What causes false-negative PET findings for solid-type lung cancer? Poster No.: C-1206 Congress: ECR 2013 Type: Authors: Keywords: DOI: Scientific Exhibit S. Iwano, S. Ito, K. Tsuchiya, K. Kato, S. Naganawa; Nagoya/JP Thorax, Lung, PET-CT, PET, Molecular imaging, Diagnostic procedure, Tissue characterisation 10.1594/ecr2013/C-1206 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. www.myesr.org Page 1 of 11
Purpose 18 F-Fluorodeoxyglucose positron emission tomography (FDG-PET) is an essential tool in current lung cancer practice because most lung cancers have increased FDG uptake [1-5]. However, several factors (body weight, blood glucose concentration, lesion size, respiratory motion, and lesion histological type, etc.) affect the maximum standardized uptake values (SUVmax) and cause false-negative PET results for patients with primary lung cancers [1, 6-17]. In clinical practice, solid-type lung cancers that do not show ground-glass opacity (GGO) on thin-section CT results can also show false-negative PET findings. This study retrospectively compared the PET findings of solid-type lung cancers to their clinical and pathological features to investigate the difference between PET positive and negative findings. Methods and Materials 1. Patients Selection We searched our institution's PET/CT records, the clinical records, preoperative thinsection CT images, and postoperative pathological records for the period between January 2009 and 2012. Solid-type primary lung cancers #40 mm in diameter Definitively diagnosed by surgical resection The histopathological types were classified into four categories: 1. bronchioloalveolar carcinoma (BAC) and well-differentiated adenocarcinoma (W/D AC) 2. moderately-differentiated and poorly-differentiated adenocarcinoma (M/D and P/D AC) 3. squamous cell carcinoma (SqCC) and adenosquamous carcinoma (ASqC) 4. large cell carcinoma (LCC) and small cell carcinoma (SCLC). 2. PET/CT scans Biography 16; Siemens Medical Solutions, Erlangen, Germany Patients were required to fast for at least 6 hours prior to imaging. Page 2 of 11
The FDG dose was determined by body weight:3.7 MBq/kg (body weight < 60 kg) or 4.07 MBq/kg (body weight # 60 kg). Fifty minutes after FDG intravenous injection, emission scans of the area between the proximal femora and the base of the skull were acquired in the 3-dimensional mode with 1.7 min at each bed position. Breath-holding and respiratory gating PET was not used. PET images with SUVmax of # 2.5 were considered PET-positive. In contrast, no focal uptake in the pulmonary lesions by visual assessment or SUVmax of < 2.5 was considered PET-negative. 3. Statistical analysis 1. The clinical and pathological characteristics between PET-positive tumours and PET-negative tumours were compared. 2. Multivariate logistic analysis was used to identify independent predictors of PET-positive or negative using the five factors noted above. 3. Receiver operating characteristic (ROC) analysis was used to determine a cut-off level for lesion size. 4. SUVmax results were compared among the pathological types. This retrospective study was approved by our Institutional Review Board. Results A total of 187 solid-type primary lung cancers in 178 patients (125 males and 53 females) that were selected. The patients' characteristics are summarized in Table 1. Table 2 shows comparisons of the characteristics for PET-negative and PET-positive tumours. There were no significant differences between the two groups for body weight (p=0.106), blood glucose level (p=0.426), tumour location (p=0.226). However, there were significant differences between these groups for lesion sizes (p<0.001) and histopathological types (p<0.001). Table 3 shows the results of multivariate logistic analysis. Both the lesion size (p<0.001) and the histopathological tumour type (p<0.001) were significant factors for determining whether PET results were negative or positive. Table 4 shows SUVmax results for each pathological type. BACs and W/D ACs exhibited significantly lower SUVmax results than the other histological types (p<0.001). Fig. 1 shows the ROC curve for lesion size. The area under the curve (AUC) was 0.766 and a suitable cut-off value was estimated to be 2.0 cm. The false negative rate was Page 3 of 11
significantly higher for lesion sizes of # 2.0 cm than for lesion sizes of > 2.0cm (56.7% vs. 10.0%; p<0.001). Fig. 2-4 show three PET-negative cases. Images for this section: Table 1: Characteristics of patients Page 4 of 11
Table 2: Comparisons of characteristics for PET-negative and positive tumours Page 5 of 11
Table 3: Multivariate logistic analysis for determining whether PET negative or positive. Page 6 of 11
Table 4: SUVmax results for each pathological type. Page 7 of 11
Fig. 1: The ROC curve for lesion size. Page 8 of 11
Fig. 2: PET findings for a 60-year-old male. A moderately-differentiated adenocarcinoma is in the right upper lobe (arrow). The lesion is 8 mm in diameter and the SUVmax is 0.9. (a) Thin-section CT, (b) PET/CT. Fig. 3: PET findings for a 79-year-old male. A well-differentiated adenocarcinoma is in the left S6. The lesion is 20 mm in diameter and no focal uptake is observed on the PET/ CT image. (a) Thin-section CT, (b) PET/CT. Fig. 4: PET findings for a 60-year-old male. A well-differentiated adenocarcinoma is in the right S2. The lesion is 22 mm in diameter and the SUVmax is 1.9. (a) Thin-section CT, (b) PET/CT. Page 9 of 11
Conclusion Among solid-type lung cancers, lesion size and histopathological findings were associated with FDG uptake. In particular, it warrants attention that lesions # 2 cm in diameter or solid-types of bronchioloalveolar carcinoma and well-differentiated carcinoma on thin-section CT images have a tendency for negative findings on PET scans. References [1] Bryant AS, Cerfolio RJ (2006) The maximum standardized uptake values on integrated FDG-PET/CT is useful in differentiating benign from malignant pulmonary nodules. Ann Thorac Surg 82:1016-1020. [2] Huang YE, Pu YL, Huang YJ, et al. (2010) The utility of the nonattenuation corrected 18F-FDG PET images in the characterization of solitary pulmonary lesions. Nucl Med Commun 31:945-951. [3] Khalaf M, Abdel-Nabi H, Baker J, Shao Y, Lamonica D, Gona J (2008) Relation between nodule size and 18F-FDG-PET SUV for malignant and benign pulmonary nodules. J Hematol Oncol 1:13. [4] Higashi K, Ueda Y, Sakuma T, et al. (2001) Comparison of [(18)F]FDG PET and (201)Tl SPECT in evaluation of pulmonary nodules. J Nucl Med 42:1489-1496. [5] Grgic A, Yuksel Y, Groschel A, et al. (2010) Risk stratification of solitary pulmonary nodules by means of PET using (18)F-fluorodeoxyglucose and SUV quantification. Eur J Nucl Med Mol Imaging 37:1087-1094. [6] Cheran SK, Nielsen ND, Patz EF Jr (2004) False-negative findings for primary lung tumors on FDG positron emission tomography: staging and prognostic implications. AJR Am J Roentgenol 182:1129-1132. [7] Awab A, Hamadani M, Peyton M, Brown B (2007) False-negative PET scan with bronchioloalveolar carcinoma: an important diagnostic caveat. Am J Med Sci 334:311-313. [8] Higashi K, Ueda Y, Seki H, et al. (1998) Fluorine-18-FDG PET imaging is negative in bronchioloalveolar lung carcinoma. J Nucl Med 39:1016-1020. Page 10 of 11
[9] Nomori H, Watanabe K, Ohtsuka T, Naruke T, Suemasu K, Uno K (2004) 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 45:19-27. [10] Shim SS, Lee KS, Kim BT, Choi JY, Chung MJ, Lee EJ (2006) Focal parenchymal lung lesions showing a potential of false-positive and false-negative interpretations on integrated PET/CT. AJR Am J Roentgenol 186:639-648. [11] Nomori H, Ohba Y, Yoshimoto K, Shibata H, Shiraishi K, Mori T (2009) Positron emission tomography in lung cancer. Gen Thorac Cardiovasc Surg 57:184-191. [12] Hallett WA, Marsden PK, Cronin BF, O'Doherty MJ (2001) Effect of corrections for blood glucose and body size on [18F]FDG PET standardised uptake values in lung cancer. Eur J Nucl Med 28:919-922. [13] Ding HJ, Shiau YC, Wang JJ, Ho ST, Kao A (2002) The influences of blood glucose and duration of fasting on myocardial glucose uptake of [18F]fluoro-2-deoxy-D-glucose. Nucl Med Commun 23:961-965. [14] Suzawa N, Ito M, Qiao S, et al. (2011) Assessment of factors influencing FDG uptake in non-small cell lung cancer on PET/CT by investigating histological differences in expression of glucose transporters 1 and 3 and tumour size. Lung Cancer 72:191-198. [15] Hatt M, Cheze-le Rest C, van Baardwijk A, Lambin P, Pradier O, Visvikis D (2011) Impact of tumor size and tracer uptake heterogeneity in (18)F-FDG PET and CT nonsmall cell lung cancer tumor delineation. J Nucl Med 52:1690-1697. [16] Keyes JW Jr 1995) SUV: standard uptake or silly useless value? J Nucl Med 36:1836-1839. [17] Kawano T, Ohtake E, Inoue T (2008) Deep-inspiration breath-hold PET/CT of lung cancer: maximum standardized uptake value analysis of 108 patients. J Nucl Med 49:1223-1231. Personal Information Shingo Iwano, M.D. Ph.D. Department of Radiology, Nagoya University Graduate School of Medicine Page 11 of 11