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Accuracy of Whole-Body Dual-Modality Fluorine-18–2-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography and Computed Tomography (FDG-PET/CT) for Tumor Staging in Solid Tumors: Comparison With CT and PET

From the Department of Diagnostic and Interventional Radiology, and Department of Nuclear Medicine, University Hospital Essen, Essen; and Institute of Medical Biometry and Statistics, University at Lübeck, Lübeck, Germany

Address reprint requests to Gerald Antoch, MD, Department of Diagnostic and Interventional Radiology, University Hospital Essen, Hufelandstrasse 55, 45122 Essen, Germany; e-mail: gerald.antoch{at}uni-essen.de

	ABSTRACT

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... REFERENCES

 
PURPOSE: To assess the accuracy of positron emission tomography/computed tomography (PET/CT) when staging different malignant diseases.

PATIENTS AND METHODS: This was a retrospective, blinded, investigator-initiated study of 260 patients with various oncological diseases who underwent fluorine-18–2-fluoro-2-deoxy-D-glucose PET/CT for tumor staging. CT images alone, PET images alone, PET + CT data viewed side by side, and fused PET/CT images were evaluated separately according to the tumor-node-metastasis system. One hundred forty patients with tumors not staged according to the tumor-node-metastasis system or a lack of reference standard were excluded from data analysis; 260 patients were included. Diagnostic accuracies were determined for each of the four image sets. Histopathology and a clinical follow-up of 311 (± 125) days served as standards of reference.

RESULTS: PET/CT proved significantly more accurate in assessing tumor-node-metastasis system stage compared with CT alone, PET alone, and side-by-side PET + CT (P < .0001). Of 260 patients, 218 (84%; 95% CI, 79% to 88%) were correctly staged with PET/CT, 197 (76%; 95% CI, 70% to 81%) with side-by-side PET + CT, 163 (63%; 95% CI, 57% to 69%) with CT alone, and 166 (64%; 95% CI, 58% to 70%) with PET alone. Combined PET/CT had an impact on the treatment plan in 16, 39, and 43 patients when compared with PET + CT, CT alone, and PET alone, respectively.

CONCLUSION: Tumor staging with PET/CT is significantly more accurate than CT alone, PET alone, and side-by-side PET + CT. This diagnostic advantage translates into treatment plan changes in a substantial number of patients.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... REFERENCES

 
Initiation of a stage-adapted therapy is known to improve patient survival for a variety of malignant tumors.^1-4 In addition to histopathologic tissue-based staging, radiologic imaging procedures provide essential data on the tumor stage. These have a profound influence on subsequent therapy decisions. There are, however, well-known limitations inherent to radiologic imaging studies that limit their diagnostic accuracy in assessing tumor stages. Thus, computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound provide mainly morphologic information on the primary tumor and potential metastases. The lack of functional information frequently limits their value when assessing lymph nodes for metastatic spread.^{5, 6} Furthermore, differentiation of smaller parenchymal lesions into benign or malignant status may be difficult without additional functional data.

Fluorine-18–2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) provides functional data on tumor metabolism and has been demonstrated to be of complementary value to morphologic imaging studies.^7-9 However, limited anatomic information in FDG-PET images frequently renders localization of a lesion and its potential infiltration into adjacent organs difficult.^{10, 11} Thus, for maximal diagnostic benefit, functional data sets should be read in conjunction with morphologic images.

Image fusion and side-by-side image evaluation of morphologic and functional data sets have been proposed.¹² Although morphologic and functional images of the brain may be fused successfully, accurate image coregistration of two extracranial image volumes is often found to be compromised by motion-induced misregistration.¹³ This limitation can only be overcome by collecting functional and morphologic data in one examination. The recent availability of dual-modality PET/CT tomographs provides the technical basis for intrinsically aligned functional and morphologic data sets.¹⁴ Preliminary studies report promising results when malignant diseases are assessed with combined PET/CT.^15-18

The aim of this study was to determine the diagnostic accuracy of dual-modality PET/CT in staging different malignant diseases relative to CT alone, PET alone, and PET + CT viewed side by side.

	PATIENTS AND METHODS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... REFERENCES

 
Four hundred patients underwent dual-modality FDG-PET/CT for staging different suspected or proven malignancies in a university hospital setting from November 2001 until April 2002. All patients undergoing PET/CT imaging during this time period were included in the study. The study was approved by the local institutional review board.

Of the 400 patients, 140 patients with either tumors not staged according to the tumor-node-metastasis system or with insufficient clinical data (defined as no histopathology of the primary tumor and no clinical and radiologic follow-up of at least 6 months) were excluded from the study. Thus, retrospective analysis was based on 260 patients (Table 1) . Data analysis and reporting of the acquired data were performed according to the Standards for Reporting Studies of Diagnostic Accuracy.¹⁹ The flow diagram for patient inclusion is shown in Fig 1.

View larger version (23K): [in this window] [in a new window]   Fig 1. Flow diagram for patient inclusion. PET, positron emission tomography; CT, computed tomography.

Whole-body coverage was performed in 212 patients with an axial scan range from the head to the upper thighs. In 48 patients, the field of view was limited to a smaller body region of interest.

The CT has a minimum gantry rotation time of 800 msec and a maximal scan time of 100 seconds. CT images were acquired in spiral mode with 130 mAs, 130 kV, a slice width of 5 mm, and a table feed of 8 mm/gantry rotation. Images were reconstructed at 2.4-mm increments. All patients were scanned using a limited breath-hold technique to avoid image misregistration in the area of the diaphragm.²⁰ To ensure diagnostic CT data, intravenous and oral contrast agents were administered in all patients without known contraindications. Between 100 (scan of a single body region) and 140 mL (whole-body scan) of an iodinated contrast agent (Xenetix 300 [300 mg iodine/mL]; Guerbet GmbH, Sulzbach, Germany) was administered by using an automated injector (Liebel; Flarsheim, Germany). The small bowel was distended by administration of 1,000 mL of barium sulfate (Micropaque CT; Guerbet GmbH).

The PET component provides an in-plane spatial resolution of 4.6 mm and an axial field of view of 15.5 cm for a single bed position. PET emission data were acquired in three-dimensional mode 60 minutes after administering 350 MBq of FDG covering the same field of view as the CT. Blood glucose levels were tested before injection of the radioactive tracer. The time to acquire a single bed position was set to 4 minutes and was adapted in overweight patients. PET images were corrected for attenuation based on the CT data.²¹ Images were scatter-corrected and iteratively reconstructed.

Image Evaluation
Image assessment was performed separately for CT, PET, side-by-side PET + CT, and fused PET/CT data. CT images alone were read by two radiologists in consensus (one board-certified radiologist, one resident with 2 years of CT experience). Evaluation of malignancy on CT was based on tumor morphology and the pattern of contrast enhancement. Lymph nodes were interpreted as positive for metastatic spread if their size exceeded 10 mm in the short-axis diameter. Furthermore, the presence of necrosis within a lymph node was considered a sign of malignancy independent of the size. PET images alone were evaluated by two nuclear medicine physicians in consensus (one board-certified nuclear medicine physician, one resident with 1.5 years of PET experience). Visual analysis was performed for regions of focally increased glucose metabolism. Furthermore, images were evaluated quantitatively by maximal standardized uptake values normalized for body weight. A lesion was considered malignant if its glucose uptake was found to be above levels of the surrounding tissue on qualitative analysis, with a standardized uptake value higher than 2.5 (3.5 for the liver) supporting the diagnosis of malignancy.^{22, 23} Each reader team was unaware of the results of the complementary imaging procedure and the reference standard.

After a time interval of 1 month chosen to avoid recognition bias, PET and CT images were read side by side by a board-certified radiologist and a board-certified nuclear medicine physician in consensus. The evaluating physicians were part of the two teams assessing CT and PET images alone. Side-by-side PET + CT image evaluation was performed after CT and PET data sets had been manually misregistered by a third person, who was not involved in the process of image evaluation. Finally, fused PET/CT data sets were assessed by the same physicians in consensus after an additional time interval of at least 8 weeks. When evaluating PET and CT images side by side and when evaluating fused PET/CT data sets, the same criteria to determine malignancy were applied as for CT and PET. However, lymph nodes were graded as malignant or benign based on functional criteria independent of their size. All readers were supplied with the same clinical information about each patient. Assessment of malignant disease was based on the recently revised American Joint Committee on Cancer staging classification.²⁴

The diagnostic accuracy of FDG-PET may be influenced by the type of tumor, given that some tumors may not show increased glucose metabolism. The study, however, includes a broad spectrum of different malignant diseases. Furthermore, glucose metabolism of malignant cells may be altered in patients undergoing radiotherapy or chemotherapy. For better comparison of PET sensitivities and specificities from this study with data available from the literature, patients with common PET indications (defined as indications reimbursed according to the Centers of Medicare and Medicaid Services, United States²⁵) who did not undergo treatment (n = 123) were also evaluated separately (Table 1).

Standard of Reference
Histology and clinical follow-up served as the standards of reference. The tumor-node-metastasis system stage of every patient was defined by a tumor board consisting of a nuclear medicine physician and a radiologist. The tumor board was supplied with all clinical and radiologic data. Members of the tumor board were not involved in image evaluation for the study and were not aware of staging results from the index test. Characterization of the tumor-node-metastasis system stage by the tumor board was based on histopathology and all data from the follow-up period. The follow-up period was defined as the total of all clinical information available after the PET/CT examination, including clinical examinations, laboratory tests, radiologic procedures, and histopathology from operative procedures performed at a later date. Histopathologic verification or exclusion of malignant disease was available in all patients. Tumor resection with pathologic T-stage verification was performed in 77 of 260 patients. The comparison of the different imaging procedures for assessment of T stage was limited to these 77 patients. Operative assessment of N stage was performed in 72 of 260 patients, and M stage was pathologically verified in 57 of 260 patients. A mean follow-up time of 311 days (± 125 days) served as the standard of reference for verification of N and M stages in patients without histopathology. The follow-up time ranged from 63 to 535 days. Short follow-up times were due to cancer-related deaths of the patients. Comparison of the different imaging procedures for assessment of N and M stages was based on all 260 patients. Patients in whom T, N, or M stages were overestimated were called overstaged, whereas those underestimated were characterized as understaged.

Impact on Therapy
The impact of differences in tumor-node-metastasis system staging between CT, PET, side-by-side PET + CT, and fused PET/CT on patient management was determined retrospectively based on therapy recommendations for each tumor entity. When assessing the different imaging procedures this resulted in definition of a tumor-node-metastasis system tumor stage for CT, PET, PET + CT, and PET/CT in every patient. For these tumor stages the recommended therapy was based on locally adapted tumor-specific therapy guidelines.²⁶ Therefore, all imaging procedures resulted in a therapy recommendation based on the tumor-node-metastasis system stage. Correlation of tumor-node-metastasis system stages with therapy guidelines was done by a physician unaware of the standard of reference. The therapy recommendation of each imaging procedure was compared with the therapy defined as the appropriate therapy for each patient according to the standard of reference. More accurate tumor-node-metastasis system staging with one imaging modality as compared with another imaging modality may result in a change of the therapy recommendation. When therapy recommendations were compared on the basis of CT, PET, PET + CT, and PET/CT, a clinically relevant impact on patient management was defined as a change in the therapy recommendation between curative and palliative, curative and neoadjuvant, or palliative and neoadjuvant.

Statistical Analysis
The primary analysis of the study was the correct classification of the tumor-node-metastasis system tumor stage using CT, PET, side-by-side PET + CT, and fused PET/CT. Differences in the assessment of the tumor-node-metastasis system stage between the different imaging procedures were tested for significance by McNemar's test (exact). Bonferroni correction was applied to account for multiple comparisons. To maintain a global significance level of .05, the nominal significance level to evaluate the six hypotheses of the primary analysis has to be .008. In cases of nonsignificant findings when the different imaging procedures were compared for the primary end point of the study, a power-analysis was performed.

Differences in the assessment of the T, N, and M stage between the different imaging procedures (secondary end points) were tested for significance by McNemar's test (exact) with a significance level of .05.

Sensitivities, specificities, negative predictive values (NPVs), positive predictive values (PPVs), and accuracies were calculated regarding their ability to detect malignant lymph nodes (N stage) and distant metastases (M stage; with exact 95% CIs calculated for sensitivities, specificities, and the number of correctly staged patients). This was performed for the whole patient population (N = 260) as well as for the subgroup of untreated patients with typical PET indications (n = 123). Statistical analyses were performed with SAS statistical software (Version 8.2, SAS Institute Inc, Cary, NC).

	RESULTS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... REFERENCES

 
Patients
One hundred twelve of the 260 included patients (mean age, 56 years; range, 16 to 94 years; 93 males and 167 females) underwent PET/CT for primary tumor staging, whereas 148 patients were referred for suspected recurrent disease after initial tumor treatment. All patients underwent the index test (PET/CT) and the reference standard.

The 140 patients excluded from data analysis (mean age, 56 years; range, 20 to 88 years; 69 males and 71 females) suffered from thyroid carcinoma (40 patients), lung cancer (20 patients), lymphoma (20 patients), gastrointestinal tumors (17 patients), head and neck tumors (13 patients), cancer of unknown primary (nine patients), soft tissue or bone tumors (seven patients), genitourinary tumors (six patients), breast cancer (six patients), liver tumors (one patient), and adrenal tumors (one patient). A comparison of the two groups (included patients, n = 260; excluded patients, n = 140) revealed a statistically significant difference for patient sex (P < .01) and tumor diagnoses (P < .01), whereas no statistically significant difference was found for patient age (P > .05).

Overall Tumor-Node-Metastasis System Stage and Impact on Patient Management
Fused PET/CT images provided significantly more accurate interpretations regarding the overall tumor-node-metastasis system stage than either of the separate data sets or PET + CT. Fused PET/CT correctly characterized the tumor-node-metastasis system stage in 218 of 260 patients (84%; 95% CI, 79% to 88%). Side-by-side PET + CT, CT, and PET were found to be accurate in 197 of 260 patients (76%; 95% CI, 70% to 81%), 163 of 260 patients (63%; 95% CI, 57% to 69%), and 166 of 260 patients (64%; 95% CI, 58% to 70%), respectively (Fig 2). Furthermore, differences between side-by-side PET + CT and either CT alone and PET alone were of statistical significance (P < .0001). A comparison of CT with PET did not reveal a statistically significant difference (P > .008; power < 0.2). Fused PET/CT resulted in a change in patient management in 16 of 260 patients (6%) compared with PET + CT, in 39 of 260 patients (15%) compared with CT, and in 43 of 260 patients (17%) compared with PET (Table 2). Alterations in patient management with PET/CT compared with side-by-side PET + CT were based on more accurate assessment of T, N, and M stages in eight, four, and three patients, respectively. Furthermore, PET/CT was able to detect a primary tumor that was not detected by PET + CT.

View larger version (18K): [in this window] [in a new window]   Fig 2. Overall tumor-node-metastasis system assessment of different malignancies in 260 patients by the different imaging procedures. Fused positron emission tomography and computed tomography (PET/CT) proved significantly superior to side-by-side PET + CT, PET alone, and CT alone. P values are based on 2 x 2 contingency tables (correct v incorrect) comparing PET/CT imaging with the other imaging procedures.

View larger version (41K): [in this window] [in a new window]   Fig 3. A 48-year-old male patient with carcinoma of the base of the tongue. (A) On computed tomography (CT) alone, the tumor was not detected. Positron emission tomography (PET) imaging as well as PET and CT assessed side by side rated the area of increased glucose metabolism as a T2 tumor stage. (C) Fused PET/CT data suggest infiltration of the mandible (T4 tumor stage), which was later confirmed on resection with histopathology.

View larger version (26K): [in this window] [in a new window]   Fig 4. Assessment of the T stage in 77 patients by the different imaging procedures. Fused positron emission tomography and computed tomography (PET/CT) proved superior to PET alone, CT alone, and side-by-side PET + CT. P values are based on 2 x 2 contingency tables (correct v incorrect) comparing PET/CT imaging with the other imaging procedures.

View larger version (38K): [in this window] [in a new window]   Fig 5. A 66-year-old male patient with carcinoma of the hypopharynx. (A) Normal-sized lymph node on computed tomography (CT) not suspected to harbor a metastasis. (B) Increased glucose metabolism was found on positron emission tomography (PET), diagnosed as N1 disease right cervically. (C) Fused PET/CT localizes the area of increased glucose metabolism to the lymph node missed on CT alone.

View larger version (22K): [in this window] [in a new window]   Fig 6. Assessment of the N stage in 260 patients by the different imaging procedures. Fused positron emission tomography and computed tomography (PET/CT) proved more accurate than side-by-side PET + CT, PET alone, and CT alone. P values are based on 2 x 2 contingency tables (correct v incorrect) comparing PET/CT imaging with the other imaging procedures.

View larger version (68K): [in this window] [in a new window]   Fig 7. A 51-year-old male patient with bronchial carcinoma. (A) Normal-appearing osseous structures on computed tomography (CT), which staged this patient as M0. (B) Positron emission tomography (PET), side-by-side image evaluation, and fused (C) PET/CT detected a bone metastases in the pelvis, staging this patient as M1. Follow-up revealed M1 disease to the bone.

View larger version (62K): [in this window] [in a new window]   Fig 8. A 68-year-old male patient with bronchial carcinoma. (A) Computed tomography (CT) revealed multiple hepatic metastases, whereas (B) positron emission tomography images were negative for distant metastases. (C) M1 disease was diagnosed on side-by-side images as well as fused images based on the CT data.

View larger version (17K): [in this window] [in a new window]   Fig 9. Correct determination of the M stage in 260 patients when assessed by the different imaging procedures. Although fused positron emission tomography and computed tomography (PET/CT) proved superior to PET alone and CT alone, no statistically significant difference could be detected when comparing PET/CT with side-by-side PET + CT. P values are based on 2 x 2 contingency tables (correct v incorrect) comparing PET/CT imaging with the other imaging procedures.

	DISCUSSION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... REFERENCES

T staging with fused PET/CT proved significantly more accurate when compared with interpretations based on CT alone and PET alone. Limitations inherent to both morphologic and functional imaging studies regarding the assessment of primary tumor extent are well documented. Lacking functional information, CT imaging is frequently compromised by its inability to differentiate viable tumor from adjacent structures.^{6, 27} PET, on the other hand, offers functional data well suited for the identification of viable tumor regions. Limited anatomic information, however, hampers correct determination of T stage with PET. The integration of function and morphology into a single examination procedure helps to overcome these limitations.

PET has been demonstrated to provide additional information regarding metastases to regional lymph nodes when compared with CT.^{28, 29} Results from this study further support this observation. Differentiation of benign from malignant lymph nodes with CT is mainly based on lymph node size. Sizes of both benign and malignant lymph nodes, however, vary markedly. Thus, previous studies have found up to 21% of nodes smaller than 1 cm to be malignant, whereas 40% of those larger than 1 cm were demonstrated to be benign.^{30, 31}

PET sensitivities and specificities for N staging are well in accordance with the published literature.³² Advantages of fused PET/CT over PET alone were based on accurate anatomic correlation of an area of increased glucose metabolism leading to significantly improved N staging. These data are in accordance with preliminary reports demonstrating an increase of diagnostic accuracy when correlating PET with CT images.^{15, 18} Our study, however, revealed advantages of PET/CT not only over PET, but also over side-by-side PET + CT. By localizing an area of FDG uptake previously not determined pathological by PET + CT, to a specific lymph node, PET/CT increased the sensitivity in detecting lymph node metastases compared with PET + CT. Conversely, PET/CT was able to coregister areas of increased glucose metabolism previously determined to be malignant on PET + CT to organs with physiologic FDG uptake (esophagus, stomach, bowel, uterus), thus decreasing the number of false-positive findings compared with visual image correlation.

Distant metastases were assessed similarly well with PET/CT and side-by-side PET + CT. Therefore, we conclude that accurate image fusion does not seem to be mandatory for assessing M stage. However, combining morphology and function (either fused or read side by side) was found to be significantly more accurate than either imaging modality alone. Thus, M staging should not be based on function or morphology, but rather on a combination of the two. Interestingly, no statistically significant difference could be determined between CT and PET for assessment of M stage. This finding is in contrast to other published data demonstrating an advantage of PET over CT.^{8, 29} These studies, however, included CT data with only a limited field of view (single body region). Furthermore, neither, intravenous nor oral contrast agents were routinely applied. Thus, the good CT performance regarding M staging in this study may be explained by the optimized CT protocol. Similarly, differences between CT and PET for overall tumor-node-metastasis system assessment were not statistically significant. Analysis of the data revealed only a poor power of less than 0.2. Thus the number of patients would have to be increased substantially to reach statistical significance when comparing CT alone and PET alone for tumor-node-metastasis system staging.

Sensitivities for detection of distant metastases with PET were found to be lower when compared with the published literature. This difference is thought to be due to patient selection. When considering only the subgroup of patients with common PET indications, the sensitivity for detecting distant metastases increased to 84%, which is well in accordance with previously published data.³² Furthermore, specificities of 98% and 99% indicate that images were evaluated specifically, which is known to influence sensitivity.

This study has some limitations. Comparison of PET/CT with CT alone, PET alone, and side-by-side PET + CT was based on data from a single PET/CT examination. An issue of potential bias relates to the effect of CT contrast agents onto the PET emission data. Extensive evaluations of oral and intravenous contrast agents, however, have revealed only a minor effect in selected cases.^33-37 Thus, the application of both intravenous and oral contrast agents is not expected to limit the quality of the PET data, and image quality of CT and PET acquired on the combined imaging system can be considered comparable with separately acquired data sets.^{35, 38} However, image acquisition on a single system may have an effect on side-by-side image evaluation. In cases for which combined PET/CT is not available, separate CT and PET data sets are typically acquired on independent imaging systems. Thus, differences in the coaxial imaging range, the respiration state, and the location of movable organs between the two imaging procedures are to be expected. These differences may complicate side-by-side image evaluation. In contrast, images viewed side by side in our study were collected on the same imaging system with the same field of view, and PET data were acquired immediately after CT to minimize organ shift. We tried to account for this limitation by manually misregistering the PET with respect to the CT for side-by-side image evaluation. However, PET and CT images derived from a single PET/CT acquisition may overestimate the diagnostic performance of side-by-side PET + CT despite manual misregistration of the datasets. Nevertheless, the acquisition of separate CT and PET data sets in addition to the combined PET/CT imaging approach increases the radiation exposure set on the patient, making such a study design ethically unacceptable.

Comparison of the two groups of included and excluded patients revealed a statistically significant difference for tumor diagnosis and patient sex, whereas patient age did not differ significantly. Nevertheless, demographic differences between the two groups had to be expected to some degree. All patients with tumors not staged according to the tumor-node-metastasis system were excluded from data analysis, given that the primary end point of this study was the correct determination of the tumor-node-metastasis system stage. Therefore, study results are not applicable to tumors not staged according to the tumor-node-metastasis system. The second tumor entity that must be considered responsible for group differences was differentiated thyroid carcinoma. Thyroid carcinoma is known to grow slowly. Thus, intervals for tumor follow-up are larger than for most other tumor entities, leading to a lack of reference standard for many patients with thyroid cancer. Thus, study results must be interpreted with caution when addressing patients with thyroid cancer.

Reproducibility of the results is an important issue because in daily clinical routine, typically only one physician may be available for diagnostic image review. According to high diagnostic standards, two physicians must be available for side-by-side image evaluation (PET + CT) and fused PET/CT data if both CT and PET are acquired in a diagnostic manner. The PET must be read by a nuclear medicine specialist, whereas CT should be assessed by a radiologist. If PET + CT or PET/CT results are read only by a single physician, this must be someone trained in both disciplines. However, in some institutions, PET/CT is performed using low-dose CT without contrast agents. In these cases only a nuclear medicine physician reports on the images because CT is used only for anatomic correlation of PET. Additional diagnostic CT examinations are frequently required in this imaging scenario, and will be read by a radiologist. In this study, PET/CT was performed with diagnostic CT; thus, two specialists were required for image review. CT alone and PET alone were read by a resident and board-certified physician in consensus. This reading scenario represents daily clinical routine in which image assessment is performed either by a single board-certified physician or by a resident under supervision of a board-certified physician.

PET/CT may be able to detect more lesions than PET + CT, but clinical relevance will only be reached if these additional lesions lead to a change in the tumor-node-metastasis system stage. In an even smaller number of patients, this change in tumor-node-metastasis system stage will lead to a change in patient management. Comparison of the different imaging procedures in this study, therefore, was based on differences in tumor-node-metastasis system staging with special emphasis on the impact on patient management. The authors believe that a change in patient management in 6% of patients with PET/CT compared with PET + CT of strong clinical relevance considering a potential impact of correct patient treatment on patient prognosis. The actual impact of more accurate tumor staging with PET/CT beyond therapeutic decision making on patient survival, however, will have to be determined in future studies.

	Authors' Disclosures of Potential Conflicts of Interest

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... REFERENCES

 
The authors indicated no potential conflicts of interest.

	Acknowledgment

 
We thank Bärbel Terschüren and Sandra Pabst for their assistance in acquiring the PET/CT data, as well as Walter Jentzen, PhD, and Stefan Käpplinger for their technical support with the PET/CT system.

	NOTES

 
Authors' disclosures of potential conflicts of interest are found at the end of this article.

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TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... REFERENCES

 
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Submitted August 18, 2003; accepted August 23, 2004.

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