Diagnostic performance of prospective same-day 18F-FDG PET/MRI and 18F-FDG PET/CT in the staging and response assessment of lymphoma.

BACKGROUND: Accurate staging and response assessment are essential for prognosis and to guide treatment in patients with lymphoma. The aim of this study was to compare the diagnostic performance of FDG PET/MRI versus FDG PET/CT in adult patients with newly diagnosed Hodgkin and Non- Hodgkin lymphoma. METHODS: In this single centre study, 50 patients were prospectively recruited. FDG PET/MRI was performed after staging FDG PET/CT using a single injection of 18F-FDG. Patients were invited to complete same-day FDG PET/MRI with FDG PET/CT at interim and end of treatment response assessments. Performance was assessed using PET/CT as the reference standard for disease site identification, staging, response assessment with Deauville score and concordance in metabolic activity. RESULTS: Staging assessment showed perfect agreement (κ = 1.0, P = 0) between PET/MRI and PET/CT using Ann Arbor staging. There was excellent intermodality correlation with disease site identification at staging (κ = 0.976, P < 0.001) with FDG PET/MRI sensitivity of 96% (95% CI, 94-98%) and specificity of 100% (95% CI, 99-100%). There was good correlation of disease site identification at interim assessment (κ = 0.819, P < 0.001) and excellent correlation at end-of-treatment assessment (κ = 1.0, P < 0.001). Intermodality agreement for Deauville scores was good at interim assessment (κ = 0.808, P < 0.001) and excellent at end-of-treatment assessment (κ = 1.0, P = 0). There was good-excellent concordance in SUV max and mean between modalities across timepoints. Minimum calculated radiation patient effective dose saving was 54% between the two modalities per scan. CONCLUSION: With high concordance in disease site identification, staging and response assessment, PET/MR is a potentially viable alternative to PET/CT in lymphoma that minimises radiation exposure.

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.

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.

Discrepancies between positron emission tomography/magnetic resonance imaging and positron emission tomography/computed tomography in a cohort of oncological patients.

INTRODUCTION: This study aims to evaluate discrepant findings between positron emission tomography/magnetic resonance imaging (PET/MRI) and positron emission tomography/computed tomography (PET/CT) in a cohort of oncological patients and to undertake a phantom study to assess the potential for extended PET acquisitions to lead to false-positive findings on PET/MRI. METHODS: Discrepant findings from a series of 106 patients undergoing same-day 18 F-fluorodeoxyglucose (FDG)-PET/CT and PET/MRI were reviewed. Phantom studies explored the potential for PET acquisition time to contribute to discrepancy. RESULTS: There were 14 discrepant cases, 5 (35.7%) of which related to PET/MRI acquisitions that had been extended to 10 min. Three of these five cases proved to be falsely positive. Phantom studies showed greater contrast recovery and signal to noise ratio for 10-min PET/MRI acquisitions compared to 2-min acquisitions using PET/CT. There were no discrepancies when PET/CT showed disseminated disease (P = 0.036). CONCLUSIONS: Extended PET/MRI acquisitions used to accommodate multiple MRI sequences may be associated with false-positive findings compared to PET/CT. PET/MRI is more likely to have incremental value when the prior probability for disseminated disease is low.

Combination bone marrow imaging using positron emission tomography (PET)-MRI in plasma cell dyscrasias: correlation with prognostic laboratory values and clinicopathological diagnosis.

OBJECTIVE: This prospective observational study of positron emission tomography (PET)-MRI findings in 16 consecutive newly diagnosed patients with a plasma cell dyscrasia describes and compares MRI-detected myeloma lesions with 18F-fludeoxyglucose PET-avid myeloma lesions, and correlates quantitative imaging findings to a range of biochemical and prognostic parameters. METHODS: Simultaneously acquired whole body PET and MRI images were evaluated qualitatively for the presence of focal or generalised abnormalities of bone marrow (BM) on either modality. Quantitative analysis comprised mean standardised uptake values (SUVmean) and fractional water content of the BM measured from PET and chemical shift MRI images of the second to fourth lumbar vertebrae. RESULTS: Final diagnoses comprised symptomatic myeloma (n = 10), asymptomatic myeloma (n = 4) and monoclonal gammopathy of uncertain significance (n = 2). 8/10 patients with symptomatic myeloma demonstrated BM abnormalities on qualitative assessment of MRI compared to 4/10 on PET. BM SUVmean inversely correlated with serum albumin (r = 0.57, p = 0.017). BM water fraction correlated with trephine cellularity and blood platelet count (r = 0.78, p = 0.00039 and r = 0.61, p = 0.0013 respectively). BM water fraction correlated with SUVmean in patients with low plasma cell burden (r = 0.91, p = 0.0015) but not in patients with high plasma cell burden (r = 0.18, p = 0.61). CONCLUSION: PET-MRI shows promise in both morphological and functional multiparametric quantitative assessment of myeloma. ADVANCES IN KNOWLEDGE: For the first time, multiparametric imaging in myeloma has been shown to predict BM abnormalities and correlate with known biochemical prognostic markers, moving PET-MRI beyond simple diagnostic applications into potential prognostic and treatment selection applications.

Additional Clinical Value for PET/MRI in Oncology: Moving Beyond Simple Diagnosis.

Initial clinical research comparing the diagnostic performance of PET/MRI and PET/CT has largely shown equivalent diagnostic capabilities for these modalities in oncology. These uncertainties about the magnitude of diagnostic benefit are compounded by the considerable health economic challenges associated with clinical implementation. Therefore, there is a need to identify ways to extend the use of this technology beyond simple diagnosis so that PET/MRI can add sufficient clinical value beyond PET/CT or MRI alone and become a cost-effective imaging modality in clinical practice. A major advantage of PET/MRI over other imaging modalities is the ability to generate multiple quantitative images from a single examination. This article describes how a multiparametric PET/MRI approach not only can add clinical value through contributing to precision medicine but also can establish PET/MRI as a potentially cost-effective imaging modality in oncology.

Concordance of 18F-FDG PET Uptake in Tumor and Normal Tissues on PET/MRI and PET/CT.

AIM: The aim of this study was to assess the concordance of PET measurements of F-FDG uptake in tumor and normal tissues obtained on Australia's first clinical PET/MRI scanner in comparison to PET/CT, with comparison against published data. METHODS: One hundred subjects were prospectively recruited from an unselected, heterogeneous group of cancer patients to undergo F-FDG PET/CT and PET/MRI on the same day. SUVs of physiological regions and tumor tissues obtained by PET/MRI and PET/CT were compared and benchmarked against existing published data. Physiological activity was measured in the thoracic aorta and right lobe of the liver. Tumor SUVs were analyzed by cancer type, body region, and a combined group of all lesions. RESULTS: There was an excellent correlation between SUV measurements in tumor lesions obtained by PET/MRI and PET/CT, across all body regions and in all tumor types studied. There was a less robust correlation for SUVs measured in areas of physiological activity, but the level of agreement still fell within 2 SDs of mean. Data from this study showed comparable or smaller systemic biases and narrower confidence limits than existing studies in the literature comparing SUVs from PET/MRI and PET/CT. CONCLUSIONS: F-FDG PET/MRI appears promising as an adjunct or alternative to PET/CT for quantitative evaluation in oncology, independent of body region and tumor type, across a wide range of SUVs.

Imaging biomarker roadmap for cancer studies.

Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing 'translational gaps' through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored 'roadmap'. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use.

How to use CT texture analysis for prognostication of non-small cell lung cancer.

Patients with non-small cell lung cancer frequently demonstrate differing clinical courses, even when they express the same tumour stage. Additional markers of prognostic significance could allow further stratification of treatment for these patients. By generating quantitative information about tumour heterogeneity as reflected by the distribution of pixel values within the tumour, CT texture analysis (CTTA) can provide prognostic information for patients with NSCLC. In addition to describing the practical application of CTTA to NSCLC, this article discusses a range of issues that need to be addressed when CTTA is included as part of routine clinical care as opposed to its use in a research setting. The use of quantitative imaging to provide prognostic information is a new and exciting development within cancer imaging that can expand the imaging specialist's existing role in tumour evaluation. Derivation of prognostic information through the application of image processing techniques such as CTTA, to images acquired as part of routine care can help imaging specialists make best use of the technologies they deploy for the benefit of patients with cancer.

Gallium-68 PSMA uptake in adrenal adenoma.

Gallium-68 (Ga-68) labelled prostate-specific membrane antigen (PSMA) imaging by positron emission tomography (PET) has emerged as a promising tool for staging of prostate cancer and restaging of disease in recurrence or biochemical failure after definitive treatment of prostate cancer. Ga-68 PSMA PET produces high target-to-background images of prostate cancer and its metastases which are reflective of the significant overexpression of PSMA in these cells and greatly facilitates tumour detection. However, relatively little is known about the PSMA expression of benign neoplasms and non-prostate epithelial malignancies. This is a case report of PSMA uptake in an adrenal adenoma incidentally discovered on PET performed for restaging of biochemically suspected prostate cancer recurrence. With the increasing use of PSMA PET in the management of prostate cancer - and the not infrequent occurrence of adrenal adenomas - the appearance of low- to moderate-grade PSMA uptake in adrenal adenomas should be one with which reporting clinicians are familiar.

Old tracer for a new purpose: potential role for 99mTc-2-Methoxyisobutylisonitrile (99mTc-MIBI) in renal transplant care.

AIM: Calcineurin inhibitors are substrates for P-glycoprotein (P-gp), the expression of which is associated with ABCB1 C3435T polymorphism. Individual P-gp response to calcineurin inhibitor may be linked to nephrotoxicity or rejection. Tc-2-Methoxyisobutylisonitrile (Tc-MIBI) is also a P-gp substrate. The aim of this study, therefore, was to determine Tc-MIBI organ kinetics and compare them with ABCB1 genotype with a view to replacing Tc-mercaptoacetyltriglycine (Tc-MAG3) with Tc-MIBI in renal transplant care. METHODS: Thirty prospective donors (13 male) were imaged for 20 min after administration of Tc-MIBI (400 MBq) intravenously. Posterior images of the abdomen were acquired at 30 and 120 min. Organ 30 min/peak count rate ratios and exponential two-point (30-120 min) rate constants (k, min) were calculated. Nineteen donors were genotyped for C3435T (exon 26), G2677T (exon 21), C1236T (exon 12), and G1199A (exon 11) ABCB1 polymorphisms using a PCR-based technique. RESULTS: Tc-MIBI and Tc-MAG3 gave similar perfusion images. Although their patterns of renal elimination were different, differential renal function was not significantly different. There was a negative trend between the hepatic 30 min/peak ratio and C3435T genotype (CC: 0.8374 ± 0.0502; TC: 0.6806 ± 0.1300; TT: 0.6919 ± 0.1506; P=0.083). Renal k showed a negative trend with C3435T (CC: 0.0021 ± 0.0020; TC: 0.0037 ± 0.0013; TT: 0.0040 ± 0.0012 min; P=0.087) but with no other genotypes. There were no significant sex-related differences in Tc-MIBI kinetics. CONCLUSION: Tc-MIBI can replace Tc-MAG3 for pretransplant workup. The ABCB1 C3435T polymorphism may influence Tc-MIBI kinetics and thus have a role in renal transplant care. Further prospective trials are required to establish the full potential of Tc-MIBI in renal transplant management.

Noninvasive image texture analysis differentiates K-ras mutation from pan-wildtype NSCLC and is prognostic.

BACKGROUND: Non-invasive characterization of a tumor's molecular features could enhance treatment management. Quantitative computed tomography (CT) based texture analysis (QTA) has been used to derive tumor heterogeneity information, and the appearance of the tumors has been shown to relate to patient outcome in non-small cell lung cancer (NSCLC) and other cancers. In this study, we examined the potential of tumoral QTA to differentiate K-ras mutant from pan-wildtype tumors and its prognostic potential using baseline pre-treatment non-contrast CT imaging in NSCLC. METHODS: Tumor DNA from patients with early-stage NSCLC was analyzed on the LungCarta Panel. Cases with a K-ras mutation or pan-wildtype for 26 oncogenes and tumor suppressor genes were selected for QTA. QTA was applied to regions of interest in the primary tumor. Non-parametric Mann Whitney test assessed the ability of the QTA, clinical and patient characteristics to differentiate between K-ras mutation from pan-wildtype. A recursive decision tree was developed to determine whether the differentiation of K-ras mutant from pan-wildtype tumors could be improved by sequential application of QTA parameters. Kaplan-Meier survival analysis assessed the ability of these markers to predict survival. RESULTS: QTA was applied to 48 cases identified, 27 had a K-ras mutation and 21 cases were pan-wildtype. Positive skewness and lower kurtosis were significantly associated with the presence of a K-ras mutation. A five node decision tree had sensitivity, specificity, and accuracy values (95% CI) of 96.3% (78.1-100), 81.0% (50.5-97.4), and 89.6% (72.9-97.0); respectively. Kurtosis was a significant predictor of OS and DFS, with a lower kurtosis value linked with poorer survival. CONCLUSIONS: Lower kurtosis and positive skewness are significantly associated with K-ras mutations. A QTA feature such as kurtosis is prognostic for OS and DFS. Non-invasive QTA can differentiate the presence of K-ras mutation from pan-wildtype NSCLC and is associated with patient survival.

Multifunctional imaging signature for V-KI-RAS2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in colorectal cancer.

UNLABELLED: This study explores the potential for multifunctional imaging to provide a signature for V-KI-RAS2 Kirsten rat sarcoma viral oncogene homolog (KRAS) gene mutations in colorectal cancer. METHODS: This prospective study approved by the institutional review board comprised 33 patients undergoing PET/CT before surgery for proven primary colorectal cancer. Tumor tissue was examined histologically for presence of the KRAS mutations and for expression of hypoxia-inducible factor-1 (HIF-1) and minichromosome maintenance protein 2 (mcm2). The following imaging parameters were derived for each tumor: (18)F-FDG uptake ((18)F-FDG maximum standardized uptake value [SUVmax]), CT texture (expressed as mean of positive pixels [MPP]), and blood flow measured by dynamic contrast-enhanced CT. A recursive decision tree was developed in which the imaging investigations were applied sequentially to identify tumors with KRAS mutations. Monte Carlo analysis provided mean values and 95% confidence intervals for sensitivity, specificity, and accuracy. RESULTS: The final decision tree comprised 4 decision nodes and 5 terminal nodes, 2 of which identified KRAS mutants. The true-positive rate, false-positive rate, and accuracy (95% confidence intervals) of the decision tree were 82.4% (63.9%-93.9%), 0% (0%-10.4%), and 90.1% (79.2%-96.0%), respectively. KRAS mutants with high (18)F-FDG SUVmax and low MPP showed greater frequency of HIF-1 expression (P = 0.032). KRAS mutants with low (18)F-FDG SUV(max), high MPP, and high blood flow expressed mcm2 (P = 0.036). CONCLUSION: Multifunctional imaging with PET/CT and recursive decision-tree analysis to combine measurements of tumor (18)F-FDG uptake, CT texture, and perfusion has the potential to identify imaging signatures for colorectal cancers with KRAS mutations exhibiting hypoxic or proliferative phenotypes.

Combined (99m)Tc-methoxyisobutylisonitrile scintigraphy and fine-needle aspiration cytology offers an accurate and potentially cost-effective investigative strategy for the assessment of solitary or dominant thyroid nodules.

PURPOSE: Fine-needle aspiration (FNA) has revolutionised the care of patients with thyroid nodules and is the initial investigation of choice. However, as a result of nondiagnostic (Thy1) and nonneoplastic (Thy2) specimens, it remains an imperfect sole solution with a range of sensitivities and a high inadequate ratio. Therefore the British Thyroid Association (BTA) guidelines recommend a second FNA immediately for Thy1 specimens and 3-6 months later for Thy2 specimens. Patients must be followed up to exclude malignancy. In this study we assessed the performance of MIBI scintigraphy for diagnosing thyroid malignancy and the cost-effectiveness of a combined FNA/MIBI investigative strategy for the management of thyroid nodules. METHODS: The diagnostic performance of MIBI scintigraphy was calculated from a retrospective review of local data combined with a meta-analysis of the published literature. Decision tree analysis was used to calculate the cost-effectiveness of a combined FNA/MIBI investigative strategy compared to the BTA guidelines. RESULTS: From 712 patients, the sensitivity, specificity, PPV and NPV of MIBI scintigraphy for the diagnosis of malignancy were 96 %, 46 %, 34 % and 97 %, respectively. MIBI-based strategies were more accurate and associated with lower cost per patient (£1,855/2,125 vs. £2,445/2,801) and lower cost per cancer diagnosed (£1,902/2,179 vs. £2,469/2,828) with negligible change in life expectancy. CONCLUSION: Due to its high NPV, MIBI scintigraphy can usefully exclude malignancy for Thy1 and Thy2 lesions. Its low specificity means MIBI scintigraphy cannot be recommended as a first-line investigation, but as a second-line investigation MIBI scintigraphy may lead to a lower rate of unnecessary thyroidectomies. Combined FNA/MIBI strategies are potentially cost-effective in the management of solitary or dominant thyroid nodules.

Incorporating prognostic imaging biomarkers into clinical practice.

A prognostic imaging biomarker can be defined as an imaging characteristic that is objectively measurable and provides information on the likely outcome of the cancer disease in an untreated individual and should be distinguished from predictive imaging biomarkers and imaging markers of response. A range of tumour characteristics of potential prognostic value can be measured using a variety imaging modalities. However, none has currently been adopted into routine clinical practice. This article considers key examples of emerging prognostic imaging biomarkers and proposes an evaluation framework that aims to demonstrate clinical efficacy and so support their introduction into the clinical arena. With appropriate validation within an established evaluation framework, prognostic imaging biomarkers have the potential to contribute to individualized cancer care, in some cases reducing the financial burden of expensive cancer treatments by facilitating their more rational use.

Predicting tumour response.

Response prediction is an important emerging concept in oncologic imaging, with tailored, individualized treatment regimens increasingly becoming the standard of care. This review aims to define tumour response and illustrate the ways in which imaging techniques can demonstrate tumour biological characteristics that provide information on the likely benefit to be received by treatment. Two imaging approaches are described: identification of therapeutic targets and depiction of the treatment-resistant phenotype. The former approach is exemplified by the use of radionuclide imaging to confirm target expression before radionuclide therapy but with angiogenesis imaging and imaging correlates for genetic response predictors also demonstrating potential utility. Techniques to assess the treatment-resistant phenotype include demonstration of hypoperfusion with dynamic contrast-enhanced computed tomography and magnetic resonance imaging (MRI), depiction of necrosis with diffusion-weighted MRI, imaging of hypoxia and tumour adaption to hypoxia, and 99mTc-MIBI imaging of P-glycoprotein mediated drug resistance. To date, introduction of these techniques into clinical practice has often been constrained by inadequate cross-validation of predictive criteria and lack of verification against appropriate response end points such as survival. With further refinement, imaging predictors of response could play an important role in oncology, contributing to individualization of therapy based on the specific tumour phenotype. This ability to predict tumour response will have implications for improving efficacy of treatment, cost-effectiveness and omission of futile therapy.

CT texture analysis using the filtration-histogram method: what do the measurements mean?

Analysis of texture within tumours on computed tomography (CT) is emerging as a potentially useful tool in assessing prognosis and treatment response for patients with cancer. This article illustrates the image and histological features that correlate with CT texture parameters obtained from tumours using the filtration-histogram approach, which comprises image filtration to highlight image features of a specified size followed by histogram analysis for quantification. Computer modelling can be used to generate texture parameters for a range of simple hypothetical images with specified image features. The model results are useful in explaining relationships between image features and texture parameters. The main image features that can be related to texture parameters are the number of objects highlighted by the filter, the brightness and/or contrast of highlighted objects relative to background attenuation, and the variability of brightness/contrast of highlighted objects. These relationships are also demonstrable by texture analysis of clinical CT images. The results of computer modelling may facilitate the interpretation of the reported associations between CT texture and histopathology in human tumours. The histogram parameters derived during the filtration-histogram method of CT texture analysis have specific relationships with a range of image features. Knowledge of these relationships can assist the understanding of results obtained from clinical CT texture analysis studies in oncology.

Tumor heterogeneity and permeability as measured on the CT component of PET/CT predict survival in patients with non-small cell lung cancer.

PURPOSE: We prospectively examined the role of tumor textural heterogeneity on positron emission tomography/computed tomography (PET/CT) in predicting survival compared with other clinical and imaging parameters in patients with non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: The feasibility study consisted of 56 assessed consecutive patients with NSCLC (32 males, 24 females; mean age 67 ± 9.7 years) who underwent combined fluorodeoxyglucose (FDG) PET/CT. The validation study population consisted of 66 prospectively recruited consecutive consenting patients with NSCLC (37 males, 29 females; mean age, 67.5 ± 7.8 years) who successfully underwent combined FDG PET/CT-dynamic contrast-enhanced (DCE) CT. Images were used to derive tumoral PET/CT textural heterogeneity, DCE CT permeability, and FDG uptake (SUVmax). The mean follow-up periods were 22.6 ± 13.3 months and 28.5± 13.2 months for the feasibility and validation studies, respectively. Optimum threshold was determined for clinical stage and each of the above biomarkers (where available) from the feasibility study population. Kaplan-Meier analysis was used to assess the ability of the biomarkers to predict survival in the validation study. Cox regression determined survival factor independence. RESULTS: Univariate analysis revealed that tumor CT-derived heterogeneity (P < 0.001), PET-derived heterogeneity (P = 0.003), CT-derived permeability (P = 0.002), and stage (P < 0.001) were all significant survival predictors. The thresholds used in this study were derived from a previously conducted feasibility study. Tumor SUVmax did not predict survival. Using multivariable analysis, tumor CT textural heterogeneity (P = 0.021), stage (P = 0.001), and permeability (P < 0.001) were independent survival predictors. These predictors were independent of patient treatment. CONCLUSIONS: Tumor stage and CT-derived textural heterogeneity were the best predictors of survival in NSCLC. The use of CT-derived textural heterogeneity should assist the management of many patients with NSCLC.

Quantifying tumour heterogeneity with CT.

Heterogeneity is a key feature of malignancy associated with adverse tumour biology. Quantifying heterogeneity could provide a useful non-invasive imaging biomarker. Heterogeneity on computed tomography (CT) can be quantified using texture analysis which extracts spatial information from CT images (unenhanced, contrast-enhanced and derived images such as CT perfusion) that may not be perceptible to the naked eye. The main components of texture analysis can be categorized into image transformation and quantification. Image transformation filters the conventional image into its basic components (spatial, frequency, etc.) to produce derived subimages. Texture quantification techniques include structural-, model- (fractal dimensions), statistical- and frequency-based methods. The underlying tumour biology that CT texture analysis may reflect includes (but is not limited to) tumour hypoxia and angiogenesis. Emerging studies show that CT texture analysis has the potential to be a useful adjunct in clinical oncologic imaging, providing important information about tumour characterization, prognosis and treatment prediction and response.