Fluorodeoxyglucose (FDG)-PET has expanding applications in the field of interventional radiology. FDG-PET provides both qualitative and quantitative assessments of malignancy, infection, and inflammation. These assessments can assist interventional radiologists in selecting the most appropriate treatment options for their oncology patients. FDG-PET is also useful for evaluating the response to interventional treatments and in predicting the prognosis of oncology patients. Finally, FDG-PET can assist the interventional radiologist in diagnosing and monitoring response to treatment of infection and inflammation. Nevertheless, there is a need for additional prospective studies to further establish the role of FDG-PET in these applications.

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.

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.

Multicentre comparative accuracy trial.

Secondary or tertiary outpatient settings at 16 hospitals in the UK.

Participants with solitary pulmonary nodules of ≥ 8 mm and of ≤ 30 mm in size with no malignancy in the previous 2 years were included.

Baseline positron emission tomography-computerised tomography and dynamic contrast-enhanced computer tomography with 2 years' follow-up.

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.

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).

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.

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.

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.

This study is registered as PROSPERO CRD42018112215 and CRD42019124299, and the trial is registered as ISRCTN30784948 and ClinicalTrials.gov NCT02013063.

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.

Multiple trials have attempted to assess the diagnostic value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in osteosarcoma with results remaining inconclusive. This study aims to investigate the effectiveness of 18F-FDG PET and PET/CT in the diagnosis, staging, recurrence and metastasis formation observations of osteosarcoma through systematic review followed by meta-analysis.

Three electronic databases, Medline/PubMed, Embase and the Cochrane Library were utilized in this study. Eligible studies that assessed the performance of 18F-FDG PET/CT for the diagnosis, staging, restaging and recurrence monitoring of osteosarcoma were retrieved utilizing specific search criteria. After screening and diluting out the non-conforming articles, all relevant articles and their data were identified and extracted to calculate the summary metrics involving sensitivity, specificity, diagnostic odd ratio (DOR), and area under the curve (AUC) to determine the effectiveness of 18F-FDG PET in diagnosing osteosarcoma clinically.

Out of 1976 articles searched, twenty-six studies were identified that were viable. All data from these articles, utilized in the quantitative analyses, showed after meta-analysis that when utilizing 18F-FDG PET or PET/CT it was better with a success rate of 90-100% for detecting primary lesions and distant metastases of patients with osteosarcoma. Similar results were also obtained for detecting lung and bone metastases in a subgroup analysis.

As such the investigation demonstrated that 18F-FDG PET and PET/CT are very accurate for the diagnosis, staging and recurrence monitoring of osteosarcoma. 18F-FDG-avid lesions should be further examined in osteosarcoma, especially for suspicious lung lesions.

The aim of this study was to analyze the economic efficiency of second-line diagnostic investigations in patients with undetermined lung nodules.

A retrospective review of all surgical cases included in the DANTE trial from 2001 to 2006 for lung cancer screening was performed. Overall, 217 patients and 261 lung nodules were analyzed. The cohort was divided into patients investigated with PET and/or computed tomography (CT)-guided biopsy (PET-CTB protocol; N=100), compared with those assessed with serial low-dose CT scans (standard protocol; N=161). Outpatient's and inpatient's costs were expressed in euros and derived from the Italian National Health Service. Ineffective costs were defined as the cost of procedures that lead to avoidable surgical intervention.

The diagnostic accuracy of the two protocols was 91% for the standard (sensitivity 100%, specificity 91%, positive predictive value 26%, and negative predictive value 100%) and 90% for the PET-CTB protocol (sensitivity 98%, specificity 81%, positive predictive value 85%, and negative predictive value 97%). Average costs for outpatient's diagnostics were 694 and 1.462 euros, respectively, for the standard and PET-CTB protocol. Average inpatient's costs for both protocols were 12.121 euros. The two protocols showed comparable effectiveness in terms of outpatient's costs (94 and 90%, respectively; P=0.252). Inpatient's costs were effective in 36% of cases monitored according to the standard protocol compared with 85% of patients investigated with PET-CTB protocol. Ineffective costs corresponded to 64 and 15%, respectively (P<0.0001).

Despite a higher average cost for outpatient's diagnostics, the implementation of PET imaging with or without CT-guided needle biopsy in the workup of suspicious lung nodules results in reduced unnecessary harm and costs related to inpatient's procedures.

Patients with solitary pulmonary nodule (SPN) are usually sent to total-body positron emission tomography/computed tomography (PET/CT) examination with 18F-fluorodeoxyglucose (FDG). However, a segmental scan strategy may improve cost/effectiveness in this category of patients.

A segmental PET/CT scan only at the chest level could be performed in patients with indeterminate SPN. Limiting the PET/CT field to the thoracic region would greatly affect on radiobiology, department organization and health-care costs.

A solitary pulmonary nodule is a common, often incidental, radiographic finding. The investigation and differential diagnosis of solitary pulmonary nodules remain complex, because there are overlaps between the characteristics of benign and malignant processes. There are currently many strategies for evaluating solitary pulmonary nodules. The main objective is to identify benign lesions, in order to avoid exposing patients to the risks of invasive methods, and to detect cases of lung cancer accurately, in order to avoid delaying potentially curative treatment. The focus of this study was to review the evaluation of solitary pulmonary nodules, to discuss the current role of (18)F-fluorodeoxyglucose positron-emission tomography, addressing its accuracy and cost-effectiveness, and to detail the current recommendations for the examination in this scenario.

The aim of this review is to provide an outline of current evidence for the use of F-18-fluoro-deoxy-glucose PET computed tomography (FDG-PET/CT) in nonsmall cell lung cancer (NSCLC) for diagnosis, staging, radiotherapy planning, response assessment and response monitoring.

Management of patients with NSCLC requires a multimodality approach to accurately diagnose and stage patients. In this approach, FDG-PET/CT has become a standard staging instrument in lung cancer. FDG-PET/CT is, in addition to staging, also valuable for the characterization of the solitary pulmonary nodule. An increased uptake in the nodule as compared with mediastinal blood pool is suspected for malignancy. In radiotherapy planning, FDG-PET/CT can assist the radiation oncologist for optimal dose delivery to the tumour, while sparing healthy tissues. Evidence of the prognostic and predictive implications of FDG-PET/CT is accumulating. Volumetric parameters of PET, such as metabolic active tumour volume and total lesion glycolysis, are promising predictive and prognostic biomarkers. However, for implementation of metabolic response parameters in clinical practice, more randomized, PET-based, multicentre trials are necessary. The introduction of integrated PET and MRI scanners did not change the pivotal role of standard FDG-PET/CT yet, as with current technology, PET/MRI did not show superior performance in thoracic staging.

The role of PET is described for diagnosis, staging and response assessment.

Molecular imaging employing PET/CT enables in vivo visualization, characterization, and measurement of biologic processes in tumors at a molecular and cellular level. Using specific metabolic tracers, information about the integrated function of multiple transporters and enzymes involved in tumor metabolic pathways can be depicted, and the tracers can be directly applied as biomarkers of tumor biology. In this review, we discuss the role of F-18-fluorodeoxyglucose (FDG) as an in vivo glycolytic marker which reflects alterations of glucose metabolism in cancer cells. This functional molecular imaging technique offers a complementary approach to anatomic imaging such as computed tomography (CT) and magnetic resonance imaging (MRI) and has found widespread application as a diagnostic modality in oncology to monitor tumor biology, optimize the therapeutic management, and guide patient care. Moreover, emerging methods for PET imaging of further biologic processes relevant to cancer are reviewed, with a focus on tumor hypoxia and aberrant tumor perfusion. Hypoxic tumors are associated with poor disease control and increased resistance to cytotoxic and radiation treatment. In vivo imaging of hypoxia, perfusion, and mismatch of metabolism and perfusion has the potential to identify specific features of tumor microenvironment associated with poor treatment outcome and, thus, contribute to personalized treatment approaches.

Positron emission tomography (PET) combined with fludeoxyglucose F 18 (FDG) is recommended for the noninvasive diagnosis of pulmonary nodules suspicious for lung cancer. In populations with endemic infectious lung disease, FDG-PET may not accurately identify malignant lesions.

To estimate the diagnostic accuracy of FDG-PET for pulmonary nodules suspicious for lung cancer in regions where infectious lung disease is endemic and compare the test accuracy in regions where infectious lung disease is rare.

Databases of MEDLINE, EMBASE, and the Web of Science were searched from October 1, 2000, through April 28, 2014. Articles reporting information sufficient to calculate sensitivity and specificity of FDG-PET to diagnose lung cancer were included. Only studies that enrolled more than 10 participants with benign and malignant lesions were included. Database searches yielded 1923 articles, of which 257 were assessed for eligibility. Seventy studies were included in the analysis. Studies reported on a total of 8511 nodules; 5105 (60%) were malignant.

Abstracts meeting eligibility criteria were collected by a research librarian and reviewed by 2 independent reviewers. Hierarchical summary receiver operating characteristic curves were constructed. A random-effects logistic regression model was used to summarize and assess the effect of endemic infectious lung disease on test performance.

The sensitivity and specificity for FDG-PET test performance.

Heterogeneity for sensitivity (I2 = 87%) and specificity (I2 = 82%) was observed across studies. The pooled (unadjusted) sensitivity was 89% (95% CI, 86%-91%) and specificity was 75% (95% CI, 71%-79%). There was a 16% lower average adjusted specificity in regions with endemic infectious lung disease (61% [95% CI, 49%-72%]) compared with nonendemic regions (77% [95% CI, 73%-80%]). Lower specificity was observed when the analysis was limited to rigorously conducted and well-controlled studies. In general, sensitivity did not change appreciably by endemic infection status, even after adjusting for relevant factors.

The accuracy of FDG-PET for diagnosing lung nodules was extremely heterogeneous. Use of FDG-PET combined with computed tomography was less specific in diagnosing malignancy in populations with endemic infectious lung disease compared with nonendemic regions. These data do not support the use of FDG-PET to diagnose lung cancer in endemic regions unless an institution achieves test performance accuracy similar to that found in nonendemic regions.

Imaging has an important role in the multidisciplinary management of primary lung cancer. This article reviews the current state-of-the-art imaging modalities used for the evaluation, staging and post-treatment follow-up and surveillance of lung cancers, and image-guided percutaneous techniques for biopsy to confirm the diagnosis and for local therapy in non-surgical candidates.

This communication presents an update on the current role of positron emission tomography-computed tomography (PET-CT) in the various clinical decision-making steps in lung carcinoma. The modality has been reported to be useful in characterizing solitary pulmonary nodules, improving lung cancer staging, especially for the detection of nodal and metastatic site involvement, guiding therapy, monitoring treatment response, and predicting outcome in non-small cell lung carcinoma (NSCLC). Its role has been more extensively evaluated in NSCLC than small cell lung carcinoma (SCLC). Limitations in FDG PET-CT are encountered in cases of tumor histotypes characterized by low glucose uptake (mucinous forms, bronchioalveolar carcinoma, neuroendocrine tumors), in the assessment of brain metastases (high physiologic 18F-FDG uptake in the brain) and in cases presenting with associated inflammation. The future potentials of newer PET tracers beyond FDG are enumerated. An evolving area is PET-guided assessment of targeted therapy (e.g., EGFR and EGFR tyrosine kinase overexpression) in tumors which have significant potential for drug development.

Implementation of positron-emission tomography (PET) is variable depending on jurisdiction in part due to uncertainty about cost-effectiveness. Our objective was to perform a systematic review describing cost-effectiveness of PET in staging of non-small-cell lung cancer (NSCLC) and management of solitary pulmonary nodules (SPN). Systematic literature searches were conducted using separate search strategies for multiple databases. Our validity criteria included measurement of study quality by means of the validated Quality of Health Economic Studies (QHES) instrument. Metrics such as mean PET costs, median average cost savings per patient, incremental cost-effectiveness ratio based on life years saved and quality-adjusted life years were calculated. Eighteen studies met our inclusion criteria with average QHES scores > 75. Studies were primarily based on the national health insurance payer perspective from 10 different countries. Cost-effectiveness was assessed primarily using decision-tree modeling and sensitivity analysis to determine the effects of changing variables on expected cost and life expectancy. After adjusting for currency exchange rates and inflation to 2010 United States dollars, the mean cost of PET was $1478. The cost-effectiveness metrics used in these studies were variable depending on sensitivity and specificity of diagnostic tests used in the models, probability of malignancy, and baseline strategy. Despite observed study heterogeneity, the consensus of these studies conclude that the additional information gained from PET imaging in the staging of NSCLC and diagnosis of SPNs is worth the cost in context of proper medical indications.

This work investigates the correlation between positron emission tomography (PET) images and the expressions of survivin, Ki67, and CD34, as well as the clinicopathological characteristics of non-small-cell lung cancer (NSCLC).

Thirty-three NSCLC cases were scanned with ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG), PET before surgery. Tumor resections were used to evaluate the expressions of survivin, Ki67, and CD34 by immunohistochemical assay. Maximum standardized uptake value (SUVmax), immunohistochemical results, as well as clinicopathological characteristics in NSCLC were compared and analyzed.

The average SUVmax for the 33 NSCLC was 10.5 ± 5.4. The expressions of survivin and Ki67 were 84.8% (28 of 33) and 72.7% (24 of 33), respectively. The median count of microvasculature vessel density labeled by CD34 was 24.5 ± 6.7. In the entire group, SUVmax was significantly correlated to Ki67, histological type, as well as clinical type (P = 0.010, 0.048, 0.029, respectively). It revealed a median survival of 33 ± 0.6 months for SUVmax below 11 versus a median survival of 27 ± 1.3 months for SUVmax values above 11 (P = 0.013). There were no significant correlations between SUVmax and expressions of survivin and CD34, and no correlations involving age, sex, differentiation, tumor node metastasis stage, and lymph node metastasis.

SUV-indexed FDG metabolic activity correlated significantly with proliferative activity (Ki67 expression) as well as the histological and clinical tumor type. These biological predictive markers combined with ¹⁸F-FDG PET might provide more useful information on the diagnosis and prognosis of patients with NSCLC. These conclusions require confirmation with further studies.

PET and PET/CT have changed the diagnostic algorithm in oncology. Health care systems worldwide have recently approved reimbursement for PET and PET/CT for staging of non-small cell lung cancer and differential diagnosis of solitary pulmonary nodules because PET and PET/CT have been found to be cost-effective for those uses. Additional indications that are covered by health care systems in the United States and several European countries include staging of gastrointestinal tract cancers, breast cancer, malignant lymphoma, melanoma, and head and neck cancers. Regarding these indications, diagnostic effectiveness and superiority over conventional imaging modalities have been shown, whereas cost-effectiveness has been demonstrated only in part. This article reports on the current knowledge of economic evaluations of PET and PET/CT in oncologic applications. Because more economic evaluations are needed for several clinical indications, we also report on the methodologies for conducting economic evaluations of diagnostic tests and suggest an approach toward the implementation of these tests in future clinical studies.

Dedicated positron emission tomography (PET)/CT scanners using BGO and related detectors (d-PET) have become standard imaging instruments in many malignancies. Hybrid gamma camera systems using NaI detectors in coincidence mode (g-PET) have been compared to d-PET but reported usefulness has been variable when gamma cameras with half-inch to three-fourth-inch thick crystals have been used without CT. Our aim was to compare g-PET with a 1-in.-thick crystal and inbuilt CT for lesion localization and attenuation correction (g-PET/CT) and d-PET/CT in patients presenting with potential and confirmed lung malignancies. One hour after (18)F-fluorodeoxyglucose (FDG), patients underwent BGO d-PET/CT from jaw to proximal thigh. This was followed by one to two bed position g-PET/CT 194 +/- 27 min after FDG. Each study pair was independently analysed with concurrent CT. d-PET/CT was interpreted by a radiologist experienced in both PET and CT, and g-PET/CT by consensus reading of an experienced PET physician and an experienced CT radiologist. A TNM score was assigned and studies were then unblinded and compared. Fifty-seven patients underwent 58 scan pairs over 2 years. Eighty-nine per cent concordance was shown between g-PET/CT and d-PET/CT for the assessment of intrapulmonary lesions, with 100% concordance for intrapulmonary lesions >10 mm (36 of 36). Eighty-eight per cent (51 of 58) concordance was shown between g-PET/CT and d-PET/CT for TNM staging. Coincidence imaging using an optimized dual-head 1-in.-thick crystal gamma camera with inbuilt CT compares reasonably well with dedicated PET/CT for evaluation of indeterminate pulmonary lesions and staging of pulmonary malignancies and may be of some value when d-PET/CT is not readily available.

No prior study to our knowledge has observed the cost of managing solitary pulmonary nodules of patient groups defined by PET scan results.

We combined study and administrative data over 2 years of follow-up.

Of 375 individuals with a definitive diagnosis, 54.4% had a malignant nodule and 62.1% had positive PET scan results. Mortality risk was 5.0 times higher (CI, 3.1-8.2) and cost was greater (50,233 dollars vs 22,461 dollars, P<.0001) among patients with malignant nodule. Mortality risk was 4.1 times higher (CI, 2.4-7.0) and cost was greater (47,823 dollars vs 20,744 dollars, P<.0001) among patients with a positive PET scan result. Among patients with a malignant nodule, 4.9% had a false-negative PET scan, but cost and survival were not different from true positives. Among patients with a benign nodule, 22.8% had a false-positive PET scan. These patients had greater cost (33,783 dollars vs 19,115 dollars, P<.01), more surgeries and biopsies, and 3.8 times the mortality risk (CI, 1.6-9.2) of true negatives. Just over one-half (54.5%) of individuals with positive PET scans received surgery. Most individuals with negative PET scans (85.2%) were managed by watchful waiting. They incurred fewer costs than patients with negative PET scans who were managed more aggressively (19,378 dollars vs 28,611 dollars, P<.01).

Management of solitary pulmonary nodules is expensive, especially if the nodule is malignant or if the PET scan result is false positive. Among patients with malignant nodules, 2-year survival is poor. Compared with true-positive PET scan results, false-negative results are not associated with lower costs or better outcomes.

Combined positron emission tomography and computed tomography (PET/CT) might improve the accuracy of PET tracer quantification by providing the exact tumour contour from coregistered CT images. We compared various semiquantitative approaches for the characterization of solitary pulmonary nodules (SPNs) using F-18 fluorodeoxyglucose PET/CT.

The final diagnosis of 49 SPNs (46 patients) was based on histopathology (n=33) or patient follow-up (n=16). The regions of interest (ROIs) were drawn around lesions based on the CT tumour contour and mirrored to the coregistered PET images. Quantification of F-18 fluorodeoxyglucose uptake was accomplished by calculating the standardized uptake value (SUV) using three different methods based on: activity from the maximum-valued pixel within the tumour (SUV-max); the mean ROI activity within the transaxial slice containing the maximum-valued pixel (SUV-mean); and the mean activity over the full tumour volume (SUV-vol). SUVs were corrected for partial volume effects and normalized by body surface area, lean body weight, and blood glucose. Recovery coefficients for partial-volume correction were derived from phantom studies. The ability of various SUVs to differentiate between benign and malignant SPNs was determined by calculating the area under the receiver operating characteristic (ROC) curves.

Twenty-six SPNs were malignant and 23 were benign. The area under the ROC curve was 0.78 for SUV-mean, 0.83 for SUV-max, and 0.78 for SUV-vol. SUV-max and its normalizations yielded the highest area under the ROC curve (0.83-0.85); SUV-mean-partial volume corrected-lean body weight resulted in the lowest area under the ROC curve (0.76). At a specificity of 80%, SUV-max-body surface area provided the highest sensitivity (81%) and accuracy (80%) to detect malignant SPN. Using SUV-max with a cutoff of 2.4 at a specificity of 80% resulted in a sensitivity of 62% (accuracy 71%).

Various normalizations applied to SUV-max provided the highest diagnostic accuracy for characterization of SPNs. Quantification methods using the exact tumour contour derived from CT in combined PET/CT imaging (ROI mean activity within a single transaxial slice and mean tumour volume activity) did not result in improved differentiation between benign and malignant SPN. Obtaining SUV-max might be sufficient in the clinical setting.

The American College of Surgeons Oncology Group (ACOSOG) Z0050 trial demonstrated that positron emission tomography (PET) prevents nontherapeutic thoracotomies in a substantial fraction of patients with known or suspected non-small cell lung cancer (NSCLC). However, the benefit of PET in clinical stage IA patients has been questioned due to the lower prevalence of metastases and poor ability to discriminate benign from malignant lung lesions. This study evaluates whether PET prevents nontherapeutic pulmonary resections in clinical stage IA patients by finding advanced disease or by declaring a nodule as benign.

We reanalyzed all patients with clinical stage IA NSCLC from ACOSOG Z0050. The clinical, PET, and pathologic stages were compared for this prospective cohort.

One hundred twenty-two clinical stage IA patients were evaluated and 78.7% (96 of 122; 95% confidence interval [CI], 70.4 to 85.6) were eventually shown to have cancer. PET correctly showed 7.4% (9 of 122; 95% CI, 3.4 to 13.5) of patients to have advanced disease (stages IIIA to IV). However, due to a high false positive rate, the positive predictive value for advanced disease was only 33.3% (9 of 27; 95% CI, 16.5 to 54.0). The negative predictive value of PET to predict benign lesions was only 57% (16 of 28; 95% CI, 37.2 to 75.5). Thus, 43% (12 of 28; 95% CI, 24.5 to 62.8) of patients with a PET negative primary lesion actually had cancer, and all of these had resectable disease (stages IA to IIB).

In clinical stage IA lung cancer patients, PET prevents nontherapeutic pulmonary resections less than 10% of the time. If a strategy of no surgery and serial computed tomographic scans is chosen for PET negative lesions, over 40% of patients with NSCLC will have surgery delayed. A prospective trial comparing PET versus resection for clinical stage IA lesions would clarify the value of PET for these patients.

Serum lactate dehydrogenase (LDH) concentration is an indicator of tissue injury. It may be locally secreted in some conditions. This study was performed in order to investigate the value of LDH levels in bronchoalveolar lavage fluid (BALF) in the differentiation of a bening, from a malignant solitary pulmonary nodules (SPN) and to assess its relationship with serum LDH levels.

The study was a prospective clinical study. It included 59 patients with a SPN. They underwent bronchoscopy with bronchoalveolar lavage (BAL). Both total serum and BAL LDH levels were measured.

BALF LDH level was increased in all patients with malignant SPN. The mean BALF LDH level was significantly higher in patients with malignant SPN (342.23 +/- 89.98) as compared to the benign ones (17.62 +/- 7.90) (P < 0.001). There was no correlation between BALF LDH and serum LDH level in patients with SPNs (P = 0.595).

BALF LDH levels are increased in patients with malignant SPN, but had no significant rise in benign SPN. This factor is useful in differentiating the benign SPNs from malignant SPNs.

The available tools for diagnosing and staging lung cancer patients can be broadly categorized into non-invasive, minimally invasive and invasive (surgical) modalities. Non-invasive modalities include CT and PET. Minimally invasive modalities are endoscopic approaches, including endoscopic ultrasound, endobronchial ultrasound and transbronchial fine needle aspiration without ultrasound guidance. This review focuses on the non-invasive and minimally invasive techniques involving imaging. Application of Bayesian principles indicates that tests with a high sensitivity and specificity for detection of both systemic metastases and mediastinal nodal involvement are required for treatment selection and planning in patients with non-small cell lung cancer who would be considered for treatment with curative intent. Combined PET/CT using the glucose analogue fluorine-18 fluorodeoxyglucose currently provides the best diagnostic performance for this purpose and should now be considered the standard of care for staging non-small cell lung cancer. Endoscopic ultrasound and endobronchial ultrasound have important complementary roles to allow further evaluation of equivocal nodal abnormalities on PET or CT and to allow pathological samples to be obtained. Diagnostic CT has an important role in defining tumour relations for patients deemed suitable for surgical resection and as the initial investigation for patients with potential symptoms of lung cancer or proven lung cancer that would not be considered for curative treatment on medical grounds.

Accurate staging of cancer is of fundamental importance to treatment selection and planning. Current staging paradigms focus, first, on a detailed delineation of the primary tumour in order to determine its suitability for resection, and, thereafter, on assessment of the presence of metastatic spread that would alter the surgical approach, or mandate non-surgical therapies. This approach has, at its core, the assumption that the best, and sometimes the only, way to cure a patient of cancer is by surgical resection. Unfortunately, all non-invasive techniques in current use have imperfect ability to identify those primary tumours that are able to be completely excised, and even worse ability to define the extent of metastatic spread. Nevertheless, because of relatively low cost and widespread availability, computed tomography (CT) scanning is the preferred methodology for tumour, nodal and systemic metastasis (TNM) staging. This is often supplemented by other tests that have improved performance in particular staging domains. For example, magnetic resonance imaging (MRI), mammography, or endoscopic ultrasound may be used as complementary tests for T-staging; surgical nodal sampling for N-staging; and bone scanning, MRI or ultrasound for M-staging. Accordingly, many patients undergo a battery of investigations but, even then, are found to have been incorrectly staged based on subsequent outcomes. Even for those staged surgically, pathology can only identify metastases within the resection specimens and has no capability for detecting remote disease. As a result of this, many patients undergo futile operations for disease that could never have been cured by surgery. In the case of restaging, the situation is even worse. The sequelae of prior treatment can be difficult to differentiate from residual cancer and the likelihood of successful salvage therapy is even less than at presentation. More deleteriously, patients may be subjected to additional morbid treatments when cure has already been achieved. Thus, in post-treatment follow-up, the presence and extent of disease is equally critical to treatment selection and patient outcome as it is in primary staging. One of the major strengths of positron emission tomography (PET)/CT as a cancer staging modality is its ability to identify systemic metastases. At any phase of cancer evaluation, demonstration of systemic metastasis has profound therapeutic and prognostic implications. Only in the absence of systemic metastasis does nodal status become important, and only when unresectable nodal metastasis has been excluded does T-stage become important. There are now accumulating data that PET/CT could be used as the first, rather than the last test to assess M- and N-stage for evaluating cancers with an intermediate to high pre-test likelihood of metastatic disease based on poor long-term survival. In this scenario, there is great opportunity for subsequently selecting and tailoring the performance of anatomically based imaging modalities to define the structural relations of abnormalities identified by PET, when this information would be of relevance to management planning. Primary staging of oesophageal cancer and restaging of colorectal cancer are illustrative examples of a new paradigm for cancer imaging.

Metabolic imaging with fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) is increasing rapidly worldwide because of superior accuracy compared with conventional non-invasive techniques used for evaluating cancer. Limited anatomical information from FDG-PET images alone dictates that complementary use with structural imaging is required to optimise benefit. Recently, combined positron emission tomography/computed tomography (PET/CT) scanners have overtaken standalone PET scanners as the most commonly purchased PET devices. We describe our experience of over 5500 scans performed since the first PET/CT scanner in Australia was commissioned at the Peter MacCallum Cancer Centre (PMCC), Melbourne, in January 2002. Clinical indications for PET/CT scans performed at PMCC largely reflect current Medicare reimbursement policy. Advantages of PET/CT include greater patient comfort and higher throughput, greater diagnostic certainty and accuracy, improved biopsy methods, and better treatment planning. We believe PET/CT will underpin more effective and efficient imaging paradigms for many common tumours, and lead to a decrease in imaging costs.

The aim of this study was to evaluate the relationships among [18F]fluorodeoxyglucose ([18F]-FDG) uptake, Glut-1 and HK-II expressions, and grade of inflammation in resected lung lesions.

Sixty patients had undergone preoperative 18F-FDG-PET imaging and thoracotomy. For semiquantitative analysis of 18F-FDG uptake, partial volume effect corrected maximum standardized uptake values (pSUVs) were calculated. Immunohistochemical staining was performed in resected specimens using anti-Glut-1, anti-HK-II, and anti-proliferative cellular nuclear antigen (PCNA) antibodies, and immunoreactivities were scored as G-, H-, and P-indexes on a five-point scale (0: 0%; 1: 20%, 2: 40%; 3: 60%; 4: 80%, and 5: 100% percentages of strongly immunoreactive cells).Grade of inflammation was also evaluated.

The malignant lesions had higher pSUV and higher G- and H- than nonmalignant lesions. pSUVs correlated with the G- (p < .001), H- (p < .01), and P-indexes (p < .01) in malignant lesions. In adenocarcinomas, cancers with lower differentiation showed higher expression of Glut-1 and HK-II than those with higher differentiation. A positive linear regression was observed between pSUVs and the grading of inflammation in nonmalignant lesions (p < .05).

Our study indicates that 18F-FDG uptake in lung cancer correlates well with the Glut-1, HK-II, and PCNA expression. For nonmalignant lesions, the presence of a higher inflammatory process correlated with 18F-FDG uptake.

(18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging is an important staging procedure in patients with non-small cell lung cancer (NSCLC). We aimed to demonstrate, through a decision tree model and the incorporation of real costs of each component, that routine FDG-PET imaging as a prelude to curative surgery will reduce requirements for routine mediastinoscopy and overall hospital costs.

A decision tree model comparing routine whole-body FDG-PET imaging to routine staging mediastinoscopy was used, with baseline variables of sensitivity, specificity and prevalence of non-operable and metastatic disease obtained from institutional data and a literature review. Costings for hospital admissions for mediastinoscopy and thoracotomy of actual patients with NSCLC were determined. The overall and average cost of managing patients was then calculated over a range of FDG-PET costs to derive projected cost savings to the community.

The prevalence of histologically proven mediastinal involvement in patients with NSCLC presenting for surgical assessment at our institution is 20%, and the prevalence of distant metastatic disease is 6%. Based on literature review, the pooled sensitivity and specificity of FDG-PET for detection of mediastinal spread are 84% and 89% respectively, and for mediastinoscopy, 81% and 100%. The average cost of mediastinoscopy for NSCLC in our institution is 4,160 AUD, while that of thoracotomy is 15,642 AUD. The cost of an FDG-PET scan is estimated to be 1,500 AUD. Using these figures and the decision tree model, the average cost saving is 2,128 AUDper patient.

Routine FDG-PET scanning with selective mediastinoscopy will save 2,128 AUD per patient and will potentially reduce inappropriate surgery. These cost savings remain robust over a wide range of disease prevalence and FDG-PET costs.

Because of the expected high performances of scintigraphic scans with [18F]-fluorodeoxyglucose (FDG) not only in diagnostics and but also in therapeutic impact, especially in thoracic oncology, there are a lot of French nuclear medicine departments which will soon be equipped with a positron emission tomograph (PET).

The Nuclear Medicine Department of the Hôpital d'Instructions des Armées du Val-de-Grâce, Paris, led a retrospective study among physicians interested in 338 FDG-PET exams performed between may 2000 and march 2002 in order to compare its own results with international literature concerning four indications for lung cancer: pulmonary nodule or mass malignancy diagnostic, lung carcinoma extension evaluation, therapeutic efficiency, recurrence suspicion.

There seems to be no divergence, regarding limitation induced by the not exhaustive analysis of the retrospective study: more than every two FDG-PET exam highly influenced the effective therapy.

That is why clinical FDG-PET has to be widely developed to investigate lung cancer.

Treatment of oesophageal cancer depends on staging and the general health of the patient. In stages I-II b, as well as in some stage III diseases, surgical resection remains the therapy of choice for cure, but a curative approach is not possible in stage IV. In our hospital we give preoperative radio-chemotherapy to all patients with an oesophageal cancer T>1, Nx, M0. Therefore, the main purpose of the clinical staging of oesophageal cancer is the exclusion of M1 and T4 disease with infiltration into the tracheobronchial system or the aorta. The aim of the investigation was the assessment of positron emission tomography for detection of M1 disease.

Between 1998 and 2002, 84 patients with oesophageal cancer (64% squamous cell carcinoma and 36% adenocarcinoma) were enrolled into the study. Of these, 48.8% were operated on; 35.7% of the patients were not operated on, for oncological reasons, 7.1% for medical reasons, 3.6% chose not to be operated on, and, for unknown reasons, 4.8% were not operated on.

Twenty-five patients had stage IV disease or additional, synchronous cancer of the head and neck ( n=2). As the only investigational procedure, positron emission tomography revealed M1 stage in 11 of 25 patients (44%). In 13/25 (52%) both computed tomography and positron emission tomography revealed stage IV disease. False positive results by positron emission tomography were observed in three patients. The sensitivity and specificity of positron emission tomography (PET) was 0.96 and 0.95, respectively. Most of the metastases detected by PET only, were localised within the neck, liver and bone. With regard to the 66 of 84 patients deemed medically fit for operation and without local infiltration into the tracheobronchial system (T4) PET as the only imaging procedure changed the therapeutic strategy in 11 of 66 (16.6%) patients with to M1 disease.

Our results demonstrated clearly the impact of the PET scan for decision-making in patients with oesophageal carcinoma. PET should be performed prior to therapy with curative intention. However, addition of a computed tomography scan of the neck might reduce the rate of unexpected metastases detected by PET.

With expenditure on imaging patients with cancer set to increase in line with rising cancer prevalence, there is a need to demonstrate the cost-effectiveness of advanced cancer imaging techniques. Cost-effectiveness studies aim to quantify the cost of providing a service relative to the amount of desirable outcome gained, such as improvements in patient survival. Yet, the impact of imaging on the survival of patients with cancer is small compared to the impact of treatment and is therefore hard to measure directly. Hence, techniques such as decision-tree analysis, that model the impact of imaging on survival, are increasingly used for cost-effectiveness evaluations. Using such techniques, imaging strategies that utilise computed tomography, magnetic resonance imaging and positron emission tomography have been shown to be more cost-effective than non-imaging approaches for the management of certain cancers including lung, prostate and lymphoma. There is stronger evidence to support the cost-effectiveness of advanced cancer imaging for diagnosis, staging and monitoring therapy than for screening. The results of cost-effectiveness evaluations are not directly transferable between countries or tumour types and hence more studies are needed. As many of the techniques developed to assess the evidence base for therapeutic modalities are not readily applicable to diagnostic tests, cancer imaging specialists need to define the methods for health technology assessment that are most appropriate to their speciality.

Positron emission tomography (PET) represents a dramatic advance in the imaging of lung cancer. It is valuable for the diagnosis, staging, prognosis, and restaging of disease, and is most useful in patients considered for potentially curative therapy for non-small-cell lung cancer (NSCLC). In this work the current status and potential future applications of PET scanning in lung cancer are discussed. The relevant literature is also discussed, with an emphasis on studies with clinical applicability. Most of these studies involved the use of 18F-fluorodeoxyglucose (FDG). Numerous studies of the use of PET to assess undiagnosed pulmonary nodules have reported significant improvements in accurate diagnosis or exclusion of malignancy compared to conventional structural imaging alone. All of these studies, including metaanalysis, have shown that PET is more accurate than CT-based structural imaging in staging the mediastinum in surgical candidates. PET may have value in radiotherapy planning, and PET-based staging more accurately predicts survival in radiotherapy-treated patients than conventional staging. The rate of unsuspected distant metastasis detection in stage III disease exceeds 20%. PET also facilitates an accurate assessment of response in patients treated with radical chemoradiation or neoadjuvant therapy prior to surgery. PET has rapidly become an indispensable part of the evaluation of patients with potentially curable lung cancer; however, more work is required to define its role.

To determine the impact of quantitative contrast-enhanced computed tomography (QECT) on the cost-effectiveness of diagnostic strategies for the assessment of solitary pulmonary nodules (SPNs).

Four diagnostic strategies were evaluated using decision tree analysis: conventional CT alone; conventional CT followed by QECT; conventional CT followed positron emission tomography (PET); and conventional CT followed by QECT and PET (QECT+PET). The average cost per patient, accuracy of management and incremental cost:accuracy ratio (ICAR) were determined for each strategy. Although baseline assumptions reflected the Australian setting, sensitivity analysis was used to extrapolate the results to the UK.

At the baseline prevalence of malignancy (54%) and cost of PET relative to surgery (16%), the QECT strategy incurs the least cost (5560 dollars/patient) but the QECT+PET strategy is the most cost-effective (ICAR 12,059 dollars/patient). At reported levels of disease prevalence (68.5%) and cost of PET relative to surgery (29.9%) in the UK, the QECT strategy is the most cost-effective.

QECT offers a cost-effective approach to evaluation of SPNs. Whether QECT is used alone or in combination with PET will depend upon local availability and regional values for prior probability of malignancy within SPNs and the cost of PET relative to surgery.

Currently, up to 50% of the operations in early-stage non-small cell lung cancer (NSCLC) are futile owing to the presence of locally advanced tumour or distant metastases. More accurate pre-operative staging is required in order to reduce the number of futile operations. The cost-effectiveness of fluorine-18 fluorodeoxyglucose positron emission tomography ((18)FDG-PET) added to the conventional diagnostic work-up was studied in the PLUS study. Prior to invasive staging and/or thoracotomy, 188 patients with (suspected) NSCLC were randomly assigned to conventional work-up (CWU) and whole-body PET or to CWU alone. CWU was based on prevailing guidelines. Pre-operative staging was followed by 1 year of follow-up. Outcomes are expressed in the percentage of correctly staged patients and the associated costs. The cost price of PET varied between <euro>736 and <euro>1,588 depending on the (hospital) setting and the procurement of (18)FDG commercially or from on-site production. In the CWU group, 41% of the patients underwent a futile thoracotomy, whereas in the PET group 21% of the thoracotomies were considered futile ( P=0.003). The average costs per patient in the CWU group were <euro>9,573 and in the PET group, <euro>8,284. The major cost driver was the number of hospital days related to recovery from surgery. Sensitivity analysis on the cost and accuracy of PET showed that the results were robust, i.e. in favour of the PET group. The addition of PET to CWU prevented futile surgery in one out of five patients with suspected NSCLC. Despite the additional PET costs, the total costs were lower in the PET group, mainly due to a reduction in the number of futile operations. The additional use of PET in the staging of patients with NSCLC is feasible, safe and cost saving from a clinical and from an economic perspective.