Effectiveness of FDG-PET Scans in the Evaluation of Patients with Single Pulmonary Nodules in Taiwan

Transcription

1 Effectiveness of FDG-PET Scans in the Evaluation of Patients with Single Pulmonary Nodules in Taiwan Wan-Yu Lin 1, Gee-Chen Chang 2, Shyh-Jen Wang 1 1 Department of Nuclear Medicine, Taichung Veterans General Hospital, Taichung, Taiwan 2 Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan Background: Lung cancer is one of the most frequent malignancies and a major cause of mortality. FDG-PET scan has been proven to be very useful in the evaluation of single pulmonary nodules in western countries. However, its clinical value for Taiwanese who have a high incidence of infectious disease such as tuberculosis is still not clear. In this study, 15 Taiwanese patients were diagnosed with single pulmonary nodule by CT scans. All these patients were further evaluated with FDG-PET scans for differentiating benign lesion from malignancy. Methods: Fifteen patients with suspected primary pulmonary neoplasm were enrolled in this study. All patients received a thoracic CT scan and a whole body FDG-PET scan before surgery or biopsy. All patients were given a final diagnosis in a histopathologic report from thoracic surgery, CT-guide biopsy or bronchoalveolar brushing. Results: There were 11 lung cancers and four benign lesions in our study. The sensitivity, specificity and accuracy for FDG-PET were 81.8%, 25% and 66.7%, respectively, using a SUV of 2.5 as a cut-off value. Using a SUV of 3 as a cut-off value, the sensitivity, specificity and Received 1/29/2004; revised 2/11/2004; accepted 2/19/2004. For correspondence and reprints contact: Wan-Yu Lin, M.D., Department of Nuclear Medicine, Taichung Veterans General Hospital, 160 Section 3, Taichung Harbor Road, Taichung 407, Taiwan. Tel: (886) , Fax: (886) , wylin@vghtc.vghtc.gov.tw accuracy were 81.8%, 50% and 73.3%, respectively. Conclusion: Our preliminary study showed that the sensitivity of FDG-PET in the detection of lung malignancy is high, but the specificity is suboptimal when compared to the results in the literature. High incidence of pulmonary infection rate may play a role in low specificity. Based on our preliminary study, a higher SUV as a cut-off value may be useful in improving the specificity in Taiwan. Key words: FDG-PET, lung cancer, single pulmonary nodule, benign, malignancy Ann Nucl Med Sci 2004;17:63-68 Introduction Lung cancer is the most common cause of cancer-related death in the West. Distant metastases and the presence of mediastinal lymph nodes profoundly affect the prognosis of non-small-cell lung cancer (NSCLC), making accurate staging important for selecting appropriate treatment. Most of the conventional standard methods in staging, such as computed tomography (CT), ultrasonography, and radionuclide bone scanning, when used alone, are not ideal. As a functional study, whole-body positron-emission tomography (PET) with 18 F-fluorodeoxyglucose (FDG) as a tracer is a new imaging technique that relies on the fact that there is increased metabolism of glucose in tumor cells [1,2]. Over the past 15 years, FDG-PET has been extensively studied and widely applied to lung carcinoma [3-9]. A quantitative review by Fischer et al.

2 Lin WY et al identified 55 original studies on the diagnostic performance of PET with FDG in the investigation of lung cancer [7]. For diagnosis of lung cancer, the mean sensitivities and specificities were, respectively, 96% and 78% for dedicated PET. In the mediastinal staging of lung cancer, the results were 83% and 96% for sensitivities and specificities, respectively. However, these results were mostly based on western research. In Taiwan, the incidence of infectious disease such as tuberculosis has been increasing [10]. Both infection and inflammation are known to cause FDG accumulation, which can interfere with the interpretation of FDG-PET scans [11-13]. Therefore, the effectiveness of FDG-PET scans in the evaluation of pulmonary lesions in Taiwan is still unclear. In this study, we performed FDG-PET scans on 15 Taiwanese with suspected pulmonary neoplasm in order to evaluate the effectiveness of FDG.-PET scans for them. CT of the Chest CT of the chest and upper abdomen including the adrenal glands was performed with a 120-KV, 125-mA tomoscan (model SR 7000, Philips Medical Systems, Enthoven, the Netherlands) with a slice thickness of 10 mm and a scanning time of one second per slice. During CT, 200 ml of contrast medium (Omnipaque, iohexol, Nycomed, Amersham, Princeton, NJ, USA) was administered intravenously at a rate of 1.5 ml per second. Imaging Interpretation All imaging studies were analyzed by two independent observers who were not aware of the patients clinical information. For the interpretation of FDG-PET scans, SUV was measured for abnormal FDG-avid lesion in the pulmonary lesions. Materials and Methods Patients Fifteen patients (12 men, 3 females; aged 31 to 84 years with an average age of 62.5 years) with suspected primary pulmonary neoplasm were enrolled in this study. All patients were given a final diagnosis in a histopathologic report from thoracic surgery, CT-guide biopsy or bronchoalveolar brushing. FDG-PET Imaging The FDG-PET study was performed using a whole body PET scanner (Siemens Ecat Exact HR plus, Knoxville, TN, USA). All patients were imaged after fasting for a minimum of 6 hours except for water and medications. Their blood sugar levels were checked prior to injection and in all patients were less than 120 mg/dl. FDG was injected intravenously in doses of 8 to 12 mci. Imaging was commenced 40 min after injection. The patients were asked to lie supine on the imaging bed of the PET camera with both arms alongside the body. A transmission scan, used for attenuation correction, was performed prior to the injection of FDG with a germanium-68 source. The image was performed at each level from the head to the upper thigh and was reconstructed and displayed in 3-D and axial, sagittal and coronal reconstructions for interpretation. Results All these 15 patients were diagnosed with single pulmonary nodule by CT scans. The patients data, FDG-PET and pathologic results are shown in Table 1. There are 11 lung cancers including 7 adenocarcinomas, 3 squamous cell carcinomas and 1 bronchioloalveolar carcinoma and four benign lesions including two of tuberculosis, one fibroma and one cryptococcus infection. Of the 11 cases with lung cancers, 7 had thoracic surgeries but 4 received neoadjuvant chemotherapy or chemotherapy instead because of advanced disease. All of the 11 malignant pulmonary lesions were found by FDG-PET scans (Figure 1); however two lesions had low SUVs (1.6 and 2.2, respectively) (Figure 2). Of the four benign lesions, three had increased FDG uptakes with SUVs of 2.9, 8.4, and 17.6, respectively (Figure 3). The sensitivity, specificity and accuracy were 81.8%, 25% and 66.7%, respectively, using a SUV of 2.5 as a cut-off value. Using a SUV of 3 as a cut-off value, the sensitivity, specificity and accuracy were 81.8%, 50% and 73.3%, respectively. Discussion Lung tumor cells have a much higher rate of glycolysis in comparison with non-neoplastic cells, and an increased cellular uptake of glucose, probably due to an increased Ann Nucl Med Sci 2004;17:63-68 Vol. 17 No. 2 June

3 FDG-PET FDG-PET in single pulmonary nodules in Taiwanese adults Table 1. Patients data, FDG-PET and pathologic results Patient Size PET result Sex Age Location No. (cm) (SUV) Treatment Pathologic Result 1 M 56 LUL Surgery Adenocarcinoma 2 M 50 RLL Surgery Squamous cell carcinoma 3 M 78 LUL Surgery Squamous cell carcinoma 4 M 66 LUL Surgery Adenocarcinoma 5 M 69 RUL Surgery Adenocarcinoma 6 F 51 LUL Surgery Bronchioloalveolar carcinoma 7 F 65 LUL Surgery Adenocarcinoma 8 M 70 LLL Neoadjuvant Squamous cell carcinoma chemotherapy 9 M 75 RUL Neoadjuvant chemotherapy Adenocarcinoma 10 M 45 LUL Neoadjuvant chemotherapy Adenocarcinoma 11 M 73 LUL Chemotherapy Adenocarcinoma 12 M 73 RUL Surgery Tuberculosis 13 M 84 RUL Surgery Tuberculosis 14 M 31 RLL Surgery Cryptococcus infection 15 F 50 RUL Negative Surgery Fibroma Figure 1. Patient No. 5. FDG-PET shows a FDG-avid lesion over the right middle lung field with a SUV of 9.4 (arrow). The final diagnosis was adenocarcinoma. Figure 2. Patient No. 7. FDG-PET shows a small area of mildly increased FDG uptake at the left upper lung field with a SUV of only 1.6 (arrow). The final diagnosis was adenocarcinoma with a size of cm. Figure 3. Patient No. 13. FDG-PET shows a FDG-avid lesion over the right upper lung field with a SUV of 8.4 (arrow). The final diagnosis was tuberculosis. expression of glucose transporter proteins [14,15]. FDG-PET has been studied extensively in the evaluation of indeterminate lung lesions [3,16,17]. The FDG-PET has been proven to be accurate in differentiating benign from malignant lesions as small as 1 cm and can reach an overall sensitivity of 96% and specificity of 78% [7]. The sensitivity, specificity and accuracy of PET imaging for lung lesions were significantly higher than those of CT scan [18,19]. In our study, the sensitivity was 81.8%. Of the 11 lung tumors, 2 (18.2%) were missed by the FDG-PET using a SUV of 2.5 as a cutoff value. One small adenocarcinoma about 1x0.8 cm showed a SUV of only 1.6. When the tumor size is smaller than 1 cm, the SUV may be underestimated because of partial volume effect. Therefore, we should be careful in the interpretation of FDG-PET images when a pulmonary nodule is small. Another false negative case had a bronchi- 2004;17:

4 Lin WY et al oloalveolar carcinoma with a size of A lower diagnostic accuracy of FDG-PET for diagnosis and staging of bronchioloalveolar carcinoma has been reported [20,21]. Bronchioloalveolar carcinoma can be a potential cause of false-negative findings of malignancy on FDG-PET scans. When bronchioloalveolar carcinoma is suspected, FDG-PET results should be interpreted in combination with high-resolution CT findings. The specificity in our study was as low as 25% when using a SUV of 2.5 as a cut-off value and was 50% when using a SUV of 3.0. Of the 4 benign lesions, only one fibroma showed no SUV uptake. The other three, including two of tuberculosis and one cryptococcus infection, had SUVs greater than 2.5. Cryptococcus infection is rare but has been reported to cause false positive in a FDG-PET study [22]. Tuberculosis has been more frequently reported to be the cause of false positive [12, 23]. It is not easy to differentiate active tuberculosis from pulmonary malignancy by FDG- PET. According to a report by Wang et al., the incidence of tuberculosis increased from 1994 to 2000 with an average annual increase of 7.73% and 9.93% for males and females, respectively, in Taipei [11]. In developed countries, the incidence of tuberculosis has also increased because of acquired immune deficiency syndrome (AIDS) [24, 25]. Therefore, the false positive rate may become higher along with the increased incidence rate of tuberculosis infection for FDG- PET. Research on other radiopharmaceuticals such as 11 C- choline may be helpful in the differentiation. In the study by Hara et al., the SUVs of both FDG and 11 C-choline were high in lung cancer patients. In tuberculosis patients, the SUV of FDG was high, but the SUV of 11 C-choline was low [12]. A SUV of 2.5 is frequently used as a cut-off value for the differentiation of benign lesion from malignancy [22, 26]. However, a higher SUV such as 3.0 can effectively increase specificity with no decrease in sensitivity. Of course, the sample size in this study was small. For greater confirmation, studies with larger sample sizes are recommended. Conclusion The sensitivity of FDG-PET in the detection of lung malignancy is high, but the specificity is suboptimal due to high incidence of pulmonary infection in Taiwan. Based on our preliminary study, a higher SUV as a cut-off value may be useful in improving the specificity. Acknowledgment This study was supported in part by a grant from the Taichung Veterans General Hospital Research Program (TCVGH C). References 1. Nolop KB, Rhodes CG, Brudin LH, et al. Glucose utilization in vivo by human pulmonary neoplasms. Cancer 1987;60: Sazon DA, Santiago SM, Soo Hoo GW, et al. Fluorodeoxyglucose-positron emission tomography in the detection and staging of lung cancer. Am J Respir Crit Care Med 1996;153: Dewan NA, Gupta NC, Redepenning LS, Phalen JJ, Frick MP. Diagnostic efficacy of PET-FDG imaging in solitary pulmonary nodules: Potential role in evaluation and management. Chest 1993;104: Chin R Jr, Ward R, Keyes JW, et al. Mediastinal staging of non-small-cell lung cancer with positron emission tomography. Am J Respir Crit Care Med 1995;152: Steinert HC, Hauser M, Allemann F, et al. Non-small cell lung cancer: Nodal staging with FDG-PET versus CT with correlative lymph node mapping and sampling. Radiology 1997;202: Vansteenkiste JF, Stroobants SG, De Leyn PR, et al. Lymph node staging in non-small-cell lung cancer with FDG-PET scan: A prospective study on 690 lymph node stations from 68 patients. J Clin Oncol 1998;16: Fischer BM, Mortensen J, Hojgaard L. Positron emission tomography in the diagnosis and staging of lung cancer: a systematic, quantitative review. Lancet Oncol 2001;2: Valk PE, Pounds TR, Tesa RD, et al. Cost-effectiveness of PET imaging in clinical oncology. Nucl Med Biol 1996;23: Scott WJ, Shepherd J, Gambhir SS. Cost-effectiveness of FDG-PET for staging non-small cell lung cancer: A deci- Ann Nucl Med Sci 2004;17:63-68 Vol. 17 No. 2 June

5 FDG-PET FDG-PET in single pulmonary nodules in Taiwanese adults sion analysis. Ann Thorac Surg 1998;66: Wang PD. Epidemiology and control of tuberculosis in Taipei. J Infect 2002;45: Hara T, Kosaka N, Suzuki T, Kudo K, Niino H. Uptake rates of 18 F-fluorodeoxyglucose and 11 C-choline in lung cancer and pulmonary tuberculosis: a positron emission tomography study. Chest 2003;124: Schuster DP, Kozlowski J, Hogue L. Imaging lung inflammation in a murine model of Pseudomonas infection: a positron emission tomography study. Exp Lung Res 2003;29: Zhuang H, Duarte PS, Rebenstock A, Feng Q, Alavi A. Pulmonary clostridium perfringens infection detected by FDG positron emission tomography. Clin Nucl Med 2003;28: Nelson CA, Wang JQ, Leave I, Crane PD. The interaction among glucose transport, hexokinase, and glucose- 6-phosphatase with respect to 3 H-2-deoxyglucose retention in murine tumor models. Nuclear Med Biol 1996;23: Yamamoto T, Seino Y, Fukumoto H, et al. Over-expression of facilitative glucose transporter genes in human cancer. Biochem Biophys Res Commun 1990;170: Lowe VJ, Fletcher JW, Gobar L, et al. Prospective investigation of positron emission tomography in lung nodules. J Clin Oncol 1998;16: Gupta N, Gill H, Graeber G, Bishop H, Hurst J, Stephens T. Dynamic positron emission tomography with F-18 fluorodeoxyglucose imaging in differentiation of benign from malignant lung/mediastinal lesions. Chest 1998;114: Goldsmith SJ, Kostakoglu L. Role of nuclear medicine in the evaluation of the solitary pulmonary nodule. Semin Ultrasound CT MR 2000;21: Takanashi N, Nobe Y, Asoh H, Yano T, Ichinose Y. The diagnostic accuracy of a solitary pulmonary nodule, using thin-section high resolution CT: a solitary pulmonary nodule by HRCT. Lung Cancer 1995;13: Higashi K, Ueda Y, Sakuma T, et al. Comparison of [ 18 F] FDG-PET and 201 Tl SPECT in evaluation of pulmonary nodules. J Nucl Med 2001;42: Kim BT, Kim Y, Lee KS, et al. Localized form of bronchioloalveolar carcinoma: FDG-PET findings. Am J Roentgenol 1998;170: Hung GU, Shiau YC, Tsai SC, Ho YJ, Kao CH, Yen RF. Differentiation of radiographically indeterminate solitary pulmonary nodules with [ 18 F] fluoro-2-deoxyglucose positron emission tomography. J Clin Oncol 2001;31: Pitman AG, Hicks RJ, Binns DS, et al. Performance of sodium iodide based 18 F-fluorodeoxyglucose positron emission tomography in the characterization of indeterminate pulmonary nodules or masses. Br J Radiol 2002;75: Bruno R, Sacchi P, Filice G. Overview on the incidence and the characteristics of HIV-related opportunistic infections and neoplasms of the heart: Impact of highly active antiretroviral therapy. AIDS 2003;17:S Schneider E, Castro KG. Tuberculosis trends in the United States, Tuberculosis 2003;83: Hickeson M, Yun M, Matthies A, et al. Use of a corrected standardized uptake value based on the lesion size on CT permits accurate characterization of lung nodules on FDG-PET. Eur J Nucl Med Mol Imaging 2002;29: ;17:

6 Lin WY et al , -18 ( ) % 25% 66.7% % 50% 73.3% -18, 2004;17: (04) (04) wylin@vghtc.vghtc.gov.tw Ann Nucl Med Sci 2004;17:63-68 Vol. 17 No. 2 June