Maximum Standard Uptake Value of Mediastinal Lymph Nodes on Integrated FDG-PET-CT Predicts Pathology in Patients with Non-Small Cell Lung Cancer

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1 Maximum Standard Uptake Value of Mediastinal Lymph odes on Integrated FDG-PET-CT Predicts Pathology in Patients with on-small Cell Lung Cancer Ayesha S. Bryant, MSPH, MD, Robert J. Cerfolio, MD, FACS, Katrin M. Klemm, MD, and Buddhiwardhan Ojha, MD Department of Surgery, Emory University, Atlanta, Georgia; Division of Cardiothoracic Surgery, University of Alabama at Birmingham, Division of Cardiothoracic Surgery, Department of Surgery, Birmingham Veterans Administration Hospital, Department of Pathology, and Division of uclear Radiology, University of Alabama at Birmingham Hospital, Birmingham, Alabama GEERAL THORACIC Background. Positron emission tomography (PET) scans often help direct biopsies of mediastinal lymph nodes in patients with non-small cell lung cancer (SCLC), but the maximum standard uptake value (max- SUV) of individual nodes has not been evaluated. Methods. This is a prospective study of consecutive patients with SCLC, all of whom underwent integrated fluorodeoxyglucose-positron emission-computed tomography (FDG-PET-CT) and had biopsy or resection of their mediastinal lymph nodes. Results. There were 397 patients. One-hundred and forty-three patients had 2 disease and 1,252 2 nodes were pathologically examined. The median maxsuv of the nodes that had metastatic disease were the following: for the 2R node, 10.4 (range, ); for 4R, 8.6 (range, ); for 5, 8.9 (range, ); for 6, 7.6 (range, ); for 7, 7.7 (range, 0 14); for 8 and 9, 5.4 (range, 0 8.9). The median maxsuv for all of the 2 nodes that were benign was 0 (range, ) (p < 0.05 for all stations except for nodes 8 and 9). When a maxsuv of 5.3 is used the accuracy of integrated FDG-PET-CT for each 2 nodal station is maximized and is at least 92% for each. Conclusions. The maxsuv of individual mediastinal lymph nodes is a predictor of malignancy. There is overlap between false and true positives. Definitive biopsies are required to prove cancer irrespective of the maxsuv value. However, when a maxsuv of 5.3 is used instead of the traditional value of 2.5, the accuracy for FDG-PET-CT for each 2 nodal station increases to at least 92%. (Ann Thorac Surg 2006;82:417 23) 2006 by The Society of Thoracic Surgeons Treatment of non-small cell lung cancer (SCLC) depends on the stage. One of the increasingly ordered tests used to assess this stage is a positron emission tomography scan using fluorodeoxyglucose (FDG-PET) scan. The maximum standard uptake value (maxsuv) generated on an integrated FDG-PET-computed tomographic (CT) scan provides information on the metabolic activity of the primary pulmonary mass [1, 2]. However, there is little information on the clinical importance of the maxsuv of individual mediastinal (2) lymph nodes. While many recent studies have shown that the use of integrated FDG-PET-CT scanning is superior to both CT alone and dedicated FDG- PET scan in the staging of patients with SCLC [3], the pathologic stage often differs from the predicted clinical stage [4 7]. Thus we decided to prospectively assess the accuracy Accepted for publication Dec 13, Presented at the Fifty-second Annual Meeting of the Southern Thoracic Surgical Association, Orlando, FL, ov 10 12, Address correspondence to Dr Bryant, Division of Cardiothoracic Surgery, University of Alabama at Birmingham, 1900 University Blvd., THT 712, Birmingham, AL 35294; abryant@uab.edu. of integrated FDG-PET-CT for each 2 mediastinal lymph node station by comparing the maxsuv value with the actual pathology. We also wanted to identify causes of false positives and negatives, determine the median maxsuv for lymph nodes that harbored metastatic cancer, and compare it with lymph nodes that were benign. Finally, we wanted to identify the maxsuv value that maximized sensitivity, specificity, and accuracy and to examine the prevalence of microscopic nodal disease for those lymph nodes falsely negative and missed by FDG-PET-CT scan. Patients and Methods Patient Selection Patients who presented to one surgeon between January 2003 and December 2004 with an indeterminate pulmonary nodule or biopsy proven SCLC and who underwent integrated FDG-PET-CT at our institution were eligible to participate in this study. Patients were excluded if they were less than 19 years old, had type I diabetes, had a Pancoast tumor, were T4 tumor from mediastinal invasion 2006 by The Society of Thoracic Surgeons /06/$32.00 Published by Elsevier Inc doi: /j.athoracsur

2 GEERAL THORACIC 418 BRYAT ET AL Ann Thorac Surg MaxSUV OF 2 LYMPH ODES 2006;82: Fig 1. Study algorithm. (SCLC patients with non-small cell lung cancer; PET-CT positron emission tomography-computed tomography.) or from a malignant effusion, or if they received neoadjuvant chemotherapy or radiation. Patients who had a biopsy proven M1 disease were also excluded. All patients were clinically staged using the T,, and M classification system [8] based on FDG-PET-CT results. Radiologic Imaging The FDG-PET-CT scans were performed on an integrated FDG-PET-CT scanner (GE Discovery LS PET-CT Scanner, Milwaukee, WI). This type of PET scan performs both a dedicated PET and a CT scan together in one sitting. It allows for the integration of both the molecular findings of the FDG-PET scan and the anatomic information of the CT scan to be merged. Patients were asked to fast for four hours and then subsequently received 555 MBq (15 mci) of FDG intravenously followed by positron emission tomography after one hour. The scans were performed from the skull base to mid-thigh level. The CT examination was used for attenuation correction of PET images. The scanning time for emission PET was 5 minutes per bed position. Iterative reconstruction with CT attenuation correction was performed. The most recent CT scan of the chest was also available for visual correlation. Maximum SUV of the primary lung lesion and of each suspicious lymph node station was determined by drawing regions of interest (ROI) on the attenuation corrected FDG-PET images around it. It was then calculated by the software contained within the PET or PET-CT scanner by the formula [9] C Ci ml maxsuv, ID( Ci) w(kg) where C activity at a pixel within the tissue defined by an ROI, ID injected dose, and w patients body weight in kilograms. The maximum SUV within the selected region of interest was used (maxsuv) throughout this study exclusively. Staging As shown in Figure 1, all suspicious 2, 3, or M1 areas (maxsuv 2.5) were biopsied prior to pulmonary resection. Mediastinoscopy was used to biopsy suspicious lymph nodes in the paratracheal area (stations 2R, 4R, 2L, and 4L) and the superior portion of the subcarinal lymph node. Either video-assisted thoracoscopic surgery (VATS) or endoscopic transesophageal ultrasound (EUS) was used to biopsy suspicious posterior aortopulmonary window lymph nodes, subcarinal, periesophageal, and inferior pulmonary ligament nodes. Microscopic disease was defined as tumor invasion of 2 mm or less [10] or disease only detected on immunohistochemical staining. The latter was performed in selected cases only as per the pathologist s discretion. In general there were two slices per lymph nodes used. The University of Alabama at Birmingham s institutional review board approved this study and the electronic prospective database used. In addition, individual patient consent was obtained. Statistical Methods Data were stored using an Excel database (Microsoft, Seattle, WA) and analyzed using SAS 9.0 (SAS Institute, Cary, C). Receiver operating characteristic (ROC) analysis [11, 12] was used to determine the maxsuv for individual mediastinal lymph node stations that maximized the sensitivity, the specificity, and thus the accuracy. Areas under the curve were compared and a p value

3 Ann Thorac Surg BRYAT ET AL 2006;82: MaxSUV OF 2 LYMPH ODES Table 1. The Distribution of 2 Disease by Lymph ode Station With the Corresponding maxsuv Values a Lymph ode Station umber of odes Pathology Positive and Positive on PET-CT (True Positives) umber of odes Pathologically Positive but egative on PET-CT (False egatives) umber of odes Pathologically egative but Positive on PET-CT (False Positives) umber of odes Pathologically egative and egative on PET-CT (True egatives) 419 GEERAL THORACIC 2R (11.9) (0) (9.8) (0) 4R (10.5) (0) (4) (0) (9.7) (0) (4.5) (0) (8.5) (0) (4.6) (0) (8.2) (0) (4.2) (0) 8, (5.8) (0) 2 4.1, (0) a This chart includes all false negative nodes, even in patients who had some 2 positive nodes. Some patients only underwent one biopsy test; for example, if EUS-FA was positive at the subcarinal lymph node, then the patient did not undergo a mediastinoscopy. Only lymph nodes that were pathologically assessed were used in the calculation of the true positives and negatives. CT computed tomography; EUS-FA endoscopic ultra sound guided-fine needle aspiration; maxsuv maximum standard uptake value; PET-CT positron emission tomography-computed tomography. less than 0.05 was considered to show a statistically significant difference between curves. Standard definitions were used to calculate accuracy [13]. For example, a patient may have had a PET scan that predicted the os. 4L, 5, and 6 lymph nodes to be malignant. If the patient had only a o. 8 L that was positive after resection with thoracic lymphadenectomy the PET was falsely positive for the 4L, 5, and 6 and falsely negative for the 8. If he had only an endoscopic ultrasound-guided fine-needle aspiration that proved the o. 8 lymph node was positive and the other lymph nodes were not assessed it was recorded as a false negative for the o. 8 only. Of the 397 patients, 120 had pathological stage I disease, 108 had stage II disease, 143 had stage III disease, and 26 had stage IV disease. The incidence of pathologically proven disease and the median maxsuv of each lymph node station are shown in Table 1. The most common locations for positive nodal mediastinal disease were in the 4R and 7 lymph nodes. The paratracheal lymph nodes (2R and 4R) had the greatest median maxsuv. Figure 2 depicts the maxsuv of the different lymph nodes stations and compares the pathologically positive lymph nodes with the pathologically negative lymph nodes. A statistically significant difference is noted for each nodal station Results There were 397 patients (251 men) who met the eligibility criteria for this study. The median age was 67 years (range, 23 to 82 years). One hundred and forty-three (36%) patients of these 397 patients had pathologically confirmed 2, staged IIIa disease as shown in Figure 1. Fig 2. Median maxsuv of lymph nodes that were pathologically positive (solid line) compared with those nodes that were pathologically negative (dashed line) by lymph node station. (maxsuv maximum standard uptake value.) Fig 3. Receiver operating characteristic curve for 2 nodes. Dashed lines indicate the 95% confidence interval. Optimal cutoff value maxsuv 5.3 (sensitivity 91%, specificity 88%, [C 0.85, p 0.001]). (C activity at a pixel within the tissue defined by a region of interest; maxsuv maximum standard uptake value.)

4 GEERAL THORACIC 420 BRYAT ET AL Ann Thorac Surg MaxSUV OF 2 LYMPH ODES 2006;82: Table 3. Pathology of the 104 Lymph odes That Were Pathologically egative and Falsely Positive by FDG-PET- CT Scan Pathology umber of nodes Lymph ode Station 2R 4R 5, 6 7 8, 9 Fig 4. The accuracy (%) of fluorodeoxyglucose-positron emissioncomputed tomography scan for predicting non-small lung cancer in mediastinal lymph nodes using the maximum standard uptake value of 2.5 or greater (gray bars) and 5.3 or greater (black bars) as the negative cutoff value for all lymph nodes. Granulomatous disease Infection Histoplasmosis Other fungal Other Calcified Fibrosis Other / OS Median maxsuv FDG-PET-CT fluorodeoxyglucose-positron emission-computed tomography; maxsuv maximum standard uptake value. OS not otherwise specified Comment except stations os.8 and 9. Interestingly, the 2R and 4R lymph nodes had the greatest discrepancy between the maxsuv of their pathologically positive and negative lymph nodes. Figure 3 shows the ROC curve. It identified the optimal maxsuv cutoff value of 5.3 for all mediastinal stations. We thus compared the accuracy of each lymph node station using the arbitrarily chosen maxsuv of 2.5 (used in this study and most others in the past) with the cutoff point identified by the ROC curves we generated. The accuracy using the maxsuv of 5.3 is higher at all stations as compared with the value of 2.5 as shown in Figure 4. The accuracy of station 4R is improved the most, possibly due to the higher number of false negatives at this station. Tables 2 and 3 identify the pathological characteristics of the false positive lymph nodes and the false negative lymph nodes on FDG-PET-CT. Table 2 shows that microscopic disease was present in 35% of the FDG-PET-CT scans that predicted the lymph nodes to be benign. It was more prevalent in the posterior mediastinal nodes (57%) than the anterior mediastinal nodes (17%). To our knowledge, this is the first manuscript that evaluates the maxsuv of individual mediastinal 2 lymph node stations and correlates it to histology. We found that the maxsuv is a predictor of pathology and a statistically significant difference exists between the max- SUV of almost all 2 nodal stations that harbor cancer compared with those lymph nodes that are benign. The strengths of this study are the following: its prospective design, its rigorous entry criteria, the fact that all lymph nodes sued to calculate sensitivity and specificity were definitively biopsied and/or completely removed, and that confounders were limited because a single surgeon and a single integrated FDG-PET-CT center were used. Conversely, the latter two points could also be construed as potential limitations to this study. Additionally only select samples were examined for microscopic disease by immunohistochemical staining. Accuracy of FDG-PET-CT maxsuv for 2 odal Stations In two of our previous studies, one in 2003 with 400 patients [14] that evaluated dedicated FDG-PET and the Table 2. Histology of 34 Lymph odes (L) That Were Pathologically Positive and False egative on FDG-PET-CT Scan a Lymph ode Station Pathology umber of nodes 2R L 4R L 5, 6 L 7 L 8,9 L Squamous Adenocarcinoma Other Microscopic (% of lymph nodes falsely negative on PET-CT scan with microscopic disease) 12 0 (0%) a Only 12 patients had unsuspected 2 disease; however, some patients who were pathologically staged with IIIa disease also had falsely negative lymph nodes. This table considers all nodes that were missed. It does not consider patients but rather lymph nodes. FDG-PET-CT fluorodeoxyglucose-positron emission-computed tomography. 2 (25%) 2 (29%) 6 (75%) 2 (40%)

5 Ann Thorac Surg BRYAT ET AL 2006;82: MaxSUV OF 2 LYMPH ODES other in 2004 with 129 patients that evaluated integrated FDG-PET-CT [3], we reported the accuracy of PET at each lymph node station. In those reports, as in this study, an arbitrary value for the maxsuv of 2.5 was chosen. Mediastinal 2 lymph nodes with a value of 2.5 or greater were considered positive. We chose this relatively conservative value because we did not want to miss any malignant disease in the 2 lymph nodes prior to resection. Thus we set the threshold low so as to avoid false negatives and in so doing accept a higher incidence of false positives. The accuracy for each nodal station reported in those two studies is remarkably similar to the accuracy reported in this study; thus the data and findings are consistent with other literature. Interestingly the accuracy was quite low for the 4R node and 7 lymph node stations. This is clinically important because the 4R and 7 nodal stations are the two most common locations for metastatic 2 disease to occur [15]. In order to maximize the accuracy of integrated FDG- PET-CT we generate ROC curves. These curves identify the maxsuv value that maximizes the sensitivity and specificity and consequently the accuracy. The value found was 5.3. When a maxsuv value of 5.3 or greater is used to label any 2 node as positive on FDG-PET-CT and less than 5.3 as negative, the accuracy of all stations (as shown in Fig 4) is at least 92%. False Positive and egatives Thirty-five percent of the 34 2 falsely negative nodes from integrated FDG-PET-CT had microscopic or only immunohistochemically positive disease. The true clinical import of missing microscopic 2 disease prior to resection is unknown. Whether neoadjuvant therapy improves survival in this subset of patients over resection followed by adjuvant chemotherapy is not documented. The current standard of care is to use neoadjuvant therapy. If a maxsuv of less than 5.3 had been used, there would have been no increase in the undetected 2 disease. However, our goal as surgeons should be to identify all metastatic mediastinal nodal (2) disease prior to resection to entertain the concept of neoadjuvant therapy. The most common cause of false positive lymph nodes in this study was histoplasmosis infection. The degree and the type of false positives for FDG-PET for mediastinal lymph nodes are often determined by regional factors. For instance, silicosis has been found to be a cause of false positives in Germany [16] and histoplasmosis has been a common cause in the Southeastern United States. The surgeon and radiologist must be aware of these regional differences. odal Trends in maxsuv Uptake The median maxsuv of lymph nodes that are malignant becomes smaller as one goes from the anterior mediastinal nodes to the posterior mediastinal nodes. The reason for this increase is unclear. The median maxsuv for all the anterior or superior lymph nodes (2R, 4R, 2L, 4L, and 6) is 8.5, whereas it is only 7.2 for the posterior or inferior mediastinal lymph nodes (5, 7, 8, and 9). While it is not yet completely understood, there are a few hypotheses regarding increasing FDG uptake in the lower mediastinum (and thus lower maxsuvs). One is that hypermetabolic brown fat, which is more prevalent in the posterior mediastinum, results in a higher background uptake and this leads to a lower maxsuv [17]. Conclusion In conclusion, we and others have shown the clinical importance and relevance of the maxsuv of a primary non-small cell lung tumor [1]. It provides information on a tumor s biologic aggressiveness, key pathologic features, and its potential to spread. This report illustrates the importance of the maxsuv of mediastinal (2) lymph nodes. The maxsuv of the primary tumor along with each lymph node (as well as any potential metastatic site) that is hypermetabolic should be provided by the nuclear radiologist in the text of every PET report. The causes of false positives and false negatives need to be carefully considered based on each patient s individual clinical scenario. For now we still recommend biopsies of all suspicious lymph nodes and a high maxsuv should not be equated with malignancy until tissue confirmation is obtained. However, the maxsuv of mediastinal 2 lymph nodes does provide significant predictive power. Finally, an important unanswered question remains if the maxsuv data from this report are translatable from one center to another. It is known that there may be a 15% to 20% variable rate of the maxsuv between different PET centers for a primary lung tumor. This important potential problem is being minimized as each PET center adopts standardized techniques. Further prospective studies are needed at other centers to evaluate the translatability of the maxsuv of the primary tumor as well as of the lymph nodes at different PET centers around the world. References Cerfolio RJ, Bryant AS, Ohja B, Bartolucci AA. The maximum standardized uptake value on positron emission tomography of a non-small cell lung cancer predict stage, recurrence, and survival. J Thorac Cardiovasc Surg 2005;130: Downey RJ, Akhurst T, Gonen M, et al. Preoperative F-18 fluorodeoxyglucose-positron emission tomography maximum standardized uptake value predicts survival after lung cancer resection. J Clin Oncol 2004;22: Cerfolio RJ, Buddhiwardhan O, Bryant AS, Raghuveer V, Mountz JM, Bartolucci AA. 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 2004;78: Antoch G, Stattaus J, emat AT, et al. on-small cell lung cancer: dual modality PET/CT in preoperative staging. Radiology 2003;229: Lardinois D, Weder W, Hany TF, et al. Staging of non-small cell lung cancer with integrated positron emission tomography and computed tomography. Engl J Med 2003;348: Aquino SL, Asmuth JC, Alpert M, et al. Improved radiologic staging of lung cancer with 2-[18]-fluoro-2-deoxy-Dglucose-positron emission tomography and computed to- GEERAL THORACIC

6 GEERAL THORACIC 422 BRYAT ET AL Ann Thorac Surg MaxSUV OF 2 LYMPH ODES 2006;82: mography registration. J Comput Assist Tomogr 2003;27: Cerfolio RJ, Bryant AS, Ojha B, Eloubeidi M. Improving the inaccuracies of clinical staging of patients with SCLC: a prospective trial. Ann Thorac Surg 2005;80: Mountain CF. Revisions in the international systems for staging lung cancer. Chest 1997;111: abi HA, Zubeldia JM. Clinical applications of F18-FDG in oncology. J ucl Med Technol 2002;30: Surveillance epidemiology and end results (SEER) coding manual Available at: Jones C, Athanasiou T. Summary receiver operating characteristic curve analysis techniques in the evaluation of diagnostic tests. Ann Thorac Surg 2005;79: Grunkemeier GL, Jin R. Receiver operating characteristic curve analysis of clinical risk models. Ann Thorac Surg 2001;72: Beck J. Likelihood ratios: another enhancement of sensitivity and specificity. Arch Pathol Lab Med 1986;110: Cerfolio RJ, Ohja B, Bryant AS, Bass CS, Bartalucci AA, Mountz JM. The role of FDG-PET scan in staging patients with nonsmall cell carcinoma. Ann Thorac Surg 2003;76; Cerfolio RJ, Bryant AS. Distribution and likelihood of lymph node metastasis based on the lobar location of nonsmall-cell lung cancer. Ann Thorac Surg 2006;81: Graeter TP, Hellwig D, Hoffmann K, Ukena D, Kirsch C-M, Schäfers H-J. Mediastinal lymph node staging in suspected lung cancer: comparison of positron emission tomography with F-18-fluorodeoxyglucose and mediastinoscopy. Ann Thorac Surg 2003;75: Truong MT, Erasmus JJ, Munden RF, et al. Focal FDG uptake in mediastinal brown fat mimicking malignancy: a potential pitfall resolved on PET/CT. AJR Am J Roentgenol 2004;183: DISCUSSIO DR JOH A. HOWIGTO (Cincinnati, OH): Doctor Bryant, first I would like to congratulate you on an excellent presentation. In addition, I would like to thank the authors for providing me a copy of the manuscript prior to the start of the meeting. I would like to comment first that your well-designed prospective clinical trials continue to improve our ability to be more accurate and effective in the care of lung cancer patients. I have three questions for you. First, why do you regard max SUV as a more accurate predictor of clinical stage than mean SUV? Second, you have reported 12 patients with 34 false negative 2 nodes. Can you tell us how often unsuspected 2 nodes were identified at thoracotomy? And thirdly, drawing from the authors prior trials looking at integrated PET-CT for clinical staging and lobar location as a predictor of 2 nodes and your current paper on max SUV for predicting 2 nodes, do you have an algorithm you could share with us on which patients you would perform cervical mediastinoscopy, which patients you would perform EUS FA, and which patients a left VATS for level 5 and 6 lymph node sampling? Thank you. DR BRYAT: Thank you for your excellent questions, Dr Howington. Your first question was regarding mean SUV versus the max SUV. The mean SUV is calculated by taking an average SUV in a particular region of interest, so therefore the region of interest is variable. The max SUV, however, is represented by the brightest pixel in the entire area and therefore it is more reproducible and more objective. Of the 34 false negatives, all of our patients were found at the time of thoracotomy. And lastly, yes, we do now perform preoperative nodal evaluation in almost any patient who presents with a max SUV greater than 10 or who has had a needle biopsy prior that shows poorly differentiated carcinoma. Also, if the primary is in the right upper lobe, we tend to perform a mediastinoscopy, if it is in the lower lobe, we go with an EUS FA, and if it is in the left upper lobe, we sample the nodes with a VATS. Additionally, we usually biopsy any lymph node with a max SUV of 2.5 or greater, and we definitely biopsy any lymph node that shows a max SUV of 5.3 or greater. DR THOMAS A. D AMICO (Durham, C): Dr Bryant, I very much enjoyed your presentation. I have two questions. You made a point that the use of an integrated PET-CT was used in all patients. I wonder if you could comment on whether or not the specific use of an integrated scan helped you in diagnosing these patients and was that part of why your sensitivity and specificity is better than recent papers? And secondly, you note that the sensitivity and specificity have improved with PET regardless of the site, so not just the mediastinum. Are any patients at your institution currently treated on the basis of a PET scan for a single focus of disease without a biopsy, with chemotherapy or radiation therapy? Thank you very much. DR BRYAT: Thank you, Dr D Amico, for your excellent questions as well. We do find integrated PET-CT superior than dedicated PET-CT. In a recently published prospective randomized study, we evaluated dedicated PET-CT compared to integrated PET-CT and found that integrated PET-CT was indeed superior at staging the mediastinum as well as locating 1 and 2 disease. So therefore if somebody is developing a new center, we do recommend that they get an integrated PET-CT over a dedicated PET-CT, not only because it is more accurate but because the CT portion of the machine can be used by itself, therefore increasing its efficiency. Your second question, at our institution we hardly ever go ahead and treat a patient based on the PET scan results. However, in the real world, if the max SUV of the primary tumor and that of the lymph node is equivalent, and the lymph nodes, such as the five and six, are difficult to get to, for example, if there is a bulky tumor obstructing access to those nodes, then, yes, we would go ahead and treat based on the PET scan results. DR MARK I. BLOCK (Hollywood, FL): Congratulations on a nice presentation. I continue to be impressed by your institution s ability to gather a huge amount of data and make lots of meaningful conclusions based on that. Two questions. The first has to do with the reproducibility of SUVs. My understanding in talking with nuclear medicine physicians is that they are increasingly moving away from quantitating the SUV value because of the difficulty in reproducing it not only from patient to patient but from institution to institution, time of day, etc. There are a number of factors that affect the SUV. I think the downside of this is that we see patients come in from referrings that, well, the PET scan was hot, the SUV was 4, therefore it is cancer, or it was only 1.5, therefore it is not cancer. So I would like to get your sense of whether your nuclear medicine physicians feel that this is going to be applicable broadly, and I wonder if they are wondering whether we are trying to put them out of business? If all you need is a number, then you don t need a nuclear medicine physician to interpret the scan for you. The second question is about methodology. You take a collection of data, you do an ROC curve analysis on it, and then use the results to re-analyze the same data and conclude that your derived test

7 Ann Thorac Surg BRYAT ET AL 2006;82: MaxSUV OF 2 LYMPH ODES works. What you really need to do is take the results and look at a different set of data. You probably have the data already to do that and I presume you are already doing it. I just wanted to point that out. Thank you. DR BRYAT: Thank you for your excellent questions. The reproducibility of an SUV, that is an excellent question that we are currently looking at. At our institution, our nuclear radiologists continue to provide us the max SUV. We feel that 423 it is a predictor of the pathology of the tumor. The SUV is generated by a standardized equation, and the one factor in the equation, the timing of the dose, is what tends to be variable across different PET centers, and the nuclear radiologists are attempting to standardize that. Additionally, I think that looking at just the trends within one institution itself is helpful. Also, regarding the ROC curve, yes, I think we definitely should take the 5.3 value and apply that and look at it with other data. GEERAL THORACIC Requirements for Recertification/Maintenance of Certification in 2006 Diplomates of the American Board of Thoracic Surgery who plan to participate in the Recertification/ Maintenance of Certification process in 2006 must hold an active medical license and must hold clinical privileges in thoracic surgery. In addition, a valid certificate is an absolute requirement for entrance into the recertification/maintenance of certification process. if your certificate has expired, the only pathway for renewal of a certificate is to take and pass the Part I (written) and the Part II (oral) certifying examinations. The American Board of Thoracic Surgery will no longer publish the names of individuals who have not recertified in the American Board of Medical Specialties directories. The Diplomate s name will be published upon successful completion of the recertification/maintenance of certification process. The CME requirements are 70 Category I credits in either cardiothoracic surgery or general surgery earned during the 2 years prior to application. SESATS and SESAPS are the only self-instructional materials allowed for credit. Category II credits are not allowed. The Physicians Recognition Award for recertifying in general surgery is not allowed in fulfillment of the CME requirements. Interested individuals should refer to the Booklet of Information for a complete description of acceptable CME credits. Diplomates should maintain a documented list of their major cases performed during the year prior to application for recertification. This practice review should consist of 1 year s consecutive major operative experiences. If more than 100 cases occur in 1 year, only 100 should be listed. Candidates for recertification/maintenance of certification will be required to complete all sections of the SESATS self-assessment examination. It is not necessary for candidates to purchase SESATS individually because it will be sent to candidates after their application has been approved. Diplomates may recertify the year their certificate expires, or if they wish to do so, they may recertify up to two years before it expires. However, the new certificate will be dated 10 years from the date of expiration of their original certificate or most recent recertification certificate. In other words, recertifying early does not alter the 10-year validation. Recertification/maintenance of certification is also open to Diplomates with an unlimited certificate and will in no way affect the validity of their original certificate. The deadline for submission of applications for the recertification/maintenance of certification process is May 10 each year. A brochure outlining the rules and requirements for recertification/maintenance of certification in thoracic surgery is available upon request from the American Board of Thoracic Surgery, 633 St. Clair St, Suite 2320, Chicago, IL 60611; telephone: (312) ; fax: (312) ; info@abts.org. This booklet is also published on the website: by The Society of Thoracic Surgeons Ann Thorac Surg 2006;82: /06/$32.00 Published by Elsevier Inc