Meta-Analysis of Positron Emission Tomographic and Computed Tomographic Imaging in Detecting Mediastinal Lymph Node Metastases in Nonsmall Cell Lung Cancer
2004; Elsevier BV; Volume: 79; Issue: 1 Linguagem: Inglês
10.1016/j.athoracsur.2004.06.041
ISSN1552-6259
AutoresÖzcan Birim, A. Pieter Kappetein, Theo Stijnen, Ad J.J.C. Bogers,
Tópico(s)Medical Imaging and Pathology Studies
ResumoA systematic review was undertaken to select studies that compared the accuracy of 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography with computed tomographic imaging in detecting mediastinal lymph node metastases in patients with nonsmall cell lung cancer. Two authors selected relevant articles according to predefined criteria. With a meta-analytic method, summary receiver operating characteristic curves were constructed. The point on the receiver operating characteristic curve with equal sensitivity and specificity for 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography was Q* = 0.90 (95% confidence interval [CI], 0.86 to 0.95). For computed tomography it was 0.70 (95% CI, 0.65 to 0.75). The difference was highly significant (p < 0.0001). We conclude that 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography is more accurate than computed tomography in detecting mediastinal lymph node metastases. A systematic review was undertaken to select studies that compared the accuracy of 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography with computed tomographic imaging in detecting mediastinal lymph node metastases in patients with nonsmall cell lung cancer. Two authors selected relevant articles according to predefined criteria. With a meta-analytic method, summary receiver operating characteristic curves were constructed. The point on the receiver operating characteristic curve with equal sensitivity and specificity for 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography was Q* = 0.90 (95% confidence interval [CI], 0.86 to 0.95). For computed tomography it was 0.70 (95% CI, 0.65 to 0.75). The difference was highly significant (p < 0.0001). We conclude that 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography is more accurate than computed tomography in detecting mediastinal lymph node metastases. Lung cancer is the most common cause of death by malignancy in industrialized countries. Approximately only 15% of patients can be cured to enjoy long-term survival. The optimal management of patients with nonsmall cell lung cancer (NSCLC) depends on the accuracy of appropriate staging strategies. In this regard, chest roentgenograms and computed tomographic (CT) See page 365; for editorial comment, see page 16images are frequently performed on patients with suspected lung cancer. These diagnostic modalities provide anatomic and morphologic information and are noninvasive, but they are limited in distinguishing between benign and malignant abnormalities. The likelihood of the surgical cure of primary NSCLC is strongly dependent on the local extent of the cancer, particularly whether or not the mediastinal lymph nodes are involved with cancer or whether extrathoracic metastases are present [1Mountain C.F. Revision of the international system for staging lung cancer.Chest. 1997; 111: 1710-1717Crossref PubMed Scopus (4563) Google Scholar]. Therefore, diagnostic evaluation of mediastinal lymph nodes should be accurate. Patients with metastases to the mediastinal lymph nodes have an average 5-year survival rate of approximately 23% as compared with a survival rate of 50% when there is no mediastinal involvement [1Mountain C.F. Revision of the international system for staging lung cancer.Chest. 1997; 111: 1710-1717Crossref PubMed Scopus (4563) Google Scholar]. Dales and colleagues [2Dales R.E. Stark R.M. Raman S. Computed tomography to stage lung cancer: approaching a controversy using meta-analysis.Am Rev Respir Dis. 1990; 141: 1096-1101Crossref PubMed Google Scholar] found an overall accuracy of 79% of chest CT imaging in detecting mediastinal metastases. Presently the most accurate method for staging the mediastinal lymph nodes is mediastinoscopy, an invasive procedure that has a sensitivity of approximately 90% for malignant disease [3Gdeedo A. van Schil P. Corthouts B. van Mieghem F. van Meerbeeck J. van Marck E. Prospective evaluation of the computed tomography and mediastinoscopy in mediastinal lymph node staging.Eur Respir J. 1997; 10: 1547-1551Crossref PubMed Scopus (174) Google Scholar, 4van Schil P.E. van Hee R.H. Schoofs E.L. The value of mediastinoscopy in preoperative staging of bronchogenic carcinoma.J Thorac Cardiovasc Surg. 1989; 97: 240-244PubMed Google Scholar]. In the last decade, attention has focused on positron emission tomography (PET), a new noninvasive imaging modality using 2-[18F]-fluoro-2-deoxy-D-glucose (FDG); this method has demonstrated increased glucose metabolism in malignant cells and pulmonary malignancies [5Nolop K.B. Rhodes L.G. Brudin L.H. et al.Glucose utilization in vivo by human pulmonary neoplasm.Cancer. 1987; 60: 2682-2689Crossref PubMed Scopus (263) Google Scholar]. The principal mechanism for which it is based was an observation made in 1930. Warburg [6Warburg O. Wind F. Neglers E. On the metabolism of tumors in the body.in: Warburg O. Metabolism of tumors. Constable, London1930: 254-270Google Scholar] observed that cancer cells are characterized by higher glycolitic rate than normal cells. The glucose analogue FDG undergoes membrane transport and phosphorylation by hexokinase and is trapped intracellularly. Therefore, intracellular FDG concentration reflects intracellular glucose metabolism and permits differentiation between benign and malignant tissue. The FDG PET imaging is performed in the fasting state to minimize competitive inhibition of FDG uptake by glucose. Several studies have addressed the diagnostic accuracy of FDG PET for detecting mediastinal lymph node metastases, but most studies have enrolled a small numbers of patients. The purpose of this study is to perform a meta-analysis to estimate the diagnostic accuracy of FDG PET versus CT imaging on detecting mediastinal lymph node metastases in patients with NSCLC. We attempted to identify all studies that examined functional imaging with FDG PET and CT scanning for diagnosis of mediastinal lymph node metastases in patients with NSCLC. Articles were identified by an electronic search of MEDLINE using specific keywords (ie, positron emission tomography, computed tomography, FDG, lung cancer, staging). The references reported in all the identified studies were used for completion of the literature search. When authors reported on the same patient population in several publications, only the most recent or complete study was included in the analysis. Articles by the same author or research group were identified for analysis only when it was obvious that different patient populations had been used. The search ended in January 2003. The following items were searched for in each of these series: number of patients, mean age, design of the study, reference standard, sensitivity and specificity of FDG PET and CT scan. Two investigators (ÖB, APK) independently evaluated potential English language studies for inclusion and subsequently resolved disagreements by discussion. To be eligible for this analysis, reports had to have primary nonsmall cell lung cancer cases only, have enrolled at least 15 patients, have evaluated the correlation of FDG PET and mediastinal lymph node metastases, have evaluated the correlation of CT imaging and mediastinal lymph node metastases, have presented sufficient data to allow calculation of sensitivity and specificity for malignancy, and had to have been published as a full article in the English language peer-reviewed literature. Abstracts were excluded from this analysis because of insufficient data to evaluate the methodological quality and to allow the calculation of sensitivity and specificity. We designed criteria to assess the quality of the different studies. The trial quality was assessed according to the information provided in the publication. Each trial was read and scored independently by two investigators (ÖB, APK), and disagreements were subsequently resolved by discussion. To identify high-quality studies, we selected criteria for methodological quality from a checklist for reporting diagnostic accuracy studies proposed by the STARD (Standards for Reporting of Diagnostic Accuracy) group [7Bossuyt P.M. Reitsma J.B. Bruns D.E. et al.Toward complete and accurate reporting of studies of diagnostic accuracy the STARD initiative.BMJ. 2003; 326: 41-44Crossref PubMed Scopus (1184) Google Scholar]. The STARD checklist consists of 25 items. We selected eight general quality criteria covering eight dimensions: (1) descriptions of the study population, (2) cohort assembly, and (3) study design, (4) a clear description of CT technique, (5) a clear description of FDG PET technique, (6) a technical quality of the reference standard, (7) a clear definition of cut-off levels, and (8) interpretation of both FDG PET and CT scans independent of each other and without knowledge of histology. A value between 0 and 2 was attributed to each dimension (2 = adequate and complete description or prospective design, 1 = partial or not optimal description or retrospective design, and 0 = not performed or not mentioned), giving a maximum possible score of 16. The raw data were summarized according to a method described previously by Irwig and associates [8Irwig L. Macaskill P. Glasziou P. Fahey M. Meta-analytic methods for diagnostic test accuracy.J Clin Epidemiol. 1995; 48: 119-130Abstract Full Text PDF PubMed Scopus (398) Google Scholar]. For each study, sensitivity, specificity and diagnostic odds ratios (DOR) were calculated from the 2 × 2 tables of true-positive, true-negative, false-positive, and false-negative results. The DOR is a simple statistic to express the discriminative power of a test. It is defined as the ratio of sensitivity/(1-sensitivity) over (1-specificity)/specificity. In simpler terms, the DOR is the odds of a positive test result if mediastinal lymph nodes are involved with cancer, divided by the odds of a positive test result if mediastinal lymph nodes are free from cancer. A DOR greater than 1 indicates that a test has discriminative power, which increases with the magnitude of the DOR. To prevent division by 0 when calculating the DOR, the conventional correction by adding 0.5 to each cell in the 2 × 2 tables was applied [9Haldane J.B.S. The estimation and significance of the logarithm of a ratio of frequencies.Ann Hum Genet. 1955; 48: 309-314Google Scholar]. The DOR was analyzed using a random effect meta-analysis model for the logarithm of the DOR, leading to an overall estimate of the DOR and a corresponding 95% confidence interval (95% CI), taking possible heterogeneity between studies into account [10van Houwelingen J.C. Arends L.R. Stijnen T. Advanced methods in meta-analysis multivariate approach and meta-regression.Stat Med. 2002; 21: 589-624Crossref PubMed Scopus (1252) Google Scholar]. Sensitivity and specificity were analyzed in an analogous way, using the logit transformation. The models contained study as random factor and did not contain fixed factors, except for a constant. These analyses were carried out with SAS proc mixed as described by van Houwelingen and colleagues [10van Houwelingen J.C. Arends L.R. Stijnen T. Advanced methods in meta-analysis multivariate approach and meta-regression.Stat Med. 2002; 21: 589-624Crossref PubMed Scopus (1252) Google Scholar]. To quantitatively summarize the diagnostic test performance of FDG PET and CT imaging, we also used a meta-analytic method to construct summary receiver operating characteristic (ROC) curves [11Moses L.E. Shapiro D. Littenber B. Combining independent studies of a diagnostic test into a summary ROC curve: data-analytic approaches and some additional considerations.Stat Med. 1993; 12: 1293-1316Crossref PubMed Scopus (1196) Google Scholar, 12Owens D.K. Holodniy M. Garber A.M. et al.Polymerase chain reaction for the diagnosis of HIV infection in adults: a meta-analysis with recommendations for clinical practice and study design.Ann Intern Med. 1996; 124: 803-815Crossref PubMed Scopus (47) Google Scholar]. Receiver operating characteristic curves illustrate the trade-off between sensitivity and specificity as the threshold for defining a positive test that varies from the most stringent to the least stringent. Construction of a summary ROC curve involves calculation of the sum and difference of the logit transforms of the true-positive and false-positive rates for each study [8Irwig L. Macaskill P. Glasziou P. Fahey M. Meta-analytic methods for diagnostic test accuracy.J Clin Epidemiol. 1995; 48: 119-130Abstract Full Text PDF PubMed Scopus (398) Google Scholar]. Our method assumes that each individual study represents a unique point on a common ROC curve. To construct the common ROC curves, we applied the equally weighted least squares method described by Moses and colleagues [11Moses L.E. Shapiro D. Littenber B. Combining independent studies of a diagnostic test into a summary ROC curve: data-analytic approaches and some additional considerations.Stat Med. 1993; 12: 1293-1316Crossref PubMed Scopus (1196) Google Scholar]. We defined the maximum joint sensitivity and specificity as the intersection point of the ROC curve and the diagonal line that runs from the top left corner to the bottom right corner of the ROC diagram. This point Q*, at which sensitivity and specificity are equal, is a global measure of test accuracy, similar to the area under the ROC curve. The maximum joint sensitivity and specificity of a perfect test is 1.0, and a maximum joint sensitivity and specificity of a test that has no discriminative ability is 0.5, meaning that probability of correctly identifying disease would be 50%. We calculated Q* and its corresponding standard error by the method described by Moses and colleagues [11Moses L.E. Shapiro D. Littenber B. Combining independent studies of a diagnostic test into a summary ROC curve: data-analytic approaches and some additional considerations.Stat Med. 1993; 12: 1293-1316Crossref PubMed Scopus (1196) Google Scholar]. A larger value of Q* means that the ROC curve tends to be positioned more towards the left upper corner and the better is the test [13Hanley J.A. Receiver operating characteristics methodology: the state of the art.Crit Rev Diagn Imaging. 1989; 29: 307-335PubMed Google Scholar, 14Centor R.M. Schwartz J.S. An evaluation of methods for estimating the area under the receiver operating characteristic (ROC) curve.Med Decis Making. 1985; 5: 149-156Crossref PubMed Scopus (105) Google Scholar]. The analysis was carried out with SPSS. To assess publication bias, funnel plots were made accompanied by the linear regression test on symmetry [15Egger M. Davey Smith G. Scheinder M. Bias in meta-analysis detected by a simple, graphical test.BMJ. 1997; 315: 629-634Crossref PubMed Scopus (37678) Google Scholar]. Our search identified 49 potentially relevant studies. We excluded 26 studies after scanning their abstracts, including 12 studies written in another language other than English, five studies that evaluated small cell lung cancer, eight review articles, and one study that evaluated not only NSCLC. Twenty-three potentially eligible studies were subsequently appraised. Of these, we excluded six studies because the same patient population as another more recently published article was used [16Gupta N.C. Graeber M. Rogers J.F. Bishop H.A. Comparative efficacy of positron emission tomography with FDG and computed tomographic scanning in preoperative staging of non-small cell lung cancer.Ann Surg. 1999; 229: 286-291Crossref PubMed Scopus (119) Google Scholar], because only the accuracy of FDG PET was evaluated [17Vesselle H. Pugsley J.M. Vallières E. Wood D.E. The impact of fluorodeoxyglucose F 18 positron-emission tomography on the surgical staging of non-small cell lung cancer.J Thorac Cardiovasc Surg. 2002; 124: 511-519Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar], because only patients with stage I NSCLC on CT imaging were included [18Farrell M.A. McAdams H.P. Herndon J.E. Patz E.F. Non-small cell lung cancer FDG PET for nodal staging in patients with stage I disease.Radiology. 2000; 215: 886-890Crossref PubMed Scopus (110) Google Scholar], because only patients with probable N1-disease were included [19Vansteenkiste J.F. Stroobants S.G. Dupont P.J. et al.FDG-PET scan in potentially operable non-small cell lung cancer: Do anatometabolic PET-CT fusion images improve the localisation of regional lymph node metastases?.Eur J Nucl Med. 1998; 25: 1495-1501Crossref PubMed Scopus (135) Google Scholar], because there was insufficient data reported to allow the calculation of sensitivity and specificity [20Bury T. Dowlati A. Paulus P. Hustinx R. Radermecker M. Rigo P. Staging of non-small-cell lung cancer by whole-body fluorine-18 deoxyglucose positron emission tomography.Eur J Nucl Med. 1996; 23: 204-206Crossref PubMed Scopus (76) Google Scholar], or because only the number of mediastinal nodal stations examined were reported and not the number of patients [21Patz E.F. Lowe V.J. Goodman P.C. Herndon J. Thoracic nodal staging with PET imaging with 18FDG in patients with bronchogenic carcinoma.Chest. 1995; 108: 1617-1621Crossref PubMed Scopus (170) Google Scholar], respectively. The remaining 17 studies were published between 1994 and 2001 [22Scott W.J. Schwabe J.L. Gupta N.C. Dewan N.A. Reeb S.D. Sugimoto J.T. Positron emission tomography of lung tumors and mediastinal lymph nodes using.Ann Thorac Surg. 1994; 58 ([18F]fluorodeoxyglucose): 698-703Abstract Full Text PDF PubMed Scopus (179) Google Scholar, 23Wahl R.L. Quint L.E. Greenough R.L. Meyer C.R. White R.I. Orringer M.B. Staging of mediastinal non-small cell lung cancer with FDG PET, CT, and fusion images: preliminary prospective evaluation.Radiology. 1994; 191: 371-377PubMed Google Scholar, 24Chin R. Ward R. Keyes J.W. et al.Mediasinal staging of non-small cell lung cancer with positron emission tomography.Am J Respir Crit Care Med. 1995; 152: 2090-2096Crossref PubMed Scopus (163) Google Scholar, 25Valk P.E. Pounds T.R. Hopkins D.M. et al.Staging non-small cell lung cancer by whole-body positron emission tomographic imaging.Ann Thorac Surg. 1995; 60: 1573-1582Abstract Full Text PDF PubMed Scopus (283) Google Scholar, 26Scott W.J. Gobar L.S. Terry J.D. Dewan N.A. Sunderland J.J. Mediastinal lymph node staging of non-small-cell lung cancer: a prospective comparison of computed tomography and positron emission tomography.J Thorac Cardiovasc Surg. 1996; 111: 642-648Abstract Full Text Full Text PDF PubMed Scopus (185) Google Scholar, 27Sazon D.A.D. Santiago S.M. Soo Hoo G.W. et al.Fluorodeoxyglucose-positron emission tomography in the detection and staging of lung cancer.Am J Respir Crit Care Med. 1996; 153: 417-421Crossref PubMed Scopus (183) Google Scholar, 28Sasaki M. Ichiya Y. Kuwabara Y. et al.The usefulness of FDG positron emission tomography for the detection of mediastinal lymph node metastases in patients with non-small cell lung cancer a comparative study with X-ray computed tomography.Eur J Nucl Med. 1996; 23: 741-747Crossref PubMed Scopus (139) Google Scholar, 29Vansteenkiste J.F. Stroobants S.G. De Leyn P.R. et al.Mediastinal lymph node staging with FDG-PET scan in patients with potentially operable non-small cell lung cancer a prospective analysis of 50 cases.Chest. 1997; 112: 1480-1486Crossref PubMed Scopus (177) Google Scholar, 30Steinert H.C. Hauser M. Allemann F. et al.Non-small cell lung cancer: nodal staging with FDG PET versus CT with correlative lymph node mapping and sampling.Radiology. 1997; 202: 441-446PubMed Google Scholar, 31Guhlmann A. Storck M. Kotzerke J. Moog F. Sunder-Plassmann L. Reske R.N. Lymph node staging in non-small cell lung cancer evaluation by [18F] FDG positron emission tomography (PET).Thorax. 1997; 52: 438-441Crossref PubMed Scopus (147) Google Scholar, 32Hagberg R.C. Segall G.M. Stark P. Burdon T.A. Pompili M.F. Characterization of pulmonary nodules and mediastinal staging of bronchogenic carcinoma with F-18 fluorodeoxyglucose positron emission tomography.Eur J Cardiothorac Surg. 1997; 12: 92-97Crossref PubMed Scopus (41) Google Scholar, 33Bury T. Dowlati A. Paulus P. et al.Whole-body 18FDG positron emission tomography in the staging of non-small cell lung cancer.Eur Respir J. 1997; 10: 2529-2534Crossref PubMed Scopus (157) Google Scholar, 34Saunders C.A.B. Dussek J.E. O'Doherty M.J. Maisey M.N. Evaluation of fluorine-18-fluorodeoxyglucose whole body positron emission tomography imaging in the staging of lung cancer.Ann Thorac Surg. 1999; 67: 790-797Abstract Full Text Full Text PDF PubMed Scopus (189) Google Scholar, 35Marom E.M. McAdams H.P. Erasmus J.J. et al.Staging non-small cell lung cancer with whole-body PET.Radiology. 1999; 212: 803-809Crossref PubMed Google Scholar, 36Pieterman R.M. van Putten J.W.G. Meuzelaar J.J. et al.Preoperative staging of non-small cell lung cancer with positron-emission tomography.N Eng J Medy. 2000; 343: 254-261Crossref PubMed Scopus (1065) Google Scholar, 37Gupta N.C. Graeber G.F. Bishop H.A. Comparative efficacy of positron emission tomography with fluorodeoxyglucose in evaluation of small ( 3 cm) lymph node lesions.Chest. 2000; 117: 773-778Crossref PubMed Scopus (214) Google Scholar, 38Poncelet A.J. Lonneux M. Coche E. Weynand B. Noirhomme Ph PET-FDG scan enhances but does not replace preoperative surgical staging in non-small cell lung cancer.Eur J Cardiothorac Surg. 2001; 20: 468-475Crossref PubMed Scopus (75) Google Scholar]. The main characteristics of the 17 eligible studies are outlined in Table 1. The total number of patients included was 833, ranging from 18 to 102 patients by report. There were no data reported on age in 11 studies. The sex distribution was only reported in three studies. Five studies evaluated the role of whole-body FDG PET and CT imaging in the staging of NSCLC (pulmonary nodules, lymph node metastases, and distant metastases) [25Valk P.E. Pounds T.R. Hopkins D.M. et al.Staging non-small cell lung cancer by whole-body positron emission tomographic imaging.Ann Thorac Surg. 1995; 60: 1573-1582Abstract Full Text PDF PubMed Scopus (283) Google Scholar, 33Bury T. Dowlati A. Paulus P. et al.Whole-body 18FDG positron emission tomography in the staging of non-small cell lung cancer.Eur Respir J. 1997; 10: 2529-2534Crossref PubMed Scopus (157) Google Scholar, 34Saunders C.A.B. Dussek J.E. O'Doherty M.J. Maisey M.N. Evaluation of fluorine-18-fluorodeoxyglucose whole body positron emission tomography imaging in the staging of lung cancer.Ann Thorac Surg. 1999; 67: 790-797Abstract Full Text Full Text PDF PubMed Scopus (189) Google Scholar, 35Marom E.M. McAdams H.P. Erasmus J.J. et al.Staging non-small cell lung cancer with whole-body PET.Radiology. 1999; 212: 803-809Crossref PubMed Google Scholar, 36Pieterman R.M. van Putten J.W.G. Meuzelaar J.J. et al.Preoperative staging of non-small cell lung cancer with positron-emission tomography.N Eng J Medy. 2000; 343: 254-261Crossref PubMed Scopus (1065) Google Scholar], three studies assessed the role of FDG PET and CT imaging on detecting pulmonary nodules and mediastinal metastases [22Scott W.J. Schwabe J.L. Gupta N.C. Dewan N.A. Reeb S.D. Sugimoto J.T. Positron emission tomography of lung tumors and mediastinal lymph nodes using.Ann Thorac Surg. 1994; 58 ([18F]fluorodeoxyglucose): 698-703Abstract Full Text PDF PubMed Scopus (179) Google Scholar, 27Sazon D.A.D. Santiago S.M. Soo Hoo G.W. et al.Fluorodeoxyglucose-positron emission tomography in the detection and staging of lung cancer.Am J Respir Crit Care Med. 1996; 153: 417-421Crossref PubMed Scopus (183) Google Scholar, 32Hagberg R.C. Segall G.M. Stark P. Burdon T.A. Pompili M.F. Characterization of pulmonary nodules and mediastinal staging of bronchogenic carcinoma with F-18 fluorodeoxyglucose positron emission tomography.Eur J Cardiothorac Surg. 1997; 12: 92-97Crossref PubMed Scopus (41) Google Scholar], three studies evaluated lymph node metastases [30Steinert H.C. Hauser M. Allemann F. et al.Non-small cell lung cancer: nodal staging with FDG PET versus CT with correlative lymph node mapping and sampling.Radiology. 1997; 202: 441-446PubMed Google Scholar, 37Gupta N.C. Graeber G.F. Bishop H.A. Comparative efficacy of positron emission tomography with fluorodeoxyglucose in evaluation of small ( 3 cm) lymph node lesions.Chest. 2000; 117: 773-778Crossref PubMed Scopus (214) Google Scholar, 38Poncelet A.J. Lonneux M. Coche E. Weynand B. Noirhomme Ph PET-FDG scan enhances but does not replace preoperative surgical staging in non-small cell lung cancer.Eur J Cardiothorac Surg. 2001; 20: 468-475Crossref PubMed Scopus (75) Google Scholar], and six trials only assessed mediastinal lymph node staging of NSCLC [23Wahl R.L. Quint L.E. Greenough R.L. Meyer C.R. White R.I. Orringer M.B. Staging of mediastinal non-small cell lung cancer with FDG PET, CT, and fusion images: preliminary prospective evaluation.Radiology. 1994; 191: 371-377PubMed Google Scholar, 24Chin R. Ward R. Keyes J.W. et al.Mediasinal staging of non-small cell lung cancer with positron emission tomography.Am J Respir Crit Care Med. 1995; 152: 2090-2096Crossref PubMed Scopus (163) Google Scholar, 26Scott W.J. Gobar L.S. Terry J.D. Dewan N.A. Sunderland J.J. Mediastinal lymph node staging of non-small-cell lung cancer: a prospective comparison of computed tomography and positron emission tomography.J Thorac Cardiovasc Surg. 1996; 111: 642-648Abstract Full Text Full Text PDF PubMed Scopus (185) Google Scholar, 28Sasaki M. Ichiya Y. Kuwabara Y. et al.The usefulness of FDG positron emission tomography for the detection of mediastinal lymph node metastases in patients with non-small cell lung cancer a comparative study with X-ray computed tomography.Eur J Nucl Med. 1996; 23: 741-747Crossref PubMed Scopus (139) Google Scholar, 29Vansteenkiste J.F. Stroobants S.G. De Leyn P.R. et al.Mediastinal lymph node staging with FDG-PET scan in patients with potentially operable non-small cell lung cancer a prospective analysis of 50 cases.Chest. 1997; 112: 1480-1486Crossref PubMed Scopus (177) Google Scholar, 31Guhlmann A. Storck M. Kotzerke J. Moog F. Sunder-Plassmann L. Reske R.N. Lymph node staging in non-small cell lung cancer evaluation by [18F] FDG positron emission tomography (PET).Thorax. 1997; 52: 438-441Crossref PubMed Scopus (147) Google Scholar]. The patients included in the studies were found operable on CT scan findings if mediastinal lymph nodes were ≤10 mm in diameter. If mediastinal lymph nodes were larger, patients underwent mediastinoscopy before surgery. All patients underwent FDG PET imaging. Histology was confirmed by mediastinoscopy or thoracotomy, or both. Thirty-two patients (in two studies, respectively in 1 and 31 patients [23Wahl R.L. Quint L.E. Greenough R.L. Meyer C.R. White R.I. Orringer M.B. Staging of mediastinal non-small cell lung cancer with FDG PET, CT, and fusion images: preliminary prospective evaluation.Radiology. 1994; 191: 371-377PubMed Google Scholar, 35Marom E.M. McAdams H.P. Erasmus J.J. et al.Staging non-small cell lung cancer with whole-body PET.Radiology. 1999; 212: 803-809Crossref PubMed Google Scholar]) were followed-up with CT scan. Lymph nodes were recorded as pathologic if there was a substantial growth in size. Studies did not report which and how many patients underwent mediastinoscopy on FDG PET findings before thoracotomy. Only six studies [30Steinert H.C. Hauser M. Allemann F. et al.Non-small cell lung cancer: nodal staging with FDG PET versus CT with correlative lymph node mapping and sampling.Radiology. 1997; 202: 441-446PubMed Google Scholar, 31Guhlmann A. Storck M. Kotzerke J. Moog F. Sunder-Plassmann L. Reske R.N. Lymph node staging in non-small cell lung cancer evaluation by [18F] FDG positron emission tomography (PET).Thorax. 1997; 52: 438-441Crossref PubMed Scopus (147) Google Scholar, 33Bury T. Dowlati A. Paulus P. et al.Whole-body 18FDG positron emission tomography in the staging of non-small cell lung cancer.Eur Respir J. 1997; 10: 2529-2534Crossref PubMed Scopus (157) Google Scholar, 35Marom E.M. McAdams H.P. Erasmus J.J. et al.Staging non-small cell lung cancer with whole-body PET.Radiology. 1999; 212: 803-809Crossref PubMed Google Scholar, 38Poncelet A.J. Lonneux M. Coche E. Weynand B. Noirhomme Ph PET-FDG scan enhances but does not replace preoperative surgical staging in non-small cell lung cancer.Eur J Cardiothorac Surg. 2001; 20: 468-475Crossref PubMed Scopus (75) Google Scholar] described a differentiation between N2 and N3 disease. Two studies [30Steinert H.C. Hauser M. Allemann F. et al.Non-small cell lung cancer: nodal staging with FDG PET versus CT with correlative lymph node mapping and sampling.Radiology. 1997; 202: 441-446PubMed Google Scholar, 37Gupta N.C. Graeber G.F. Bishop H.A. Comparative efficacy of positron emission tomography with fluorodeoxyglucose in evaluation of small ( 3 cm) lymph node lesions.Chest. 2000; 117: 773-778Crossref PubMed Scopus (214) Google Scholar] reported results by using lymph nodes as the unit of analysis and differentiated between single versus multiple nodes. The results of the remaining studies were reported by using the patient as the unit of analysis.Table 1Studies Comparing 2-[18F]-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography and Computed Tomography in Mediastinal Lymph Node Staging of Nonsmall Cell Lung CancerReference, YearPatients (% Male)Mean Age (Range)DesignReference StandardaModalityTrue-PositiveFalse-NegativeFalse-PositiveTrue-NegativeSensitivity (%)Specificity (%)p ValueDiagnostic ORScott et al, 1994 [22Scott W.J. Schwabe J.L. Gupta N.C. Dewan N.A. Reeb S.D. Sugimoto J.T. Positron emission tomography of lung tumors and mediastinal lymph nodes using.Ann Thorac Surg. 1994; 58 ([18F]fluorodeoxyglucose): 698-703Abstract Full Text PDF PubMed Scopus (179) Google
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