Is There a Role for FDG PET in the Management of Lung Cancer Manifesting Predominantly as Ground-Glass Opacity?

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1 Cardiopulmonary Imaging Original Research Kim et al. Role of FDG PET in Ground-Glass Opacity Lung Cancer Cardiopulmonary Imaging Original Research Tae Jung Kim 1 Chang Min Park 2 Jin Mo Goo 2 Kyung Won Lee 1 Kim TJ, Park CM, Goo JM, Lee KW Keywords: FDG PET, ground-glass opacity, lung cancer, staging DOI: /AJR Received March 15, 2011; accepted after revision May 13, Department of Radiology, Seoul National University Bundang Hospital, 166 Gumiro, Bundang-gu, Seongnam-si, Gyeonggi-do, , Republic of Korea. Address correspondence to K. W. Lee (taejung.kim1@gmail.com). 2 Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea. AJR 2012; 198: X/12/ American Roentgen Ray Society Is There a Role for FDG PET in the Management of Lung Cancer Manifesting Predominantly as Ground-Glass Opacity? OBJECTIVE. The purposes of our study were to evaluate 18 F-FDG PET findings of ground-glass opacity (GGO) nodules and to determine the value of FDG PET for the preoperative staging of lung cancer manifesting predominantly as GGO. MATERIALS AND METHODS. Eighty-nine patients (46 men and 43 women; mean [± SD] age, 62.4 ± 7.2 years [range, years] and 61.7 ± 6.7 years [range, years], respectively) with 134 GGO nodules (56 single and 78 multiple) who underwent CT and FDG PET before surgery were included. CT and PET findings were assessed in terms of lesion size, GGO percentage, multiplicity, and maximum standardized uptake value (SUV max ). SUV max was correlated with lesion size and GGO percentage using linear regression. The SUV max and hypermetabolism rates of solitary and multiple GGO nodules were compared using the Student t test or Fisher exact test. Lymph node and distant organ metastasis staging by FDG PET were correlated with histopathologic findings. RESULTS. SUV max was positively correlated with lesion size (mean, 14.5 mm; range, 5 37 mm) (r = ; p < ) and was negatively correlated with GGO percentage (mean, 77%; range, %) (r = ; p < ). Solitary nodules showed higher hypermetabolism rates (73% [41/56]) than did multiple nodules (27% [21/78]) (p = ), but SUV max was not significantly different between solitary and multiple nodules. There was no true-positive interpretation of nodal or distant metastasis from GGO nodules by FDG PET. CONCLUSION. FDG PET showed no clear advantage for the staging of lung cancer with predominant GGO because of the low incidences of nodal and distant metastasis. P ET with 18F-FDG is a noninvasive diagnostic technique that provides information about glucose metabolism in lesions and is used routinely for the preoperative staging of nonsmall-cell lung cancer (NSCLC) because of its higher sensitivity and specificity than other diagnostic modalities [1, 2]. In the most widely cited metaanalysis of FDG PET in NSCLC, Gould et al. [1] found that the technique has a sensitivity of 96.8% and a specificity of 77.8% for lung cancer. However, although FDG PET is a valuable imaging modality for lung cancer staging, there are several pitfalls. It has been reported that bronchoalveolar carcinoma (BAC), which typically manifests as groundglass opacity (GGO) on CT, is falsely negative on PET [3 5]. Although numerous studies have addressed the performance characteristics of FDG PET in patients with known or suspected lung cancer, few studies have examined the accuracy of PET for BAC or adenocarcinoma with BAC components [6 8]. In addition, the clinical utility of FDG PET for the staging of lung cancer manifesting predominantly as GGO has not been thoroughly examined. The purposes of our study were to retrospectively evaluate FDG PET findings of GGO nodules and to determine the value of FDG PET for the preoperative staging of lung cancer manifesting predominantly as GGO. Materials and Methods The institutional review board of Seoul National University Bundang Hospital approved this study and waived the requirement for patient consent (IRB no. B ). Study Population Patients were identified by a retrospective data search using the terms ground-glass and GGO from the radiologic information system among the patients who underwent curative lung surgery in two tertiary hospitals (Seoul National University Bundang Hospital and Seoul National AJR:198, January

2 Kim et al. University Hospital) during January 2002 to February Patients who fulfilled the following criteria were included: pulmonary nodules with a GGO percentage of 50% or more, pulmonary nodules with pathologic confirmation by surgery, preoperative FDG PET and CT performed within 2 weeks of each other, and surgery performed within 2 weeks after PET. The percentage of GGO was calculated as follows: [(D GGO D) / D GGO ] 100, where D GGO is the greatest diameter of the lesion, including the GGO area, and D is the greatest diameter of the lesion without GGO [9, 10]. The study cohort comprised 89 patients (46 men and 43 women; mean [± SD] age, 62.4 ± 7.2 years [range, years] and 61.7 ± 6.7 years [range, years], respectively) with 134 pathologically confirmed GGO nodules. PET and CT: Imaging Protocol and Analysis PET was performed using one of two dedicated scanners (Allegro or Gemini, Philips Healthcare). All patients fasted for at least 6 hours before PET. FDG was IV injected at 5.18 MBq/kg, and whole-body scanning was performed at 50 minutes after FDG administration. The 3D row-action maximum-likelihood algorithm was used for the reconstruction of transaxial images of resolution 4.8 mm. For qualitative analysis, the degree of FDG activity in the nodules was defined as either negative (i.e., less than mediastinal blood-pool activity) or positive (i.e., same as or greater than mediastinal blood-pool activity). To analyze FDG accumulation, a circular region of interest was drawn by a board-certified nuclear medicine physician over GGO nodules on transaxial images on a slice-by-slice basis, so as to cover whole lesion A Fig year-old woman with known colon cancer. A, Axial CT image shows 1.2-cm pure ground-glass opacity nodule (arrow) in left upper lobe with negative FDG activity (maximum standardized uptake value [SUV max ] = 0.5). B, Axial CT image shows 1.5-cm solid nodule (arrow) in left lower lobe (SUV max = 1.9; data not shown). C, Coronal whole-body PET image shows hypermetabolism (arrow) (SUV max = 9.4) at colon cancer at hepatic flexure. Left upper lobe nodule was confirmed to be bronchoalveolar cell carcinoma, and left lower lobe nodule was confirmed to be pulmonary metastasis from colon cancer. volumes. In some patients, no nodules could be detected by PET because of very low FDG uptake. In these patients, regions of interest were drawn on chest CT predicted locations. Maximum standardized uptake value (SUV max ) was considered representative of FDG uptakes. FDG uptake by lymph nodes and by distant metastases and the presences of concurrent malignancies were also evaluated. When a lymph node had an SUV max of less than 2.5 g/ml or was read as no uptake, the node was considered negative. CT was performed using several CT scanners (Brilliance-64 and MX-8000 IDT, Philips Healthcare; Sensation-16 and Somatom Plus 4, Siemens Fig year-old woman with adenocarcinoma with bronchoalveolar cell carcinoma components. A, Axial CT image shows 2.8-cm mixed ground-glass opacity nodule (arrow) in right lower lobe. B, Coronal whole-body PET image shows mild hypermetabolism (arrow) (maximum standardized uptake value = 1.4). B A Healthcare; and LightSpeed Ultra and HiSpeed Advantage, GE Healthcare) with 120 kvp, ma, and a pitch of Thin-section CT images were reconstructed into 0.67 to 1.25-mm-thick sections using high-frequency algorithms. Thicksection CT images were reconstructed as 3 to 5-mmthick sections using lung reconstruction algorithms. Images were displayed with lung (level, 600 HU; width, 1500 HU) and mediastinal (level, 30 HU; width, 400 HU) window settings. One chest radiologist with 8 years of experience in chest CT interpretation, who was unaware of clinical findings and histologic diagnosis, reviewed all CT images and measured lesion size and GGO percentage. C B 84 AJR:198, January 2012

3 Role of FDG PET in Ground-Glass Opacity Lung Cancer Fig year-old woman with adenocarcinoma with bronchoalveolar cell carcinoma (BAC) components. A, Axial CT image shows 2.1-cm mixed ground-glass opacity nodule (arrow) in right upper lobe. B, Coronal whole-body PET image shows hypermetabolism at right upper lobe nodule (small arrow) (maximum standardized uptake value [SUV max ] = 2.4), right paratracheal lymph node (arrowhead) (SUV max = 4.0), and subcarinal lymph node (large arrow) (SUV max = 3.9). Right upper lobe nodule was confirmed to be adenocarcinoma with BAC components, and mediastinal lymph nodes turned out to be chronic granulomatous inflammation of tuberculosis. Pathologic Diagnoses and Postoperative Follow-Up Pathologic examinations were performed over the entire volumes of GGO nodules. Resected specimens were fixed in formalin and embedded in paraffin, and all lesion sections were stained with H and E. Hilar or mediastinal lymph node metastases were evaluated when lymph node dissection was performed. In cases with multiple primary tumors, each tumor was staged independently as a primary tumor. Lymph node metastasis or postoperative recurrence was regarded to have resulted from tumors with the most advanced stage or the largest size. Postoperative follow-up results were evaluated on the basis of clinical surveillance and CT findings. Follow-up CT was performed at 3- or 6-month intervals (BAC or adenocarcinoma with BAC components) or at 6- or 12-month intervals (atypical adenomatous hyperplasia [AAH] or focal interstitial fibrosis) in accordance with postsurgical pathologic findings. Statistical Analysis The SUV max was correlated with lesion size and GGO percentage, and the GGO percentage was correlated with lesion size with linear regression analysis. The mean SUV max and hypermetabolism rates on FDG PET were compared between nodules with different histologic profiles and between solitary and multiple GGO nodules using the unpaired Student t test or Fisher exact test, as appropriate. The GGO percentage was also compared between solitary and multiple GGO nodules using an unpaired Student t test. The proportion of AAH or BAC was compared between solitary and multiple GGO nodules using Fisher exact test; p values of less than 0.05 were considered to indicate statistical significance. Statistical analysis was performed with a statistical software package (SPSS version 15.0, SPSS). Results Demographic Findings and Histologic Diagnoses Of the 89 patients with 134 pathologically confirmed GGO nodules (mean, 1.5 nodules/ patient; range, 1 5 nodules/patient), 56 had a solitary GGO nodule and 33 had 78 multiple GGO nodules among a total of 188 GGO nodules detected by CT (mean, 2 nodules/ patient; range, 2 15 nodules/patient). The interval between PET and surgery ranged from 1 to 14 days (mean, 7 days). Pathologic specimens were obtained by lobectomy for 105 nodules, by segmentectomy for four, and by wedge resection for 25. Histologic diagnoses of the 56 solitary GGO nodules in 19 women and 37 men (mean age, 57; age range, years) included AAH (n = 3), BAC (n = 7) (Fig. 1), adenocarcinoma with BAC components (n = 45) (Figs. 2 and 3), and focal interstitial fibrosis (n = 1), and the histologic diagnoses of 78 multiple GGO nodules in 24 women and nine men (mean age, 56 years; age range, years) included AAH (n = 19), BAC (n = 26), adenocarcinoma with BAC components (n = 30), and focal interstitial fibrosis (n = 3). The proportion of AAH or BAC A in multiple GGO nodules (58% [45/78]) was significantly higher than that of solitary GGO nodules (18% [10/56]) (p = ). CT and PET Findings CT and PET results according to histologies and multiplicities of nodules are summarized in Table 1. The mean diameter of GGO nodules was 15 mm (range, 5 37 mm), and GGO nodule diameter was positively correlated with SUV max (mean, 1.2; range, ) (r = 0.67; p < ). The mean diameter of solitary GGO nodules (17 ± 8.1 mm) was significantly larger than that of multiple GGO nodules (12 ± 7.9 mm) (p < 0.001). The mean GGO percentage was 77% (range, %) and negatively correlated with SUV max (r = 0.75; p < ) and lesion size (r = 0.588; p < 0.001). Hypermetabolism rate, mean SUV max, and mean diameter of adenocarcinoma with BAC components were significantly larger than those of BAC, AAH, or focal fibrosis (p < , respectively). The mean GGO percentage of adenocarcinoma with BAC components was significantly smaller than those of BAC, AAH, or focal fibrosis (p < 0.001, respectively). The hypermetabolism rate and the mean SUV max of BAC were much larger than those of AAH (p < ). In terms of multiplicity, 41 of the 56 (73%) solitary GGO nodules showed hypermetabolism, and 21 of the 78 (27%) multiple GGO nodules showed hypermetabolism (per lesion base). The mean SUV max was 1.3 (range, ) in solitary GGO nodules and B AJR:198, January

4 Kim et al. 0.5 (range, ) in multiple GGO nodules. The hypermetabolism rate was higher for solitary than multiple GGO nodules (p = ), but the mean SUV max of solitary compared with multiple GGO nodules was not significantly different (p = ). The GGO percentage of multiple GGO nodules was significantly larger than that of solitary GGO nodules (p = ). Lung Cancer Staging: PET and Pathologic Correlations All patients with malignant nodules underwent curative resection by video-assisted thoracoscopic surgery or open thoracotomy. All malignant GGO nodules were either BAC or adenocarcinoma with BAC components; pt1n0 (n = 93) was the most common stage for both multiple and solitary GGO nodules, followed by pt2n0 (n = 15). Nodal metastases detected by both PET and pathology in two patients with a solitary GGO nodule (one pn1 and one pn2) were regarded to have resulted from concurrent solid lung cancer with a more advanced stage (pt2 adenocarcinomas) rather than from GGO nodules (pt1 BAC and pt1 adenocarcinoma, respectively). Three interpretations of mediastinal nodal metastases by PET turned out to be chronic granulomatous inflammation that was suggested by pathologic examination to be due to tuberculosis (Fig. 3); two nodes (< 10 mm in short-axis diameter) showed peripheral calcification, and one node (12 mm in short-axis diameter) showed diffuse higher attenuation (110 HU) than that in surrounding great vessels. Therefore, in the current study, there was no true-positive interpretation of nodal or distant metastasis from GGO nodules by PET. PET depicted hypermetabolism due to concurrent malignancies (n = 6) that were known at the time of PET, including concurrent solid lung cancer in three patients, pulmonary metastasis resulting from gastrointestinal malignancy in one patient, colon cancer in one patient (Fig. 1), and chondrosarcoma in the humerus in one patient. There was no recurrence over an average follow-up period of 30 months (range, months), except for one patient with adenocarcinoma (pt2n0). None of our patients died of the disease during the follow-up period. Discussion FDG PET has been shown to accurately stage NSCLC, and as a result has been widely adopted as the standard care for the evaluation of patients with NSCLC. However, the role of PET in the diagnosis and staging of BAC or adenocarcinoma with BAC components, which typically manifest as GGO at CT, has not been determined. Most studies have addressed the presence or absence of FDG uptake in terms of differentiating benign and malignant lesions [4, 11] or BAC from adenocarcinoma with BAC components [6]. Furthermore, few data are available on relationships between CT and PET findings of pulmonary GGO lesions. In the current study, SUV max showed a positive correlation with lesion size and a negative correlation with GGO percentage, both of which are known to be well correlated with histologic invasiveness and prognosis of BAC and adenocarcinoma with BAC components [12]. This concurs with the findings of Goudarzi et al. [6], who found a correlation between CT findings (i.e., size and CT density) and SUV max in BAC and adenocarcinoma with BAC components. In terms of the multiplicity of GGO nodules, we found that nodule size and hypermetabolism rate were significantly greater for solitary than multiple GGO nodules. This can be explained by the high incidence of AAH and BAC in multiple GGO nodules, because AAH and BAC are smaller and are associated with a larger proportion of GGO than those of adenocarcinoma with BAC components [10]. TABLE 1: CT and PET Results According to Histology and Multiplicity Compared with CT, PET was found to contribute little to the primary tumor staging (T staging) of lung cancer with predominant GGO; only 24% of BACs and 69% of adenocarcinomas with BAC components were FDG avid, which was similar to the results of other studies. Higashi et al. [4] reported that four of seven BACs showed negative results on PET, whereas only one of 23 non- BAC tumors showed a negative result. Port et al. [13] found that 23% of adenocarcinomas with BAC components and 58% of adenocarcinomas were FDG avid as compared with 88% of FDG-avid tumors with other histologic profiles. Although Goudarzi et al. [6] asserted that the combined findings from PET and CT could be useful for the diagnosis and management of BAC and adenocarcinoma with BAC components, preoperative differentiation of pure BAC and adenocarcinoma with BAC components cannot be accurate given that the current criteria for BAC mandate that the diagnosis be made only on examination of large (i.e., surgical) biopsy specimens [14]. In addition, although most imaging modalities used for lung cancer staging are generally not able to provide specific information on histologic subtype, lung cancer with predominant GGO at CT can strongly suggest a diagnosis of BAC or adenocarcinoma with BAC components. Therefore, the characteristic CT finding of predominant GGO has more important implications than PET results for these lesions. It is widely accepted that PET improves the detection of local and distant metastases and can prevent futile thoracotomy in patients with NSCLC [15 18]. However, it is unlikely to detect occult lymph nodes or distant metastasis in lung cancer with predominant GGO because of the low rate of metastases shown by these lesions. In the current study, no nodal or distant metastasis was found for lung cancer with predominant GGO, whereas Histologic Profile Nodule Diameter (mm) GGO Percentage PET Positivity, No. (%) of Nodules SUV max BAC (n = 33) 10 ± 6.6 (4 26) 90 ± 20 (51 100) 8 (24) 1.8 ± 1.0 ( ) Adenocarcinoma (n = 75) 20 ± 6.7 (7 36) 63 ± 19 (51 100) 52 (69) 2.9 ± 1.1 ( ) AAH (n = 22) 5 ± 2.2 (3 12) 100 ± 0 1 (5) 0.7 ± 0.5 ( ) Focal fibrosis (n = 4) 6 ± 2.0 (5 9) 89 ± 22 (56 100) 1 (25) 1.0 ± 0.9 ( ) Multiplicity Solitary GGO (n = 56) 17 ± 8.1 (5 32) 79 ± 20 (51 100) 41 (73) 1.3 ± 1.0 ( ) Multiple GGO (n = 78) 12 ± 7.9 (5 37) 92 ± 19 (51 100) 21 (27) 0.5 ± 1.1 ( ) Note Except where indicated otherwise, data are mean ± SD (range). AAH = atypical adenomatous hyperplasia, BAC = bronchoalveolar cell carcinoma, GGO = ground-glass opacity, SUV max = maximum standardized uptake value. 86 AJR:198, January 2012

5 Role of FDG PET in Ground-Glass Opacity Lung Cancer in three patients, false-positive interpretations of mediastinal nodal metastases were made by PET. According to a study on the prognostic importance of thin-section CT features in peripheral lung adenocarcinoma [12], all adenocarcinomas smaller than 2 cm with a GGO proportion exceeding 50% of tumor volume were free of lymph node metastasis and vessel invasion, and all these patients remained alive without recurrence 10 years later. After numerous initial reports proclaiming the benefits of PET in lung cancer staging, several reports have been published on the limitations of PET for the evaluation of small early lung cancer. Port et al. [13] concluded that PET has no demonstrable benefit in terms of diagnosis, staging, or prognosis in patients with a lung cancer of 2 cm or smaller because of the low prevalence of mediastinal nodal and distant metastases. In a study by Kozower et al. [19], PET prevented nontherapeutic thoracotomy in 7.4% of patients with clinical stage IA NSCLC by identifying metastatic disease, and this is significantly lower than 20% prevention rate suggested by two recent trials that both evaluated patients with potentially resectable cancer (stages IA IIIA) [16, 17]. The frequent false-positive results of PET for early lung cancer and the subsequent burden of expensive and bothersome confirmatory studies are also worrisome. False-positive results of nodal metastasis by PET occur for reactive hyperplasia or granulomatous inflammation, and thus, false-positive rates are highly dependent on the patient population [20]. In our study, all three false-positive interpretations of mediastinal nodal metastases by PET turned out to be granulomatous inflammation of tuberculosis. The standard treatment for operable NSCLC, even clinical T1N0 disease, remains lobectomy with hilar and mediastinal lymph node dissection [21]. However, clinical investigations to date have suggested that limited resection could be successfully performed for BAC that typically manifests as GGO at CT [22 24]. In addition, a recent study by Okada et al. [25] found that the nodules with GGO greater than 50% had up to 6% of nodal metastasis and up to 4% of recurrence rate and that both decreased to only 1% when the nodules had SUV max less than 1.5. In our study, FDG PET showed a higher rate of hypermetabolism in adenocarcinoma with BAC components than in BAC. These findings may suggest that a selection of sublobar resection based on a combination of information from both CT and FDG PET could be a potential clinical implication in terms of limited resection [26]. There are several limitations to this study. First, the retrospective nature of the study unavoidably introduces the issue of inherent bias. Second, SUV max analyzed in our study was subject to variability among subjects, much more than normalized SUV ratios (e.g., normalization by the liver uptake). Third, it was not feasible to evaluate the diagnostic accuracy of PET in the assessment of nodal or distant metastasis staging because no true-positive metastasis case was included. Fourth, the postoperative follow-up period was inadequate in terms of evaluating survival or disease recurrence, and longterm follow-up over several years is needed to assess prognosis accurately in lung cancer with predominant GGO. Fifth, data clustering is another possible limitation, because we included multiple nodules per patient. However, we did not adopt a statistical method, such as a generalized estimating equation approach, to manage this issue, because recent multiclonal BAC and adenocarcinoma studies have suggested that these lesions behave in an independent manner [27 29]. In summary, when CT shows a pulmonary nodule with predominant GGO, FDG PET frequently produces negative results. Furthermore, FDG PET is unlikely to detect lymph nodes or distant metastasis because of their low prevalence and, thus, does not appear to offer a clear advantage in patients with lung cancer manifesting as predominant GGO. References 1. Gould MK, Maclean CC, Kuschner WG, Rydzak CE, Owens DK. Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions: a meta-analysis. JAMA 2001; 285: Lardinois D, Weder W, Hany T, et al. Staging of non-small-cell lung cancer with integrated positron-emission tomography and computed tomography. N Engl J Med 2003; 348: Cook GJR, Wegner EA, Fogelman I. Pitfalls and artifacts in 18FDG PET and PET/CT oncologic imaging. Semin Nucl Med 2004; 34: Higashi K, Ueda Y, Seki H, et al. Fluorine- 18-FDG PET imaging is negative in bronchioloalveolar lung carcinoma. J Nucl Med 1998; 39: Kim BT, Kim Y, Lee KS, et al. Localized form of bronchioloalveolar carcinoma: FDG PET findings. AJR 1998; 170: Goudarzi B, Jacene HA, Wahl RL. Diagnosis and differentiation of bronchioloalveolar carcinoma from adenocarcinoma with bronchioloalveolar components with metabolic and anatomic characteristics using PET/CT. J Nucl Med 2008; 49: Lee HY, Lee KS, Han J, et al. Mucinous versus nonmucinous solitary pulmonary nodular bronchioloalveolar carcinoma: CT and FDG PET findings and pathologic comparisons. Lung Cancer 2009; 65: Okada M, Tauchi S, Iwanaga K, et al. Associations among bronchioloalveolar carcinoma components, positron emission tomographic and computed tomographic findings, and malignant behavior in small lung adenocarcinomas. J Thorac Cardiovasc Surg 2007; 133: Kim TJ, Lee J-H, Lee C-T, et al. Diagnostic accuracy of CT-guided core biopsy of ground-glass opacity pulmonary lesions. AJR 2008; 190: Kim TJ, Goo JM, Lee KW, Park CM, Lee HJ. Clinical, pathological and thin-section CT features of persistent multiple ground-glass opacity nodules: comparison with solitary ground-glass opacity nodule. Lung Cancer 2009; 64: Heyneman LE, Patz EF. PET imaging in patients with bronchioloalveolar cell carcinoma. Lung Cancer 2002; 38: Aoki T, Tomoda Y, Watanabe H, et al. Peripheral lung adenocarcinoma: correlation of thin-section CT findings with histologic prognostic factors and survival. Radiology 2001; 220: Port JL, Andrade RS, Levin MA, et al. 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 2005; 130: Travis WD, Garg K, Franklin WA, et al. Bronchioloalveolar carcinoma and lung adenocarcinoma: the clinical importance and research relevance of the 2004 World Health Organization Pathologic Criteria. J Thorac Oncol 2006; 1:S13 S Pieterman RM, van Putten JW, Meuzelaar JJ, et al. Preoperative staging of non-small-cell lung cancer with positron-emission tomography. N Engl J Med 2000; 343: Reed CE, Harpole DH, Posther KE, et al. Results of the American College of Surgeons Oncology Group Z0050 trial: the utility of positron emission tomography in staging potentially operable nonsmall cell lung cancer. J Thorac Cardiovasc Surg 2003; 126: van Tinteren H, Hoekstra OS, Smit EF, et al. Effectiveness of positron emission tomography in the preoperative assessment of patients with suspected non-small-cell lung cancer: the PLUS mul- AJR:198, January

6 Kim et al. ticentre randomised trial. Lancet 2002; 359: Viney RC, Boyer MJ, King MT, et al. Randomized controlled trial of the role of positron emission tomography in the management of stage I and II non-small-cell lung cancer. J Clin Oncol 2004; 22: Kozower BD, Meyers BF, Reed CE, Jones DR, Decker PA, Putnam JB Jr. Does positron emission tomography prevent nontherapeutic pulmonary resections for clinical stage IA lung cancer? Ann Thorac Surg 2008; 85: Shim SS, Lee KS, Kim B-T, et al. Non-small cell lung cancer: prospective comparison of integrated FDG PET/CT and CT alone for preoperative staging. Radiology 2005; 236: Ginsberg RJ, Rubinstein LV. Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Lung Cancer Study Group. Ann Thorac Surg 1995; 60: Arenberg D. Bronchioloalveolar lung cancer: ACCP evidence-based clinical practice guidelines 2nd edition. Chest 2007; 132:306S 313S 23. Kodama K, Higashiyama M, Takami K, et al. Treatment strategy for patients with small peripheral lung lesion(s): intermediate-term results of prospective study. Eur J Cardiothorac Surg 2008; 34: Koike T, Yamato Y, Yoshiya K, Shimoyama T, Suzuki R. Intentional limited pulmonary resection for peripheral T1 N0 M0 small-sized lung cancer. J Thorac Cardiovasc Surg 2003; 125: Okada M, Nakayama H, Okumura S, et al. Multicenter analysis of high-resolution computed tomography and positron emission tomography/ computed tomography findings to choose therapeutic strategies for clinical stage IA lung adenocarcinoma. J Thorac Cardiovasc Surg 2011; 141: Yoshioka M, Ichiguchi O. Selection of sublobar resection for c-stage IA non-small cell lung cancer based on a combination of structural imaging by CT and functional imaging by FDG PET. Ann Thorac Cardiovasc Surg 2009; 15: Nanki N, Fujita J, Hojo S, et al. Evaluation of the clonality of multilobar bronchioloalveolar carcinoma of the lung: case report. Am J Clin Oncol 2002; 25: Barsky SH, Grossman DA, Ho J, Holmes EC. The multifocality of bronchioloalveolar lung carcinoma: evidence and implications of a multiclonal origin. Mod Pathol 1994; 7: Okubo K, Mark EJ, Flieder D, et al. Bronchoalveolar carcinoma: clinical, radiologic, and pathologic factors and survival. J Thorac Cardiovasc Surg 1999; 118: FOR YOUR INFORMATION The comprehensive book based on the ARRS 2011 annual meeting categorical course on Imaging of the Active Lifestyle: From the Weekend Warrior to the Pro Athlete is now available! For more information or to purchase a copy, see 88 AJR:198, January 2012