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a Department of Thoracic Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
b Department of Diagnostic Radiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
c Japanese Red Cross Kumamoto Health Care Center, Kumamoto, Japan
d Division of General Thoracic Surgery, Department of Surgery, School of Medicine, Keio University, Tokyo, Japan
Accepted for publication September 30, 2008.
* Address correspondence to Dr Ohba, Department of Thoracic Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan (Email: oyasumi{at}kumamoto-u.ac.jp).
| Abstract |
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Methods: Positron emission tomography data were analyzed for 130 pulmonary nodules from 1 to 3 cm in size (101 malignant and 29 benign nodules). The FDG uptake was measured by maximum standard uptake value (SUVmax), the contrast ratio (CR) of the SUV to the cerebellum (CR brain), and the CR of the SUV to the contralateral lung (CR lung). The CR lung was calculated from the SUV of the tumor (T) and that of the contralateral normal lung (N) and then was measured by two formulas, namely, T–N/T+N and T/N.
Results: The sensitivities of both CR lung T–N/T+N and CR lung T/N were significantly higher than those of visual assessment, SUVmax, and CR brain (p = 0.01 to p < 0.001). No significant difference in sensitivity was observed between the CR lung T–N/T+N and CR lung T/N. Both CR lung T–N/T+N and CR lung T+N successfully imaged well-differentiated lung adenocarcinoma more frequently than the visual assessment, SUVmax, and CR brain (p = 0.002 to p < 0.001), whereas there were no significant differences of sensitivity among those five methods for the diagnosis of other histologic types of pulmonary malignancies.
Conclusions: The FDG uptake evaluated by the CR lung is superior to that evaluated using the visual assessment, SUVmax, and CR brain for the diagnosis of pulmonary malignancies, especially for well-differentiated lung adenocarcinoma. The simplified formula of CR lung with T/N can be used in place of that with T–N/T+N.
| Introduction |
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There have been reported several ways for evaluating FDG uptake on PET. Nomori and colleagues [19] compared sensitivities and specificities of the SUVmax, the contrast ratio (CR) of the SUV to the lung, and the CR of the SUV to the brain for diagnosing malignant pulmonary nodules, and reported that the CR of the SUV to the lung or brain was more sensitive than the SUVmax for nodules that were faintly positive based on visual findings [19]. The CR of the SUV to the lung in their study was calculated from the SUV of the tumor (T) and that of the contralateral normal lung (N) and then was measured using the formula T–N/T+N. Their study was further supported in a study by Obrzut and coworkers [20], who reported that the CR of the SUV to the brain was more sensitive than SUVmax for diagnosing malignant pulmonary tumors.
The purposes of the present study were as follows: (1) to determine the optimum method of evaluating FDG uptake to discriminate between malignant and benign nodules by comparing the visual assessment, SUVmax, the CR to the brain, and the CR to the contralateral lung; (2) to evaluate the utility of the simplified formula of CR to the lung, namely, T/N, by comparing it with that of T–N/T+N; and (3) to examine the histologic type of malignant nodules with false negative results according to each of the above criteria. In the present study, we targeted malignant tumors less than 3 cm in size because of the following reasons: (1) FDG uptake is dependent on tumor size [15]; and (2) the usefulness of FDG-PET should be examined for pulmonary nodules less than 3 cm because pulmonary masses larger than 3 cm are usually not difficult to diagnose even without FDG-PET.
| Material and Methods |
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Patients
Between April 2005 and April 2008, a total of 155 patients with 195 pulmonary nodules less than 3 cm in size that were suspected of being or were diagnosed as pulmonary malignancies, underwent FDG-PET in the department of thoracic surgery of Kumamoto University Hospital before surgery. The size of the nodules was measured on computed tomography (CT) using an electric caliber. Of these, 36 nodules with ground glass opacity images on CT and 29 lesions less than 1 cm in size were excluded, because such lesions are known to be difficult to identify using FDG-PET and therefore are usually out of indication for FDG-PET [5]. The remaining 130 nodules in 107 patients, including 89 nonsmall-cell lung cancers (NSCLC), 12 metastatic lung cancers, and 29 benign nodules, were examined in the present study (Table 1).
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PET-CT Scanning
The PET scanning in all patients was conducted in the Japanese Red Cross Kumamoto Health Care Center in Kumamoto by using an integrated PET/CT device (Discovery ST; GE Medical Systems, Kumamoto, Japan) that consisted of a PET scanner (Advance Nx; GE Medical Systems) and an eight-section CT scanner (Light Speed Plus; GE Medical Systems). Patients were instructed to fast for at least 5 hours before intravenous administration of FDG. The dose of FDG administered was 100 µCi/kg (3.7 MBq/kg) of body weight. Before the examination of PET, blood sugar level was confirmed to be less than 150 mg/dL in all patients. For patients with the blood sugar level higher than 150 mg/dL, the PET examination was postponed. The PET imaging was performed approximately 60 minutes after intravenous administration of FDG. All images were acquired under shallow-breathing conditions.
The acquisition time for PET in three-dimensional mode was 3 minutes per table position. The CT data were resized from a 512 x 512 matrix to a 128 x 128 matrix to match the PET data to allow image fusion, and a CT transmission map was generated. The PET image data were reconstructed iteratively using the ordered subsets expectation-maximization algorithm with segmented attenuation correction (4 iterations, 28 subsets) and the CT data. The 3.75-mm thick transaxial CT images were reconstructed at 3.27-mm intervals (transaxial) for fusion with the transaxial PET images. The PET, CT, and fused images were available for review in the axial, coronal, and sagittal planes using Xeleris software (GE Medical Systems) on a computer workstation.
PET Data Analysis
Images were reviewed on a consensus basis by two observers who were unaware of the clinical data. Each observer recorded a visual assessment for each nodule by comparison with FDG uptake on mediastinal blood flow. Lesions with greater FDG uptake than the mediastinal blood flow was defined as positive, and those with less FDG uptake as negative. A consensus was reached if any difference in their opinions existed.
The PET data were used to calculate the SUVmax, the CR of the SUV to the contralateral lung (CR lung), and the CR of the SUV to the brain (CR brain). After image reconstruction, a two-dimensional circular region of interest (ROI) was drawn in a slice after visual detection of the highest count on the fused CT images. From these ROI, the maximum activity in the ROI was calculated as lesion activity/injected dose/body weight. The contrast ratio of the SUV between the lesions and the lung (CR lung) and that between the lesions and the brain (CR brain) were then calculated, as described previously [5,19]. Briefly, to calculate the CR brain, the SUVmax in the tumor (T) ROI and the cerebellum (C) were measured, and the CR brain was calculated using the formula T/C, as described previously [19]. To calculate the CR lung, ROIs were placed over the tumor and the contralateral normal lung; then the SUVmax in the tumor (T) ROI and that in the normal lung (N) were measured. The CR lung was then calculated by two kinds of formulas, namely, T–N/T+N and T/N. Finally, the visual assessment, SUVmax, CR lung T–N/T+N, CR lung T/N, and CR brain were compared with each other.
Determining Cutoff Value of Each Criterion
A receiver operating characteristic curve was constructed according to each criterion using SPSS software (SPSS 15.0 J for Windows; SPSS, Chicago, IL), and the cutoff values were determined for benign/malignant discrimination. Nodules with more than the cutoff value of FDG uptake were defined as positive on FDG-PET.
Statistical Analysis
The Fisher exact test was used to compare the distribution of size between malignant and benign nodules. True positive, true negative, false positive, and false negative results of each criterion for detecting NSCLC were compared with the pathologic diagnosis. Sensitivity was calculated as [true positive/true positive + false negative], and specificity as [true negative/true negative + false positive], and the differences among the criteria were analyzed using the McNemar test. Statistical analysis was performed using SPSS software. All values in the text and tables are given as mean ± SD.
| Results |
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| Comment |
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Although SUVmax has been frequently used for the semiquantitative analysis of FDG uptake, it has been reported that several factors can affect the SUV, such as body size [8–10], blood glucose level [11–13], and lesion size [14, 15]. In breast cancers, Wahl and colleagues [23] have demonstrated that a ratio of SUV between the tumor and contralateral normal breast tissue was more reliable than the absolute SUV of tumor for diagnosing breast malignancies. Nomori and coworkers [5, 24] have used a CR lung calculated using the formula T–N/T+N to diagnose pulmonary malignancies; this formula is according to that used in the study on breast cancer [25]. In the present study, to simplify the formula of T–N/T+N, we evaluated CR lung using the formula of T/N. As a result, both the CR lung T–N/T+N and CR lung T/N showed higher sensitivity than visual assessment, SUVmax, and CR brain, and there was no significant difference between the CR lung T–N/T+N and CR lung T/N. Therefore, we conclude that both formulas of CR lung are superior to SUVmax and CR brain for diagnosis, and also that the simple formula of CR lung T/N can be used in place of CR lung T–N/T+N.
The present study showed that most of the malignant tumors with false negative results by each criterion were WD lung adenocarcinomas. It has been reported that FDG-PET gives false negative results for low-grade lung cancer, such as bronchioloalveolar carcinoma and WD adenocarcinoma, because of the low glucose metabolism and low tumor cell density [5, 6, 26]. In the present study, both the CR lung T–N/T+N and the CR lung T/N showed higher sensitivity for the diagnosis of WD adenocarcinoma than the visual assessment, SUVmax, and CR brain, whereas there was no significant difference in sensitivity for the diagnosis of MD or PD adenocarcinoma or nonadenocarcinoma among those five criteria. Therefore, the FDG uptake of WD adenocarcinoma should be evaluated using the CR lung rather than the visual assessment, SUVmax, or CR brain.
While SUVmax with a cutoff value of 2.5 has been frequently used as a criterion for diagnosing pulmonary malignancies using FDG-PET [27], the cutoff values of SUVmax in the present study was much lower, namely, 1.1. This difference could be due to the following: (1) whereas a cutoff value of 2.5 for SUVmax has been used to diagnose pulmonary tumors, including tumors larger than 3 cm, the present study restricted the size of pulmonary nodules to between 1 cm and 3 cm; and (2) the 69 of 89 NSCLC (78%) examined in the present study were adenocarcinomas, which are known to usually show a lower FDG uptake than nonadenocarcinoma NSCLC [5, 19, 26].
We conclude that FDG uptake evaluated by CR lung is superior to that evaluated by the visual assessment, SUVmax, or CR brain for the diagnosis of pulmonary malignancies, especially for WD adenocarcinoma. Because there was no significant difference between CR lung T–N/T+N and CR lung T/N, the simpler latter formula can be used in place of the former for the diagnosis of pulmonary malignancies.
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