1Department of Radiotherapy and Oncology, Turku University Hospital, Turku, Finland; 2Radiation Oncology, Peter MacCallum Cancer Institute, Melbourne, Australia
Received 10 August 2001; accepted 14 November 2001.
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Abstract |
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Key words: FDG-PET, non-small-cell lung cancer, outcome, staging, treatment
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Introduction |
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Positron emission tomography (PET) scanning with fluorodeoxyglucose (FDG) utilises the fundamental biochemical differences in glucose metabolism between normal cells and cancer cells to differentiate between benign and neoplastic processes. The glucose analogue 18F-fluoro-2-deoxy-D-glucose is trapped inside tumour cells because these abnormal cells are unable to metabolise FDG after phosphorylation [7]. The accumulation of labelled FDG in cancer cells can be detected with high resolution by the PET camera, and imaging of neoplastic tissue with this method is in many clinical situations more sensitive than with structural imaging with computed tomography (CT) and magentic resonance imaging (MRI). PET has proven to be more sensitive and specific compared with conventional imaging of NSCLC in several crucial areas, principally in staging of the mediastinum [811] and the detection of distant metastases [1217].
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Staging of lung cancer with FDG-PET compared with CT |
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PET has emerged as the most accurate non-invasive method available to characterise mediastinal lymph node status in the preoperative staging of NSCLC [19, 2123]. The use of PET in preoperative staging resulted in a different stage from that determined by standard methods in about half of patients, with the stage lowered in 20% and raised in 41% of patients. In surgically managed patients, PET has been shown to improve sensitivity and specificity of mediastinal node assessment by 1020% compared with structural imaging techniques, and to change and improve patient management in 1530% of cases. A meta-analysis [12] has firmly established the superior accuracy of metabolic staging compared with anatomical staging in the detection of mediastinal nodal metastases. Overall, the sensitivity, specificity and accuracy of FDG-PET for staging mediastinal lymph nodes was 96, 93 and 94%, respectively. This has been confirmed recently with a German meta-analysis, including >1000 patients and also evaluating the sensitivity, specificity and accuracy in other metastatic sites, with the same conclusion: high diagnostic efficacy of FDG-PET is superior to conventional imaging in lung cancer [17].
Most patients with NSCLC considered for radical radiation therapy have stage III disease following conventional staging procedures. Most of these patients ultimately die of distant metastases, and it is therefore likely that conventional staging often underestimates the true extent of disease at presentation. In the series reported by Mac Manus and co-workers [24], there was an increase in the incidence of PET detection of distant metastases with increasing pre-PET stage from stage I (7.5%) to stage II (18%) to stage III (24%, P = 0.016). Additionally, in stage IIIA and IIIB, 26 and 21% of patients, respectively, had unsuspected metastases detected by PET. In no case was the PET-detected metastasis found to be false positive. In the meta-analysis [17], unexpected extrathoracic metastases were detected in 12% of lung cancer patients with FDG-PET, and the therapeutic management was changed in 18% of patients due to FDG-PET staging [17].
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Evaluation of treatment outcome with PET |
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Is PET cost-effective in the management of NSCLC? |
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New forms of technology, such as PET, can be widely implemented only when they are proved to be cost-effective [31]. In the USA, FDG-PET, when available, has become a standard investigation in the diagnosis of solitary lung nodules and in the pre-operative staging of lung carcinoma. The cost benefits of PET have been largely attributed to the reduction in the number of patients with unresectable mediastinal disease who earlier underwent unnecessary attempts at curative surgery [32]. Additional savings could result if PET is used to exclude patients with occult distant metastases from surgery [33]. A recent analysis on cost-effectiveness by Dietlein et al. [34] shows that the use of FDG-PET leads to cost savings and additional life-expectancy in the case of an intermediate pre-test probability of malignancy, and that the use of FDG-PET was most cost-effective in potentially operable lung cancer patients with normal mediastinal lymph nodes on CT. In the US, Medicare and many third-party insurers have approved reimbursement for PET with 18F-fluorodeoxyglucose for the staging of NSCLC. In the UK, the Royal Society of Surgeons has accepted PET as part of the recommended staging for pre-surgical evaluation in lung cancer, and the use of FDG-PET for lung cancer staging is now contained within the guidelines issued by the British Thoracic Society and the Society for Cardiothoracic Surgeons [35], as it is in the recommendations of the German Consensus Conference [17]. Ongoing prospective studies will further clarify the issue of cost-effectiveness. For most indications, FDG-PET is used in addition to other diagnostic modalities.
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Appropriate treatment according to the true extent of lung cancer |
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Footnotes |
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References |
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