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(Radiology. 1999;213:530-536.)
© RSNA, 1999

Nuclear Medicine

Metastases from Non-Small Cell Lung Cancer: Mediastinal Staging in the 1990s-Meta-analytic Comparison Of PET and CT1

Ben A. Dwamena, MB, ChB, Seema S. Sonnad, PhD, Jeff O. Angobaldo, MS and Richard L. Wahl, MD

1 From the Department of Internal Medicine, Division of Nuclear Medicine (B.A.D., J.O.A., R.L.W.), the Departments of Radiology (R.L.W.) and Surgery (S.S.S.), and the Consortium for Health Outcomes, Innovation, and Cost Effectiveness Studies (CHOICES) (S.S.S.), University of Michigan Medical Center, 1500 E Medical Center Dr, UH B1G 412, Ann Arbor, MI 48109-0028. From the 1997 RSNA scientific assembly. Received April 26, 1998; revision requested November 9; revision received February 4, 1999; accepted June 8. Address reprint requests to R.L.W.


   Abstract
TOP
 Abstract
Introduction
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
PURPOSE: To meta-analytically compare 2-[fluorine 18]fluoro-2-deoxy-D-glucose positron emission tomography (PET) and computed tomography (CT) for the demonstration of mediastinal nodal metastases in patients with non–small cell lung cancer.

MATERIALS AND METHODS: English-language reports on the diagnostic performance of PET (14 studies, 514 patients) and/or CT (29 studies, 2,226 patients) for demonstration of mediastinal nodal metastases from NSCLC were selected by using the MEDLINE database. In eligible studies, an objective diagnostic standard was used, data were presented to allow recalculation of contingency tables, and established diagnostic criteria were used for abnormal test results. Summary receiver operating characteristic (ROC) curves were calculated.

RESULTS: Pooled point estimates of diagnostic performance and summary ROC curves indicated that PET was significantly more accurate than CT for demonstration of nodal metastases (P < .001). Mean sensitivity and specificity (± 95% CI) were 0.79 ± 0.03 and 0.91 ± 0.02, respectively, for PET and 0.60 ± 0.02 and 0.77 ± 0.02, respectively, for CT. The log odds ratios were 1.79 (95% CI: 1.49, 2.09) for CT and 3.77 (95% CI: 2.77, 4.77) for PET (P < .001). Subgroup analyses did not alter findings.

CONCLUSION: PET is superior to CT for mediastinal staging of non–small cell lung cancer, independent of performance index or clinical context of PET imaging.

Index terms: Computed tomography (CT), comparative studies, 996.1291 • Positron emission tomography (PET), comparative studies, 996.12963 • Lung neoplasms, metastases, 60.321, 67.33 • Lymphatic system, neoplasms, 996.33 • Lymphatic system, CT, 996.1291 • Lymphatic system, radionuclide studies, 996.12963 • Mediastinum, neoplasms, 67.33


   Introduction
TOP
 Abstract
 Introduction
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
The non–small cell variety of bronchogenic carcinoma constitutes approximately 80% of the 171,500 new cases of lung cancer diagnosed per year in North America (1). Surgical resection has been the mainstay of treatment for non–small cell lung cancer (NSCLC). The likelihood of a surgical cure of newly diagnosed, primary NSCLC is strongly dependent upon the local extent of the cancer, particularly whether or not the mediastinal lymph nodes are involved with cancer (2). Patients with metastases to the mediastinal lymph nodes have an average 5-year survival rate of approximately 10%, as compared with a survival rate of 50% when there are no mediastinal metastases (2,3). The potentially curative surgical procedures of thoracotomy with lobectomy or pneumonectomy cause substantial mortality and morbidity (4) and are inappropriate if the patient's disease burden is so extensive as to be nonresectable.

Currently, mediastinal lymph nodes shown at x-ray computed tomography (CT) or magnetic resonance (MR) imaging to be larger than or equal to 1 cm in short-axis diameter are considered to be "abnormal" and are subsequently evaluated either with bronchoscopy and transbronchial needle aspiration biopsy or with mediastinoscopy. Patients with mediastinal nodes smaller than 1 cm are presumed to be free of local-regional metastatic disease and, if there are no contraindications to thoracic surgery, are offered an opportunity to undergo surgical resection. McKenna and colleagues (5) found no correlation between the presence of mediastinal nodal metastases and nodal size. In fact, metastases may be found in 21% of normal nodes (6), and up to 40% of enlarged nodes in some series (7) are not cancerous. Thus, it has been suggested (8) that important advances in the noninvasive detection of metastases to the lymph nodes must await an approach that is fundamentally different from CT for determination of lymph node abnormality on the basis of size.

The authors of studies (9,10) in which the tumor-localizing properties of 2-[fluorine 18]fluoro-2-deoxy-D-glucose (FDG) were used have described the application of positron emission tomography (PET) to diagnostic evaluation for a variety of tumors, including breast cancer, brain tumors, lymphomas, and lung cancer. In contrast to CT, which is primarily dependent on anatomic imaging features, FDG PET is mainly dependent on the metabolic characteristics of a tissue for assistance in the diagnosis of disease.

Wahl and colleagues (11) prospectively evaluated PET in a head-to-head trial with CT for the evaluation of mediastinal lymph nodes in patients with NSCLC. In their study of 23 patients with newly diagnosed or possible NSCLC who were undergoing both CT and PET with pathologic correlation, PET demonstrated 82% sensitivity and 81% specificity, as compared with 64% sensitivity and 44% specificity for CT, for the staging of mediastinal nodal disease (11). Subsequently, other researchers (12–24) have conducted single-institution studies, with results even more favorable with regard to PET. However, these studies lacked the statistical power to help determine whether the differences between CT and PET were significant. In a meta-analysis of 42 studies with CT published before the 1990s, Dales and colleagues (8) reported sensitivity and specificity for mediastinal metastases of 0.79 and 0.78, respectively.

With the emergence of newer-generation CT scanners and better imaging algorithms, however, the contemporary diagnostic performance of CT in the staging of mediastinal NSCLC has not been well characterized. It also is not clear what differences may exist in diagnostic performance between PET used as a substitute for CT and PET used as a complementary modality to CT. We undertook a meta-analysis of the published literature to compare the discriminatory power of the two modalities and to place in perspective the role of FDG PET relative to that of CT in the staging of mediastinal NSCLC.


   MATERIALS AND METHODS
TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 References
 
Data Sources
This quantitative, systematic review was initiated with a comprehensive computer search of the MEDLINE database of the English-language medical literature published from January 1990 to January 1998. We used combinations of the following key words to identify all original, peer-reviewed, full-length articles in which FDG PET and/or CT had been evaluated for the demonstration of mediastinal nodal metastases from NSCLC in humans: (computed tomography or CT or positron emission tomography or PET) and (mediastinal or intrathoracic or thoracic) and (lymph nodes or metastases or staging) and (non–small cell lung cancer or bronchogenic carcinoma) and (sensitivity and specificity). Bibliographies of retrieved articles and recent journals were searched independently and checked for additional studies. Early reports of data later published in full and abstracts were excluded. No attempt was made to include unpublished data.

Study Selection
Two of the authors (B.A.D., J.O.A.) independently reviewed the articles to determine eligibility for detailed analysis, with disagreements resolved by means of repeat review and discussion. Articles selected for inclusion and analysis met the following criteria: (a) evaluation of the diagnostic performance of FDG PET and/or CT for the detection of mediastinal nodal metastases from NSCLC, (b) comparison of imaging results with an objective diagnostic standard (ie, mediastinal nodal status established with results from histologic samples obtained at mediastinoscopy, thoracotomy, and/or autopsy), (c) reporting of results in sufficient detail to allow reconstruction of contingency tables of the raw data (ie, true-positive, true-negative, false-positive, and false-negative results), and (d) use of established diagnostic criteria for abnormal test results (eg, at CT, abnormal lymph node >= 10 mm in short-axis diameter; at PET, abnormal lymph node uptake exceeding that of mediastinal blood pool).

Data Extraction and Assessment of Methodological Quality
Two authors (B.A.D., J.O.A.) abstracted the following information from the eligible articles in a nonblinded fashion: author names; journal name; year of publication; number of patients; mode of analysis (patients or nodal stations); and true-positive, true-negative, false-positive, and false-negative rates for the presence of nodal metastases. We independently assessed the quality of each study according to the following prospectively developed criteria modified from well-accepted methodological standards for the evaluation of quality in diagnostic test research (25–30), with disagreements resolved by means of discussion and consensus.

Description and quality of imaging procedure.—This standard required that the imaging protocol was adequately described and conformed to accepted standards for technical quality. For PET, this was fulfilled if (a) the type of scanner was third generation or later, (b) patients fasted at least 4 hours before scanning, (c) the dose of FDG was mentioned, and (d) transmission scanning with attenuation correction, emission imaging protocol, reconstruction algorithm, and criteria for interpretation were described in full. An adequate CT examination required (a) use of a third- or fourth-generation scanner, (b) section scanning time of 2 seconds or less, (c) maximum section thickness and interval of 10 mm, (d) scanning area included from above the apices through the adrenal glands, and (e) full description of criteria for interpretation.

Technical quality of reference test.—Technically adequate reference testing required nodal tissue sampling with fine-needle aspiration biopsy or biopsy at mediastinoscopy, thoracotomy, and/or autopsy.

Uniform application of reference test.—The purpose of this standard was to help prevent verification bias. The standard was met if verification was obtained by means of reference test(s), regardless of imaging results.

Independence of interpretation.—This standard refers to blinding of interpretations of the results of index tests and reference standards. This criterion helped prevent review bias and required a statement about independence or blinding in interpretation of the results of both the imaging test(s) and the reference test.

Clinical description and spectrum composition.—Description of the study population included at least three of the following descriptors: age distribution; sex distribution; summary of symptoms at presentation, disease stage, or both; and eligibility criteria for study subjects. Ability to generalize results was determined by means of adequacy of the spectrum composition.

Cohort assembly.—Fulfillment of this standard required prospective enrollment of patients.

Sample size.—This standard refers to the number of cases included in the study. This standard was met if the population with disease and the population without disease both had more than 35 subjects. A sample size of 35 is the minimum for which the lower bound of the 95% CI for a sensitivity or specificity of 1.0 would exceed 0.9.

Adequate reporting of results.—This required both summary and subgroup indexes of accuracy, with precision estimates (such as CIs) and a summary measure of observer variability.

Data Analyses
Diagnostic performance indexes (sensitivity, specificity, accuracy, and predictive values) were recalculated for each report from the reconstructed contingency tables of true-positive, true-negative, false-positive, and false-negative results. The pooling of sensitivity and specificity, which has traditionally been used in the meta-analysis of diagnostic test data, ignores the fact that both performance indexes are dependent on the cutoff value used to define a positive test result; a stricter cutoff value will increase the specificity at the expense of the sensitivity. Thus, test performance was calculated by using summary receiver operating characteristic (ROC) curve analysis to distinguish variations in decision thresholds from actual differences in accuracy.

We used the logistic transform method of Littenberg and Moses, the properties and details of which have been described elsewhere (31,32). In brief, construction of a summary ROC curve involves calculation of the sum and the difference of the logit transforms of the true-positive and false-positive rates for each study. Once the sum S and difference D have been calculated, D becomes the dependent variable, and S becomes the independent variable in an ordinary least-squares regression. The slope of the resultant regression line indicates the departure from symmetry of the summary ROC curve, and the intercept is correlated with overall diagnostic accuracy. D is the log odds ratio from the respective two-by-two table and is a measure of accuracy, whereas S corresponds to the leniency of the positivity criterion. The final step involves conversion of the regression line back from the transformed space (S, D) to a summary ROC curve in the original space (false-positive rate, true-positive rate). As is the case with conventional ROC curves, a summary ROC curve closer to the upper left-hand corner of the graph indicates better overall diagnostic performance of the technology summarized.

Significant differences between summary ROC curves with slopes between -0.5 and +0.5 were calculated by using the Student t test to analyze differences between the intercepts of the regression lines corresponding to the summary ROC curves. The mean difference value was used as a basic summary statistical measure of test performance. The false-positive rate was restricted to the range 0.04–0.60, and the true-positive rate was restricted to that actually reported from the eligible studies.

It was predetermined at the time of study design to perform subgroup analyses of CT versus FDG PET by using the following variables: (a) type of study (prospective vs retrospective), (b) method of subject analysis (patient vs nodal station), (c) sample size (<=35 patients vs >35 patients), (d) publication year or period (during or before 1995 vs after 1995), (e) geographic origin of study (North America vs other origin), (f) clinical context of PET imaging (PET substituted for CT vs PET complementary to CT).


   RESULTS
TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 References
 
Descriptive and Qualitative Analysis
In our literature search, we retrieved 29 peer-reviewed, English-language articles eligible for detailed analysis on the basis of the prospective selection criteria described earlier. The characteristics of the eligible studies are shown in Tables 1–3. Fourteen studies were comparative (both FDG PET and CT were used in the same patients in each primary study), and the other 15 involved CT only. Forty percent of all reports and 57% of PET studies were from North American centers. All eligible publications were case series with internal control patients (ie, those with benign nodes) as a comparison group.


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  		TABLE 1. Characteristics of Eligible Studies
 

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  		TABLE 2. Performance Data from Eligible CT Studies
 

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  		TABLE 3. Performance Data From Eligible FDG PET Studies
 
None of the studies satisfied all of our prospectively determined criteria for methodological quality. The results of our quality assessments are shown in Table 4. The reported mean age was 21 years (range, 57–67 years). Age range alone was reported in one study, and median age (rather than mean age) was reported in another. There were no data on age in five studies. The reported proportion of men was 55%–87% (13%–45% women), with no information on sex distribution in six studies. All studies used acceptable reference tests and applied them in all patients regardless of imaging results. Ten studies satisfied the criterion for sample size, all of which were studies with CT only. Although all reports provided summary sensitivity and specificity data, only two provided information on test accuracy precision, one provided information on interobserver variability, and three provided accuracy data for subgroups of patients. Ninety percent of all studies (93% of PET studies) provided an adequate description of patients. Seventy percent of all studies (71% of PET studies) were prospective.


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  		TABLE 4. Number of Studies Meeting Specific Methodological Standards
 
Quantitative Analysis
The mean sensitivity and specificity of FDG PET were 0.79 (range, 0.62–0.97; 95% CI, ±0.03) and 0.91 (range,0.79–0.99; 95% CI, ±0.02). For CT, the mean sensitivity and specificity were 0.60 (range, 0.25–0.89; 95% CI, ±0.02) and 0.77 (range, 0.44–0.95; 95% CI, ±0.02), respectively. The overall diagnostic accuracy and predictive values are shown in Table 5. These parameters all demonstrated a superiority of FDG PET over CT. The summary ROC curves for both FDG PET and CT are shown in the Figure. The results of our analysis indicated that the slopes of the fitted regression lines for both CT and PET did not differ significantly from 0, which indicated symmetry and a justification for the use of the log odds ratio as a summary statistical measure for comparisons of test performance. The log odds ratios (± standard error) were 3.77 ± 0.51 and 1.79 ± 0.15 for FDG PET and CT, respectively, which indicated that PET was significantly more accurate than CT (P < .001).


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  		TABLE 5. Summary Point Estimates of Accuracy and Predictive Values
 


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  		Figure 1. Summary ROC curves obtained from regression analyses. The comparisons of FDG PET and CT were based on all eligible studies (A), studies with a sample size of more than 35 patients (B), prospective studies (C), and substitutive studies (D) (see text). The y axis represents the true-positive rate (TPR), or sensitivity (the proportion of patients with mediastinal nodal involvement correctly identified on the basis of test results), and the x axis represents the false-positive rate (FPR), or 1 - specificity (the proportion of patients without nodal involvement but falsely classified as having nodal disease). The upper left-hand corner (false-positive rate of 0, true-positive rate of 1) indicates perfect discrimination between patients with and those without nodal metastases. The curves for the overall (A) and subgroup (B-D) analyses indicate that FDG PET is superior to CT for mediastinal staging of NSCLC. In qualitative terms, all summary ROC curves for PET are closer to the upper left-hand corner than are those for CT; in quantitative terms, differences in log odds ratios were significant (P < .001).

 
We were able to perform "statistically meaningful" subgroup analyses (the number of studies needed for analysis, chosen arbitrarily, was more than five for both groups and/or at least 10 in one group) by using the summary ROC curves for studies with more than 35 patients, for prospective studies, and for substitutive studies (ie, those in which PET results were interpreted independently of CT results). Results are shown in the Figure and in Table 6. The results of these comparisons, which were based visually on the summary ROC curves and quantitatively on the mean log odds ratios, helped confirm the findings of the overall assessment; namely, that FDG PET was superior to CT. Other variables could not be used because of the small numbers of studies within the groups.


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  		TABLE 6. Subgroup Comparisons
 

   DISCUSSION
TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
References
 
We applied the statistical technique of meta-analysis to the comparative assessment of the accuracy of CT and FDG PET in the evaluation of mediastinal lymph nodes in patients with NSCLC. We used this approach because primary studies in which CT and/or FDG PET were used varied considerably in terms of case mix, study design, and the statistical analyses used, and the authors of such studies reported data based on relatively small sample sizes. A meta-analysis provides advantages, such as an increase in statistical power, the ability to assess sources of heterogeneity when there is no consistency of outcomes across studies, and a rational basis for clinical decision making on the basis of the aggregate of pertinent knowledge rather than on the basis of results of a single study or of personal experience.

The systematic evaluation of diagnostic tests before they enter widespread use may help improve the quality of diagnostic test information, eliminate poor or useless tests before they are widely applied, reduce the costs of health care, and improve the care of patients. The assessment of PET is important because, as an emerging clinical diagnostic tool with a potentially high capital investment, it is imperative that the diagnostic usefulness of PET be established prior to widespread diffusion into clinical practice.

The comparison of PET with CT is justified by the fact that the latter, which currently is the noninvasive test of choice, has substantial limitations. For example, it is not possible to reliably differentiate malignant mediastinal nodes from benign nodes on the basis of size alone, and there is a high frequency of normal-sized N2 nodes in patients with an operable stage of lung cancer.

By using pooled point estimates of diagnostic performance and summary ROC curves derived from the available published evidence, we showed that FDG PET was significantly more accurate than CT for help in detection of mediastinal nodal metastases in patients with NSCLC. All differences in diagnostic performances were notably significant, with P values of less than .001. It is important to note that the superiority of FDG PET over CT was maintained across all subgroup analyses. The lower false-positive rate means that fewer patients will be denied the opportunity to undergo curative resection, and the high sensitivity of FDG PET implies that PET will help reduce the number of unnecessary thoracotomies, as compared with the number that would be performed on the basis of CT findings. The log odds ratios show that PET findings were much better for help in discriminating between benign and metastatic lymph node enlargement.

Traditionally, simple measures of effectiveness, such as the pooled sensitivity and the specificity, have been used in meta-analyses of diagnostic tests. These measures, although widely recognized and easy to understand, are subject to definitional arbitrariness, and positivity thresholds commonly differ across studies. The marked variability in sensitivity and specificity, especially for CT, illustrates why summary ROC curve analysis may offer a better comparison between alternative diagnostic tests (31,32).

In our critical analyses of the eligible primary studies, we detected important limitations in methodological quality that potentially introduced bias and weakened estimates of diagnostic performance. Whereas appropriate reference tests were applied uniformly in all patients across studies, only 34% of studies had a sample size of 35 or more patients, the minimum required for the lower bound of the 95% CI to exceed 0.90 for a sensitivity or specificity of 1.0. Because of the small sample sizes, especially in the PET studies, CIs were wide. However, there was no overlap of CIs of the summary log odds ratios for FDG PET and CT studies.

Other limitations were related to the poor reporting of test results, the methods of cohort assembly, and the independence of interpretation. Although the selected reports provided estimates of sensitivity and accuracy, only three reports provided such measures for subgroups, and only one provided a measure of interobserver variability. For successful application of either test in clinical practice, separate indexes of accuracy are needed for pertinent individual subgroups within the spectrum of patients evaluated. Assessment of reproducibility (interobserver variability) is critical, especially for these imaging techniques, which often require interpretation of results tempered with subjective judgements (28).

Apart from the limitations associated with the primary studies are those common to meta-analysis, such as publication bias, selection bias, and blinded selection of articles (50–53). Publication bias refers to the fact that studies with statistically significant results are more likely to be published than are those with negative results (52,53). Because meta-analyses such as ours are based on published reports, the potential for underrepresentation of negative studies in the literature is a major concern (53). However, the wisdom of the inclusion of unpublished data has been contested (54). Unpublished studies have not undergone formal peer review, and the fact that the study was not submitted for publication raises questions about the quality of the work. Although there are statistical methods for correcting for publication bias in meta-analysis of treatment trials (55,56), no validated procedures exist for meta-analysis of diagnostic test data.

Despite the retrospective nature and limitations of meta-analysis and a lack of methodological rigor in the primary studies, we believe our results provide the best picture currently available to inform clinicians, patients, and policy makers about the accuracy of PET relative to that of CT. This is because the expense, practical difficulties, and entrenchment of CT in clinical practice make it unlikely that a methodologically rigorous comparison of CT and PET, with a sample size sufficient to provide more precise data, will be performed.

We conclude from the results of our meta-analytic evaluation that FDG PET is significantly more accurate than CT for characterization of mediastinal lymph nodes in patients with NSCLC. This accuracy is independent of our selected subgroup analyses and method of data analysis. In the future, however, investigators must attempt to improve study design, especially in the areas of cohort assembly, blinded interpretation of both imaging and reference test results, and presentation of results.


   Footnotes
 
Abbreviations: FDG = 2-[fluorine 18]fluoro-2-deoxy-D-glucose NSCLC = non–small cell lung cancer ROC = receiver operating characteristic

Author contributions: Guarantor of integrity of entire study, R.L.W.; study concepts and design, B.A.D., S.S.S., R.L.W.; definition of intellectual content, B.A.D., S.S.S., R.L.W.; literature research, B.A.D., J.O.A., R.L.W.; data acquisition and analysis, B.A.D., J.O.A.; statistical analysis, B.A.D., S.S.S.; manuscript preparation, B.A.D., S.S.S.; manuscript editing, B.A.D., S.S.S., R.L.W.; manuscript review, all authors.


   References
TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 

  1. Landis SH, Murray T, Bolden S, Wingo PA. Cancer statistics, 1998. CA Cancer J Clin 1998; 48:6-29.[Abstract]
  2. Mountain CF. Value of the new TNM staging system for lung cancer. Chest 1989; 96(suppl 1):47S-49S.[Free Full Text]
  3. Kadri MA, Dussek JE. Survival and prognosis following resection of primary non small cell bronchogenic carcinoma. Eur J Cardiothorac Surg 1991; 5:132-136.[Abstract]
  4. Deslauriers J, Ginsberg RJ, Piantadosi S, Fournier B. Prospective assessment of 30-day operative morbidity for surgical resections in lung cancer. Chest 1994; 106(suppl 6):329S-330S.[Medline]
  5. McKenna RJ, Jr, Libshitz HI, Mountain CE, McMurtrey MJ. Roentgenographic evaluation of mediastinal nodes for preoperative assessment in lung cancer. Chest 1985; 88:206-210.[Abstract/Free Full Text]
  6. Arita T, Kuramitsu T, Kawamura M, et al. Bronchogenic carcinoma: incidence of metastases to normal sized lymph nodes. Thorax 1995; 50:1267-1269.[Abstract]
  7. Arita T, Matsumoto T, Kuramitsu T, et al. Is it possible to differentiate malignant mediastinal nodes from benign nodes by size? reevaluation by CT, transesophageal echocardiography, and nodal specimen. Chest 1996; 110:1004-1008.[Abstract/Free Full Text]
  8. Dales RE, Stark RM, Raman S. Computed tomography to stage lung cancer: approaching a controversy using meta-analysis. Am Rev Respir Dis 1990; 141:1096-1101.[Medline]
  9. Conti PS, Lilien DL, Hawley K, Keppler J, Grafton ST, Bading JR. PET and [18F]-FDG in oncology: a clinical update. Nucl Med Biol 1996; 23:717-735.[Medline]
  10. Rigo P, Paulus P, Kaschten BJ, et al. Oncological applications of positron emission tomography with fluorine-18 fluorodeoxyglucose. Eur J Nucl Med 1996; 23:1641-1674.[Medline]
  11. Wahl RL, Quint LE, Greenough RL, Meyer CR, White RI, Orringer MB. Staging of mediastinal non–small cell lung cancer with FDG PET, CT, and fusion images: preliminary prospective evaluation. Radiology 1994; 191:371-377.[Abstract/Free Full Text]
  12. Bury 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; 23:204-206.[Medline]
  13. Chin R, Jr, Ward R, Keyes JW, et al. Mediastinal staging of non-small-cell lung cancer with positron emission tomography. Am J Respir Crit Care Med 1995; 152:2090-2096.[Abstract]
  14. Guhlmann A, Storck M, Kotzerke J, Moog F, Sunder-Plassmann L, Reske SN. Lymph node staging in non-small cell lung cancer: evaluation by [18F]FDG positron emission tomography (PET). Thorax 1997; 52:438-441.[Abstract]
  15. Hagberg RC, Segall GM, Stark P, Burdon TA, Pompili MF. Characterization of pulmonary nodules and mediastinal staging of bronchogenic carcinoma with F-18 fluorodeoxyglucose positron emission tomography. Eur J Cardiothorac Surg 1997; 12:92-97.[Abstract]
  16. Higashi K, Nishikawa T, Seki H, et al. Comparison of fluorine-18-FDG PET and thallium-201 SPECT in evaluation of lung cancer. J Nucl Med 1998; 39:9-15.[Abstract/Free Full Text]
  17. Patz EF, Jr, Lowe VJ, Goodman PC, Herndon J. Thoracic nodal staging with PET imaging with 18FDG in patients with bronchogenic carcinoma. Chest 1995; 108:1617-1621.[Abstract/Free Full Text]
  18. Sasaki 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; 23:741-747.[Medline]
  19. Sazon DA, Santiago SM, Soo Hoo GW, et al. Fluorodeoxyglucose-positron emission tomography in the detection and staging of lung cancer. Am J Respir Crit Care Med 1996; 153:417-421.[Abstract]
  20. Scott WJ, Schwabe JL, Gupta NC, Dewan NA, Reeb SD, Sugimoto JT. Positron emission tomography of lung tumors and mediastinal lymph nodes using [18F]fluorodeoxyglucose: the members of the PET-Lung Tumor Study Group. Ann Thorac Surg 1994; 58:698-703.[Abstract]
  21. Scott WJ, Gobar LS, Terry JD, Dewan NA, Sunderland JJ. 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; 111:642-648.[Abstract/Free Full Text]
  22. Steinert HC, 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; 202:441-446.[Abstract/Free Full Text]
  23. Valk PE, Pounds TR, Hopkins DM, et al. Staging non-small cell lung cancer by whole-body positron emission tomographic imaging. Ann Thorac Surg 1995; 60:1573-1581.[Abstract/Free Full Text]
  24. Vansteenkiste JF, Stroobants SG, De Leyn PR, 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—Leuven Lung Cancer Group. Chest 1997; 112:1480-1486.[Abstract/Free Full Text]
  25. Mulrow CD, Linn WD, Gaul MK, Pugh JA. Assessing quality of a diagnostic test evaluation. J Gen Intern Med 1989; 4:288-295.[Medline]
  26. Owens DK, Holodniy M, Garber AM, 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; 124:803-815.[Abstract/Free Full Text]
  27. Owens DK, Holodniy M, McDonald TW, Scott J, Sonnad S. A meta-analytic evaluation of the polymerase chain reaction for the diagnosis of HIV infection in infants. JAMA 1996; 275:1342-1348.[Abstract]
  28. Reid MC, Lachs MS, Feinstein AR. Use of methodological standards in diagnostic test research: getting better but still not good. JAMA 1995; 274:645-651.[Abstract]
  29. Kent DL, Haynor DR, Larson EB, Deyo RA. Diagnosis of lumbar spinal stenosis in adults: a metaanalysis of the accuracy of CT, MR, and myelography. AJR 1992; 158:1135-1144.[Abstract/Free Full Text]
  30. Hoffman RM, Kent DL, Deyo RA. Diagnostic accuracy and clinical utility of thermography for lumbar radiculopathy: a meta-analysis. Spine 1991; 16:623-628.[Medline]
  31. Littenberg B, Moses LE. Estimating diagnostic accuracy from multiple conflicting reports: a new meta-analytic method. Med Decis Making 1993; 13:313-321.
  32. Moses LE, Shapiro D, Littenberg B. Combining independent studies of a diagnostic test into a summary ROC curve: data-analytic approaches and some additional considerations. Stat Med 1993; 12:1293-1316.[Medline]
  33. Georgian D, Rice TW, Mehta AC, Wiedemann HP, Stoller JK, O'Donovan PB. Intrathoracic lymph node evaluation by CT and MRI with histopathologic correlation in non-small cell bronchogenic carcinoma. Clin Imaging 1990; 14:35-40.[Medline]
  34. Ikezoe J, Kadowaki K, Morimoto S, et al. Mediastinal lymph node metastases from nonsmall cell bronchogenic carcinoma: reevaluation with CT. J Comput Assist Tomogr 1990; 14:340-344.[Medline]
  35. Ratto GB, Frola C, Cantoni S, Motta G. Improving clinical efficacy of computed tomographic scan in the preoperative assessment of patients with non-small cell lung cancer. J Thorac Cardiovasc Surg 1990; 99:416-425.[Abstract]
  36. McLoud TC, Bourgouin PM, Greenberg RW, et al. Bronchogenic carcinoma: analysis of staging in the mediastinum with CT by correlative lymph node mapping and sampling. Radiology 1992; 182:319-323.[Abstract/Free Full Text]
  37. Izbicki J, Thetter O, Karg O, et al. Accuracy of computed tomographic scan and surgical assessment for staging of bronchial carcinoma: a prospective study. J Thorac Cardiovasc Surg 1992; 104:413-420.[Abstract]
  38. Seely JM, Mayo JR, Miller RR, Müller NL. T1 lung cancer: prevalence of mediastinal nodal metastases and diagnostic accuracy of CT. Radiology 1993; 186:129-132.[Abstract/Free Full Text]
  39. Verhoeven GT, Kho GS, Ausema L, Krenning EP, Hilvering C. Planar cobalt-57 bleomycin scintigraphy compared with CT-scan in the diagnosis and staging of lung cancer. Neth J Med 1994; 44:116-121.[Medline]
  40. White PG, Adams H, Crane MD, Butchart KG. Preoperative staging of carcinoma of the bronchus: can computed tomographic scanning reliably identify stage III tumours?. Thorax 1994; 49:951-957.[Abstract]
  41. Yokoi K, Okuyama A, Mori K, et al. Mediastinal lymph node metastasis from lung cancer: evaluation with Tl-201 SPECT—comparison with CT. Radiology 1994; 192:813-817.[Abstract/Free Full Text]
  42. Dillemans B, Deneffe G, Verschakelen J, Decramer M. Value of computed tomography and mediastinoscopy in preoperative evaluation of mediastinal nodes in non-small cell lung cancer: a study of 569 patients. Eur J Cardiothorac Surg 1994; 8:37-42.[Abstract]
  43. Primack SL, Lee KS, Logan PM, Miller RR, Müller NL. Bronchogenic carcinoma: utility of CT in the evaluation of patients with suspected lesions. Radiology 1994; 193:795-800.[Abstract/Free Full Text]
  44. Aaby C, Kristensen S, Nielsen SM. Mediastinal staging of non-small-cell lung cancer: computed tomography and cervical mediastinoscopy. ORL J Otorhinolaryngol Relat Spec 1995; 57:279-285.[Medline]
  45. Sasaki 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; 23:741-747.
  46. Bury T, Paulus P, Dowlati A, et al. Staging of the mediastinum: value of positron emission tomography imaging in non-small cell lung cancer. Eur Respir J 1996; 9:2560-2564.[Abstract]
  47. Potepan P, Meroni E, Spagnoli I, et al. Non-small-cell lung cancer: detection of mediastinal lymph node metastases by endoscopic ultrasound and CT. Eur Radiol 1996; 6:19-24.[Medline]
  48. Buccheri G, Biggi A, Ferrigno D, et al. Anti-CEA immunoscintigraphy and computed tomographic scanning in the preoperative evaluation of mediastinal lymph nodes in lung cancer. Thorax 1996; 51:359-363.[Abstract]
  49. Gdeedo A, Van Schil P, Corthouts B, Van Mieghem F, Van Meerbeeck J, Van Marck E. Prospective evaluation of computed tomography and mediastinoscopy in mediastinal lymph node staging. Eur Respir J 1997; 10:1547-1551.[Abstract]
  50. Irwig L, Macaskill P, Glasziou P, Fahey M. Meta-analytic methods for diagnostic test accuracy. J Clin Epidemiol 1995; 48:119-130.[Medline]
  51. Bangert-Drowns RL. Some limiting factors in meta-analysis. NIDA Res Monogr 1997; 170:234-252.[Medline]
  52. Begg CB. Biases in the assessment of diagnostic tests. Stat Med 1987; 6:411-423.[Medline]
  53. Begg CB, Berlin JA. Publication bias and dissemination of clinical research. J Natl Cancer Inst 1989; 81:107-115.[Abstract/Free Full Text]
  54. Dickersin K, Berlin JA. Meta-analysis: state-of-the-science. Epidemiol Rev 1992; 14:154-176.[Free Full Text]
  55. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994; 50:1088-1101.[Medline]
  56. Vandenbroucke JP. Passive smoking and lung cancer: a publication bias?. Br Med J (Clin Res Ed) 1988; 296:391-392.



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