Dynamic contrast-enhanced CT compared with positron emission tomography CT to characterise solitary pulmonary nodules: the SPUtNIk diagnostic accuracy study and economic modelling

BACKGROUND: Current pathways recommend positron emission tomography-computerised tomography for the characterisation of solitary pulmonary nodules. Dynamic contrast-enhanced computerised tomography may be a more cost-effective approach. OBJECTIVES: To determine the diagnostic performances of dynamic contrast-enhanced computerised tomography and positron emission tomography-computerised tomography in the NHS for solitary pulmonary nodules. Systematic reviews and a health economic evaluation contributed to the decision-analytic modelling to assess the likely costs and health outcomes resulting from incorporation of dynamic contrast-enhanced computerised tomography into management strategies. DESIGN: Multicentre comparative accuracy trial. SETTING: Secondary or tertiary outpatient settings at 16 hospitals in the UK. PARTICIPANTS: Participants with solitary pulmonary nodules of ≥ 8 mm and of ≤ 30 mm in size with no malignancy in the previous 2 years were included. INTERVENTIONS: Baseline positron emission tomography-computerised tomography and dynamic contrast-enhanced computer tomography with 2 years' follow-up. MAIN OUTCOME MEASURES: Primary outcome measures were sensitivity, specificity and diagnostic accuracy for positron emission tomography-computerised tomography and dynamic contrast-enhanced computerised tomography. Incremental cost-effectiveness ratios compared management strategies that used dynamic contrast-enhanced computerised tomography with management strategies that did not use dynamic contrast-enhanced computerised tomography. RESULTS: A total of 380 patients were recruited (median age 69 years). Of 312 patients with matched dynamic contrast-enhanced computer tomography and positron emission tomography-computerised tomography examinations, 191 (61%) were cancer patients. The sensitivity, specificity and diagnostic accuracy for positron emission tomography-computerised tomography and dynamic contrast-enhanced computer tomography were 72.8% (95% confidence interval 66.1% to 78.6%), 81.8% (95% confidence interval 74.0% to 87.7%), 76.3% (95% confidence interval 71.3% to 80.7%) and 95.3% (95% confidence interval 91.3% to 97.5%), 29.8% (95% confidence interval 22.3% to 38.4%) and 69.9% (95% confidence interval 64.6% to 74.7%), respectively. Exploratory modelling showed that maximum standardised uptake values had the best diagnostic accuracy, with an area under the curve of 0.87, which increased to 0.90 if combined with dynamic contrast-enhanced computerised tomography peak enhancement. The economic analysis showed that, over 24 months, dynamic contrast-enhanced computerised tomography was less costly (£3305, 95% confidence interval £2952 to £3746) than positron emission tomography-computerised tomography (£4013, 95% confidence interval £3673 to £4498) or a strategy combining the two tests (£4058, 95% confidence interval £3702 to £4547). Positron emission tomography-computerised tomography led to more patients with malignant nodules being correctly managed, 0.44 on average (95% confidence interval 0.39 to 0.49), compared with 0.40 (95% confidence interval 0.35 to 0.45); using both tests further increased this (0.47, 95% confidence interval 0.42 to 0.51). LIMITATIONS: The high prevalence of malignancy in nodules observed in this trial, compared with that observed in nodules identified within screening programmes, limits the generalisation of the current results to nodules identified by screening. CONCLUSIONS: Findings from this research indicate that positron emission tomography-computerised tomography is more accurate than dynamic contrast-enhanced computerised tomography for the characterisation of solitary pulmonary nodules. A combination of maximum standardised uptake value and peak enhancement had the highest accuracy with a small increase in costs. Findings from this research also indicate that a combined positron emission tomography-dynamic contrast-enhanced computerised tomography approach with a slightly higher willingness to pay to avoid missing small cancers or to avoid a 'watch and wait' policy may be an approach to consider. FUTURE WORK: Integration of the dynamic contrast-enhanced component into the positron emission tomography-computerised tomography examination and the feasibility of dynamic contrast-enhanced computerised tomography at lung screening for the characterisation of solitary pulmonary nodules should be explored, together with a lower radiation dose protocol

Symptoms that predict chest X-ray results suspicious for lung cancer in UK primary care: results from a prospective study

Background/introduction:?Predictive values of lung cancer (LC) symptoms that inform UK LC referral guidelines have been calculated from GP records and databases, with the potential for recording bias by GPs. The Identifying Symptom Predictors of Chest and Respiratory Disease (IPCARD) self-completion questionnaire was designed, for use in prospective studies, to obtain accurate positive predictive values (PPVs) of patient-elicited potential LC symptoms. The IPCARD Feasibility Study provides the first prospectively collected, patient-elicited comprehensive symptom data to identify PPVs of potential LC symptoms in UK primary care.Research question:?Which patient-elicited symptoms predict chest X-rays (CXR) suspicious for LC in a GP-referred CXR population (LC incidence 1%)?Methods:?GP-referred CXR attendees (1414) at three UK sites completed IPCARD before CXR; LC diagnosis was obtained 6 months post-CXR. Multiple logistic regression was used to calculate PPVs of symptoms for abnormal CXR, adjusting for age and sex; and stratifying by smoking status and COPD.Results:?Common chest symptoms – cough for longer than 3 weeks, generic chest aches/pains, and breathlessness – did not predict suspicious CXR. Weight loss and less common variants of chest pain (pain in side of chest/ribs, severe pain, and pain that ‘feels like indigestion – not associated with eating’ in patients with non-progressive/less severe pain) predicted CXR suspicious for LC in this high risk, referred population.Discussion/conclusion:?Common chest systems, identified as referral criteria by NICE, and included in UK ‘Be Clear about Cancer’ public awareness campaigns, although potentially predicting LC in a lower risk pre-referral population, did not predict CXR suspicious for LC in this referred population with higher rates of non-malignant chest and respiratory disease. The possibility that weight loss, and variants of chest pain, might also predict LC in pre-referral primary care populations with chronic respiratory disease will be investigated in ongoing studies using IPCARD

Eliciting symptoms interpreted as normal by patients with early-stage lung cancer: could GP elicitation of normalised symptoms reduce delay in diagnosis? Cross-sectional interview study

Objectives: To investigate why symptoms indicative of early-stage lung cancer (LC) were not presented to general practitioners (GPs) and how early symptoms might be better elicited within primary care.Design, setting and participants: A qualitative cross-sectional interview study about symptoms and help-seeking in 20 patients from three south England counties, awaiting resection of LC (suspected or histologically confirmed). Analysis drew on principles of discourse analysis and constant comparison to identify processes involved in interpretation and communication about symptoms, and explain nonpresentation.Results: Most participants experienced health changes possibly indicative of LC which had not been presented during GP consultations. Symptoms that were episodic, or potentially caused by ageing or lifestyle, were frequently not presented to GPs. In interviews, open questions about health changes/symptoms in general did not elicit these symptoms; they only emerged in response to closed questions detailing specific changes in health. Questions using disease-related labels, for example, pain or breathlessness, were less likely to elicit symptoms than questions that used non-disease terminology, such as aches, discomfort or ‘getting out of breath’. Most participants described themselves as feeling well and were reluctant to associate potentially explained, nonspecific or episodic symptoms with LC, even after diagnosis.Conclusions: Patients with early LC are unlikely to present symptoms possibly indicative of LC that they associate with normal processes, when attending primary care before diagnosis. Faced with patients at high LC risk, GPs will need to actively elicit potential LC symptoms not presented by the patient. Closed questions using non-disease terminology might better elicit normalised symptoms

Comparative accuracy and cost-effectiveness of dynamic contrast-enhanced CT and positron emission tomography in the characterisation of solitary pulmonary nodules.

INTRODUCTION: Dynamic contrast-enhanced CT (DCE-CT) and positron emission tomography/CT (PET/CT) have a high reported accuracy for the diagnosis of malignancy in solitary pulmonary nodules (SPNs). The aim of this study was to compare the accuracy and cost-effectiveness of these. METHODS: In this prospective multicentre trial, 380 participants with an SPN (8-30 mm) and no recent history of malignancy underwent DCE-CT and PET/CT. All patients underwent either biopsy with histological diagnosis or completed CT follow-up. Primary outcome measures were sensitivity, specificity and overall diagnostic accuracy for PET/CT and DCE-CT. Costs and cost-effectiveness were estimated from a healthcare provider perspective using a decision-model. RESULTS: 312 participants (47% female, 68.1±9.0 years) completed the study, with 61% rate of malignancy at 2 years. The sensitivity, specificity, positive predictive value and negative predictive values for DCE-CT were 95.3% (95% CI 91.3 to 97.5), 29.8% (95% CI 22.3 to 38.4), 68.2% (95% CI 62.4% to 73.5%) and 80.0% (95% CI 66.2 to 89.1), respectively, and for PET/CT were 79.1% (95% CI 72.7 to 84.2), 81.8% (95% CI 74.0 to 87.7), 87.3% (95% CI 81.5 to 91.5) and 71.2% (95% CI 63.2 to 78.1). The area under the receiver operator characteristic curve (AUROC) for DCE-CT and PET/CT was 0.62 (95% CI 0.58 to 0.67) and 0.80 (95% CI 0.76 to 0.85), respectively (p<0.001). Combined results significantly increased diagnostic accuracy over PET/CT alone (AUROC=0.90 (95% CI 0.86 to 0.93), p<0.001). DCE-CT was preferred when the willingness to pay per incremental cost per correctly treated malignancy was below £9000. Above £15 500 a combined approach was preferred. CONCLUSIONS: PET/CT has a superior diagnostic accuracy to DCE-CT for the diagnosis of SPNs. Combining both techniques improves the diagnostic accuracy over either test alone and could be cost-effective. TRIAL REGISTRATION NUMBER: NCT02013063.The trial is funded by the NIHR HTA Programme (grant no: 09/22/117) and is being run by Southampton Clinical Trials Unit who are part funded by CRUK. AJC, VB and JEH are part-funded by the National Institute for Health Research Applied Research Collaboration North West Coast (NIHR ARC NWC). FJG is an NIHR Senior Investigator. RCR is part funded by the Cambridge Biomedical Research Centre, Cancer Research UK Cambridge Centre and the Cancer Research Network: Eastern. NRQ is part funded by the Cambridge Biomedical Research Centre. Part of the current works was performed at Cambridge which receives a portion of its funding form the UK's NIHR Biomedical Centre funding scheme. Part of the current works was performed at UCL/H which receives a portion of its funding form the UK's NIHR Biomedical Centre funding scheme

Diagnostic accuracy of a convolutional neural network assessment of solitary pulmonary nodules compared with PET with CT imaging and dynamic contrast-enhanced CT imaging using unenhanced and contrast-enhanced CT imaging

Background: solitary pulmonary nodules (SPNs) measuring 8 to 30 mm in diameter require further workup to determine the likelihood of malignancy. Research Question: What is the diagnostic performance of a lung cancer prediction convolutional neural network (LCP-CNN) in SPNs using unenhanced and contrast-enhanced CT imaging compared with the current clinical workup? Study Design and Methods: this was a post hoc analysis of the Single Pulmonary Nodule Investigation: Accuracy and Cost-Effectiveness of Dynamic Contrast Enhanced Computed Tomography in the Characterisation of Solitary Pulmonary Nodules trial, a prospective multicenter study comparing the diagnostic accuracy of dynamic contrast-enhanced (DCE) CT imaging with PET imaging in SPNs. The LCP-CNN was designed and validated in an external cohort. LCP-CNN-generated risk scores were created from the noncontrast and contrast-enhanced CT scan images from the DCE CT imaging. The gold standard was histologic analysis or 2 years of follow-up. The area under the receiver operating characteristic curves (AUC) were calculated using LCP-CNN score, maximum standardized uptake value, and DCE CT scan maximum enhancement and were compared using the DeLong test. Results: two hundred seventy participants (mean ± SD age, 68.3 ± 8.8 years; 49% women) underwent PET with CT scan imaging and DCE CT imaging with CT scan data available centrally for LCP-CNN analysis. The accuracy of the LCP-CNN on the noncontrast images (AUC, 0.83; 95% CI, 0.79-0.88) was superior to that of DCE CT imaging (AUC, 0.76; 95% CI, 0.69-0.82; P = .03) and equal to that of PET with CT scan imaging (AUC, 0.86; 95% CI, 0.81-0.90; P = .35). The presence of contrast resulted in a small reduction in diagnostic accuracy, with the AUC falling from 0.83 (95% CI, 0.79-0.88) on the noncontrast images to 0.80 to 0.83 after contrast (P &lt; .05 for 240 s after contrast only). Interpretation: an LCP-CNN algorithm provides an AUC equivalent to PET with CT scan imaging in the diagnosis of solitary pulmonary nodules. Trial Registration: ClinicalTrials.gov Identifier; No.: NCT02013063</p