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Blood-based assays have shown increasing ability to detect circulating tumour DNA (ctDNA) in patients with early-stage cancer. However, detection of ctDNA in patients with non-small cell lung cancer (NSCLC) has continued to prove challenging. We performed retrospective analysis to quantify ctDNA levels in a cohort of 100 patients with early-stage NSCLC prior to treatment with curative intent enrolled in the LUCID study (NCT04153526). Where tumour tissue was available for whole exome sequencing, mutations identified were used to define patient-specific sequencing assays. For those 90 patients, plasma cell-free DNA was sequenced to high depth across capture panels targeting a median of 328 mutations specific to each patient. Data was analysed using Integration of Variant Reads (INVAR), detecting ctDNA in 66.7% of patients, including 52.7% (29 of 55) patients with stage I disease and >88% detection for patients with stage II and III disease (16/18 and 15/17). ctDNA was detected in plasma at fractional concentrations as low as 9.1×10−6, and in patients with tumour volumes as low as 0.23 cm3. A 36-gene sequencing panel (InVisionFirst-Lung™) was used to analyse plasma DNA in 27 samples including the 10 cases without tumour exome data, and detected ctDNA in 59% of samples tested (16 of 27). Across the entire cohort, detection rates were higher in squamous cell carcinoma patients compared to adenocarcinoma patients (81% vs. 59%). Detection of ctDNA prior to treatment was associated with significantly shorter time free from relapse, across all patients and in patient subgroups, with Hazard Ratios >11 for selected patient subsets. Our analysis indicates that for patients with stage I NSCLC, the median ctDNA fraction in plasma is approx. 12 parts per million (0.0012%). This indicates the limits of detection that would be required for ctDNA-based liquid biopsies to detect ctDNA in the majority of patients with early-stage NSCLC.

Purpose To compare qualitative and semi-quantitative PET/CT criteria, and the impact of nodule size on the diagnosis of solitary pulmonary nodules in a prospective multicentre trial. Methods Patients with an SPN on CT ≥ 8 and ≤ 30 mm were recruited to the SPUTNIK trial at 16 sites accredited by the UK PET Core Lab. Qualitative assessment used a five-point ordinal PET-grade compared to the mediastinal blood pool, and a combined PET/CT grade using the CT features. Semi-quantitative measures included SUVmax of the nodule, and as an uptake ratio to the mediastinal blood pool (SURBLOOD) or liver (SURLIVER). The endpoints were diagnosis of lung cancer via biopsy/histology or completion of 2-year follow-up. Impact of nodule size was analysed by comparison between nodule size tertiles. Results Three hundred fifty-five participants completed PET/CT and 2-year follow-up, with 59% (209/355) malignant nodules. The AUCs of the three techniques were SUVmax 0.87 (95% CI 0.83;0.91); SURBLOOD 0.87 (95% CI 0.83; 0.91, p = 0.30 versus SUVmax); and SURLIVER 0.87 (95% CI 0.83; 0.91, p = 0.09 vs. SUVmax). The AUCs for all techniques remained stable across size tertiles (p > 0.1 for difference), although the optimal diagnostic threshold varied by size. For nodules 16 mm, an SUVmax ≥ 3.6 or visual PET uptake greater than the mediastinum was the most accurate. Conclusion In this multicentre trial, SUVmax was the most accurate technique for the diagnosis of solitary pulmonary nodules. Diagnostic thresholds should be altered according to nodule size. Trial registration ISRCTN - ISRCTN30784948. ClinicalTrials.gov - NCT02013063

A systematic review and meta-analysis were performed to determine the diagnostic performance of dynamic contrast–enhanced computed tomography (DCE-CT) for the differentiation between malignant and benign pulmonary nodules. Ovid MEDLINE and EMBASE were searched for studies published up to October 2018 on the diagnostic accuracy of DCE-CT for the characterisation of pulmonary nodules. For the index test, studies with a minimum of a pre- and post-contrast computed tomography scan were evaluated. Studies with a reference standard of biopsy for malignancy, and biopsy or 2-year follow-up for benign disease were included. Study bias was assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies). The sensitivities, specificities, and diagnostic odds ratios were determined along with 95% confidence intervals (CIs) using a bivariate random effects model. Twenty-three studies were included, including 2397 study participants with 2514 nodules of which 55.3% were malignant (1389/2514). The pooled accuracy results were sensitivity 94.8% (95% CI 91.5; 96.9), specificity 75.5% (69.4; 80.6), and diagnostic odds ratio 56.6 (24.2–88.9). QUADAS 2 assessment showed intermediate/high risk of bias in a large proportion of the studies (52–78% across the domains). No difference was present in sensitivity or specificity between subgroups when studies were split based on CT technique, sample size, nodule size, or publication date. DCE-CT has a high diagnostic accuracy for the diagnosis of pulmonary nodules although study quality was indeterminate in a large number of cases. • The pooled accuracy results were sensitivity 95.1% and specificity 73.8% although individual studies showed wide ranges of values. • This is comparable to the results of previous meta-analyses of PET/CT (positron emission tomography/computed tomography) diagnostic accuracy for the diagnosis of solitary pulmonary nodules. • Robust direct comparative accuracy and cost-effectiveness studies are warranted to determine the optimal use of DCE-CT and PET/CT in the diagnosis of SPNs.

Introduction Overall survival of non-small-cell lung cancer (NSCLC) patients remains poor as patients are frequently diagnosed at late stage. The evaluation of circulating tumor DNA (ctDNA) has been shown to offer a non-invasive method for cancer detection. However, detection rates of ctDNA in patients with early stage cancers have been low. The distribution of ctDNA levels in this population is unknown, and the analytical requirements for a test to detect the majority of cancers cannot be defined. Methods The LUCID study (LUng cancer - CIrculating tumour DNA study) recruited 100 patients with stage I-IIIB NSCLC according to the TNM 7th edition and collected plasma samples before and after radical treatment by surgery or radiotherapy +/- chemotherapy with curative intent. To measure levels of ctDNA in patients with early stage disease and very low tumor burden we developed a method for INtegration of VAriant Reads (INVAR), which uses sequencing data across hundreds to thousands of tumor-mutated loci to detect ctDNA in plasma samples at high sensitivity. We applied INVAR to 90 of the patients from the LUCID study, where tumor sequencing data was available. To measure ctDNA in the remaining LUCID patients, we applied the InVision® amplicon-based plasma sequencing assay. Results Across the 100 patients, ctDNA signals were observed in 67% of samples obtained prior to treatment. ctDNA was detected in 66% of cases, with ctDNA levels as low as 9.1x10-6 (9 parts per million), at a detection threshold with 95% specificity. ctDNA was detected in 52% of 60 patients with stage I NSCLC and in 88% of 40 patients with stage II/III disease. Analyzing different histological subtypes, ctDNA was detected in 79% of squamous cell carcinomas and 60% of adenocarcinomas. We found a good agreement when comparing the ctDNA results obtained from INVAR and the InVision® assay. Conclusions Our findings suggest that an assay with sensitivity to below 10 parts per million may be able to detect ctDNA in as many as 2/3 of patients with early stage NSCLC prior to treatment, including the majority of adenocarcinoma cases. Additionally, patient-specific analysis of ctDNA has the potential to aid in longitudinal cancer monitoring and in detection of low tumor burden and minimal residual disease. We aim to apply this approach to serial samples obtained through the LUCID study to investigate its application in treatment management. Citation Format: Katrin Heider, Jonathan C. Wan, Davina Gale, Andrea Ruiz-Valdepenas, Florent Mouliere, James Morris, Nagmi R. Qureshi, Wendi Qian, Jerome Wulff, Nikolaos Demiris, Karen Howarth, Emma Green, Viona Rundell, Tim Eisen, Wendy Cooper, Christopher G. Smith, Charles Massie, Susan Harden, Doris M. Rassl, Robert C. Rintoul, Nitzan Rosenfeld. ctDNA detection in early stage non-small cell lung cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 736.

Imaging plays an important role in the diagnosis and subsequent management of patients with pleural disease. The presence of a pleural abnormality is usually suggested following a routine chest x-ray, with a number of imaging modalities available for further characterization. This article describes the radiographic and cross-sectional appearances of pleural diseases, which are commonly encountered in every day practice. The conditions covered include benign and malignant pleural thickening, pleural effusions, empyema and pneumothoraces. The relative merits of CT, MRI and PET in the assessment of these conditions and the role of image-guided intervention are discussed.

Avian influenza is caused by the H5N1 subtype of the influenza A virus. Human transmission is either directly through close contact with infected birds usually poultry or their secretions. To date 178 people throughout South East Asia have been infected with 85 deaths. Patients usually present with a rapidly progressive pneumonia that can result in respiratory failure and acute respiratory distress syndrome. The chest radiograph therefore remains the most convenient and accessible imaging modality. Studies have shown that most radiographs are abnormal at the time of presentation with multifocal consolidation the commonest radiographic finding. During the course of disease, pleural effusions and cavitation can also develop. Consolidation that involves > or = 4 zones on presentation or at day 7 after the onset of symptoms and subsequent development of acute respiratory distress syndrome are generally associated with an adverse outcome. Chest CT examinations performed during the convalescent period have demonstrated persistent ground glass attenuation and segmental consolidation. Additional features included pseudocavitation, pneumatocoele formation, lymphadenopathy, and centrilobular nodules. Overall the appearances are suggestive of mild fibrosis.

Background: Malignant pleural effusion (MPE) is a common clinical problem with described investigation pathways. While thoracic ultrasound (TUS) has been shown to be accurate in pleural fluid detection, its use in the diagnosis of malignant pleural disease has not been assessed. A study was undertaken to assess the diagnostic accuracy of TUS in differentiating malignant and benign pleural disease. Methods: 52 consecutive patients with suspected MPE underwent TUS and contrast-enhanced CT (CECT). TUS was used to assess pleural surfaces using previously published CT imaging criteria for malignancy, diaphragmatic thickness/nodularity, effusion size/nature and presence of hepatic metastasis (in right-sided effusions). A TUS diagnosis of malignant or benign disease was made blind to clinical data/other investigations by a second blinded operator using anonymised TUS video clips. The TUS diagnosis was compared with the definitive clinical diagnosis and in addition to the diagnosis found at CECT. Results: A definitive malignant diagnosis was based on histocytology (30/33; 91%) and clinical/CT follow-up (3/33; 9%). Benign diagnoses were based on negative histocytology and follow-up over 12 months in 19/19 patients. TUS correctly diagnosed malignancy in 26/33 patients (sensitivity 73%, specificity 100%, positive predictive value 100%, negative predictive value 79%) and benign disease in 19/19. Pleural thickening >1 cm, pleural nodularity and diaphragmatic thickening >7 mm were highly suggestive of malignant disease. Conclusion: TUS is useful in differentiating malignant from benign pleural disease in patients presenting with suspected MPE and may become an important adjunct in the diagnostic pathway.

With the advent of multi-detector computed tomography, the identification of solitary pulmonary nodules is becoming ever more common. Although the prevalence of malignancy in a high risk population is only 1-1.5%, accurate identification of malignant nodules is essential to allow optimal treatment. In this article we review the most common causes of solitary pulmonary nodules and discuss diagnostic algorithms as well as some of the novel diagnostic imaging techniques in development.

INTRODUCTION: Solitary pulmonary nodules (SPNs) are common on CT. The most cost-effective investigation algorithm is still to be determined. Dynamic contrast-enhanced CT (DCE-CT) is an established diagnostic test not widely available in the UK currently.METHODS AND ANALYSIS: The SPUtNIk study will assess the diagnostic accuracy, clinical utility and cost-effectiveness of DCE-CT, alongside the current CT and 18-flurodeoxyglucose-positron emission tomography) ((18)FDG-PET)-CT nodule characterisation strategies in the National Health Service (NHS). Image acquisition and data analysis for (18)FDG-PET-CT and DCE-CT will follow a standardised protocol with central review of 10% to ensure quality assurance. Decision analytic modelling will assess the likely costs and health outcomes resulting from incorporation of DCE-CT into management strategies for patients with SPNs.ETHICS AND DISSEMINATION: Approval has been granted by the South West Research Ethics Committee. Ethics reference number 12/SW/0206. The results of the trial will be presented at national and international meetings and published in an Health Technology Assessment (HTA) Monograph and in peer-reviewed journals.TRIAL REGISTRATION NUMBER: ISRCTN30784948; Pre-results.

A 70-year-old man presented with non-specific chest pains. A low-grade tubulovillous adenoma had previously been removed from his colon and he was an ex-smoker. A chest radiograph revealed multiple pulmonary masses. He subsequently underwent a …

Chest wall resection for liposarcoma was performed. To reconstruct the chest wall we used a novel titanium rib bridge system and preserved anatomically equivalent layers.

A 75-year-woman with a Duke’s B adenocarcinoma of the caecum underwent a staging CT examination which revealed an oval, 3.6×2.5 cm fluid attenuation mass (18 Hounsfield units) superior to the carina, posterior to the trachea and medial to the oesophagus (figure 1). She had no symptoms relating to the mediastinal mass. Radiologically the lesion was thought to be most in keeping with …