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

18F-FDG PET-CT in the evaluation of paraneoplastic syndromes experience at a regional oncology centre

Objectives: Paraneoplastic syndromes (PNS) are remote manifestations of malignancy unrelated to tumour invasion or metastases. They pose a diagnostic challenge because of diverse presentations. 18F-Fluorodeoxyglucose (18F-FDG) PET-CT is an emerging technique for the detection of malignancy; however, there is a paucity of data with regard to its role in the evaluation of PNS and its relation to pretest clinical risk. Methods: A retrospective review of the database at the West of Scotland PET centre from 2007 to 2010 was conducted. Data extracted included demographics, clinical and pathological diagnosis, presence of classical syndromes, cross-sectional imaging, PET-CT imaging and management changes. A clinical scoring system was constructed to evaluate the pretest likelihood of having PNS, and the impact of a subsequent positive PET-CTscan was evaluated. Results: A total of 68 consecutive patients with a median age (range) of 58 (23–82) years, of whom 44 (65%) were female, were included. Symptoms were neurological in 55 (81%), musculoskeletal in five (7%), endocrine in three (4%) and constitutional in five (7%) patients. Forty-three (62%) patients had a classical paraneoplastic syndrome and 34 (50%) had positive biomarkers. Eighteen (26%) patients had a positive PET-CT result. PET-CT was concordant with the clinical scoring in 49 (72%) patients; it upgraded the score in eight (12%) patients, and downgraded the score in 11 (16%) patients. Eight (12%) patients had confirmed malignancy. PET-CT was estimated to have 100% sensitivity, 82% specificity, 42% positive predictive value and 100% negative predictive value. Conclusion: PET-CT is a highly sensitive and specific imaging technique in the evaluation of PNS and adds confidence to clinical likelihood

PET-CT evaluation of solitary pulmonary nodules: correlation with maximum standardized uptake value and pathology

Purpose: 18-fluorine fluorodeoxyglucose (18F-FDG) positron emission tomography–computed tomography (PET–CT) has an established role for the characterization of solitary pulmonary nodules (SPN). Visual assessment of nodule morphology, together with maximum standardized uptake value (SUVmax), is used to estimate likelihood of malignancy. We correlated SUVmax value with pathology of SPN and assessed diagnostic accuracy in differentiating malignant from benign nodule, using 2.5 as threshold SUVmax. Methods: Retrospective review of PET–CT scans for SPN characterization between April 2008 and June 2011 was performed. Only cases with pathological verification were included. Results: A total of 641 PET-CTs were performed for SPN characterization and staging; 186 patients (77 males, 109 females) with pathological confirmation were included, and 158 (85 %) nodules were malignant: adenocarcinomas (n = 66), squamous cell carcinomas (n = 40), and metastases (n = 20) were the commonest. 28 lesions (15 %) were benign, including granuloma/chronic inflammation (n = 8), infection (n = 7), and hamartomas (n = 5). Using cutoff SUVmax of 2.5, the accuracy of PET–CT in diagnosing malignant SPN is 81.2 %, with sensitivity 86.7 %, specificity 50 %, PPV 90.7 %, and NPV 40 %. The likelihood of malignancy increases with SUVmax. Nevertheless, even with SUVmax <2.5, there is a 62 % chance that a nodule is malignant. Conclusions: Although PET–CT is useful in diagnostic workup of SPN, it cannot replace “gold standard” tissue diagnosis

Dual-isotope subtraction SPECT-CT in parathyroid localization

Objective: The aim of this study was to investigate the accuracy of locating parathyroid adenomas using dual-Isotope subtraction single-photon emission computed tomography-computed tomography (SPECT-CT) in comparison with clinical follow-up and pathology findings from surgery. Patients and methods: A retrospective cohort study of dual-isotope subtraction SPECT-CT was carried out on 224 consecutive patients who were diagnosed with primary hyperparathyroidism. All the patients were injected with 20 MBq of iodine-123-iodide, followed 20 min later by 900 MBq of technetium-99m-sestamibi. Planar neck and chest views and SPECT-CT images were acquired 15 min after administration, followed by an additional planar image set at 2 h to view washout; all images were dual energy. In all, 115 out of 224 of the patients imaged underwent parathyroid surgery. The imaging results were compared with pathology findings when available and, in those who did not undergo surgery, and in some complex cases, with clinical measures after a 2-year clinical follow-up period. Findings: Out of the 224 patients, 135 patients had complete pathology and/or clinical follow-up data and were included in the analysis. The sensitivity of the subtraction SPECT-CT findings was measured to be 95%, with a specificity of 89% for the detection and localization of parathyroid adenomas. The positive predictive value was found to be 97% and the negative predictive value was found to be 83%. The accuracy of the technique was 94% in detecting parathyroid adenoma and 92% in accurate localization. Conclusion: Dual-isotope subtraction SPECT-CT imaging has a very high sensitivity and specificity in detecting and locating a parathyroid adenoma, showing that it is a very reliable preoperative imaging technique in primary hyperparathyroidism

Combination therapy with sulfasalazine and methotrexate is more effective than either drug alone in patients with rheumatoid arthritis with a suboptimal response to sulfasalazine: results from the double‐blind placebo‐controlled MASCOT study

BACKGROUND: Optimal use of disease‐modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis is vital if progression of disease is to be reduced. Methotrexate (MTX) and sulfasalazine (SASP) are widely used inexpensive DMARDs, recently often combined despite no firm evidence of benefit from previous studies. AIM: To establish whether a combination of SASP and MTX is superior to either drug alone in patients with rheumatoid arthritis with a suboptimal response to 6 months of SASP. METHODS: A randomised controlled study of step‐up DMARD treatment in early rheumatoid arthritis. In phase I, 687 patients received SASP for 6 months. Those with a disease activity score (DAS) ⩾2.4 were offered additional treatment in phase II (SASP alone, MTX alone or a combination of the two). The primary outcome measure was change in DAS. RESULTS: At 6 months, 191 (28%) patients had a DAS <2.4, 123 (18%) were eligible but did not wish to enter phase II, 130 (19%) stopped SASP because of reversible adverse events and 165 (24%) entered phase II. DAS at 18 months was significantly lower in those who received combination treatment compared with those who received either SASP or MTX: monotherapy arms did not differ. Improvement in European League Against Rheumatism and American College of Rheumatology 20, 50 and 70 scores favoured combination therapy. CONCLUSIONS: In this “true‐to‐life” study, an inexpensive combination of DMARDs proved more effective than monotherapy in patients with rheumatoid arthritis with a suboptimal response to SASP. There was no increase in toxicity. These results provide an evidence base for the use of this combination as a component of tight control strategies

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