Japanese Journal of Clinical Oncology Advance Access originally published online on June 16, 2006
Japanese Journal of Clinical Oncology 2006 36(7):403-409; doi:10.1093/jjco/hyl043
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© 2006 Foundation for Promotion of Cancer Research
[F-18]Fluorodeoxyglucose Positron Emission Tomography Can Predict Pathological Tumor Stage and Proliferative Activity Determined by Ki-67 in Clinical Stage IA Lung Adenocarcinomas
1 Department of Thoracic Surgery and Respiratory Group, Saiseikai Central Hospital, Tokyo, 2 Department of Thoracic Surgery, Graduate School of Medicine, Kumamoto University, Kumamoto, 3 Department of Pathology, Saiseikai Central Hospital, Tokyo, 4 Nishidai Clinic, Tokyo, 5 Development in Assistive Diagnostic Technology, National Cancer Center Hospital, Tokyo and 6 Department of Surgery, Kyorin University, Mitaka, Tokyo, Japan
For all reprints and all correspondence: Hiroaki Nomori, Department of Thoracic Surgery, Graduate School of Medicine, Kumamoto University, 1-1-1, Honjo, Kumamoto 860-8556, Japan; E-mail: hnomori{at}kaiju.medic.kumamoto-u.ac.jp
Received December 18, 2005; accepted April 3, 2006
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Abstract |
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 TOP Abstract INTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONReferences |
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Objective: To predict a malignant grade of lung cancer by fluorodeoxyglucose positron emission tomography (FDG-PET) scanning, we investigated the correlation between FDG uptake and pathological tumor stage, proliferative activities determined by Ki-67 and cyclin D1, and an alteration of p53, in clinical stage (c-stage) IA lung adenocarcinomas.
Methods: FDG-PET was performed for 71 patients with c-stage IA lung adenocarcinomas. FDG uptake was measured by a contrast ratio (CR) between the tumor and contralateral lung. Ki-67, cyclin D1 and p53 staining scores were examined by immunohistochemistry.
Results: The lesions with ground-glass opacity were found in 26 patients, and solid lesions in 45 by computed tomography. The pathological tumor stages (p-stage) were stage IA in 59 and more advanced stages in 12. The latter had significantly higher CR value than the former (P < 0.001). Patients with CR 
0.55 could be predicted to be at advanced tumor stages, with a sensitivity of 0.83 and a specificity of 0.82. The CR and staining scores of Ki-67 were significantly correlated with each other (P < 0.0001), and both the values were significantly higher in advanced tumor stages than in p-stage IA, and were also significantly higher in tumors with intratumoral lymphatic, vascular and pleural involvements than in those without such features (P < 0.05–0.0001).
Conclusions: In c-stage IA lung adenocarcinomas, the FDG uptake can predict p-stage and tumor proliferative activity determined by Ki-67. For c-stage IA lung adenocarcinomas showing CR 0.55, mediastinoscopy or neoadjuvant chemotherapy is indicated.
Key Words: positron emission tomography • lung cancer • adenocarcinoma • tumor stage • proliferative activity • tumor suppressor gene
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INTRODUCTION |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONReferences |
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It has been reported that tumor proliferative activity and alterations of tumor suppressor genes could be prognostic factors in non-small cell lung cancer (NSCLC). Some authors have demonstrated that proliferative activities determined by Ki-67 (1) and cyclin D1 (2–5), and an alteration of p53 were correlated with the prognosis of NSCLC patients (4,6,7). In recent years, F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has been frequently used for the diagnosis and staging of lung cancer (8–10). FDG uptake has been reported to be correlated not only with the prognosis in NSCLC patients (11,12) but also with the proliferative activity (13,14) and alteration of p53 (7) of the tumor. However, we previously reported that the FDG uptake in NSCLC tumors was dependent on histological types, that is, FDG-uptake of adenocarcinomas correlated with the pathological tumor stage and tumor invasiveness, but that of the other histological types did not (15,16). Therefore, we consider that the correlation between the FDG uptake and the proliferative activity or alteration of p53 should be examined in adenocarcinomas, but not in NSCLC including all histological types. Furthermore, FDG uptake is known to be higher in larger tumors (17,18). Therefore, in the present study, we measured the FDG uptake in clinical stage IA adenocarcinomas and investigated its relationships with the pathological tumor stage, intratumoral invasiveness, proliferative activity determined by Ki-67 and cyclin D1 and the alteration of p53.
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PATIENTS AND METHODS |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONReferences |
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PATIENTS
Between December 2001 and February 2005, FDG-PET was performed for 386 patients with pulmonary nodules. Of these, 301 patients had malignant tumors and 178 of the 301 patients had lung adenocarcinoma. Of the 178 adenocarcinoma patients, 77 were diagnosed as clinical stage IA by PET and thin section computed tomography (TSCT: <2 mm in thickness). They were treated by segmentectomy or lobectomy and lymph node dissection. Of these, we excluded six adenocarcinomas < 1 cm, because the spatial resolution of the PET scanner is 0.7–0.8 cm, making it difficult to image the pulmonary nodules that are <1 cm (16). Therefore, we studied 71 patients with clinical stage IA adenocarcinoma with a size range of 1–3 cm.
FDG-PET SCANNING
Patients were instructed to fast for at least 4 h before intravenous (i.v.) administration of F-18 FDG. The dosage of F-18 FDG administered was 125 µCi/kg (4.6 MBq/kg) for non-diabetic patients and 150 µCi/kg (5.6 MBq/kg) for diabetic patients. PET imaging was performed 
60 min after administration of FDG with a POSICAM.HZL m-POWER (Positron Co., Houston, TX, USA). No attenuation-corrected emission scans were initially obtained in two-dimensional, high-sensitivity mode for 4 min per bed position, and taken from the vertical skull through the mid-thighs. Immediately thereafter, a two-bed-position attenuation-corrected examination was performed with 6 min for the emission sequence and 6 min for the transmission sequence at each bed position.
PET IMAGE PROCESSING AND DATA ANALYSIS
The images were usually reconstructed in a 256 x 256 matrix by using ordered subset expectation maximization corresponding to a pixel size of 4 x 4 mm, with section spacing of 2.66 mm. FDG uptake was evaluated by contrast ratio (CR) with contralateral lung, as previously reported (15,16,19). Briefly, the regions of interest (ROI) were placed in the nodules and contralateral normal lung. Highest standardized uptake ratios in the tumor ROI (T) and in the contralateral lung ROI (N) were measured. The CR value was calculated by using the formula [(T – N)/(T + N)] in each nodule as an index of FDG uptake.
PATHOLOGICAL ANALYSIS
Hematoxylin and eosin and Elastica-van Gieson stainings were performed in all sections to investigate the intratumoral lymphatic and vascular invasions and pleural involvement. Pleural involvement was classified as p0, p1, p2 and p3; that is, a p0 tumor did not extend beyond the pleural elastic layer; a p1 tumor invaded the visceral pleural elastic layer, but did not reach the pleural surface; a p2 tumor included tumor exposure on the pleural surface; and a p3 tumor invaded the parietal pleura or the chest wall. The tumor stages were based on the TNM classification of the International Union Against Cancer (20): p2 tumors were classified as T2, p3 tumors were classified as T3 and tumors with intrapulmonary metastases within the same lobe were classified as T4.
PREDICTING ADVANCED TUMOR STAGES FROM FDG UPTAKE
Receiver operating characteristics (ROC) curve (21) was constructed according to the CR value, and the cut-off value was determined for predicting the pathological stages that were more advanced than stage IB.
IMMUNOHISTOCHEMICAL ANALYSIS
Immunostaining was performed by using the Dako envision system (Dako Cytomation, Glostrup, Denmark). The antibodies for Ki-67(monoclonal mouse antibody MIB-1, 1 : 100 dilution), cyclin D1 (monoclonal mouse antibody DCS-1, 1 : 50 dilution) and p53 (monoclonal mouse antibody, DO7, 1 : 400 dilution) were purchased from Dako Co. Sections of 4 µm were cut from the paraffin blocks. Immunostaining was performed with antigen-retrieval techniques.
EVALUATION OF IMMUNOHISTOCHEMICAL STAINING
Ki-67
According to the method of Martin et al. (1), the labeling index of Ki-67 was measured by determining the percentage of cells with positive nuclei in >1000 tumor cells in >4 fields.
Cyclin D1 and p53
The Allred score used to examine the staining scores of cyclin D1 as well as p53 was obtained by determining the percentage of positive tumor cells and staining intensity (22). Briefly, a percentage score was measured by determining the percentage of positive tumor cells in >1000 tumor cells in >4 fields (0, none; 1, <1/100; 2, 1/100–1/10; 3, 1/10–1/3; 4, 1/3–2/3; 5, >2/3). An intensity score was measured by the average of staining intensity (0, none; 1, weak; 2, intermediate; and 3, strong). The sum of the percentage score and the intensity score was used as the Allred score.
STATISTICAL ANALYSIS
The values of CR and staining scores of Ki-67, cyclin D1 and p53 were compared between the pathological stage IA and the more advanced stages and between the two groups with or without intratumoral lymphatic, vascular invasion and pleural involvement, by the non-parametric Mann–Whitney's U-test. The correlations between the CR values and the staining scores of Ki-67, cyclin D1 and p53 were analyzed by using the non-parametric Spearman's rank test. All values in the text and tables are given as mean ± standard deviation.
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RESULTS |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONReferences |
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Table 1 shows patients' characteristics. The lesion showing ground-glass opacity (GGO) image were found in 26 patients, and the solid lesions in 45 patients at visual TSCT findings. The pathological tumor stages were T1N0M0 in 59 patients and more advanced in 12 patients (i.e. T2N0M0 in 3, T1N1M0 in 4, T2N1M0 in 1, T1N2M0 in 1, T4N0M0 in 2 and T4N2M1 in 1).
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Figure 1 shows the distribution of CR values in 59 patients with pathological stage IA and 12 patients with more advanced stages. The mean CR value of the 12 patients with advanced stages was 0.66 ± 0.12, which was significantly higher than 0.32 ± 0.18 of the 59 patients with pathological stage IA (P < 0.001).
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Figure 2 depicts the ROC curve for predicting tumor stages more advanced than IB, showing the optimal CR cut-off value to be 0.55, of which sensitivity, specificity and accuracy were 0.83, 0.81 and 0.82, respectively. While 10 of the 12 patients (83%) with the advanced stage showed CR values
0.55, 48 of the 59 patients (81%) with pathological stage IA showed CR values < 0.55 (Table 2).
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Figures 3
–5 show the distribution of staining scores of Ki-67, cyclin D1 and p53 in the 59 patients with pathological stage IA and 12 patients with more advanced stages. The mean score for Ki-67 in the 12 patients with advanced stages was 18.0 ± 11.0, which was significantly higher than 9.4 ± 12.0 for the 59 patients with pathological stage IA (P = 0.012). However, the mean scores for cyclin D1 in the advanced tumor stages and pathological stage IA were 3.9 ± 1.7 and 4.1 ± 1.8, respectively, of which difference was not significant. The mean scores for p53 in the advanced tumor stages and pathological stage IA were 3.3 ± 3.6 and 2.6 ± 2.6, respectively, of which difference was also not significant.
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Table 3 shows the mean values of CR, Ki-67, cyclin D1 and p53 staining scores in tumors with or without intratumoral lymphatic, vascular and pleural involvements. Tumors with intratumoral lymphatic, vascular and pleural involvements had significantly higher values of both CR and Ki-67 staining scores (P < 0.05–0.001). However, there were no significant differences of tumor invasiveness in the cyclin D1 and p53 staining scores.
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Table 4 shows the mean values of CR and Ki-67 staining scores in tumors with stage IA and advanced stages in tumors with GGO and solid images. In 26 tumors with GGO image, 25 were stage IA and the other one was stage IB. The GGO tumors showed significantly lower CR and Ki-67 staining scores than the solid tumors (P < 0.001). The mean values of CR of the 25 GGO tumors with stage IA was 0.17 ± 0.14, while the CR of the one tumor with stage IB was 0.48. The mean values of Ki-67 staining scores of the 25 GGO tumors with stage IA was 4.7 ± 6.9, while the CR of the one tumor with stage IB was 0.16. In 45 tumors with solid image, 34 were stage IA and 11 were more advanced than stage IB. The mean values of CR of the 34 solid tumors with stage IA was 0.43 ± 0.20, which was significantly lower than 0.67 ± 0.11 of the 11 tumors with more advanced stages (P < 0.001). The mean values of Ki-67 staining scores of the 34 solid tumors with stage IA was 13 ± 13, which was lower than 21 ± 10 of the 11 solid tumors with more advanced stages (P = 0.056).
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The CR value and Ki-67 staining scores were significantly correlated with each other (r = 0.42, P < 0.0001) (Fig. 6). However, both cyclin D1 and p53 scores did not show any correlation with the CR values (r = 0.05 and 0.07, respectively).
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DISCUSSION |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONReferences |
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Although the standard uptake value (SUV) has been frequently used for evaluation of FDG-PET, it has been reported that several factors can affect the SUV, such as body size (23), blood glucose level (24), time after injection (25) and lesion size (17,18). In fact, the mean SUV of malignant pulmonary nodules has been reported to be various, ranging from 5.5 to 10.1 (26–29). We previously compared the results of SUV, CR with contralateral lung and CR with cerebellum for pulmonary nodules, and reported that the CR with contralateral lung or cerebellum showed significantly higher sensitivity than the SUV (19). We therefore used the CR value with contralateral lung in the present study.
The present study has demonstrated the following points: (i) tumors with high FDG uptake (CR 0.55) could be identified as those at stages that are more advanced than stage IB with the sensitivity of 0.83 and the specificity of 0.81; (ii) FDG uptake and Ki-67 staining scores correlated with the pathological tumor stage and intratumoral invasiveness, although cyclin D1 and p53 did not show such correlation; and (iii) FDG uptake and Ki-67 scores were significantly correlated with each other.
Earlier reports have indicated that adenocarcinomas with GGO image are usually N0 stage and show low FDG uptake on PET (15,16,30). The present study is basically in agreement with these results, that is, adenocarcinomas with GGO image showed lower FDG uptake than those with solid one. However, one adenocarcinoma with GGO image was stage IB, which showed rather high CR than 25 stage IA tumors. In tumors with solid image, the 11 tumors with advanced stages showed significantly higher CR values than the 34 tumors with stage IA. Therefore, the FDG uptake on PET could be an independent factor for predicting pathological stage in clinical T1N0M0 lung adenocarcinomas.
It has been reported that 25% of clinical stage IA adenocarcinomas are pathologically advanced tumor stage (31). Recently, neoadjuvant chemotherapy has been reported to improve survival in clinical stages IB, II and IIIA of NSCLC (32). The present study showed that the CR value of 0.55 could be the cut-off value for predicting advanced tumor stages more than IB. Therefore, we propose that to improve patients' prognosis in clinical stage IA adenocarcinoma, mediastinoscopy or neoadjuvant chemotherapy should be performed for clinical stage IA adenocarcinoma with CR 0.55.
The Ki-67 antigen exists in the nucleus of proliferating cells and has been reported to be a prognostic factor in lung cancer (1). Vesselle et al. (14) reported that the FDG uptake correlated with Ki-67 staining scores in 39 patients with NSCLC. They also described that the correlation between the FDG-uptake and Ki-67 staining scores was stronger in stage I than in stages I–III. Their report supported the present study, showing a significant correlation between the FDG uptake and Ki-67 staining scores in clinical stage IA lung adenocarcinomas.
Cyclin D1 is known to regulate the G1-to-S phase transition during the cell cycle, and its expression in tumor cells is reported to correlate with their proliferative activity. However, several immunohistochemical studies on involvement of cyclin D1 in lung cancer had shown different results (2–5). While some authors reported the opposite finding, that is, the cyclin D1 staining scores was a predictor of poor prognosis of NSCLC (4,5), others have questioned its role as a predictor (3). On the other hand, another report described that the negative staining for cyclin D1 correlated with poor prognosis (2). While these previous studies examined the expression of cyclin D1 in NSCLC including all histological types, the present study investigated the clinical stage IA adenocarcinomas, showing that cyclin D1 scores did not correlate with the FDG uptake, pathological tumor stage or tumor invasiveness. Our results indicate that Ki-67 is a better marker for the proliferative activity and malignant grade of adenocarcinomas than cyclin D1.
An alteration of p53 is reported to be a poor prognostic factor in many types of tumors including lung cancer (6), although one recent report has denied it (2). While Sasaki et al. (7) reported that the FDG uptake in tumors with the alteration of p53 tended to be higher than in those without, the present study did not find any correlation of p53 staining scores with the FDG uptake, tumor stage and intratumoral invasiveness in clinical stage IA lung adenocarcinomas. The differences between the report by Sasaki et al. and ours were (i) the number of the patients (28 versus 71 patients); (ii) histological types (NSCLC including all histological types versus adenocarcinoma); (iii) size of tumors (17,18) (no details about specific sizes versus 1–3 cm); (iv) measurement of FDG uptake (SUV versus CR). As described in our previous reports, the FDG uptake should be measured by CR and not by SUV, and should also be evaluated in adenocarcinomas with limited tumor size (16,19). Therefore, we believe that the alteration of p53 does not correlate with FDG uptake and therefore cannot be a dictator for the malignant grade in clinical stage IA lung adenocarcinomas.
We conclude that the FDG uptake can predict pathological tumor stage and tumor proliferative activity determined by Ki-67, but cannot predict the alteration of p53 in clinical stage IA lung adenocarcinomas. These results should be useful in determining the indication for mediastinoscopy or neoadjuvant chemotherapy in patients with clinical stage IA lung adenocarcinoma.
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Acknowledgments |
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We thank technologists of the Nishidai Clinic who cooperated for the measurement of the CR value. We also thank laboratory technicians of the Department of Pathology of Saiseikai Central Hospital for supporting the immunohistochemical study.
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References |
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1 Martin B, Paesmans M, Mascaux C, et al. Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis. Br J Cancer 2004;91:2018–25[CrossRef][Web of Science][Medline]
2 Au NH, Cheang M, Huntsman DG, et al. Evaluation of immunohistochemical markers in non-small cell lung cancer by unsupervised hierarchical clustering analysis: a tissue microarray study of 284 cases and 18 markers. J Pathol 2004;204:101–9[CrossRef][Web of Science][Medline]
3 Saitoh G, Sugio K, Ishida T, . Prognostic significance of p21waf1, cyclin D1 and retinoblastoma expression detected by immunohistochemistry in non-small cell lung cancer. Oncol Rep 2001;8:737–43[Web of Science][Medline]
4 Jin M, Inoue S, Umemura T, et al. Cyclin D1, p16 and retinoblastoma gene product expression as a predictor for prognosis in non-small cell lung cancer at stages I and II. Lung Cancer 2001;34:207–18.[CrossRef][Web of Science][Medline]
5 Oshita F, Ito H, Ikehara M, et al. Prognostic impact of survivin, cyclin D1, integrin beta1, and VEGF in patients with small adenocarcinoma of stage I lung cancer. Am J Clin Oncol 2004; 27:425–8.[CrossRef][Web of Science][Medline]
6 Mitsudomi T, Hamajima N, Ogawa M, Prognostic significance of p53 alterations in patients with non-small cell lung cancer: a meta-analysis. Clin Cancer Res 2000;6:4055–63.
7 Sasaki M, Sugio K, Kuwabara Y, et al. Alterations of tumor suppressor genes (Rb, p16, p27 and p53) and an increased FDG uptake in lung cancer. Ann Nucl Med 2003;17:189–96.[Web of Science][Medline]
8 Gould MK, Maclean CC, Kuschner WG, . Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions: a meta-analysis. JAMA 2001;285:914–24.
9 Marom EM, Sarvis S, Herndon JE II, . T1 lung cancers: sensitivity of diagnosis with fluorodeoxyglucose PET. Radiology 2002; 223:453–9.
10 Nomori H, Watanabe K, Ohtsuka T, . The size of metastatic foci and lymph nodes yielding false-negative and false-positive lymph node staging with positron emission tomography in patients with lung cancer. J Thorac Cardiovasc Surg 2004;127:1087–92.
11 Ahuja V, Coleman RE, Herndon J, . The prognostic significance of fluorodeoxyglucose positron emission tomography imaging for patients with nonsmall cell lung carcinoma. Cancer 1998;83:918–24.[CrossRef][Web of Science][Medline]
12 Vansteenkiste JF, Stroobants SG, Dupont PJ, . Prognostic importance of the standardized uptake value on (18)F-fluoro-2-deoxy-glucose-positron emission tomography scan in non-small-cell lung cancer: an analysis of 125 cases. Leuven Lung Cancer Group. J Clin Oncol 1999;17:3201–6.
13 Higashi K, Ueda Y, Yagishita M, et al. FDG PET measurement of the proliferative potential of non-small cell lung cancer. J Nucl Med 2000;41:85–92.
14 Vesselle H, Schmidt RA, Pugsley JM, et al. Lung cancer proliferation correlates with [F-18]fluorodeoxyglucose uptake by positron emission tomography. Clin Cancer Res 2000;6:3837–44.
15 Nomori H, Watanabe K, Ohtsuka T, et al. Fluorine 18-tagged fluorodeoxyglucose positron emission tomographic scanning to predict lymph node metastasis, invasiveness, or both, in clinical T1 N0 M0 lung adenocarcinoma. J Thorac Cardiovasc Surg 2004;128: 396–401.
16 Nomori H, Watanabe K, Ohtsuka T, Evaluation of F-18 fluorodeoxyglucose (FDG) PET scanning for pulmonary nodules less than 3 cm in diameter, with special reference to the CT images. Lung Cancer 2004;45:19–27.[CrossRef][Web of Science][Medline]
17 Cremerius U, Fabry U, Neuerburg J, . Positron emission tomography with 18F-FDG to detect residual disease after therapy for malignant lymphoma. Nucl Med Commun 1998;19:1055–63.[Web of Science][Medline]
18 Menda Y, Bushnell DL, Madsen MT, . Evaluation of various corrections to the standardized uptake value for diagnosis of pulmonary malignancy. Nucl Med Commun 2001;22:1077–81.[CrossRef][Web of Science][Medline]
19 Nomori H, Watanabe K, Ohtsuka T, . Visual and semiquantitative analyses for F-18 fluorodeoxyglucose PET scanning in pulmonary nodules 1 cm to 3 cm in size. Ann Thorac Surg 2005;79:984–88; discussion 989.
20 Sobin LW, Wittekind CH. UICC TNM classification of malignant tumours. 6th edn. New York: Wiley-Liss 2002;131–41.
21 Moses LE, Shapiro D, Littenberg B. Combining independent studies of a diagnostic test into a summary ROC curve: data-analytic approaches and some additional considerations. Stat Med 1993;12:1293–316.[Web of Science][Medline]
22 Allred DC, Harvey JM, Berardo M, . Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 1998;11: 155–68.[Web of Science][Medline]
23 Kim CK, Gupta NC, Chandramouli B, . Standardized uptake values of FDG: body surface area correction is preferable to body weight correction. J Nucl Med 1994;35:164–7.
24 Lindholm P, Minn H, Leskinen-Kallio S, . Influence of the blood glucose concentration on FDG uptake in cancer—a PET study. J Nucl Med 1993;34:1–6.[Medline]
25 Hamberg LM, Hunter GJ, Alpert NM, . The dose uptake ratio as an index of glucose metabolism: useful parameter or oversimplification? J Nucl Med 1994;35:1308–12.
26 Dewan NA, Gupta NC, Redepenning LS, . Diagnostic efficacy of PET-FDG imaging in solitary pulmonary nodules. Potential role in evaluation and management. Chest 1993;104:997–1002.[CrossRef][Web of Science][Medline]
27 Gupta NC, Maloof J, Gunel E. Probability of malignancy in solitary pulmonary nodules using fluorine-18-FDG and PET. J Nucl Med 1996;37:943–8.
28 Imdahl A, Jenkner S, Brink I, et al. Validation of FDG positron emission tomography for differentiation of unknown pulmonary lesions. Eur J Cardiothorac Surg 2001;20:324–9.
29 Lowe VJ, Fletcher JW, Gobar L, et al. Prospective investigation of positron emission tomography in lung nodules. J Clin Oncol 1998;16:1075–84.[Abstract]
30 Nomori H, Ohtsuka T, Naruke T, Suemasu K. Histogram analysis of computed tomography numbers of clinical T1N0M0 lung adenocarcinoma with special reference to lymph node metastasis and tumor invasiveness. J Thorac Cardiovasc Surg 2003;126:1584–9.
31 Asamura H, Nakayama H, Kondo H, . Lymph node involvement, recurrence, and prognosis in resected small, peripheral, non-small-cell lung carcinomas: are these carcinomas candidates for video-assisted lobectomy? J Thorac Cardiovasc Surg 1996;111:1125–34.
32 Depierre A, Milleron B, Moro-Sibilot D, et al. Preoperative chemotherapy followed by surgery compared with primary surgery in resectable stage I (except T1N0), II, and IIIa non-small-cell lung cancer. J Clin Oncol 2002;20:247–53.
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