| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Ann Thorac Surg 2003;76:861-866
© 2003 The Society of Thoracic Surgeons
a Section of Thoracic Surgery, , Birmingham, AL, USA
b Division of Nuclear Medicine, Clinical PET, , Birmingham, AL, USA
c Department of Epidemiology, School of Public Health, , Birmingham, AL, USA
d Department of Cardio-Thoracic Surgery, , Birmingham, AL, USA
e Department of Biostatistics, School of Public Health, Birmingham, Alabama, USA
f Division of Nuclear Medicine, Nuclear Medicine and PET, University of Alabama at Birmingham, Birmingham, AL, USA
g Birmingham Veterans Administration Hospital, Birmingham, Alabama, USA
* Address reprint requests to Dr Cerfolio, Division of Cardiothoracic Surgery, University of Alabama at Birmingham, 1900 University Blvd, THT 712, Birmingham, AL 35294, USA
e-mail: robert.cerfolio{at}ccc.uab.edu
Presented at the Poster Session of the Thirty-eighth Annual Meeting of The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 28–30, 2002.
 |
Abstract |
|---|
 Top Abstract IntroductionMaterial and methodsResultsCommentReferences |
|---|
METHODS: We prospectively studied 400 patients with NSCLC. Each patient underwent a computed tomography (CT) scan of the chest and upper abdomen, other conventional staging studies and had a FDG-PET scan within 1 month before surgery. All suspicious N2 lymph nodes by either chest CT or by FDG-PET scan were biopsied. Patients that were N2 and M1 negative underwent pulmonary resection and complete thoracic lymphadenectomy.
RESULTS: The FDG-PET had a higher sensitivity (71% vs 43%, p < 0.001), positive predictive value (44% vs 31%, p < 0.001), negative predictive value (91% vs 84%, p = 0.006), and accuracy (76% vs 68%, p = 0.037) than CT scan for N2 lymph nodes. Similarly, FDG-PET had a higher sensitivity (67% vs 41%, p < 0.001), but lower specificity (78% vs 88%, p = 0.009) than CT scan for N1 lymph nodes. FDG-PET led to unnecessary mediastinoscopy in 38 patients. FDG-PET was most commonly falsely negative in the subcarinal (#7) station and the aortopulmonary window lymph node (#5, #6) stations. It accurately upstaged 28 patients (7%) with unsuspected metastasis and it accurately downstaged 23 patients (6%).
CONCLUSIONS: The FDG-PET scan allows for improved patient selection. It more accurately stages the mediastinum, however there are many false positives lymph nodes and it may be more likely to miss N2 disease in the #5, #6, and #7 stations. A positive FDG-PET scan means a tissue biopsy is indicated in that location.
|
Introduction |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentReferences |
|---|
|
Material and methods |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentReferences |
|---|
Standard preoperative testing was performed. Patients were initially seen and examined in the University of Alabama at Birmingham (UAB) thoracic surgery clinic. In addition to CT and FDG-PET, all patients had a complete history, physical exam, and a chemistry-18 analysis. If there was an abnormality in the alkaline phosphatase an ultrasound of the liver and a bone scan was performed for further assessment. If patients complained of any new bone pain, a bone scan was performed. If patients complained of a new headache, a magnetic resonance imaging (MRI) scan of the brain was performed. Any suspicious lesion on conventional staging or on FDG-PET underwent biopsy for further evaluation.
Entry criteria into this study included a whole body FDG-PET at one center only and a CT scan both performed within 4 weeks of surgery. Patients with type 1 diabetes were excluded. Patients had either biopsied proven NSCLC before scanning or confirmed NSCLC pathologically after definitive biopsy or resection of a lymph node or nodes, or of the pulmonary mass. All patients who underwent thoracotomy and pulmonary resection had complete thoracic lymphadenectomy. A consecutive series of patients was used and prospective algorithm was used.
If either CT or FDG-PET suspected metastatic disease in any N2 station, that station was biopsied before thoracotomy. Table 1 illustrates procedures used to biopsy or remove mediastinal lymph nodes. Staging was accomplished through the recently revised TNM staging system [2]. The #2R, #4R, #2L, #4L and proximal #7 lymph nodes stations were biopsied through a mediastinoscopy. The mid and distal #7, #8 and #9 stations through a transesophageal ultrasound, and the #5 and #6 stations through a left video-assisted thoroscopy (VATS), Chamberlin, or mini-thoracotomy. If the patient was N2 positive they underwent neoadjuvant therapy, and then underwent pulmonary resection later if retesting of that same lymph node station was negative for residual cancer. FDG-PET was considered positive for an N1 or N2 lymph node if the PET report, after review with a nuclear medicine physician (J.M.M. or B.O.) and a chest CT radiologist, stated that there was hypermetabolic activity consistent with malignant disease in that numbered lymph node (characteristically defined as standard uptake value [SUV] > 2.5). All N2 stations were numbered on the reports. The only N1 nodes specifically numbered were the #10 station; the other N1 nodes (#11, #12, #13, and #14) were called intraparenchymal nodes. CT scan was considered positive if the report described a lymph node as greater than 1 cm in the short axis in a specified lymph node station.
|
The FDG-PET was considered to have accurately upstaged a patient when all other standard tests were negative (or not performed because the patient was asymptomatic) and the patient would have otherwise undergone thoracotomy, except the FDG-PET identified an area of metastatic disease that was previously unsuspected and later confirmed by tissue biopsy. FDG-PET was considered to have accurately downstaged a patient when another imaging modality called a lesion metastatic or suspicious for metastatic disease; the patient would have otherwise been turned down for thoracotomy, but the lesion had low metabolic activity on FDG-PET and subsequent tissue biopsies (or MRI if the bone) proved that lesion to be benign.
The diagnostic value of FDG-PET and CT scanning was compared with biopsy node assessment by calculating sensitivity, specificity, PPV, NPV, and accuracy using the formulas presented in Table 2. The results for this data have been reported in two ways. One method considers the values for the N2 and N1 lymph nodes by each patient individually (Table 3) and the other considers the values of each node (Table 4). The test of proportions was used to compare the sensitivity, specificity, PPV, NPV, and accuracy between FDG-PET and CT. A two-sided p value of 0.05 or less was considered as a statistically significant difference between two groups unlikely to be due to chance. The statistical analysis was performed using SAS version 8.02 (SAS Institute, Cary, NC) and EpiInfo 2002 (Centers for Disease Control, Atlanta, GA) software.
|
|
|
|
Results |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentReferences |
|---|
Mediastinoscopy
Table 4 demosntrates that the specificity for #4R, #4L, and #7 lymph node stations are lower than for other N2 stations. This means there were more false positives in these stations. Fifty patients had an FDG-PET scan that suggested N2 disease in the mediastinoscopically accessible lymph node stations (#2R, #2L, #4R, #4L, #7), 38 patients (76%) had falsely positive FDG-PET scans, 37 had granulomatous disease, and 1 patient had silicosis. However, 12 patients (24%) were found to have metastatic NSCLC. In addition to these 50 patients, there were 23 other patients that were true positives for N2 disease by both CT and FDG-PET scans.
Twenty-two patients (5.5%) had false negative FDG-PET for N2 disease. All had microscopic cancer in the N2 nodal stations. Nine of these patients were only positive in one N2 position and in 8 patients FDG-PET failed to detect microscopic cancer in the #7 lymph node. Two of these patients had atypical carcinoid tumors, but their primary tumors in the lung were FDG-PET positive. In 5 patients the aortopulmonary (#5 and #6) lymph nodes had metastatic cancer, and 4 of these 5 patients had large tumors that, in retrospect, obscured this area. Similarly, in 4 patients who had false negative right paratracheal (#2R and #4R) lymph nodes, 3 patients had adjacent large right upper lobe tumors.
Metastatic disease
The FDG-PET scans upstaged 28 patients (7%). The locations of these unsuspected metastases are illustrated in Table 5.
FDG-PET scans downstaged 23 patients (6%) and the locations of the suspected metastases, later proven to be benign as FDG-PET suggested, and are depicted in Table 6.
As indicated in Tables 5 and 6, FDG-PET scan is highly sensitive and specific for determining the presence or absence of malignancy in the adrenal gland, bone, and liver.
|
|
|
Comment |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentReferences |
|---|
It is important for physicians to differentiate a full ring dedicated PET camera from partial ring or coincidence (hybrid) systems. In fact, apparently Medicare will only cover FDA-approved full ring or partial ring scanners, or coincidence systems that have very specific features by the end of 2003. Scans performed with gamma camera PET systems with crystals thinner than 5/8 inch will not be covered. Moreover, there remain problems with standard uptake value (SUV). Despite its name it is anything but standardized. The SUVs on different PET scanners do not necessarily equate with the SUVs on another scanner. All these issues require further study and refinement and may explain why there is a wide range of sensitivities, specificities, and accuracies reported for FDG-PET for nodal and metastatic disease.
As reported in this study, FDG-PET does not replace the need for tissue biopsies for N1 or N2 lymph nodes, or for metastatic lesions. There are false positives and negatives in all stations. However, FDG-PET did result in better patient selection before pulmonary resection. It helped target areas for biopsy and led us to find unsuspected N2 and M1 disease. Therefore our recommendation is clear. We believe an FDG-PET scan should be performed before surgical resection. Our study found a lower sensitivity and specificity for N2 nodes when compared with some other PET studies [3–22], as illustrated in Table 7. There are several possible explanations for these findings. We may have had more false positives for lymph nodes because most of our patients were from the South and we found a high incidence of granulomatous disease. Also we used a SUV of 2.5 as our cutoff so as not to miss a cancer, but this led to more false positives. We may have had more false negatives because we did a complete thoracic lymphadenectomy and our pathologist performed immunohistochemical staining that discovered microscopic N2 disease that FDG-PET will not register as positive.
|
The FDG-PET is also valuable for detecting unsuspected M1 disease even in patients that have already had routine screening tests that were read as normal (bone scans, CT of the adrenal gland and liver, and brain scans). We found that 7% of patients had M1 disease and avoided unnecessary surgery. FDG-PET may be more sensitive in certain M1 locations just like it is in certain N2 stations [18, 19]. It seems to be quite good for lesions in the liver, adrenal gland, and bone, but not as good for the brain. Our study did not evaluate PET for the brain because our scans were done from the base of the brain downward. When an FDG-PET is positive in only one M1 station, that area requires definitive evaluation or biopsy before deferring potential curative resection to a patient with possible stage I disease.
Although currently the presence of N1 disease does not change the management in patients with NSCLC, several studies have reported that preoperative chemotherapy may be of benefit [1] and several ongoing trials are examining these questions. If these other trials also reveal a survival difference for patients with N1 disease who receive preoperative chemotherapy before surgical resection, then the accuracy of FDG-PET for N1 nodes will become important. In this trial neither FDG-PET nor CT scan predicted N1 disease well. It is possible that the new PET-CT fusion systems, with their ability to better localize hypermetabolic areas, will help differentiate N1 nodes from the primary tumor or alleviate the problem of large tumors obscuring N2 nodes [23]. Current studies are underway examining these issues.
The future is promising. We believe our data has demonstrated that surgical staging is not supplanted by FDG-PET, and tissue biopsy is mandatory before any treatment strategy. But FDG-PET helps direct those biopsies and finds unsuspected M1 disease in 7% of patients and downstages in 6% of patients. Clearly patients should not be denied any resection based on an FDG-PET scan alone, biopsies are needed. Further studies are needed to help standardize SUVs from one center to another to better define the ability of FDG-PET to accurately stage hilar and mediastinal nodes [24], and to evaluate new radiopharmaceutical agents besides FDG. Other agents must be tested like F-18 FDG, and their accuracy in staging patients with NSCLC will also need to be determined on an individual basis for each agent and at each nodal and anatomic location.
|
References |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentReferences |
|---|
This article has been cited by other articles:
|
|
 |
|
  C. Perigaud, B. Bridji, J. C. Roussel, C. Sagan, A. Mugniot, D. Duveau, O. Baron, and P. Despins 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., October 1, 2009; 36(4): 731 - 736. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Maeda, N. Isowa, H. Onuma, H. Miura, T. Harada, H. Touge, H. Tokuyasu, and Y. Kawasaki The maximum standardized uptake values on positron emission tomography to predict the Noguchi classification and invasiveness in clinical stage IA adenocarcinoma measuring 2 cm or less in size Interactive CardioVascular and Thoracic Surgery, July 1, 2009; 9(1): 70 - 73. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Maeda, N. Isowa, H. Onuma, H. Miura, T. Harada, H. Touge, H. Tokuyasu, and Y. Kawasaki The maximum standardized 18F-fluorodeoxyglucose uptake on positron emission tomography predicts lymph node metastasis and invasiveness in clinical stage IA non-small cell lung cancer Interactive CardioVascular and Thoracic Surgery, July 1, 2009; 9(1): 79 - 82. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. Groth, B. A. Whitson, J. D'Cunha, M. A. Maddaus, M. Alsharif, and R. S. Andrade Endobronchial Ultrasound-Guided Fine-Needle Aspiration of Mediastinal Lymph Nodes: A Single Institution's Early Learning Curve Ann. Thorac. Surg., October 1, 2008; 86(4): 1104 - 1110. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F.-X. Hanin, M. Lonneux, J. Cornet, P. Noirhomme, C. Coulon, J. Distexhe, and A. J. Poncelet Prognostic value of FDG uptake in early stage non-small cell lung cancer Eur. J. Cardiothorac. Surg., May 1, 2008; 33(5): 819 - 823. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. K. Veeramachaneni, R. J. Battafarano, B. F. Meyers, J. B. Zoole, and G. A. Patterson Risk factors for occult nodal metastasis in clinical T1N0 lung cancer: a negative impact on survival Eur. J. Cardiothorac. Surg., March 1, 2008; 33(3): 466 - 469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Cerfolio and A. S. Bryant 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., October 1, 2007; 84(4): 1092 - 1097. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K G Tournoy, S Maddens, R Gosselin, G Van Maele, J P van Meerbeeck, and A Kelles Integrated FDG-PET/CT does not make invasive staging of the intrathoracic lymph nodes in non-small cell lung cancer redundant: a prospective study Thorax, August 1, 2007; 62(8): 696 - 701. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Cerfolio and A. S. Bryant Predictors of Survival and Disease-Free Survival in Patients With Resected N1 Non-Small Cell Lung Cancer Ann. Thorac. Surg., July 1, 2007; 84(1): 182 - 190. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Okada, S. Tauchi, K. Iwanaga, T. Mimura, Y. Kitamura, H. Watanabe, S. Adachi, T. Sakuma, and C. Ohbayashi Associations among bronchioloalveolar carcinoma components, positron emission tomographic and computed tomographic findings, and malignant behavior in small lung adenocarcinomas J. Thorac. Cardiovasc. Surg., June 1, 2007; 133(6): 1448 - 1454. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A. Whitson, S. J. Runge, S. S. Groth, and M. A. Maddaus False-positive mediastinal lymph node activity on positron emission tomographic scan after adjuvant treatment of gynecologic malignancies J. Thorac. Cardiovasc. Surg., May 1, 2007; 133(5): 1385 - 1386. [Full Text] [PDF]
|
|
|
|
|
|
J. R. Roberts and J. Wadsworth Recurrent Laryngeal Nerve Monitoring During Mediastinoscopy: Predictors of Injury Ann. Thorac. Surg., February 1, 2007; 83(2): 388 - 392. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Bryant and R. J. Cerfolio 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., December 1, 2006; 132(6): 1363 - 1368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Bryant, R. J. Cerfolio, K. M. Klemm, and B. Ojha 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., August 1, 2006; 82(2): 417 - 423. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Schimmer, K. Neukam, and O. Elert Staging of non-small cell lung cancer: clinical value of positron emission tomography and mediastinoscopy Interactive CardioVascular and Thoracic Surgery, August 1, 2006; 5(4): 418 - 423. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Massard, X. Ducrocq, E. A. Kochetkova, V. A. Porhanov, and M. Riquet Sampling or node dissection for intraoperative staging of lung cancer: a multicentric cross-sectional study. Eur. J. Cardiothorac. Surg., July 1, 2006; 30(1): 164 - 167. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Inoue, M. Minami, H. Shiono, N. Sawabata, K. Ideguchi, and M. Okumura Clinicopathologic study of resected, peripheral, small-sized, non-small cell lung cancer tumors of 2 cm or less in diameter: Pleural invasion and increase of serum carcinoembryonic antigen level as predictors of nodal involvement J. Thorac. Cardiovasc. Surg., May 1, 2006; 131(5): 988 - 993. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Bunyaviroch and R. E. Coleman PET Evaluation of Lung Cancer J. Nucl. Med., March 1, 2006; 47(3): 451 - 469. [Full Text] [PDF]
|
|
|
|
|
|
J. L. Port, R. S. Andrade, M. A. Levin, R. J. Korst, P. C. Lee, D. E. Becker, and N. K. Altorki Positron emission tomographic scanning in the diagnosis and staging of non-small cell lung cancer 2 cm in size or less J. Thorac. Cardiovasc. Surg., December 1, 2005; 130(6): 1611 - 1615. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Pozo-Rodriguez, J. L. Martin de Nicolas, M. A. Sanchez-Nistal, A. Maldonado, S. Garcia de Barajas, R. Calero-Garcia, M. A. Pozo, P. Martin-Escribano, I. Martin-Garcia, R. Garcia-Lujan, et al. Accuracy of Helical Computed Tomography and [18F] Fluorodeoxyglucose Positron Emission Tomography for Identifying Lymph Node Mediastinal Metastases in Potentially Resectable Non-Small-Cell Lung Cancer J. Clin. Oncol., November 20, 2005; 23(33): 8348 - 8356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Cerfolio, A. S. Bryant, B. Ojha, and M. Eloubeidi Improving the Inaccuracies of Clinical Staging of Patients with NSCLC: A Prospective Trial Ann. Thorac. Surg., October 1, 2005; 80(4): 1207 - 1214. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Eloubeidi, A. Tamhane, V. K. Chen, and R. J. Cerfolio Endoscopic Ultrasound-Guided Fine-Needle Aspiration in Patients With Non-Small Cell Lung Cancer and Prior Negative Mediastinoscopy Ann. Thorac. Surg., October 1, 2005; 80(4): 1231 - 1239. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. T. Wang, W. Sienel, S. Eggeling, C. Ludwig, E. Stoelben, J. Mueller, C. A. Klein, and B. Passlick Detection of disseminated tumor cells in mediastinoscopic lymph node biopsies and lymphadenectomy specimens of patients with NSCLC by quantitative RT-PCR Eur. J. Cardiothorac. Surg., July 1, 2005; 28(1): 26 - 32. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Cerfolio, A. S. Bryant, B. Ohja, and A. A. Bartolucci The maximum standardized uptake values on positron emission tomography of a non-small cell lung cancer predict stage, recurrence, and survival J. Thorac. Cardiovasc. Surg., July 1, 2005; 130(1): 151 - 159. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Eloubeidi, R. J. Cerfolio, V. K. Chen, R. Desmond, S. Syed, and B. Ojha Endoscopic Ultrasound-Guided Fine Needle Aspiration of Mediastinal Lymph Node in Patients With Suspected Lung Cancer After Positron Emission Tomography and Computed Tomography Scans Ann. Thorac. Surg., January 1, 2005; 79(1): 263 - 268. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Cerfolio, A. S. Bryant, T. S. Winokur, B. Ohja, and A. A. Bartolucci Repeat FDG-PET After Neoadjuvant Therapy is a Predictor of Pathologic Response in Patients With Non-Small Cell Lung Cancer Ann. Thorac. Surg., December 1, 2004; 78(6): 1903 - 1909. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Schrevens, N. Lorent, C. Dooms, and J. Vansteenkiste The Role of PET Scan in Diagnosis, Staging, and Management of Non-Small Cell Lung Cancer Oncologist, November 1, 2004; 9(6): 633 - 643. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Cerfolio, B. Ojha, A. S. Bryant, V. Raghuveer, J. M. Mountz, and A. A. Bartolucci The accuracy of integrated PET-CT compared with dedicated pet alone for the staging of patients with nonsmall cell lung cancer Ann. Thorac. Surg., September 1, 2004; 78(3): 1017 - 1023. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. T. Rocha, M. McCormack, G. Montana, and G. Schreiber Association Between Lower Lobe Location and Upstaging for Early-Stage Non-small Cell Lung Cancer Chest, April 1, 2004; 125(4): 1424 - 1430. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ANN THORAC SURG | ASIAN CARDIOVASC THORAC ANN | EUR J CARDIOTHORAC SURG |
| J THORAC CARDIOVASC SURG | ICVTS | ALL CTSNet JOURNALS |
