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.

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

PURPOSE: 18-fluorine fluorodeoxyglucose ((18)F-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.

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. STUDY REGISTRATION: This study is registered as PROSPERO CRD42018112215 and CRD42019124299, and the trial is registered as ISRCTN30784948 and ClinicalTrials.gov NCT02013063. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 17. See the NIHR Journals Library website for further project information.

A nodule found on a lung scan can cause concern as it may be a sign of cancer. Finding lung cancer nodules when they are small (i.e. < 3 cm) is very important. Most nodules are not cancerous. Computerised tomography (cross-sectional images created from multiple X-rays) and positron emission tomography­computerised tomography (a technique that uses a radioactive tracer combined with computerised tomography) are used to see whether or not a nodule is cancerous; although they perform well, improvements are required. This study compared dynamic contrast-enhanced computerised tomography with positron emission tomography­computerised tomography scans to find out which test is best. Dynamic contrast-enhanced computerised tomography involves injection of a special dye into the bloodstream, followed by repeated scans of the nodule over several minutes. We assessed the costs to the NHS of undertaking the different scans, relative to their benefits, to judge which option was the best value for money. We recruited 380 patients from 16 hospitals across England and Scotland, of whom 312 had both dynamic contrast-enhanced computerised tomography and positron emission tomography­computerised tomography scans. We found that current positron emission tomography­computerised tomography is more accurate, providing a correct diagnosis in 76% of cases, than the new dynamic contrast-enhanced computerised tomography, which provides a correct diagnosis in 70% of cases. Although dynamic contrast-enhanced computerised tomography cannot replace positron emission tomography­computerised tomography, it may represent good-value use of NHS resources, especially if it is performed before positron emission tomography­computerised tomography and they are used in combination. Although more research is required, it may be possible in the future to perform dynamic contrast-enhanced computerised tomography at the same time as positron emission tomography­computerised tomography in patients with suspected lung cancer or if a lung nodule is found on a lung screening programme at the time of the computerised tomography examination. This may reduce the need for some people to have positron emission tomography­computerised tomography.

Preliminary experience of 99mTc-Aprotinin scintigraphy in amyloidosis.

BACKGROUND AND AIM: Radio-labelled Aprotinin has been shown to bind with amyloid fibrils in vitro as well as in vivo. The aim was to test the usefulness of 99mTc-Aprotinin imaging in systemic amyloidosis. METHODS: Thirty-five cases who had 99mTc-Aprotinin scans for the assessment of systemic amyloidosis were reviewed retrospectively. Eighteen had biopsy-proven amyloidosis and 17 were controls (amyloidosis was excluded by negative biopsies and non-invasive tests). Five of 18 patients with amyloidosis had final diagnosis of cardiac amyloid. RESULTS: Physiological uptake of 99mTc-Aprotinin was noted in the urinary tract (kidneys and bladder) and in the liver of all patients and controls; and non-specific uptake of 99mTc-Aprotinin was visualised in the spleen and oro-facial structures in the majority of both groups. Myocardial 99mTc-Aprotinin uptake was noted in all five patients with final diagnosis of cardiac amyloidosis and in none of the 30 subjects who did not have cardiac amyloid. The median heart to background uptake ratio was 2.0 in cardiac amyloid patients and 1.1 in subjects without cardiac amyloid (P = 0.0004). Single Photon Emission Tomography (SPECT) studies of the thorax confirmed that the site of uptake lay within the myocardium. In the amyloidosis group, site-specific 99mTc-Aprotinin uptake was also identified in the subcutaneous tissue of the legs and in a breast nodule shown to be positive for amyloidosis on biopsy. CONCLUSIONS: 99mTc-Aprotinin imaging may be a useful non-invasive method for the assessment of the presence and extent of extra-abdominal amyloid, particularly cardiac amyloidosis. It has little role in diagnosis of amyloidosis involving the oro-facial and abdominal structures.

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.

Imaging of solitary pulmonary nodule-a clinical review.

Current widespread use of cross-sectional imaging has led to exponential rise in detection of solitary pulmonary nodules (SPNs). Whilst large numbers of these are benign 'incidentalomas', lung cancers presenting as SPNs are often early disease, which have good prognosis. Therefore, there is rising demand and expectation for more accurate, non-invasive, diagnostic tests to characterize SPNs, aiming to avoid missed or delayed diagnosis of lung cancer. There are wide differential diagnoses of benign and malignant lesions that manifest as SPNs. On conventional imaging, the morphological features supporting benignity include stable small nodule size, smooth demarcated margins, and calcifications. Lack of significant contrast enhancement is also more suggestive of benign nodules. With improved understanding of tumor biology, for instance neo-vascularization and increased vascular permeability, imaging techniques such as dynamic contrast-enhanced computed tomography (CT) provide details on contrast uptake and wash-out kinetics, which is more closely reflecting the physiological and pathological phenomena. Positron emission tomography (PET) using 18fluorine-fluoro-deoxyglucose ((18)F-FDG) is a well-established functional imaging technique, for which one of the most common indications is differentiating between benign and malignant SPNs. Combined PET-CT integrates the anatomical, morphological and metabolic aspects in a single examination, improving overall diagnostic accuracy. Semi-quantitative analysis in FDG-PET imaging is based on measurement of maximum standardized uptake values (SUVmax). SUVmax analysis may become more useful as an assessment of tumor biology in future risk stratification models for cancers. Dual-time point FDG-PET imaging, dual-energy CT, perfusion CT, magnetic resonance (MR) imaging using dynamic contrast enhancement or diffusion-weighted imaging (DWI) techniques, are among the growing armamentarium for diagnostic imaging of SPNs. Provided there is no unacceptably high procedural or operative risk, tissue diagnosis by resection or percutaneous biopsy of SPN should be advocated in those patients identified as at moderate or high risk of malignancy, based on clinical stratification.

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. (18)F-Fluorodeoxyglucose ((18)F-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-CT scan 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.

Acute portal vein thrombosis: an important mimic of malignancy on FDG PET/CT.

The authors report a case of portal vein thrombosis, with no underlying malignant cause identified, which was initially detected by fludeoxyglucose positron emission tomography/CT (FDG PET/CT) and subsequently confirmed by both contrast enhanced CT and MRI. The multimodality imaging findings are outlined, the potential clinical implications discussed and note made of the possible FDG PET/CT mimics of this disorder.