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Lung cancer is the most common cancer diagnosed in the UK. Outcomes for patients with this disease remain poor and new strategies to treat this disease require investigation. One potential option is to combine novel agents with radiotherapy in clinical studies. Here we discuss some of the important issues to consider when combining novel agents with radiotherapy, together with potential solutions as discussed at a recent Clinical Translational Radiotherapy Group (CTRad) workshop. [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]

Background: Comorbidities have been shown to impact the presentation and treatment of patients with cancers. This study investigates the prevalence and patterns of comorbidity in a pan-cancer cohort of patients treated at a large UK specialist cancer center over a 9-year period., Methods: A retrospective review of 77,149 patients from 01/01/2014 to 15/12/2022 was conducted using the Adult Comorbidity Evaluation 27 score (ACE-27) to assess the burden of comorbidities across 12 organ systems and an overall comorbidity burden. Binary and multinomial logistic regressions were utilized to evaluate the relationships between comorbidity incidence and demographic and socio-economic factors., Results: At the time of diagnosis, 59.7% of patients had at least one comorbidity, with the highest prevalence in lung cancer and the lowest in brain/CNS and endocrine gland cancers. Cardiovascular comorbidities were the most frequent. Comorbidity severity was higher in patients from more deprived areas. Age and performance status were associated with a higher incidence of all comorbidities examined. Patients with advanced stage had a lower risk of having a severe comorbidity burden., Conclusion: Comorbidities are common across all cancers but are more prevalent in certain patient populations. Further research to understand the implications of comorbidities in cancer management is needed., (© 2024. The Author(s).)

Aims: Previous work found that during the first wave of the COVID-19 pandemic, 34% of patients with lung cancer treated with curative-intent radiotherapy in the UK had a change to their centre's usual standard of care treatment (Banfill et al. Clin Oncol 2022;34:19-27). We present the impact of these changes on patient outcomes., Materials and Methods: The COVID-RT Lung database was a prospective multicentre UK cohort study including patients with stage I-III lung cancer referred for and/or treated with radical radiotherapy between April and October 2020. Data were collected on patient demographics, radiotherapy and systemic treatments, toxicity, relapse and death. Multivariable Cox and logistic regression were used to assess the impact of having a change to radiotherapy on survival, distant relapse and grade ≥3 acute toxicity. The impact of omitting chemotherapy on survival and relapse was assessed using multivariable Cox regression., Results: Patient and follow-up forms were available for 1280 patients. Seven hundred and sixty-five (59.8%) patients were aged over 70 years and 603 (47.1%) were female. The median follow-up was 213 days (119, 376). Patients with stage I-II non-small cell lung cancer (NSCLC) who had a change to their radiotherapy had no significant increase in distant relapse (P = 0.859) or death (P = 0.884); however, they did have increased odds of grade ≥3 acute toxicity (P = 0.0348). Patients with stage III NSCLC who had a change to their radiotherapy had no significant increase in distant relapse (P = 0.216) or death (P = 0.789); however, they did have increased odds of grade ≥3 acute toxicity (P < 0.001). Patients with stage III NSCLC who had their chemotherapy omitted had no significant increase in distant relapse (P = 0.0827) or death (P = 0.0661)., Conclusion: This study suggests that changes to radiotherapy and chemotherapy made in response to the COVID-19 pandemic did not significantly affect distant relapse or survival. Changes to radiotherapy, namely increased hypofractionation, led to increased odds of grade ≥3 acute toxicity. These results are important, as hypofractionated treatments can help to reduce hospital attendances in the context of potential future emergency situations., (Copyright © 2023. Published by Elsevier Ltd.)

Aims: In response to the COVID-19 pandemic, guidelines on reduced fractionation for patients treated with curative-intent radiotherapy were published, aimed at reducing the number of hospital attendances and potential exposure of vulnerable patients to minimise the risk of COVID-19 infection. We describe the changes that took place in the management of patients with stage I-III lung cancer from April to October 2020., Materials and Methods: Lung Radiotherapy during the COVID-19 Pandemic (COVID-RT Lung) is a prospective multicentre UK cohort study. The inclusion criteria were: patients with stage I-III lung cancer referred for and/or treated with radical radiotherapy between 2nd April and 2nd October 2020. Patients who had had a change in their management and those who continued with standard management were included. Data on demographics, COVID-19 diagnosis, diagnostic work-up, radiotherapy and systemic treatment were collected and reported as counts and percentages. Patient characteristics associated with a change in treatment were analysed using multivariable binary logistic regression., Results: In total, 1553 patients were included (median age 72 years, 49% female); 93 (12%) had a change to their diagnostic investigation and 528 (34%) had a change to their treatment from their centre's standard of care as a result of the COVID-19 pandemic. Age ≥70 years, male gender and stage III disease were associated with a change in treatment on multivariable analysis. Patients who had their treatment changed had a median of 15 fractions of radiotherapy compared with a median of 20 fractions in those who did not have their treatment changed. Low rates of COVID-19 infection were seen during or after radiotherapy, with only 21 patients (1.4%) developing the disease., Conclusions: The COVID-19 pandemic resulted in changes to patient treatment in line with national recommendations. The main change was an increase in hypofractionation. Further work is ongoing to analyse the impact of these changes on patient outcomes., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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.)

Aims: There is a paucity of evidence on which to produce recommendations on neither the clinical nor the imaging follow-up of lung cancer patients after curative-intent radiotherapy. In the 2019 National Institute for Health and Care Excellence lung cancer guidelines, further research into risk-stratification models to inform follow-up protocols was recommended., Materials and Methods: A retrospective study of consecutive patients undergoing curative-intent radiotherapy for non-small cell lung cancer from 1 October 2014 to 1 October 2016 across nine UK trusts was carried out. Twenty-two demographic, clinical and treatment-related variables were collected and multivariable logistic regression was used to develop and validate two risk-stratification models to determine the risk of disease recurrence and death., Results: In total, 898 patients were included in the study. The mean age was 72 years, 63% (562/898) had a good performance status (0-1) and 43% (388/898), 15% (134/898) and 42% (376/898) were clinical stage I, II and III, respectively. Thirty-six per cent (322/898) suffered disease recurrence and 41% (369/898) died in the first 2 years after radiotherapy. The ASSENT score (age, performance status, smoking status, staging endobronchial ultrasound, N-stage, T-stage) was developed, which stratifies the risk for disease recurrence within 2 years, with an area under the receiver operating characteristic curve (AUROC) for the total score of 0.712 (0.671-0.753) and 0.72 (0.65-0.789) in the derivation and validation sets, respectively. The STEPS score (sex, performance status, staging endobronchial ultrasound, T-stage, N-stage) was developed, which stratifies the risk of death within 2 years, with an AUROC for the total score of 0.625 (0.581-0.669) and 0.607 (0.53-0.684) in the derivation and validation sets, respectively., Conclusions: These validated risk-stratification models could be used to inform follow-up protocols after curative-intent radiotherapy for lung cancer. The modest performance highlights the need for more advanced risk prediction tools., (Copyright © 2020 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

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.

Introduction: Lung cancer is the most common cause of cancer mortality in the UK, and non-small-cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Most patients present with inoperable disease; therefore, radiotherapy plays a major role in treatment. However, the majority of patients are not suitable for the gold standard treatment (concurrent chemoradiotherapy) due to performance status and comorbidities. Novel strategies integrating radiotherapy advances and radiobiological knowledge need to be evaluated in patients treated with sequential chemoradiotherapy. Four separate dose escalation accelerated radiotherapy schedules have been completed in UK (CHART-ED, IDEAL-CRT, I-START and Isotoxic IMRT). This study will compare these schedules with a UK standard sequential chemoradiotherapy schedule of 55 Gy in 20 fractions over 4 weeks. As it would be impossible to test all schedules in a phase III study, the aim is to use a combined randomised phase II screening/'pick the winner' approach to identify the best schedule to take into a randomised phase III study against conventionally fractionated radiotherapy., Methods and Analysis: Suitable patients will have histologically/cytologically confirmed, stage III NSCLC and are able to undergo chemoradiotherapy treatment. The study will recruit 360 patients; 120 on the standard arm and 60 on each experimental arm. Patients will complete 2-4 cycles of platinum-based chemotherapy before being randomised to one of the radiotherapy schedules. The primary endpoint is progression-free survival, with overall survival, time to local-regional failure, toxicity and cost-effectiveness as secondary objectives., Ethics and Dissemination: The study has received ethical approval (research ethics committee (REC) reference: 16/WS/0165) from the West of Scotland REC 1. The trial is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. Trial results will be published in a peer-reviewed journal and presented internationally., Trial Registration Number: ISRCTN47674500., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

The European Respiratory Society (ERS) task force for harmonised standards for lung cancer registration and lung cancer services in Europe recognised the need to create a single dataset for use in pan-European data collection and a manual of standards for European lung cancer services.The multidisciplinary task force considered evidence from two different sources, reviewing existing national and international datasets alongside the results of a survey of clinical data collection on lung cancer in 35 European countries. A similar process was followed for the manual of lung cancer services, with the task force using existing guidelines and national or international recommendations for lung cancer services to develop a manual of standards for services in Europe.The task force developed essential and minimum datasets for lung cancer registration to enable all countries to collect the same essential data and some to collect data with greater detail. The task force also developed a manual specifying standards for lung cancer services in Europe.Despite the wide variation in the sociopolitical landscape across Europe, the ERS is determined to encourage the delivery of high-quality lung cancer care. Both the manual of lung cancer services and the minimum dataset for lung cancer registration will support this aspiration., Competing Interests: Conflict of interest: A.L. Rich has nothing to disclose. Conflict of interest: D.R. Baldwin reports personal fees for lecturing from AstraZeneca, outside the submitted work. Conflict of interest: P. Beckett has nothing to disclose. Conflict of interest: T. Berghmans has nothing to disclose. Conflict of interest: J. Boyd is an employee of the European Lung Foundation. Conflict of interest: C. Faivre-Finn reports research funding and business travel support from Merck, AstraZeneca and Pfizer, outside the submitted work. Conflict of interest: F. Galateau Salle has nothing to disclose. Conflict of interest: F. Gamarra has nothing to disclose. Conflict of interest: B. Grigoriu has nothing to disclose. Conflict of interest: N-C.G. Hansen has nothing to disclose. Conflict of interest: G. Hardavella has nothing to disclose. Conflict of interest: E. Jakobsen has nothing to disclose. Conflict of interest: D. Jovanovic has nothing to disclose. Conflict of interest: A. Konsoulova has nothing to disclose. Conflict of interest: G. Massard has nothing to disclose. Conflict of interest: J. McPhelim reports personal fees from Roche, MSD, Pfizer, Lilly Oncology and Abbvie, outside the submitted work. Conflict of interest: A-P. Meert has nothing to disclose. Conflict of interest: R. Milroy has nothing to disclose. Conflict of interest: L. Mutti has nothing to disclose. Conflict of interest: M. Paesmans has nothing to disclose. Conflict of interest: M.D. Peake has nothing to disclose. Conflict of interest: P.M. Putora has nothing to disclose. Conflict of interest: D.K.M. de Ruysscher has nothing to disclose. Conflict of interest: J-P. Sculier has nothing to disclose. Conflict of interest: A. Schepereel has nothing to disclose. Conflict of interest: D.R. Subotic has nothing to disclose. Conflict of interest: P. Van Schil has nothing to disclose. Conflict of interest: T.G. Blum has nothing to disclose., (Copyright ©ERS 2018.)