Journal of Thoracic Oncology:
Diagnostic Performance of Integrated Positron Emission Tomography/Computed Tomography for Mediastinal Lymph Node Staging in Non-small Cell Lung Cancer: A Bivariate Systematic Review and Meta-Analysis
Lv, Yan-Ling*; Yuan, Dong-Mei†; Wang, Ke‡; Miao, Xiao-Hui†; Qian, Qian§; Wei, Shu-Zhen∥; Zhu, Xi-Xu¶; Song, Yong PhD, MD†
*Department of Respiratory Medicine, Jinling Hospital, School of Medicine, Southern Medical University (Guangzhou), Nanjing, China; †Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; ‡Institute of Respiratory Diseases, First Affiliated Hospital, Guangxi Medical University, Nanning, China; §First Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, China; ∥Department of Respiratory Disease, Tengzhou Central People's Hospital, Tengzhou, China; and ¶Department of Radiotherapy Center, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
Disclosure: The authors declare no conflicts of interest.
Address for correspondence: Yong Song, PhD, MD, Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing 210002, China. E-mail: email@example.com
Introduction: Accurate clinical staging of mediastinal lymph nodes (MLNs) of patients with non-small cell lung cancer (NSCLC) is important in determining therapeutic options and prognoses. Integrated positron emission tomography and computed tomography (PET/CT) scanning is becoming widely used for MLN staging in patients with NSCLC. We performed a bivariate meta-analysis to determine the pooled sensitivity (SEN) and specificity (SPE) of this imaging modality.
Methods: The PubMed/MEDLINE, Embase, and SpringerLink databases were searched for articles related to PET/CT for MLN staging in patients with NSCLC. SEN and SPE were calculated for every study. Hierarchical summary receiver operating characteristic curves were used to summarize overall test performance and assess study quality. Potential between-study heterogeneity was explored by subgroup analyses.
Results: Fourteen of 330 initially identified reports were included in the meta-analysis. When we did not consider the unit of analysis, the pooled weighted SEN and SPE were 0.73 (95% confidence interval [CI]: 0.65–0.79) and 0.92 (95% CI: 0.88–0.94), respectively. In the patient-based data analysis, the pooled weighted SEN was 0.76 (95% CI: 0.65–0.84) and the pooled weighted SPE was 0.88 (95% CI: 0.82–0.92). In the MLN-based data analysis, the pooled SEN was 0.68 (95% CI: 0.56–0.78) and the pooled SPE was 0.95 (95% CI: 0.91–0.97).
Conclusions: Integrated PET/CT is a relatively accurate noninvasive imaging technique, with excellent specificity for MLN staging in patients with NSCLC. Nevertheless, current evidence suggests that we should not depend on the results of PET/CT completely for MLN staging in patients with NSCLC.
Lung cancer is the leading cause of cancer deaths globally.1 Non-small cell lung cancer (NSCLC) accounts for 80% of these cases and usually metastasizes first to hilar and mediastinal lymph nodes (MLNs). Accurate clinical staging of MLNs is crucial for selecting the optimum treatment. For example, in patients with known stage IIIA NSCLC, the addition of preoperative chemotherapy can dramatically increase survival compared with surgery alone.2 Moreover, the involvement of MLNs is a very important prognostic factor in patients with potentially resectable NSCLC. Therefore, there is a great need for a more accurate, minimally invasive, and reproducible diagnostic method for MLN staging.
Computed tomography (CT) has been widely used for clinical MLN staging in NSCLC patients, but its limitation is that it relies on the size of the MLN to differentiate benign from malignant. Gupta et al3 confirmed that functional imaging with positron emission tomography (PET) surpasses using anatomic criteria to screen for MLN metastases with CT. Several meta-analyses also found that fludeoxyglucose (FDG)-PET was more accurate than CT (median sensitivity [SEN] and specificity [SPE] were 61 and 79%) for MLN staging in NSCLC.4–6 Nevertheless, the poor spatial resolution of FDG-PET can lead to inaccuracies. Although mediastinoscopy remains the gold standard, the noninvasive imaging method of combining PET and CT (i.e., PET/CT) has become increasingly used for MLN staging in patients with NSCLC, integrating as it does the anatomic information of CT and the functional information of PET. Although there have been many studies that estimated the SEN and SPE of PET/CT for MLN imaging, most included only a small number of patients. The aim of our study was to perform a meta-analysis that would determine the pooled SEN and SPE of integrated PET/CT for MLN staging in patients with NSCLC.
MATERIALS AND METHODS
We searched the MEDLINE (PubMed), Embase, and SpringerLink databases with the terms “PET,” “MLN,” “lymph node,” and “NSCLC.” The last search was updated on December 18, 2010. Titles of research articles were screened for relevance according to predetermined inclusion criteria. Abstracts were screened if this information could not be inferred from the title. The reference lists of included studies and related reviews were also searched manually, and all references cited in relevant articles were scanned to identify all additional studies. The search period was December 1992 to December 2010. We included studies written in English and Chinese that were full articles, and excluded abstracts or meeting proceedings. Results were arbitrated by a second investigator (D-.M.Y.).
All the included studies examined FDG-PET/CT imaging for MLN staging in patients with NSCLC and included histological examination of lymph nodes by surgery or biopsy, used clear diagnostic criteria, provided sufficient data (true-positive [TP], false-positive [FP], true-negative [TN], and false-negative [FN]) to permit calculation of SEN and SPE, and used the English or Chinese language. We excluded studies that were not about integrated PET/CT and MLN staging, articles that were not about NSCLC, review articles, and studies of restaging after induction chemotherapy.
Data Extraction and Quality Assessment
From the studies finally selected, two authors (Y-.L.L. and D-.M.Y.) independently gleaned the following information: the study name (first author, year of publication), journal name, proportion of males, tumor histology, and retrospective or prospective set-up of the study. TP, FP, TN, and FN results were recorded. When authors reported on the same patient population in several publications, only the most recent or complete study was included in the analysis to avoid duplication of information. Any disagreements were subsequently resolved by discussion that included the fourth author (X-.H.M.).
We assessed the quality of different studies according to the modified QUADAS tool.7 The QUADAS checklist consists of 14 items, each of which was assessed as “yes,” “no,” or “unknown.” The item “Were the same clinical data available when test results were interpreted as would be available when the test is used in practice (clinical review bias)?” was removed from the standard QUADAS list, because the clinical factors such as gender, age, and clinical symptoms would not affect the interpretation of the positive result of PET/CT for MLN staging. For each item, the two researchers (Y-.L.L. and D-.M.Y.) independently assessed whether it was satisfied (yes, no, or unknown). The responses “no” and “unclear” showed that the quality criterion was not met. Discrepancies were resolved by consensus. The total quality score was expressed as a percentage of the maximum score of 13.
For each study, we conducted 2 × 2 contingency tables of TP, TN, FP, and FN results and calculated SEN, SPE, and diagnostic OR (DOR) according to the formulas: SEN = TP/(TP + FN); SPE = TN/(TN + FP); and DOR = (TN × TP)/(FP × FN).8 SEN and SPE at a 95% confidence interval (CI) were then pooled using a bivariate regression approach.9 By using the pooled SEN and SPE, we also calculated positive likelihood ratios (PLRs) and negative likelihood ratios (NLRs). We constructed hierarchical summary receiver operating characteristic (SROC) curves to assess the interaction between SEN and SPE. The areas under the ROC curves (AUCs) were used to analyze the diagnostic precision of PET/CT for MLN staging in NSCLC.
We assessed the statistical significance of heterogeneity between different studies using the inconsistency index (I2).10 An I2 value greater than 50% was taken to indicate significant heterogeneity. When between-study heterogeneity was detected, we explored reasonable causes by subgroup analysis. Covariates requiring that at least 80% of studies reported on a particular item were analyzed. These included data collection (prospective or retrospective), the unit of analysis (patient or MLN), diagnostic criteria (quantitative or qualitative), language (English or Chinese), selection criteria (yes or no), and index test execution (yes or no).
An estimation of the potential publication bias was performed by using Deeks' funnel plots.11 A probability (p) value <0.1 was considered representative of statistically significant publication bias. All the statistical tests used in our meta-analysis were performed with STATA version 10 (STATA; College Station, TX) using the “midas” program.12
Using the keywords, the search of PubMed/MEDLINE found 330 potentially relevant articles published before December 18, 2010. Reviewing titles and abstracts from these articles resulted in 45 that were promising, of which 14 were finally included in our meta-analysis.13–26 Screening the references of these articles did not provide us with additional articles. Of the 45 articles, the main reasons for exclusion were they were not about MLN staging (13); there were insufficient data to calculate SEN and SPE (11)27–37; they contained duplicated data (3)38–40; and several were excluded because they were about restaging the mediastinum after neoadjuvant therapy (4).41–44 Finally, our systematic review covered 14 research articles that included 2550 patients. Characteristics of the included studies are presented in Table 1.
Study Descriptions and Quality Assessment
The characteristics of the included studies are presented in Table 1. The total number of patients was 2550, ranging from 46 to 674 patients per study. All patients underwent FDG PET/CT imaging. Histology was confirmed by mediastinoscopy, pulmonary resection, or both. Five studies reported results by using MLN as the unit of analysis, three studies used the patient as the unit of analysis, and the results of the remaining studies were reported by using both the patient and MLN as the unit of analysis.
Thirteen methodological quality items were assessed for each of the 20 included research articles. Quality assessment is presented as a bar graph according to the modified QUADAS criteria (Figure 1). The total methodological quality score, expressed as a percentage of the maximum score, ranged from 54 to 85% (median, 69%).
Analysis of the Patient-Based Data and SEN, SPE, PLR, NLR, DOR, and SROC Curves
We enrolled 14 research articles in which 11 studies used the patient as the unit of analysis. Four studies had standardized uptake value (SUV) cutoffs of 2.5, five considered MLNs malignant if they exhibited a focally increased SUV higher than the normal background activity as determined by qualitative analysis, and the remaining two studies had SUV cutoffs of 3 and 5.2, respectively. In the patient-based data analysis, the SEN ranged from 0.40 to 0.92, and the pooled weighted SEN was 0.76 (95% CI: 0.65–0.84), whereas the SPE ranged from 0.60 to 0.96, and the pooled SPE was 0.88 (95% CI: 0.82–0.92; Figure 2A). The PLR and NLR were 6.1 (95% CI: 4.3–8.7) and 0.28 (95% CI: 0.19–0.40), respectively. The DOR was 22 (95% CI: 13–38). I2 values of all measures were greater than 50%, indicating significant heterogeneity between studies.
Hierarchical SROC curves are shown in Figure 3. The SROC curve assesses the interaction between SEN and SPE. The AUC was 0.90 (95% CI: 0.87–0.92; Figure 3A), showing that PET/CT has an overall high diagnostic performance.
Analysis as MLN-Based Data
Nine studies used the MLN as the unit of analysis. Four studies had an SUV cutoff of 2.5, and four studies were determined by qualitative analysis, and the SUV cutoff of the remaining one study was 5.2. In the MLN-based data analysis, the pooled SEN, SPE, PLR, NLR, and DOR were 0.65 (95% CI: 0.62–0.68), 0.95 (95% CI: 0.94–0.95; Figure 2B), 11.52 (95% CI: 7.55–17.59), 0.34 (95% CI: 0.24–0.48), and 38 (95% CI: 31–48), respectively. Hierarchical SROC curves are shown in Figure 3B. The AUC was 0.92 (95% CI: 0.89–0.94). There was also significant heterogeneity. When we did not consider the unit of analysis, the pooled weighted SEN, SPE, and AUC were 0.73 (95% CI: 0.65–0.79), 0.92 (95% CI: 0.88–0.94), and 0.90 (95% CI: 0.87–0.93), respectively. Significant heterogeneity was present.
We found significant heterogeneity in the pooled analysis. This result was not unexpected because the studies adopted different SUV cutoffs as diagnostic criteria. In our meta-analysis, we included 14 articles in which 1 article had an SUV cutoff of 3, 1 reported 5.2, 7 articles reported 2.5, and the remaining 5 deemed MLNs malignant if they exhibited focally increased SUV higher than the normal background activity as determined by qualitative analysis. Based on a patient analysis with 2.5 as the SUV cutoff value, the SEN was higher than that in the qualitative analysis and had an impact on statistical significance (p < 0.05). The SPE was lower, with no significant difference (p = 0.26). Based on the MLN analysis, we obtained the same results but the SEN and SPE between two groups did not have an impact on statistical significance (p = 0.28 and 0.35, respectively). English and SUV cutoff significantly affected SEN but not SPE. Some covariates such as data collection had a significant impact on SPE but not on SEN (Figure 4).
We assessed the publication bias in the literature by performing Deeks' funnel plot. The funnel plot for the 14 reports, including 20 studies, revealed evidence of publication bias (p = 0.02). Based on the patient analysis, the results also indicated a potential for publication bias (p = 0.07; Figure 5A), but based on the MLN analysis (p = 0.42), there was no publication bias (Figure 5B).
Our results in the present meta-analysis indicate excellent overall test performance, as assessed by the AUC. In addition, integrated PET/CT has relatively high SPE (0.88 based on patient and 0.95 based on MLN) for MLN staging in patients with NSCLC. The overall SEN was 0.76 based on patient and 0.65 based on MLN. These data suggest that integrated PET/CT is likely to be helpful in MLN staging. Nevertheless, the data for PLRs and NLRs suggest that a positive result for integrated PET/CT does not signify the absence of MLN, and patients with negative results are likely to have MLN metastases.
Integrated PET/CT directly links PET data on metabolic changes with highly detailed anatomic CT information, thereby creating a single image in the same setting that is not merely additive but synergistic. Thus, it can detect lesions initially not seen on CT or PET alone and enable more precise location of lesions. Recently, integrated PET/CT is becoming widely used for MLN staging in patients with NSCLC.
To the best of our knowledge, this study is the first meta-analysis of the diagnostic performance of integrated PET/CT for MLN staging in NSCLC patients. In our study, we subdivided the included studies into a per-patient group and per-MLN group. We pooled 14 published studies including a total of 2550 patients with NSCLC, to yield summary statistics, which indicate that integrated PET/CT is a relatively accurate noninvasive imaging technique for MLN staging in patients with NSCLC. In the patient-based data analysis, the pooled-weighted SEN and SPE were 0.76 and 0.88, respectively. In the MLN-based data analysis, SEN and SPE were 0.65 and 0.95, respectively. We found that studies using MLN as the unit of analysis may overestimate diagnostic accuracy, especially SPE. The unit of analysis clinically should be the patient and not the MLN. We think that if a patient with NSCLC has one mediastinal node metastasis, then the patient is more likely to have other lymph node metastases as well. In addition, if there is a positive MLN in a patient, then the stage that the patient belongs to is at least IIIA, and treatment decisions depend on the positive presence of MLN metastasis rather than the involved number of nodes. Therefore, we emphasize the results in which the patient was used as the unit of analysis.
The SROC curve and its AUC present a global summary of test performance and display the relationship between SEN and SPE across studies, recognizing that they may have used different thresholds. Because the bivariate approach estimates the strength and the shape of the correlation between SEN and SPE, we can draw a 95% confidence ellipse and a 95% prediction ellipse. The AUC was 0.90 (95% CI: 0.87–0.92), indicating a relatively high level of overall accuracy.
The DOR of a test obtained with different combinations of SEN and SPE may be used as a single summary measure and is the ratio of the odds of positivity in disease relative to the odds of positivity in the nondiseased. The value of a DOR ranges from 0 to infinity, and the higher it is, the better it discriminates test performance. A value of 1 indicates that a test does not discriminate between patients with the disorder and those without it. Values lower than 1 point to more FN tests among the diseased. In our meta-analysis, we have found that the mean DOR was 22, indicating that integrated PET/CT seemed to be helpful for MLN staging in NSCLC. LRs are more clinically meaningful than SENs or SPEs and indicate by how much a given test would raise or lower the probability of having disease. To have the greatest diagnostic value, an LR of >10 or <0.1 would be required for ruling in and ruling out diagnoses in most circumstances, respectively.45 If the PLR is >10 and the NLR >0.1, then the test can only rule in the disease. If the PLR is <10 and the NLR <0.1, then the test can rule out the disease. If the PLR is <10 and the NLR >0.1, then the test can neither rule in nor rule out the disease. In our meta-analysis, the value of PLR was 6.10 (i.e., <10), showing that it was not high enough for the clinical purpose. However, NLR was 0.28 (i.e., >0.1), which is not low enough to rule out the disease.
Exploring the reasons for heterogeneity rather than the computation of summary measures is an important goal of meta-analysis. It is important to note that PET/CT positivity criteria varied in the different studies. Some institutions qualitatively analyzed their data and others quantitatively. Subgroup analysis revealed that, at a maximum SUV (maxSUV) of 2.5, the SEN was significantly higher in patient-based analyses than in qualitative (p < 0.05). Up to now, the ideal cutoff of the maxSUV for distinguishing malignant MLN from benign has not been determined. Most studies have defined a maxSUV of 2.5 as the upper limit of normal lymph nodes. Nevertheless, Bryant et al26 reported that when the maxSUV was 5.3, the SEN, SPE, and accuracy for detecting MLN metastasis were higher, when compared with the 2.5. Nevertheless, until more evidence is available that supports a higher maxSUVcutoff, 2.5 should be used. In addition to providing diagnostic information, a recent meta-analysis demonstrated that the maxSUV provided prognostic information as well.46
Our meta-analysis included 2550 patients with NSCLC, and one study was of 674 cases.24 That study showed that integrated PET/CT provided high SPE and low SEN for MLN staging of NSCLC. On a per-person basis, the SEN and SPE were 0.61 and 0.96, respectively, whereas on a per-MLN basis, they were 0.46 and 0.98, respectively. Because the study included so many patients, its inclusion would have skewed the overall results of our meta-analysis by its relative weight, and we therefore ruled it out. In the patient-based analysis, the final polled SEN and SPE were 0.80 and 0.86, and in the MLN-based data analysis, the polled SEN and SPE were 0.73 and 0.94.
Publication bias47 is a major concern in all forms of meta-analysis, because studies reporting positive or significant results tend to be published, whereas those whose results are nonsignificant or negative are often rejected or not even submitted. In addition, our review was restricted to articles published in English or Chinese, because other languages such as Japanese or French would not be accessible to our readers—and this was also likely to introduce bias. Another source of bias is the use of the same group of patients in different publications. It may be difficult to avoid including the same patients more than once in a meta-analysis, although studies clearly based on the results from the same patient populations were excluded; we used only the most recent and complete one.
Our meta-analysis had several limitations. First, this review may suffer from selection bias, because most studies included patients who received only surgical mediastinal nodal dissection or mediastinoscopic nodal biopsy. Therefore, many early-stage NSCLC patients were included, which may have contributed to a reduction in SEN. Second, the dissections of some specific nodal stations were guided by preoperative CT or integrated PET/CT findings, which might have induced a verification bias. In addition, the patients received a variety of procedures ranging from mediastinoscopy to thoracotomy and video-assisted thoracoscopic surgery. This may be another source of verification bias. Finally, several studies have supported the superiority of integrated PET/CT over standalone PET and CT in nodal staging for patients with NSCLC,48–50 but there are only a few studies that compare integrated PET/CT with other imaging methods for MLN staging. Therefore, we did not compare PET/CT with these other methods. It would be important for future studies to directly compare the results of CT, standalone PET, integrated PET/CT, EBUS-TBNA, and mediastinoscopy and to better define where integrated PET/CT might fit into the diagnostic algorithm.
Despite some limitations, our meta-analysis indicates that integrated PET/CT demonstrates a relatively accurate imaging technique, with excellent specificity for MLN staging in patients with NSCLC, and therefore provides great help in completing optimal therapeutic strategies. Nevertheless, current evidence suggests that we should not depend on the results of PET/CT completely to confirm the absence or presence of MLN metastases. On the basis of our data, we think biopsies of all suspicious MLNs should be done, and a positive result of PET/CT should not be equated with malignancy until getting the tissue confirmation results.
1. Jemal A, Siegel R, Xu J, et al. Cancer statistics, 2010. CA Cancer J Clin
2. Rosell R, Gomez-Codina J, Camps C, et al. A randomized trial comparing preoperative chemotherapy plus surgery with surgery alone in patients with non-small-cell lung cancer. N Engl J Med
3. Gupta NC, Graeber GM, Bishop HA. Comparative efficacy of positron emission tomography with fluorodeoxyglucose in evaluation of small (<1 cm), intermediate (1 to 3 cm), and large (>3 cm) lymph node lesions. Chest
4. Birim O, Kappetein AP, Stijnen T, et al. Meta-analysis of positron emission tomographic and computed tomographic imaging in detecting mediastinal lymph node metastases in nonsmall cell lung cancer. Ann Thorac Surg
5. Gould MK, Kuschner WG, Rydzak CE, et al. Test performance of positron emission tomography and computed tomography for mediastinal staging in patients with non-small-cell lung cancer: a meta-analysis. Ann Intern Med
6. Dwamena BA, Sonnad SS, Angobaldo JO, et al. Metastases from non-small cell lung cancer: mediastinal staging in the 1990s—meta-analytic comparison of PET and CT. Radiology
7. Whiting PF, Weswood ME, Rutjes AW, et al. Evaluation of QUADAS, a tool for the quality assessment of diagnostic accuracy studies. BMC Med Res Methodol
8. Will O, Purkayastha S, Chan C, et al. Diagnostic precision of nanoparticle-enhanced MRI for lymph-node metastases: a meta-analysis. Lancet Oncol
9. Reitsma JB, Glas AS, Rutjes AW, et al. Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews. J Clin Epidemiol
10. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med
11. Deeks JJ, Macaskill P, Irwig L. The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. J Clin Epidemiol
12. Dwamena, Ben A. Midas: A Program for Meta-Analytical Integration of Diagnostic Accuracy Studies in Stata. Ann Arbor, MI: Division of Nuclear Medicine, Department of Radiology, University of Michigan Medical School, 2007.
13. Tasci E, Tezel C, Orki A, et al. The role of integrated positron emission tomography and computed tomography in the assessment of nodal spread in cases with non-small cell lung cancer. Interact Cardiovasc Thorac Surg
14. Li XD, Yin JL, Liu WK, et al. Value of positron emission tomography-computed tomography in the diagnosis of mediastinal lymph node metastasis of non-small cell lung cancer. Nan Fang Yi Ke Da Xue Xue Bao
15. Sit AK, Sihoe AD, Suen WS, et al. Positron-emission tomography for lung cancer in a tuberculosis-endemic region. Asian Cardiovasc Thorac Ann
16. Hwangbo B, Kim SK, Lee HS, et al. Application of endobronchial ultrasound-guided transbronchial needle aspiration following integrated PET/CT in mediastinal staging of potentially operable non-small cell lung cancer. Chest
17. Bille A, Pelosi E, Skanjeti A, et al. Preoperative intrathoracic lymph node staging in patients with non-small-cell lung cancer: accuracy of integrated positron emission tomography and computed tomography. Eur J Cardiothorac Surg
18. Perigaud C, Bridji B, Roussel JC, et al. Prospective preoperative mediastinal lymph node staging by integrated positron emission tomography-computerised tomography in patients with non-small-cell lung cancer. Eur J Cardiothorac Surg
19. Sanli M, Isik AF, Zincirkeser S, et al. Reliability of positron emission tomography-computed tomography in identification of mediastinal lymph node status in patients with non-small cell lung cancer. J Thorac Cardiovasc Surg
20. Lee JW, Kim BS, Lee DS, et al. 18F-FDG PET/CT in mediastinal lymph node staging of non-small-cell lung cancer in a tuberculosis-endemic country: consideration of lymph node calcification and distribution pattern to improve specificity. Eur J Nucl Med Mol Imaging
21. Al-Sarraf N, Gately K, Lucey J, et al. Lymph node staging by means of positron emission tomography is less accurate in non-small cell lung cancer patients with enlarged lymph nodes: analysis of 1,145 lymph nodes. Lung Cancer
22. Yang W, Fu Z, Yu J, et al. Value of PET/CT versus enhanced CT for locoregional lymph nodes in non-small cell lung cancer. Lung Cancer
23. Hu M, Yu JM, Liu NB, et al. Significance of dual-time-point 18F-FDG PET imaging in evaluation of hilar and mediastinal lymph node metastasis in non-small-cell lung cancer. Zhonghua Zhong Liu Za Zhi
24. Kim YK, Lee KS, Kim BT, et al. Mediastinal nodal staging of nonsmall cell lung cancer using integrated 18F-FDG PET/CT in a tuberculosis-endemic country: diagnostic efficacy in 674 patients. Cancer
25. Lee BE, von Haag D, Lown T, et al. Advances in positron emission tomography technology have increased the need for surgical staging in non-small cell lung cancer. J Thorac Cardiovasc Surg
26. Bryant AS, Cerfolio RJ, Klemm KM, et al. Maximum standard uptake value of mediastinal lymph nodes on integrated FDG-PET-CT predicts pathology in patients with non-small cell lung cancer. Ann Thorac Surg
27. Kanzaki R, Higashiyama M, Fujiwara A, et al. Occult mediastinal lymph node metastasis in NSCLC patients diagnosed as clinical N0-1 by preoperative integrated FDG-PET/CT and CT: risk factors, pattern, and histopathological study. Lung Cancer
28. Gomez-Caro A, Garcia S, Reguart N, et al. Incidence of occult mediastinal node involvement in cN0 non-small-cell lung cancer patients after negative uptake of positron emission tomography/computer tomography scan. Eur J Cardiothorac Surg
29. Lee HJ, Kim YT, Kang WJ, et al. Integrated positron-emission tomography for nodal staging in lung cancer. Asian Cardiovasc Thorac Ann
30. Liu BJ, Dong JC, Xu CQ, et al. Accuracy of 18F-FDG PET/CT for lymph node staging in non-small-cell lung cancers. Chin Med J
31. Hsu LH, Ko JS, You DL, et al. Transbronchial needle aspiration accurately diagnoses subcentimetre mediastinal and hilar lymph nodes detected by integrated positron emission tomography and computed tomography. Respirology
32. Al-Sarraf N, Aziz R, Gately K, et al. Pattern and predictors of occult mediastinal lymph node involvement in non-small cell lung cancer patients with negative mediastinal uptake on positron emission tomography. Eur J Cardiothorac Surg
33. Liu LP, Yu JM, Guo HB, et al. Preliminary study of 18F-FDG PET-CT in defining lymph node radiation target volume for non-small-cell lung cancer patients. Zhonghua Zhong Liu Za Zhi
34. Cerfolio RJ, Bryant AS, Eloubeidi MA. Routine mediastinoscopy and esophageal ultrasound fine-needle aspiration in patients with non-small cell lung cancer who are clinically N2 negative: a prospective study. Chest
35. Bryant AS, Cerfolio RJ. The clinical stage of non-small cell lung cancer as assessed by means of fluorodeoxyglucose-positron emission tomographic/computed tomographic scanning is less accurate in cigarette smokers. J Thorac Cardiovasc Surg
36. Zhang X, Li TR, Chen ZS, et al. Comparing serum tumor antigen detection combined with CT scan with PET-CT for lung cancer diagnosis. Ai Zheng
37. Al-Sarraf N, Aziz R, Doddakula K, et al. Factors causing inaccurate staging of mediastinal nodal involvement in non-small cell lung cancer patients staged by positron emission tomography. Interact Cardiovasc Thorac Surg
38. Kim BT, Lee KS, Shim SS, et al. Stage T1 non-small cell lung cancer: preoperative mediastinal nodal staging with integrated FDG PET/CT—a prospective study. Radiology
39. Lee BE, Redwine J, Foster C, et al. Mediastinoscopy might not be necessary in patients with non-small cell lung cancer with mediastinal lymph nodes having a maximum standardized uptake value of less than 5.3. J Thorac Cardiovasc Surg
40. Yi CA, Lee KS, Kim BT, et al. Efficacy of helical dynamic CT versus integrated PET/CT for detection of mediastinal nodal metastasis in non-small cell lung cancer. AJR Am J Roentgenol
41. Stigt JA, Oostdijk AH, Timmer PR, et al. Comparison of EUS-guided fine needle aspiration and integrated PET-CT in restaging after treatment for locally advanced non-small cell lung cancer. Lung Cancer
42. Cerfolio RJ, Bryant AS. When is it best to repeat a 2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography scan on patients with non-small cell lung cancer who have received neoadjuvant chemoradiotherapy? Ann Thorac Surg
43. De Leyn P, Stroobants S, De Wever W, et al. Prospective comparative study of integrated positron emission tomography-computed tomography scan compared with remediastinoscopy in the assessment of residual mediastinal lymph node disease after induction chemotherapy for mediastinoscopy-proven stage IIIA-N2 non-small-cell lung cancer: a Leuven Lung Cancer Group Study. J Clin Oncol
44. Cerfolio RJ, Bryant AS, Ojha B. Restaging patients with N2 (stage IIIa) non-small cell lung cancer after neoadjuvant chemoradiotherapy: a prospective study. J Thorac Cardiovasc Surg
45. Jaeschke R, Guyatt GH, Sackett DL. Users' guides to the medical literature. III. How to use an article about a diagnostic test. B. What are the results and will they help me in caring for my patients? The Evidence-Based Medicine Working Group. JAMA
46. Paesmans M, Berghmans T, Dusart M, et al. Primary tumor standardized uptake value measured on fluorodeoxyglucose positron emission tomography is of prognostic value for survival in non-small cell lung cancer: update of a systematic review and meta-analysis by the European Lung Cancer Working Party for the International Association for the Study of Lung Cancer Staging Project. J Thorac Oncol
47. Begg CB, Berlin JA. Publication bias: a problem in interpreting medical data. J R Stat Soc A
48. Halpern BS, Schiepers C, Weber WA, et al. Presurgical staging of non-small cell lung cancer: positron emission tomography, integrated positron emission tomography/CT, and software image fusion. Chest
49. Lardinois D, Weder W, Hany TF, et al. Staging of non-small-cell lung cancer with integrated positron-emission tomography and computed tomography. N Engl J Med
50. Cerfolio RJ, Ojha B, Bryant AS, et al. The accuracy of integrated PET-CT compared with dedicated PET alone for the staging of patients with non-small cell lung cancer. Ann Thorac Surg
This article has been cited 2 time(s).
European Journal of Nuclear Medicine and Molecular ImagingHarmonizing SUVs in multicentre trials when using different generation PET systems: prospective validation in non-small cell lung cancer patientsEuropean Journal of Nuclear Medicine and Molecular Imaging
Journal of Thoracic and Cardiovascular SurgeryAre discordant positron emission tomography and pathological assessments of the mediastinum in non-small cell lung cancer significant?Journal of Thoracic and Cardiovascular Surgery
Integrated positron emission tomography/Computed tomography; Mediastinal lymph node staging; Non-small cell lung cancer; Systematic review; Meta-analysis
© 2011International Association for the Study of Lung Cancer
Highlight selected keywords in the article text.