A Multicentric, Retrospective, Real-world Study on Immune-related Adverse Events in Patients with Advanced Non-small Cell Lung Cancers Treated with Pembrolizumab Monotherapy.

AIMS: We present 7 years of clinical experience with single-agent pembrolizumab immune checkpoint inhibitor immunotherapy in non-small cell lung cancers (NSCLC) from four UK cancer centres. MATERIALS AND METHODS: This multi-institutional retrospective cohort study included 226 metastatic NSCLC patients. Outcomes were number and severity of immune-related adverse events (irAEs), median progression-free survival (mPFS) and median overall survival (mOS). RESULTS: Within our cohort, 119/226 (53%) patients developed irAEs. Of these, 54/119 (45%) experienced irAEs affecting two or more organ systems. The most common irAEs were diarrhoea and rash. The development of an irAE was associated with better mOS (20.7 versus 8.0 months; P < 0.001) and mPFS (12.0 versus 3.9 months; P < 0.001). The development of grade 3/4 toxicities was associated with worse outcomes compared with the development of grade 1/2 toxicities (mOS 6.1 months versus 25.2 months, P < 0.01; mPFS 5.6 months versus 19.3 months, P = 0.01, respectively). Females had a higher proportion of reported grade 3/4 toxicities (13/44 [29.5%] versus 10/74 [13.5%], P = 0.03). Using a multiple Cox regression model, the presence of irAEs was associated with a better overall survival (hazard ratio = 0.42, 95% confidence interval 0.29-0.61; P < 0.01) and better PFS (hazard ratio 0.38, 95% confidence interval 0.27-0.53; P < 0.001). CONCLUSION: In this multicentre retrospective cohort study, the development of at least one irAE was associated with significantly longer mPFS and mOS; however, more severe grade 3 and 4 irAEs were associated with worse outcomes. Delayed-onset irAEs, after the 3-month timepoint, were associated with better clinical outcomes.

The National Lung Cancer Audit: The Impact of COVID-19.

Since 2014, the National Lung Cancer Audit (NLCA) has been evaluating the performance of the UK NHS lung cancer services against established standards of care. Prior to the onset of the COVID-19 pandemic, the NLCA's annual reports revealed a steady stream of improvements in early diagnosis, access to surgery, treatment with anti-cancer therapies, input from specialist nursing and survival for patients with lung cancer in the NHS. In January 2022, the NLCA reported on the negative impact COVID-19 has had on all aspects of the lung cancer diagnosis and treatment pathway within the NHS. This article details the fundamental changes made to the NLCA data collection and analysis process during the COVID-19 pandemic and details the negative impact COVID-19 had on NHS lung cancer patient outcomes during 2020.

UK 2022 Consensus on Normal Tissue Dose-Volume Constraints for Oligometastatic, Primary Lung and Hepatocellular Carcinoma Stereotactic Ablative Radiotherapy.

The use of stereotactic ablative radiotherapy (SABR) in the UK has expanded over the past decade, in part as the result of several UK clinical trials and a recent NHS England Commissioning through Evaluation programme. A UK SABR Consortium consensus for normal tissue constraints for SABR was published in 2017, based on the existing literature at the time. The published literature regarding SABR has increased in volume over the past 5 years and multiple UK centres are currently working to develop new SABR services. A review and update of the previous consensus is therefore appropriate and timely. It is hoped that this document will provide a useful resource to facilitate safe and consistent SABR practice.

Provision of Organ at Risk Contouring Guidance in UK Radiotherapy Clinical Trials.

AIMS: Accurate delineation of organs at risk (OAR) is vital to the radiotherapy planning process. Inaccuracies in OAR delineation arising from imprecise anatomical definitions may affect plan optimisation and risk inappropriate dose delivery to normal tissues. The aim of this study was to review the provision of OAR contouring guidance in National Institute of Health Research Clinical Research Network (NIHR CRN) portfolio clinical trials. MATERIALS AND METHODS: The National Radiotherapy Quality Trials Assurance (RTTQA) Group carried out a two-round Delphi assessment to determine which OAR descriptions provided optimal guidance. RESULTS: Eighty-four clinical trials involving radiotherapy quality assurance were identified as either in recruitment or in setup within the NIHR CRN portfolio. Fifty-nine trials mandated OAR contouring. In total there were 412 OAR; 171 were uniquely named; 159 OAR had more than one name associated with a single structure, with the greatest nomenclature variation seen for the femoral head ± neck, the parotid gland, and bowel. The two-round Delphi assessment determined 42 OAR descriptions as providing optimal contouring guidance. CONCLUSIONS: This study identified the need for OAR nomenclature and contouring guidance consistency across clinical trials. In response to this study and in conjunction with the Global Quality Assurance of Radiation Therapy Clinical Trials Harmonisation Group, the RTTQA Group is in collaboration with international partners to provide consensus recommendations for OAR delineation in clinical trials.

Improving radiotherapy quality assurance in clinical trials: assessment of target volume delineation of the pre-accrual benchmark case.

As the complexity of radiotherapy (RT) trials increases, issues surrounding target volume delineation will become more important. Some form of outlining assessment prior to trial entry is increasingly being mandated in UK RT trials. This document produced by the Outlining and Imaging Subgroup (OISG) of the National Cancer Research Institute will address methods to reduce interobserver variation in clinical trials and how to conduct an assessment of outlining through a pre-accrual benchmark case. We review currently available methods of describing the variation and identify areas where further work is needed. The OISG would encourage ongoing discussion with chief investigators in order to provide advice on individual aspects of benchmark case assessment for current and future trials.

High-precision MRI-guided adaptive brachytherapy for cervical carcinoma.

Over the past 20 years advances in radiological technology have led to dramatic changes in cervical cancer management. External beam radiotherapy has evolved radically as a result of these changes. More recently, though, three-dimensional (3D) image guidance and volume-based prescribing has been adopted into cervical cancer brachytherapy. This overview covers the science and technology behind magnetic resonance imaging (MRI)-guided adaptive brachytherapy and explains why it is now considered the new international standard of care.

Bevacizumab treatment for vestibular schwannomas in neurofibromatosis type two: report of two cases, including responses after prior gamma knife and vascular endothelial growth factor inhibition therapy.

OBJECTIVES: Vestibular schwannomas are the hallmark of neurofibromatosis type two. They are difficult to treat, due to their bilateral presentation and the quest for hearing preservation. Our report describes a new treatment approach in this clinical scenario. CASE REPORT: We report two cases which confirm that bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, causes regression of vestibular schwannomas in patients with a previous history of gamma knife radiosurgery or failed treatment with another form of vascular endothelial growth factor targeted therapy. CONCLUSION: In 2009, Plotkin et al. reported the volumetric response of vestibular schwannomas to bevacizumab treatment, both in untreated patients and in patients previously treated with erlotinib, an epidermal growth factor receptor inhibitor. The presented cases support the use of bevacizumab to treat vestibular schwannomas. Given the extremely slow growth of these tumours, we note the rapidity of volume reduction following bevacizumab therapy.