The role of FDG-PET in the management of non-small cell lung carcinoma.

INTRODUCTION: Positron emission tomography (PET) using 18F-2-fluoro-2 deoxy-D-glucose (FDG) has been widely investigated and used in the non-invasive imaging of malignancy. Non-small cell lung carcinoma (NSCLC) is one of the most common and best validated indications for an FDG-PET scan. This review examines the roles of FDG-PET in the management of NSCLC and attempts to identify emerging uses and possible future developments. MATERIALS AND METHODS: Literature review of English language literature indexed on Medline. RESULTS: There is strong evidence to support the clinical efficacy and cost effectiveness of FDG-PET in the characterisation of solitary pulmonary nodules and in the staging of NSCLC. In addition, there are emerging uses in radiotherapy planning, monitoring of treatment response and prognostication. CONCLUSIONS: FDG-PET plays an integral role in the management of NSCLC and it is likely to expand as evidence supporting additional roles in the management of NSCLC becomes available.

Positron emission tomography for urological tumours.

For urological tumours, positron emission tomography (PET) is currently most useful in testicular cancer. In patients with residual masses or raised marker levels after treatment, PET is both sensitive and specific for detecting recurrent disease, at suspected and unsuspected sites. Although fewer studies are available it also appears to be useful for staging at diagnosis, although this requires further investigation. Prostate cancer imaging has been more variable, with studies showing that PET cannot reliably differentiate between tumour and hypertrophy. It is not as good as a bone scan for defining bone metastases. In renal cancer, PET can be used to define the primary tumour, providing better staging of local recurrence than computed tomography (CT), and to define metastatic disease. There are few studies in bladder cancer, and despite excretion of the tracer via the bladder in early studies, it has better results than CT or magnetic resonance imaging for local staging; again it can detect metastases. Overall, the place of PET in urological tumours is developing, with the strongest areas undoubtedly being testicular and renal cancer. Tracers other than fluorodeoxyglucose are being examined and are providing further information.

FDG-PET. A possible prognostic factor in head and neck cancer.

Previous studies have shown that high uptake of (18)F-fluoro-2-deoxy-glucose in head and neck cancer, as determined by the standardized uptake value on positron emission tomography scan, was associated with poor survival. The aim of this study was to confirm the association and to establish whether a high standardized uptake value had prognostic significance. Seventy-three consecutive patients with newly diagnosed squamous cell carcinoma of the head and neck underwent a positron emission tomography study before treatment. Age, gender, performance status tumour grade, stage, maximal tumour diameter and standardized uptake value were analyzed for their possible association with survival. The median standardized uptake value for all primary tumours was 7.16 (90% range 2.30 to 18.60). In univariate survival analysis the cumulative survival was decreased as the stage, tumour diameter and standardized uptake value increased. An standardized uptake value of 10 was taken as a cut-off for high and low uptake tumours. When these two groups were compared, an standardized uptake value >10 predicted for significantly worse outcome (P=0.003). Multivariate analysis demonstrated that an standardized uptake value >10 provided prognostic information independent of the tumour stage and diameter (P=0.002). We conclude that high FDG uptake (standardized uptake value>10) on positron emission tomography is an important marker for poor outcome in primary squamous cell carcinoma of the head and neck. Standardized uptake value may be useful in distinguishing those tumours with a more aggressive biological nature and hence identifying patients that require intensive treatment protocols including hyperfractionated radiotherapy and/or chemotherapy.

Positron emission tomography in lung cancer.

Carcinoma of the lung is one of the most frequent malignancies and a major cause of mortality. The use of positron emission tomography (PET) has been extensively investigated in patients with carcinoma of the lung and has established clinical utility and cost-effectiveness in characterization of solitary pulmonary nodules and preoperative staging of carcinoma of the lung. Evolving applications in carcinoma of the lung include detection of recurrence, assessment of treatment response, radiotherapy planning, and prognosis. In addition, there is developing interest in combined anatomic/metabolic imaging and new tracer techniques, in particular gene expression imaging. This review aims to present existing data supporting the use of PET in carcinoma of the lung and to explore the evolving indications and future prospects of PET and lung cancer.

FDG-PET as a "metabolic biopsy" tool in thoracic lesions with indeterminate biopsy.

A common problem encountered in clinical medicine is the classification of a lung lesion (nodule/opacity) on conventional imaging. Often attempts at biopsy are unsuccessful or are falsely reassuring, and the decision to send the patient for more invasive and potentially morbid procedures can be difficult. Our aim was to investigate the role of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in helping to identify more accurately those patients with malignant lesions. Sixty-three patients underwent FDG-PET scans following unsuccessful biopsy of a lung lesion or, in a lesser number of cases, when an attempt at biopsy was considered too dangerous. Follow-up was by histology or, if this was unavailable, by clinical progress to death or a minimum of 18 months post scan. Visual and quantitative analysis was performed. On visual analysis, positive and negative predictive values were 90% and 100%, respectively. On quantitative (SUV>2.5) analysis, positive and negative predictive values were 90% and 85%, respectively. We interpret these results as showing that the use of FDG-PET scans in patients in this circumstance is non-invasive and highly sensitive in diagnosing malignancy. The high positive predictive value suggests that those with a positive scan must undergo further investigation, while the 100% negative predictive value means those with no FDG uptake can safely be spared further invasive investigations

Early experience with PET scanning in thoracic tumours.

BACKGROUND: Positron emission tomography (PET) scan is an imaging technique which relies on metabolic properties of the lesions. In this study, we evaluated the potential contribution of PET for thoracic malignancy in a consecutive series of patients presenting with multiple lesions or equivocal diagnosis. METHODS: PET with 2-18 F fluorodeoxyglucose (FDG) was carried out in 41 patients. The diagnosis was primary intrathoracic malignancy in 22 (Group 1). On routine staging using CT scan we found 29 additional lesions and assessed these using PET scan. PET was performed to evaluate the number of metastatic lesions in the lung in 11 (Group 2), to characterise undiagnosed pathology in the chest in 4 (Group 3), to search clinically suspicious extrathoracic spread in 4 patients with known intrathoracic malignancy. RESULTS: In Group 1, the sensitivity and specificity of PET was 81.2% and 92.3%. The accuracy of PET in the confirmation of metastatic disease to the chest was 73%. PET was falsely positive in a patient with chronic inflammatory disease in Group 3 and highly accurate to characterise unknown pathology in Group 4. CONCLUSIONS: Even though infection may cause false positive results, PET is a useful imaging technique for the evaluation of patients with thoracic tumours.

Positron emission tomography in imaging spinal cord tumors.

The ability of positron emission tomography (PET) to detect spinal cord tumors was studied prospectively in 14 patients presenting over a 5-year period. Abnormal uptake by [18F]-fluorodeoxyglucose (FDG) or 11C-methionine was detected in all except one. These data were assessed in relation to magnetic resonance imaging (MRI) findings with regard to tumor type and extent preoperatively, findings at operation, and subsequent clinical course. The group consisted of six astrocytomas, five ependymomas, one mixed ependymoma and astrocytoma, one schwannoma, and one ganglioglioma, all confirmed histologically. This is the largest study comparing spinal PET to MRI. Accurate preoperative correlation between PET and MRI was found in all eight patients scanned at first presentation. The PET uptake was in keeping with the low-grade histology of the tumors. Postoperatively, PET and MRI findings were in agreement in nine patients. In eight of these the findings were in keeping with the subsequent clinical course. In three patients, however, the PET findings were at variance with the clinical course and MRI findings. In one, persistent FDG uptake after radiotherapy was seen where there was subsequent tumor resolution. In two patients with low-grade astrocytomas, scanned with FDG and 11C-methionine, respectively, tracer was not taken up by residual tumor. In this small group of patients, PET did not provide additional useful information. This could be because all tumors studied were low grade and the limited spatial resolution of PET does not lend itself to imaging small spinal cord tumors. The prospective study of larger numbers of patients with a wider range of tumor types is required, but this might be difficult to achieve given the rarity of spinal cord tumors.

Significance of interictal bilateral temporal hypometabolism in temporal lobe epilepsy.

OBJECTIVE: To assess the clinical implications and the pathophysiologic determinants of interictal bitemporal hypometabolism (BTH) in temporal lobe epilepsy (TLE) not associated with bilateral MRI abnormalities or intracranial space-occupying lesions. METHODS: The authors compared the clinical, interictal, and ictal EEG, Wada test, and neuropsychology data of 15 patients with intractable complex partial seizures of temporal lobe origin and BTH with those of 13 consecutive patients with unilateral TLE associated with unilateral temporal hypometabolism (UTH) who remained seizure free for more than 3 years after anterior temporal lobectomy. 18F-fluorodeoxyglucose PET scans were analyzed visually and semiquantitatively, and ratios of counts in individual temporal areas to the rest of the cerebrum were compared with the corresponding values from 11 normal control subjects and with the nonepileptogenic hemisphere of the 13 patients with UTH. BTH was defined as more than 2.5 SDs below control values for two or more temporal areas on each side irrespective of any asymmetry. RESULTS: BTH reflected bilateral independent seizure onset in eight patients (53%). The topography of the metabolic depression was not a reliable predictor of epileptogenicity, but involvement of the inferior temporal gyrus was related specifically to ipsilateral seizure onset (70% sensitivity, 100% specificity). In patients with unilateral TLE, contralateral hypometabolism was associated with longer disease duration and worst memory performance during the Wada test, which amounted to global amnesia after ipsilateral injection in three patients, precluding surgical treatment. Contralateral seizure spread in the ictal EEG was significantly faster in patients with BTH. CONCLUSIONS: In TLE, symmetric or asymmetric BTH may signal bilateral independent seizure onset in approximately half the patients, especially when involving the inferior temporal gyrus. Alternatively, it may reflect an advanced stage of the disease process, characterized by a breakdown of the inhibitory mechanisms in the contralateral hemisphere, and secondary memory deficit associated with higher risk of postoperative memory decline. Patients with TLE and BTH but without bilateral MRI changes may still be operated on successfully, but surgical suitability should be proved by comprehensive intracranial EEG studies and Wada test.

Evaluation of myocardial perfusion using positron emission tomography in infants following a neonatal arterial switch operation.

This study was performed to examine the use of positron emission tomography (PET) as a method of evaluating myocardial perfusion after the arterial switch operation for correction of transposition of the great arteries. Eleven asymptomatic patients (median age 2.3 years, range 1.3-4.3 years) post successful neonatal arterial switch repair for transposition underwent cardiac PET scanning using N(13) ammonia before and after dipyridamole infusion. Reconstructed data from static scans were analyzed for regional perfusion defects before and after pharmacological stress. Simultaneous assessment of coronary flow before and after stress was performed using a Patlak graphical analysis of data from dynamic scans. Results obtained from PET scanning were correlated with patterns of coronary artery anatomy, electrocardiogram (ECG) recordings, and echocardiographic evaluation. PET scanning demonstrated normal distribution of myocardial perfusion before and after stress in all but one patient, who was found to have a discrete inferior transmural perfusion defect. The defect was well correlated with perioperative ECG changes and a complicated postoperative course. Myocardial blood flow before dipyridamole (0.690 ml/min/g) was similar to reported adult rest values. There was a small but significant (p < 0.002) increase in myocardial blood flow after dipyridamole stress with a mean coronary flow reserve of 1.19 (+/-0.103). Echocardiographic evaluation failed to demonstrate significant wall motion abnormalities in any of the patients. Cardiac PET scanning is a reliable noninvasive method for evaluation of myocardial perfusion in small children. In this study, the incidence of myocardial perfusion defects after the arterial switch operation is lower than previously reported. The data obtained concerning coronary flow and coronary flow reserve after the arterial switch need to be interpreted with caution because normal data in children are not available.

An educational tool to illustrate cost-effectiveness in diagnostic pathways for coronary artery disease.

Rapid increases in healthcare costs have led to increased interest in the cost-effectiveness of medical interventions. Coronary artery disease is responsible for a significant share of total healthcare spending, and therefore economic evaluations of medical procedures to treat the condition are potentially very important. We have developed a spreadsheet model as an educational tool that can be used to illustrate cost-effectiveness in the selection of diagnostic pathways (a "work-up" strategy of tests designed to reach a final diagnosis) for coronary artery disease. The model, in Microsoft Excel, is easy to use, requiring no specialist computer knowledge. It is menu-driven and the user navigates the model via a number of on-screen buttons. A data entry screen allows the user to customize the data for the key model parameters, making it possible to take into account location-specific features. The data entry screen also allows the user to undertake sensitivity analysis and rate "what if" scenarios. The model demonstrates how sensitive the cost-effectiveness of different diagnostic pathways is to the pretest probability of disease. This package could also be used as a decision support tool, although it is important to recognize some of its limitations for this purpose.

18-FDG-PET as a prognostic indicator in the treatment of aggressive Non-Hodgkin's Lymphoma-comparison with CT.

Less than 50% of newly diagnosed patients with aggressive histology Non-Hodgkin's Lymphoma (NHL) are cured with standard treatment. The ability to accurately monitor response to treatment is crucial in order to select out patients who need more intensive or salvage treatment. This study assesses the accuracy of FDG-PET as compared to CT in remission assessment following treatment of aggressive NHL, and its value in estimating relapse-free survival. It also evaluates the prognostic value of early interim PET scan in prediction of treatment outcome. Forty-nine adult patients with biopsy-proven aggressive NHL between September 1993 and December 1997 were included. All patients had pre-treatment FDG-PET demonstrating increased uptake in sites of disease. Forty-five patients had a post-treatment PET to assess remission status and 4 had an interim but not a post-treatment PET. Thirty-three of these patients also had a pre- and a post-treatment CT scan. Twenty-three of the 49 patients had an interim PET during chemotherapy to assess early response. PET and CT scan results were correlated with relapse data to examine their accuracy in remission assessment and prediction of prognosis. The median follow-up duration is 30 months. Overall the result of post-treatment PET scan appears to predict disease outcome, with relapse rates of 100% (9/9) and 17% (6/36) for positive and negative PET respectively [p<0.001]. In a subgroup of 33 patients, direct comparison of post-treatment PET and CT shows that PET was more accurate than CT in assessing remission status following treatment. Relapse rate was 100% for positive PET and only 18% for negative PET (p<0.001), compared to 41% and 25% for patients with positive and negative CT respectively (p>0.1). PET was particularly useful in assessment of residual masses seen on CT scan. The interim PET provided valuable information regarding early assessment of response and long-term prognosis, with no relapses in patients with no or minimal residual uptake compared to 87.5% relapse rate in patients with persistent PET activity (p<0.001). FDG-PET is an accurate method of assessing remission and estimating prognosis following treatment of aggressive NHL, with positive and negative predictive accuracies of 100% and 82% respectively. PET is more accurate than CT in assessing remission and prediction of relapse-free survival. An interim PET scan after 2-3 cycles of chemotherapy predicts the long-term outcome early-on and has a high negative predictive value (100%). This may assist to separate at an early stage good-prognosis patients who are likely to be cured with standard chemotherapy from those patients with poorer prognosis who require alternative treatment.

Normal variants, artefacts and interpretative pitfalls in PET imaging with 18-fluoro-2-deoxyglucose and carbon-11 methionine.

Interpretation of studies from all imaging modalities requires a knowledge of the possible pitfalls that may occur due to normal variation, artefacts and processes which may mimic pathology. The applications and use of not only 18-fluoro-2-deoxyglucose but also l-[methyl-(11)C] methionine positron emission tomography (PET) are widening and it is timely that the currently recognised interpretative pitfalls are reviewed as the number of dedicated PET scanners and coincidence gamma cameras increases.

Interictal 18FDG PET findings in temporal lobe epilepsy with déjà vu.

The authors studied the functional anatomy of the déjà vu (DV) experience in nonlesional temporal lobe epilepsy (TLE), using interictal fluorine-18 fluorodeoxyglucose PET in 14 patients with and 17 patients without DV. Several clinical conditions, such as age at PET study, side of ictal onset zone, and dominance for language, were no different between the two groups. The patients with DV showed significant relative reductions in glucose metabolism in the mesial temporal structures and the parietal cortex. The findings demonstrate that ictal DV is of no lateralizing value. They further suggest that temporal lobe dysfunction is necessary but not sufficient for the generation of DV. Extensive association cortical areas may be involved as part of the network that integrates this distinct experience.

Plasma amino acids in childhood epileptic encephalopathies.

Abnormalities in plasma amino acid levels have been noted in patients with various epilepsies, and sometimes also in their first degree relatives. We sought to study plasma amino acid levels in children with epileptic encephalopathies and their parents, relating findings to the pattern of cortical glucose metabolism as determined by 18fluorodeoxyglucose (FDG) positron emission tomography (PET). Twenty-eight children with cryptogenic epileptic encephalopathies were studied prospectively. Cortical glucose metabolism was evaluated by FDG PET with combined visual and semiquantitative analysis used to detect focal cortical defects. The plasma concentration of 21 amino acids in the children and their parents was measured by ion exchange chromatography and compared with control values using non-parametric statistical methods. Multivariate analysis was used to assess antiepileptic drug effects. Children were classified as: Lennox-Gastaut syndrome following infantile spasms (six patients); de-novo Lennox-Gastaut syndrome (eight); severe myoclonic epilepsy in infancy (eight) and myoclonic-astatic epilepsy (two). Four patients remained unclassified. Fourteen patients had focal/multifocal abnormalities on PET scans. The plasma level of aspartate was significantly lower in both the children with epileptic encephalopathies and in their parents (P < 0.005). The lowered aspartate levels could not be accounted for by the antiepileptic drug medication taken by the children. Further analysis showed the lowered aspartate levels to be confined to children and their parents who lacked focal PET abnormalities. These findings suggest a possible genetic abnormality in the aspartate neurotransmitter systems in the pathogenesis of seizures in the childhood epileptic encephalopathies.

Evaluation of fluorine-18-fluorodeoxyglucose whole body positron emission tomography imaging in the staging of lung cancer.

BACKGROUND: Surgical resection of lung cancer remains the treatment of choice in appropriately staged disease, but conventional imaging techniques have limitations. Positron emission tomography (PET) may improve staging accuracy. METHODS: We studied whole body and localized thoracic PET in staging lung cancer. Standardized uptake value was calculated for the primary lesion. Ninety-seven patients under consideration for surgical resection were included. PET, computed tomography, and clinical staging were compared to stage at operation, biopsy, or final outcome. Mean follow up was 17.5 months. RESULTS: PET detected all primary lung cancers with two false-positive primary sites. Sensitivity and specificity for N2 and N3 mediastinal disease was 20% and 89.9% for computed tomography and 70.6% and 97% for PET. PET correctly altered stage in 26.8%, nodal stage in 13.4%, and detected distant metastases in 16.5%. PET missed 7 of 10 cerebral metastases. PET altered management in 37% of patients. PET staging (p<0.0001) and standardized uptake value (p<0.001) were the best predictors of time to death apart from operative staging. CONCLUSIONS: PET provides significant staging and prognostic information in lung cancer patients considered operable by standard criteria. Routine use of PET will prevent unnecessary operation and may be cost effective.

Use of positron emission tomography in evaluation of brachial plexopathy in breast cancer patients.

18-Fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) has previously been used successfully to image primary and metastatic breast cancer. In this pilot study, 19 breast cancer patients with symptoms/signs referrable to the brachial plexus were evaluated with 18FDG-PET. In 11 cases computerized tomography (CT) scanning was also performed. Of the 19 patients referred for PET study, 14 had abnormal uptake of 18FDG in the region of the symptomatic plexus. Four patients had normal PET studies and one had increased FDG uptake in the chest wall that accounted for her axillary pain. CT scans were performed in 9 of the 14 patients who had positive brachial plexus PET studies; six of these were either normal or showed no clear evidence of recurrent disease, while three CTs demonstrated clear brachial plexus involvement. Of two of the four patients with normal PET studies, one has had complete resolution of symptoms untreated while the other was found to have cervical disc herniation on magnetic resonance imaging (MRI) scan. The remaining two patients almost certainly had radiation-induced plexopathy and had normal CT, MRI and PET study. These data suggest that 18FDG-PET scanning is a useful tool in evaluation of patients with suspected metastatic plexopathy, particularly if other imaging studies are normal. It may also be useful in distinguishing between radiation-induced and metastatic plexopathy.