation therapy (RT). Radiation dose was increased until a maximum dose of 79.2 Gy was reached or 1 or more of the organs at risk met predefined constraints. RT was delivered in 1.8-Gy fractions twice daily, and an RT quality assurance program was implemented. The primary objective was the delivery of isotoxic IMRT to a dose >60 Gy equivalent dose in 2-Gy fractions (EQD2 assuming an α/β ratio of 10 Gy for acute reacting tissues)., Results: Thirty-seven patients were recruited from 7 UK centers. Median age was 69.9 years (range, 46-86 years). The male-to-female ratio was 17:18. ECOG PS was 0 to 5 in 14.2% of patients; PS was 1 to 27 in 77.1% of patients; PS was 2 to 3 in 8.6% of patients. Stage IIIA:IIIB ratio was 22:13 (62.9%:37.1%). Of 37 patients, 2 (5.4%) failed to achieve EQD2 > 60 Gy. Median prescribed tumor dose was 77.4 Gy (range, 61.2-79.2 Gy). A maximum dose of 79.2Gy was achieved in 14 patients (37.8%). Grade 3 esophagitis was reported in 2 patients, and no patients developed grade 3 to 4 pneumonitis. There were 3 grade 5 events: acute radiation pneumonitis, bronchopulmonary hemorrhage, and acute lung infection. Median follow-up at time of analysis was 25.4 months (range, 8.0-44.2) months for 11 of 35 survivors. The median survival was 18.1 months (95% confidence interval [CI], 13.9-30.6), 2-year overall survival was 33.6% (95% CI, 17.9-50.1), and progression-free survival was 23.9% (95% CI, 11.3-39.1)., Conclusions: Isotoxic IMRT is a well-tolerated and feasible approach to treatment intensification., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Stereotactic Ablative Radiotherapy (SABR) is the standard treatment for early-stage medically inoperable lung cancer. Predictors of radiation pneumonitis (RP) in patients treated with SABR are poorly defined. In this study, we investigate clinical and dosimetric parameters, which can predict symptomatic RP in early-stage lung cancer patients treated with SABR., Materials and Methods: Patients treated with lung SABR between May 2009 and August 2018, in a single United Kingdom (UK) radiotherapy center were included. The patient's baseline characteristics, treatment details, and toxicity were retrieved from the electronic medical record. Dosimetric data was extracted from Xio and Monaco treatment planning systems. Patients were treated according to the UK SABR consortium guidelines. RP was graded retrospectively using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, based on available clinical and imaging information. Univariate and multivariate binary logistic regression was performed to determine predictive factors for grade ≥ 2 radiation pneumonitis, using Statistical Package for the Social Sciences (SPSS) statistics version 21 software. The goodness of fit was assessed using the Hosmer and Lemeshow test. The optimal diagnostic threshold was tested using the Receiver operating characteristics (ROC) curve. The chi-square test was carried out to test the different risk factors against the likelihood of developing grade ≥ 2 pneumonitis., Results: A total of 1266 patients included in the analysis. The median age of patients was 75 years. Six hundred sixty-six patients (52.6%) were female. Median follow up was 56 months. Sixty-five percent of patients received 55 Gy in 5 fractions. Forty-three percent of patients had Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 and 16.2% had PS of 3. The Median Charlson comorbidity index was 6 (range 2-11). Median Standardized Uptake Value (SUV) max of the tumor was 6.5. Four hundred two patients (31.8%) had confirmed histological diagnosis; other patients were treated based on a radiological diagnosis. The median tumor size was 20 mm (range 4 mm-63 mm). Median Planning Target Volume (PTV) was 30.3 cc. Median values of R100, R50, and D2cm were 1.1, 5.6, 32.8 Gy. The median value of mean lung dose, V20, and V12.5 were 3.9 Gy, 5 %and 9.3% respectively. Eighty-five (6.7%) patients developed symptomatic RP (grade ≥ 2) with only 5(0.4%) developing grade 3 RP. Five percent of patients developed rib fractures but only 28% of these were symptomatic. On univariate analysis lower lobe tumor location, larger tumor size, PTV, mean lung dose, lung V20Gy, and V12.5 Gy were significantly associated with grade ≥ 2 RP. On multivariate analysis, only mean lung dose was associated with grade ≥ 2 pneumonitis. ROC curve analysis showed optimal diagnostic threshold for tumour size, PTV, mean lung dose, V20 and V12.5; are 22.5 mm ((Area Under Curve (AUC)-0.565)), 27.15 cc (AUC-0.58), 3.7 Gy (AUC-0.633), 4.6% (AUC-0.597), 9.5% (AUC-0.616). The incidence of ≥grade 2 RP was significantly high for values higher than the ROC threshold., Conclusion: SABR treatment resulted in a very low rate of grade 3 pneumonitis. Lower lobe tumor location, larger tumor size, PTV, mean lung dose, V20, and V12.5 were found to be significant predictors of symptomatic radiation pneumonitis., (Crown Copyright © 2020. Published by Elsevier B.V. All rights reserved.)

The impact of radiotherapy on the heart has become an area of interest in recent years. Many different cardiac dose-volume constraints have been associated with cardiac toxicity and survival; however, no consistent constraint has been found. Many patients undergoing treatment for lung cancer have risk factors for cardiovascular disease or known cardiac comorbidities; however, there is little evidence on the effects of radiotherapy on the heart in these patients. We aim to provide a summary of the existing literature on cardiac toxicity of lung cancer radiotherapy, propose strategies to avoid and manage cardiac toxicity, and suggest avenues for future research., (Copyright © 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Introduction: Lung cancer is the world's leading cause of cancer death. Low-dose computed tomography (LDCT) screening reduced lung cancer mortality by 20% in the US National Lung Screening Trial. Here, we present the Yorkshire Lung Screening Trial (YLST), which will address key questions of relevance for screening implementation., Methods and Analysis: Using a single-consent Zelen's design, ever-smokers aged 55-80 years registered with a general practice in Leeds will be randomised (1:1) to invitation to a telephone-based risk-assessment for a Lung Health Check or to usual care. The anticipated number randomised by household is 62 980 individuals. Responders at high risk will be invited for LDCT scanning for lung cancer on a mobile van in the community. There will be two rounds of screening at an interval of 2 years. Primary objectives are (1) measure participation rates, (2) compare the performance of PLCO M2012 (threshold ≥1.51%), Liverpool Lung Project (V.2) (threshold ≥5%) and US Preventive Services Task Force eligibility criteria for screening population selection and (3) assess lung cancer outcomes in the intervention and usual care arms. Secondary evaluations include health economics, quality of life, smoking rates according to intervention arm, screening programme performance with ancillary biomarker and smoking cessation studies., Ethics and Dissemination: The study has been approved by the Greater Manchester West research ethics committee (18-NW-0012) and the Health Research Authority following review by the Confidentiality Advisory Group. The results will be disseminated through publication in peer-reviewed scientific journals, presentation at conferences and on the YLST website., Trial Registration Numbers: ISRCTN42704678 and NCT03750110., Competing Interests: Competing interests: PAJC has received consultation fees and shares options from Everest Detection. PAJC is supported by the NIHR Manchester Biomedical Research Centre., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Objectives: There is an increasing interest in the quality of life (QoL) evaluation following video-assisted thoracoscopic anatomical lung resection or stereotactic ablative body radiotherapy for early-stage non-small-cell lung cancer (NSCLC). A qualitative interview study was conducted to gain insight into the optimal methods of assessing and discussing QoL in clinical practice., Methods: A prospective observational longitudinal study of patients with early-stage NSCLC was conducted where repeated QoL measures were administered either online or on paper. A subset of participants was invited for qualitative interviews after the 6-month assessment or at the end of the study. The semi-structured interviews were transcribed verbatim and thematically analysed., Results: Twenty-three patients were interviewed. Generally, patients were content with recruitment and data collection procedures. Most opted to complete the assessments on paper instead of online; this choice was influenced by the level of technology literacy. Some found the questionnaires too generic to reflect their experiences. Barriers to questionnaire completion were mostly practical, and many acknowledged benefits of QoL assessment including allowing them to express problems and health issues, and following changes over time. Generally, participants would like to discuss QoL results during clinical consultations, but reported this rarely happened., Conclusions: Lung cancer patient interviews confirm the acceptability of repeated QoL assessments, but online data capture is limited. Patients highlight the importance of discussing QoL aspects with their clinical team. Future strategies are needed to optimize the routine collection of patient-reported outcomes in clinical practice., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: 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., Methods: 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., Results: 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., Conclusion: 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., 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 © 2020 Elsevier B.V. All rights reserved.)

Background: In early-stage Non-Small Cell Lung Cancer (NSCLC) patients, little is known about how to measure patient participation in Shared-Decision Making (SDM). We examined the psychometric properties and clinical acceptability of the Decision Self-Efficacy scale (DSE) in a cohort of patients undergoing to Stereotactic Ablative Radiotherapy (SABR) or Video-assisted Thoracoscopic Surgery (VATS) to capture patient involvement in treatment decisions., Methods: In the context of a prospective longitudinal study (Life after Lung Cancer-LiLAC) involving 244 patients with early-stage NSCLC, 158 (64.7%) patients completed the DSE either on paper or electronically online prior to treatment with SABR or VATS pulmonary resection. DSE psychometric properties were examined using: principal components analysis of item properties and internal structure, and internal construct validity; we also performed a sensitivity analysis according to Eastern Cooperative Oncology Group Performance Status (ECOG PS), gender, age and treatment received (VATS or SABR) difference., Results: Exploratory factor analysis using polychoric correlations substantiated that the 11 item DSE is one scale accounting for 81% of the variance. We calculated a value of 0.96 for Cronbach's alpha for the total DSE score. DSE scores did not differ by gender (p = 0.37), between the two treatment groups (p = 0.09) and between younger and older patients (p = 0.4). However, patients with an ECOG PS > 1 have a DSE mean of 73.8 (SD 26) compared to patients with a PS 0-1 who have a DSE mean of 85.8 (SD 20.3 p = 0.002)., Conclusion: Findings provide preliminary evidence for the reliability and validity of the DSE questionnaire in this population. However, future studies are warranted to identify the most appropriate SDM tool for clinical practice in the lung cancer treatment field.

Introduction: Surgery is the standard of care for early-stage lung cancer, with stereotactic ablative body radiotherapy (SABR) a lower morbidity alternative for patients with limited physiological reserve. Comparisons of outcomes between these treatment options are limited by competing comorbidities and differences in pre-treatment pathological information. This study aims to address these issues by assessing both overall and cancer-specific survival for presumed stage I lung cancer on an intention-to-treat basis., Methods: This retrospective intention-to-treat analysis identified all patients treated for presumed stage I lung cancer within a single large UK centre. Overall survival, cancer-specific survival, and combined cancer and treatment-related survival were assessed with adjustment for confounding variables using Cox proportional hazards and Fine-Gray competing risks analyses., Results: 468 patients (including 316 surgery and 99 SABR) were included in the study population. Compared with surgery, SABR was associated with inferior overall survival on multivariable Cox modelling (SABR HR 1.84 (95% CI 1.32-2.57)), but there was no difference in cancer-specific survival (SABR HR 1.47 (95% CI 0.80-2.69)) or combined cancer and treatment-related survival (SABR HR 1.27 (95% CI 0.74-2.17)). Combined cancer and treatment-related death was no different between SABR and surgery on Fine-Gray competing risks multivariable modelling (subdistribution hazard 1.03 (95% CI 0.59-1.81)). Non-cancer-related death was significantly higher in SABR than surgery (subdistribution hazard 2.16 (95% CI 1.41-3.32))., Conclusion: In this analysis, no difference in cancer-specific survival was observed between SABR and surgery. Further work is needed to define predictors of outcome and help inform treatment decisions., Competing Interests: Conflict of interest: K.L. Spencer has nothing to disclose. Conflict of interest: M.P.T. Kennedy has nothing to disclose. Conflict of interest: K.L. Lummis has nothing to disclose. Conflict of interest: D.A.B. Ellames has nothing to disclose. Conflict of interest: M. Snee has nothing to disclose. Conflict of interest: A. Brunelli has nothing to disclose. Conflict of interest: K. Franks reports personal fees for advisory board work from Pfizer and BMS, personal fees for advisory board work and support for conference attendance from AstraZeneca, and personal fees for educational meetings and support for conference attendance from Boehringer Ingelheim, outside the submitted work. Conflict of interest: M.E.J. Callister has nothing to disclose., (Copyright ©ERS 2019.)

Objective: Stereotactic ablative radiotherapy (SABR) has become the standard of care for suitable patients with peripherally located early stage non-small cell lung cancer. Lung SABR requires strict image-guided radiotherapy (IGRT) protocols to ensure its safe delivery. The aim of this survey was to provide an assessment of current lung SABR practice in the UK., Methods: An online semi-structured survey containing a maximum of 32 questions regarding lung SABR, focussing on treatment image verification processes was piloted, developed and disseminated to the radiotherapy managers of 62 National Health Service centres across the UK., Results: The survey had a 100% complete response from NHS centres. 36 centres (58%) currently deliver lung SABR, with half treating fewer than 50 patients per year. Six centres deliver SABR despite not being commissioned by the NHS to provide this service. There is wide variation in the use of IGRT. Eight different permutations of cone beam CT order within the workflow were reported. Almost half of lung centres (17/36, 47%) believe there is a need to update national image guidance associated with lung SABR, such as the use of 'day zero', mid treatment and post treatment cone beam CTs., Conclusion: Our results demonstrate wide variation in IGRT for lung SABR. There is an opportunity to develop existing IGRT workflows and the optimal approach to image guidance. Further work is required to investigate lung SABR provision and potential barriers to its implementation., Advances in Knowledge: This survey represents the most comprehensive and accurate assessment of lung SABR practice in the UK since the 2014 SABR consortium survey.

Objectives: The aim of the study was to identify whether ventilation-to-carbon dioxide output (V E /V CO2 ) slope obtained from cardiopulmonary exercise test (CPET) as part of the preoperative functional workup was an independent prognostic factor for short and long-term survival after major lung resection., Patients and Methods: 974 consecutive patients undergoing lobectomy (n = 887) or segmentectomy (n = 87) between April 2014 to March 2018 were included. 209 (22%) underwent CPET, and pulmonary function tests and several clinical factors including age, sex, performance status and comorbidities were retrospectively investigated to identify the prognostic factors with a multivariable Cox regression analysis., Results: Among the patients with measured V E /V CO2 , the incidence of cardiopulmonary complications in patients with high V E /V CO2 slope (>40) was 37% (19 of 51) vs. 27% (33 of 121) in those with lower slope values (p = 0.19). The 90-day mortality in patients with high V E /V CO2 slope (n = 8) was 16% vs. 5% (n = 6) in those with lower slope values (p = 0.03). No overall difference in 2-year mortality was identified between the two groups (VE/VCO2 > 40: 70% (54-80) vs. VE/VCO2 ≤ 40: 72% (63-80), log-rank test, p = 0.39). In a Cox regression analysis V E /V CO2 values were associated with poorer 2-year survival (HR 1.05, 95% CI 1.01-1.10, p = 0.030)., Conclusions: We found that V E /V CO2 slope was an independent prognostic factor for the 90-day mortality and 2-year survival after anatomic pulmonary resection. This finding may assist during the multidisciplinary treatment decision-making process in high-risk patients with lung cancer., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: We tested the European Organization for Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) summary score (SumSC) to detect changes in the HRQOL after Non-small-cell lung cancer (NSCLC) surgery and compared its performance to the traditional scales., Method: EORTC QLQ-C30 data was obtained from 326 consecutive pre-operative patients submitted for anatomical lung resections for NSCLC.66 patients completed post-operative assessments 3 months after surgery. The data was analysed to evaluate the ability of the SumSC compared to the traditional scales to [1] preoperatively differentiate between clinical groups [2]; detect post-op changes and to [3] compare pre and post-op changes in clinically different groups.The importance of perioperative changes was measured by calculating the effect size (ES)., Results: Of the 326 patients, those older than 70 years, with higher DLCO value and Performance Status (PS) ≤1 had a significantly better preoperative SumScore. Physical function (PF) showed a large and significant decline (ES 0.91). Role and social function also showed a significant and medium decline (ES 0.62 and 0.41). Postoperatively some symptoms scales showed significant increases in the values, implying worse symptoms with the largest increase in dyspnoea (ES -0.88). The change in General Health score (GH) was not significant after surgery (ES 0.26, p = 0.062). The SumSc, decreased significantly postoperatively. In particular, medium or large postoperative declines of SumSc were observed in both males and females, in patients with lower FEV1, lower performance score, and in those older than 70 years. Interestingly the decline of SumSc was observed irrespective of the preoperative DLCO level., Discussion: The Summary Score was more sensitive to changes in subjects' HRQOL, than the GH score. The SumSc can be used as a parsimonious and easy to interpreted patient-reported-outcome measure in multi-institutional database and future clinical trials., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims: A systematic review of the literature evaluating the clinical use of respiratory-gated (four-dimensional; 4D) fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) compared with non-gated (three-dimensional; 3D) PET/CT for radiotherapy planning in lung cancer., Materials and Methods: A search of MEDLINE, Cochrane, Web of Science, SCOPUS and clinicaltrials.gov databases was undertaken for articles comparing 3D and 4D PET/CT tumour volume or 4D PET/CT for radiotherapy planning. PRISMA guidelines were followed., Results: Thirteen studies compared tumour volumes at 3D and 4D PET/CT; eight reported significantly smaller volumes (6.9-44.5%), three reported significantly larger volumes at 4D PET/CT (16-50%), one reported no significant difference and one reported mixed findings. Six studies, including two that reported differences in tumour volumes, compared target volumes or studied geographic misses. 4D PET/CT target volumes were significantly larger (19-40%) when compared with 3D PET/CT in all but one study, where they were smaller (3.8%). One study reported no significance in 4D PET/CT target volumes when compared with 4D CT, whereas another study reported significantly larger volumes (38.7%)., Conclusion: The use of 4D PET/CT leads to differences in target volume delineation compared with 3D PET/CT. These differences vary depending upon technique and the clinical impact currently remains uncertain. Correlation of pretreatment target volumes generated at 3D and 4D PET/CT with postsurgical histology would be ideal but technically challenging. Evaluation of patient outcomes based on 3D versus 4D PET/CT derived treatment volumes warrants further investigation., (Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Purpose: Imaging after stereotactic ablative radiation therapy (SABR) for early-stage non-small cell lung cancer can detect recurrences and second primary lung cancers; however, the optimal follow-up practice of these patients remains unclear. We sought to establish consensus recommendations for surveillance after SABR., Methods and Materials: International opinion leaders in thoracic radiation oncology and radiology were invited to participate (n = 31), with 11 accepting (9 radiation oncologists, 2 radiologists). Consensus-building was achieved using a 3-round Delphi process. Participants rated their agreement/disagreement with statements using a 5-point Likert scale. An a priori threshold of ≥75% agreement/disagreement was required for consensus., Results: A 100% response rate was achieved and final consensus statements were approved by all participants. The consensus statements were: (1.1) thoracic computed tomography (CT) scans should be ordered routinely in follow-up; (1.2) if there is a suspicion for local recurrence (LR), fludeoxyglucose positron emission tomography/CT scans are strongly recommended. Otherwise, there is limited evidence to guide routine use of fludeoxyglucose positron emission tomography /CT; (1.3) CT imaging is not recommended at 6 weeks, but is recommended at months 3, 6, and 12 in year 1 and then every 6 months in year 2 and annually in years 3 through 5; (1.4) after 5 years, CT imaging should continue, although no consensus was reached regarding the frequency. (2.1) Response Evaluation Criteria in Solid Tumors 1.1 criteria are not sufficient for detecting LR; (2.2) a formal scoring system, informed by validated data, should be used to classify high-risk imaging features predictive of LR; (2.3) CT findings suspicious for LR include: infiltration into adjacent structures, bulging margins, sustained growth, mass-like growth, spherical growth, craniocaudal growth, and loss of air bronchograms. (3) Salvage therapy without pathologic confirmation of recurrence is acceptable if imaging findings are highly suspicious and a biopsy is not safe/feasible or if an attempted biopsy was nondiagnostic., Conclusions: These guidelines provide international expert consensus on areas of uncertainty in the management of early-stage non-small cell lung cancer patients after SABR., (Copyright © 2017 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

In spite of recent improvements in both the technical delivery of radiotherapy and systemic therapy in the treatment of non-small cell lung cancer, local recurrence rates after radiotherapy remain a significant challenge. In the setting of local relapse after radiotherapy, treatments such as surgical resection or radiofrequency ablation are often not appropriate owing to disease and patient factors. Re-irradiation may be a potential treatment option. This overview considers the published evidence and potential treatment strategies., (Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Stereotactic ablative body radiotherapy (SABR) describes a radiotherapy (RT) technique where high doses of radiation are precisely delivered to an extracranial target within the body, using either a single fraction of RT or using multiple small numbers of fractions. SABR has now become the standard of care treatment for patients with early-stage non-small-cell lung cancer (NSCLC) for whom surgery is not appropriate. This systematic review considers the evidence supporting the use of SABR in early-stage NSCLC, reported toxicity rates, the use of SABR in centrally located NSCLC, the use of SABR as salvage therapy following surgery or RT, and future potential drug combinations with SABR.

Objectives: To assess whether quality of life (QOL) was associated with cardiopulmonary complications following pulmonary lobectomy for lung cancer., Methods: Retrospective analysis of 200 consecutive patients who had pulmonary lobectomy for lung cancer (September 2014-October 2015). QOL was assessed by the self-administration of the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire within 2 weeks before the operation. The individual QOL scales were tested for a possible association with cardiopulmonary complications along with other objective baseline and surgical parameters by univariable and multivariable analyses., Results: Forty-three patients (21.5%) developed postoperative cardiopulmonary complications; 4 of them died within 30 days (2%). Univariable analysis showed that, compared to patients without complications, those with complications reported a lower global health status (GHS) [59.1; standard deviation (SD) 27.2 vs 69.6; SD 20.6, P  =   0.02], were older (71.2; SD 8.4 vs 67.7; SD 9.4, P  =   0.03), had lower values of forced expiratory volume in one second (FEV1) (83.9; SD 27.2 vs 91.4; SD 20.9), P  =   0.06) and carbon monoxide lung diffusion capacity (DLCO) (67.9; SD 20.9 vs 74.2; SD 17.6, P  =   0.02) and higher performance score (0.76; SD 0.63 vs 0.53; SD 0.64, P  =   0.02). Stepwise logistic regression analysis showed that factors independently associated with cardiopulmonary complications were age [odds ratio (OR) 1.04, 95% CI 1.0-1.09, P  =   0.02] and patient-reported GHS [OR 0.98, 95% confidence interval (CI) 0.96-0.99, P  =   0.006], whereas other objective parameters (i.e. FEV1, DLCO) were not. The best cut-off value for GHS to discriminate patients with complications after surgery was 50 (c-index 0.65, 95% CI 0.58-0.72)., Conclusions: A poor GHS perceived by the patient was associated with postoperative cardiopulmonary morbidity. Patient perceptions and values should be included in the risk stratification process to tailor cancer treatment., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Introduction: The majority of stage III patients with non-small cell lung cancer (NSCLC) are unsuitable for concurrent chemoradiotherapy, the non-surgical gold standard of care. As the alternative treatment options of sequential chemoradiotherapy and radiotherapy alone are associated with high local failure rates, various intensification strategies have been employed. There is evidence to suggest that altered fractionation using hyperfractionation, acceleration, dose escalation, and individualisation may be of benefit. The MAASTRO group have pioneered the concept of 'isotoxic' radiotherapy allowing for individualised dose escalation using hyperfractionated accelerated radiotherapy based on predefined normal tissue constraints. This study aims to evaluate whether delivering isotoxic radiotherapy using intensity modulated radiotherapy (IMRT) is achievable., Methods and Analysis: Isotoxic IMRT is a multicentre feasibility study. From June 2014, a total of 35 patients from 7 UK centres, with a proven histological or cytological diagnosis of inoperable NSCLC, unsuitable for concurrent chemoradiotherapy will be recruited. A minimum of 2 cycles of induction chemotherapy is mandated before starting isotoxic radiotherapy. The dose of radiation will be increased until one or more of the organs at risk tolerance or the maximum dose of 79.2 Gy is reached. The primary end point is feasibility, with accrual rates, local control and overall survival our secondary end points. Patients will be followed up for 5 years., Ethics and Dissemination: The study has received ethical approval (REC reference: 13/NW/0480) from the National Research Ethics Service (NRES) Committee North West-Greater Manchester South. The trial is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice (GCP). The trial results will be published in a peer-reviewed journal and presented internationally., Trial Registration Number: NCT01836692; Pre-results., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: To investigate chest wall pain in patients with peripheral early stage lung cancer treated with stereotactic ablative radiotherapy (SABR), and to identify factors predictive of Common Terminology Criteria of Adverse Events Grade 2 + chest wall pain., Methods: Patients who received 55 Gy in five fractions were included. A chest wall structure was retrospectively defined on planning scans, and chest wall dosimetry and tumour-related factors recorded. Logistic regression was performed to identify factors predictive of ≥Grade 2 chest wall pain., Results: 182 patients and 187 tumours were included. There were 20 (10.9%) episodes of ≥Grade 2 chest wall pain. Multivariate logistic regression demonstrated that the maximum dose received by 1 cm(3) of chest wall (Dmax1 cm(3)) and tumour size were significant predictors of ≥Grade 2 chest wall pain [Dmax1 cm(3) odds ratio : 1.104, 95% confidence interval : 1.012-1.204, p = 0.025; tumour size (mm) odds ratio : 1.080, 95% confidence interval : 1.026-1.136, p = 0.003]. This model was an adequate fit to the data (Hosmer and Lemeshow test non-significant) and a fair discriminator for chest wall pain (area under receiver-operating characteristic curve: 0.74). Using the multivariate logistic regression model, parameters for Dmax1 cm(3) are provided, which predict <10% and <20% risks of ≥Grade 2 chest wall pain for different tumour sizes., Conclusion: Grade 2+ chest wall pain is an uncommon side effect of lung SABR. Larger tumour size and increasing Dmax1 cm(3) are significant predictors of ≥Grade 2 chest wall pain. When planning lung SABR, it is prudent to try to avoid hot volumes in the chest wall, particularly for larger tumours., Advances in Knowledge: This article demonstrates that Grade 2 or greater chest wall pain following lung SABR is more common when the tumour is larger in size and the Dmax1 cm(3) of the chest wall is higher. When planning lung SABR, the risk of chest wall pain may be reduced if maximum doses are minimized, particularly for larger tumours.

Aims: To report outcomes for the first UK cohort treated for early stage peripheral lung cancer using stereotactic ablative radiotherapy (SABR)., Materials and Methods: Patients were included who received SABR between May 2009 and May 2012. Electronic medical records were reviewed for baseline characteristics, treatment details and outcomes. Patients were treated according to the UK SABR Consortium Guidelines. Univariate and multivariate Cox regression was used to determine factors that influenced overall survival and local control., Results: In total, 273 patients received SABR for 288 lesions in the time period examined. The median follow-up was 19.7 months. The median overall survival for all patients was 27.3 months, with 1, 2 and 3 year overall survival of 78.0, 54.9 and 38.6%, respectively. The 1, 2 and 3 year rates of local control were 98.2, 95.7 and 95.7%, respectively. All patients completed the planned course of treatment and rates of Common Toxicity Criteria grade 3+ toxicity were low. On multivariate analysis, patients with Medical Research Council (MRC) breathlessness scores of 3-5 had worse overall survival compared with patients with scores of 1-2 (hazard ratio: 2.10; 95% confidence interval: 1.25-3.59) and the presence of histological diagnosis conferred improved overall survival (hazard ratio: 0.54; 95% confidence interval: 0.31-0.93), probably reflecting that patients who are considered well enough to undergo biopsy are generally fitter overall. No factors were identified that significantly influenced local control., Conclusions: SABR is an effective and well-tolerated treatment option for patients with early stage peripheral lung cancer who are not suitable for surgery. No patient cohort was identified in whom SABR was considered inappropriate. This series adds to the existing positive data that support SABR for this patient group., (Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Introduction: Stereotactic ablative body radiotherapy is a therapeutic option for patients with peripheral stage I NSCLC in whom surgical resection is considered high risk. Patients receiving SABR do not undergo systematic nodal dissection and any occult nodal metastases will therefore go undetected. Our aim was to determine what proportion of cases this might represent., Materials and Methods: We retrospectively studied patients who underwent lung resections for presumed stage I NSCLC between 2008 and 2011 at a United Kingdom teaching hospital. We reviewed postoperative pathological lymph node staging and analyzed a subset of these patients in whom SABR would have been be technically possible., Results: We reviewed 128 cases of presumed NSCLC preoperatively staged as T1/2a N0 M0. Of 89 cases with peripheral tumor location, 8 patients (8.9%) had nodal involvement at surgical resection., Conclusion: Our data show that approximately 1 in 11 patients with peripheral stage I NSCLC will have occult mediastinal/hilar nodal involvement. Although this is a relatively small proportion, routine use of EBUS-TBNA for nodal staging in patients undergoing SABR might identify a greater proportion of patients with nodal disease compared with a strategy of nodal staging directed according to positron emission tomography-computed tomography findings., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background and Purpose: Distant metastases are the dominant mode of failure after stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer (NSCLC). The primary study objective was to evaluate if the maximum standardized uptake value (SUV(max)) on pre-treatment FDG-PET/CT predicted clinical outcomes. Secondary objectives were to correlate 3-month post-SBRT SUV(max) and change in SUV(max) with outcomes., Materials and Methods: Consecutive patients with medically inoperable early-stage NSCLC and an FDG-PET/CT scan before (n=82) and 3 months after (n=62) SBRT., Results: Median follow up was 2 years. On univariate analysis baseline SUV(max) predicted for distant failure (p=0.0096), relapse free survival (RFS) (p=0.037) and local failure (p=0.044). On multivariate analysis baseline SUV(max) predicted for RFS (p=0.037). Baseline SUV(max) of above 5 was the most statistically significant cut off point for predicting distant failure (p=0.0002). Baseline SUV(max) ≥4.75 (median) was correlated with a higher risk of distant failure (p=0.012) and poorer RFS (p=0.04). Patients with a post-SBRT SUV(max) ≥2 and a reduction of <2.55 had a significantly higher rate of distant failure., Conclusions: Pre-SBRT SUV(max) on FDG-PET/CT correlated most strongly with distant failure. A cut off of ≥5 was the most significant. Post-SBRT SUV(max) ≥2 and a reduction of <2.55 were associated with a higher risk of distant failure., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

The early response of lung tumours to stereotactic radiotherapy was prospectively evaluated with 18F-fluorodeoxyglucose positron emission tomography-computed tomography. Three months after treatment, the maximum standardised uptake value and the tumour diameter fell by 64 and 30%, respectively. This imaging strategy therefore remains under ongoing evaluation with the aim of identifying predictive and prognostic factors., (Copyright © 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Purpose: To evaluate a deformable image registration (DIR) segmentation technique for semi-automating ITV production from 4DCT for lung patients, in terms of accuracy and efficiency., Methods: Twenty-five stereotactic body radiotherapy lung patients were selected in this retrospective study. ITVs were manually delineated by an oncologist and semi-automatically produced by propagating the GTV manually delineated on the mid-ventilation phase to all other phases using two different DIR algorithms, using commercial software. The two ITVs produced by DIR were compared to the manually delineated ITV using the dice similarity coefficient (DSC), mean distance between agreement and normalised DSC. DIR-produced ITVs were assessed for their clinical suitability and also the time savings were estimated., Results: Eighteen out of 25 ITVs had normalised DSC>1 indicating an agreement with the manually produced ITV within 1mm uncertainty. Four of the other seven ITVs were deemed clinically acceptable and three would require a small amount of editing. In general, ITVs produced by DIR were smoother than those produced by manual delineation. It was estimated that using this technique would save clinicians on average 28 min/patient., Conclusions: ABAS was found to be a useful tool in the production of ITVs for lung patients. The ITVs produced are either immediately clinically acceptable or require minimal editing. This approach represents a significant time saving for clinicians., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To assess the feasibility, reproducibility, and accuracy of volumetric lung image guidance using different thoracic landmarks for image registration., Methods and Materials: In 30 lung patients, four independent observers conducted automated and manual image registrations on Day 1 cone-beam computed tomography data sets using the spine, carina, and tumor (720 image registrations). The image registration was timed, and the couch displacements were recorded. The intraclass correlation was used to assess reproducibility, and the Bland-Altman analysis was used to compare the automatic and manual matching methods. Tumor coverage (accuracy) was assessed through grading the tumor position after image matching against the internal target volume and planning target volume., Results: The image-guided process took an average of 1 min for all techniques, with the exception of manual tumor matching, which took 4 min. Reproducibility was greatest for automatic carina matching (intraclass correlation, 0.90-0.93) and lowest for manual tumor matching (intraclass correlation, 0.07-0.43) in the left-right, superoinferior, and anteroposterior directions, respectively. The Bland-Altman analysis showed no significant difference between the automatic and manual registration methods. The tumor was within the internal target volume 62% and 60% of the time and was outside the internal target volume, but within the planning target volume, 38% and 40% of the time after automatic spine and automatic carina matching, respectively., Conclusion: For advanced lung cancer, the spine or carina can be used equally for cone-beam computed tomography image registration without compromising target coverage. The carina was more reproducible than the spine, but additional analysis is required to confirm its validation as a tumor surrogate. Soft-tissue registration is unsuitable at present, given the limitations in contrast resolution and the high interobserver variability.

Introduction: With the anticipation of improved outcomes, especially for patients with early-stage non-small cell lung cancer, stereotactic body radiation therapy (SBRT) has been rapidly introduced into the thoracic radiation oncology community. Although at first glance lung SBRT might seem methodologically similar to conventional radiotherapy, there are important differences in its execution that require particular consideration. The objective of this paper is to highlight these and other issues to contribute to the safe and effective diffusion of lung SBRT. We discuss practical challenges that have been encountered in the implementation of lung SBRT at a single, large institution and emphasize the importance of a systematic approach to the design of lung SBRT services., Methods: Specific technical and clinical components that were identified as being important during the development of lung SBRT at Princess Margaret Hospital are described. The clinical system that evolved from these is outlined., Results: Using this clinical framework the practical topics addressed include: patient assessment, simulation and treatment planning, tumor and organ at risk delineation, trial set up before treatment, on-line image-guidance, and patient follow-up., Conclusions: The potential gain in therapeutic ratio that is theoretically possible with lung SBRT can only be realized if the tumor is adequately irradiated and normal tissue spared. A discussion of the component parts of lung SBRT is presented. It is a complex process and specific challenges need to be overcome to effect the satisfactory transition of lung SBRT into routine practice.

Purpose: Cone-beam computed tomography (CBCT) in-room imaging allows accurate inter- and intrafraction target localization in stereotactic body radiotherapy of lung tumors., Methods and Materials: Image-guided stereotactic body radiotherapy was performed in 28 patients (89 fractions) with medically inoperable Stage T1-T2 non-small-cell lung carcinoma. The targets from the CBCT and planning data set (helical or four-dimensional CT) were matched on-line to determine the couch shift required for target localization. Matching based on the bony anatomy was also performed retrospectively. Verification of target localization was done using either megavoltage portal imaging or CBCT imaging; repeat CBCT imaging was used to assess the intrafraction tumor position., Results: The mean three-dimensional tumor motion for patients with upper lesions (n = 21) and mid-lobe or lower lobe lesions (n = 7) was 4.2 and 6.7 mm, respectively. The mean difference between the target and bony anatomy matching using CBCT was 6.8 mm (SD, 4.9, maximum, 30.3); the difference exceeded 13.9 mm in 10% of the treatment fractions. The mean residual error after target localization using CBCT imaging was 1.9 mm (SD, 1.1, maximum, 4.4). The mean intrafraction tumor deviation was significantly greater (5.3 mm vs. 2.2 mm) when the interval between localization and repeat CBCT imaging (n = 8) exceeded 34 min., Conclusion: In-room volumetric imaging, such as CBCT, is essential for target localization accuracy in lung stereotactic body radiotherapy. Imaging that relies on bony anatomy as a surrogate of the target may provide erroneous results in both localization and verification.

An image-guidance process for using cone-beam computed tomography (CBCT) for stereotactic body radiation therapy (SBRT) of peripheral lung lesions is presented. Respiration correlated CBCT on the treatment unit and four dimensional computed tomography (4DCT) from planning are evaluated for assessing respiration-induced target motion during planning and treatment fractions. Image-guided SBRT was performed for 12 patients (13 lesions) with inoperable early stage non-small cell lung carcinoma. Kilovoltage (kV) projections were acquired over a 360 degree gantry rotation and sorted based on the pixel value of an image-based aperture located at the air-tissue interface of the diaphragm. The sorted projections were reconstructed to provide volumetric respiration correlated CBCT image datasets at different phases of the respiratory cycle. The 4D volumetric datasets were directly compared with 4DCT datasets acquired at the time of planning. For ten of 12 patients treated, the lung tumour motion, as measured by respiration correlated CBCT on the treatment unit, was consistent with the tumour motion measured by 4DCT at the time of planning. However, in two patients, maximum discrepancies observed were 6 and 10 mm in the anterior-posterior and superior-inferior directions, respectively. Respiration correlated CBCT acquired on the treatment unit allows target motion to be assessed for each treatment fraction, allows target localization based on different phases on the breathing cycle, and provides the facility for adaptive margin design in radiation therapy of lung malignancies. The current study has shown that the relative motion and position of the tumour at the time of treatment may not match that of the planning 4DCT scan. Therefore, application of breathing motion data acquired at simulation for tracking or gating radiation therapy may not be suitable for all patients - even those receiving short course treatment techniques such as SBRT.