Rationale and Objectives
To investigate the accuracy of M staging (staging of metastatic disease) in esophageal carcinoma based on a visual interpretation and based on tumor volume measurements on positron emission tomography (PET) computed tomography (CT).
Materials and Methods
Fifty-nine untreated patients with gastroesophageal junction tumors were enrolled, including 36 subcardial gastric tumors (type III according to Siewert classification) and 23 adenocarcinomas of the cardia (AEG, type II Siewert). Patients were grouped in metastasis free (M0 stage, n = 34) and metastatic stages (M1 stage, n = 25). Tumor volume and mean and maximum standardized uptake value were measured on PET-CT. The accuracy of these quantitative tumor volume parameters in distinguishing metastasis-free tumors (M0 stage) from metastatic stages (M1 stage) was compared to the accuracy of a visual analysis with fused PET-CT. Furthermore, accuracy of PET-CT was compared to PET reviewed side by side with CT in a lesion-based analysis of 84 distant metastatic sites.
Results
In the visual interpretation, PET-CT (accuracy 88%, 74/84) was more accurate than PET (accuracy 78%, 66/84; P = .008) in characterizing the 84 potential metastatic sites in the 59 patients. Among the tumor parameters, the PET-CT tumor volume was the most accurate predictor of M1 stage and overall survival. With a threshold of 39 mL, PET-CT volume was able to predict M1 stage disease with a sensitivity of 96% and a specificity of 85%. The accuracy of M-staging was increased further when combining tumor volume measurements with the results from the visual analysis (combined results: sensitivity 96%, specificity 94%).
Conclusions
PET-CT was more accurate than PET (reviewed side by side with CT) in characterizing distant metastatic sites of gastroesophageal junction carcinomas. The highest accuracy for M-staging was obtained when combining the results of the visual analysis with the results from primary tumor volume measurements. Primary tumor volume was shown to be an independent prognostic factor.
Tumors of the gastroesophageal junction (GEJ) and distal esophagus are mostly classified according to location: type I (adenocarcinoma of the distal esophagus), type II (true carcinoma of the cardia and GEJ), and type III (subcardial gastric carcinoma that infiltrates the GEJ) ( ). The incidence of GEJ tumors is increasing and the prognosis remains poor with a 5-year survival of 15%–40% ( ). The presence of metastatic tumor spread is an important predictor of survival and determines the therapeutic approach in gastroesophageal tumors ( ). Metastatic disease can be assessed by a variety of modalities, including endoscopic ultrasound (EUS), computed tomography (CT), positron emission tomography (PET), and combined PET-CT. The most important clinical question for pretherapy staging is to determine patients with incurable due to distant metastasis (M1 disease). Patients with distant metastases do not benefit from a curable approach and are best served with palliative care. The present study investigates the advantage of a visual analysis on fused PET-CT over that on PET (reviewed side by side with CT) for the differentiation of distant metastatic disease (M1) from metastasis-free stages (M0). Furthermore, it was evaluated whether primary tumor volume parameters can be used to differentiate M0 from M1 tumors. Several studies have shown that the degree of the local extent of the primary tumor is predictive of metastatic spread. It is the extent of tumor both in axial and longitudinal dimension that is associated with metastatic disease and prognosis ( ). Therefore, primary tumor volume, a variable that considers axial and longitudinal progression, might be the most accurate predictor of tumor spread and metastatic disease. Studies on radiation treatment planning suggest that tumor volume might be measured more accurately with combined PET-CT than with conventional modalities becasue PET-CT provides both metabolic and anatomic information ( ). The aim of the present investigation was to investigate whether tumor volume is associated with tumor stage and can help to predict metastatic disease and overall survival.
Methods and materials
Patients
Study subjects were 59 patients with adenocarcinomas of the GEJ, including 36 patients with subcardial gastric carcinomas (type III according to the Siewert classification) and 23 patients with tumors of the cardia (type II Siewert) ( ). The study was compliant with the Health Insurance Portability and Accountability Act, and approval from the institutional review board was obtained.
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Table 1
Demographic Data in Metastasis-Free (M0 or Stage I–III) and Metastatic Disease (M1)
Sex Male Age (y) Weight (lb) Height (cm) Glucose (mg/dL) Histology: AEG II; Gastric (AEG III) Site: GE Junction; Gastric M0 ( n = 34) 26 (77%) 65.1 ± 12.6 173.1 ± 35.0 171.7 ± 10.9 108.6 ± 12.5 10 (29%); 10 (29%); 24 (71%) 24 (71%) M1 ( n = 25) 16 (64%) 66.1 ± 8.6 171.1 ± 32.2 170.4 ± 7.4 109.6 ± 12.7 13 (52%); 13 (52%); 12 (48%) 12 (48%) Differences_P_ = .39 ⁎ t = −0.32;t = 0.23t = 0.50t = −0.31P = .11 ⁎ P = .11 ⁎ P = .75 † P = .82 † P = .62 † P = .76 †
AEG II, type II adenocarcinoma of the esophagogastric (AEG) junction based on the Siewert classification (1); GE, gastroesophageal; gastric, gastric carcinoma.
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PET-CT Imaging
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Characterization of Metastatic Sites Based on Visual Analysis
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Assessing Risk of Metastatic Spread (M1 Stage) Based on Primary Tumor Volume Measurements
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Data Analysis and Statistics
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Results
Association between Tumor Volume Parameters and Risk of Metastatic Disease
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Table 2
Differentiation of M1 Stage (metastatic) from M0 Stage (metastasis-free) Based on Primary Tumor Volume
PET-CT PET SUV Max Volume (mL) SUV of Volume Volume (mL) SUV of Volume M0 ( n = 34) 24.7 ± 16.8 4.1 ± 1.0 29.7 ± 24 3.9 ± 0.9 7.7 ± 3.3 M1 ( n = 25) 84.7 ± 58 5.3 ± 1.7 94.5 ± 69.2 5.1 ± 1.7 10.6 ± 4.1 Differences_Z_ = −5.9 ⁎ t = −3.5 † Z = −5.5 ⁎ t = −3.7 † t = −3.0 † P < .001P = .001P < .001P = .001P = .004 AUC 0.954 0.741 0.922 0.744 0.718 Threshold 39.0 SUV 4.7 41 SUV 4.2 SUV 7.8 Sensitivity 96% 60% 96% 60% 88% Specificity 85% 71% 82% 68% 56%
AUC, area under the curve; CT, computed tomography; PET, position emission tomography; SUV, standardized uptake value.
Tumor volume and mean SUV were measured both on PET-CT and PET.
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Prediction of a Metastatic Stage (M1 Stage) Based on a Combination of a Visual Analysis and Tumor Volume Measurements
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Table 3
Differentiation of Metastatic from Metastasis-free Stages Based on a Visual Analysis, Based on Tumor Volume Measurements and Based on a Combination of Both
M Staging (M0 vs. M1) PET-CT PET Visual Analysis Volume (>39 mL) Combination of Both ( ⁎ combination Score ≥1) Visual Analysis Volume (>41 mL) Combination of Both ( ⁎ combination Score ≥1) Sensitivity 80% 96% 96% 72% 96% 96% Specificity 97% 85% 94% 91% 82% 88%
CT, computed tomography; PET, position emission tomography.
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Table 4
Definition of the Combination Score for the Differentiation of Metastatic from Metastasis-free Stages Based on a Combination of a Visual Interpretation (qualitative interpretation) and Tumor Volume Measurements (quantitative interpretation)
M staging (M0 vs. M1) Visual Interpretation Quantitative Interpretation (with tumor volume) Combination of Both: Combination Score: PET-CT M0 disease M1 disease ≤59 mL 59 mL Maximum score = 2 Score = 0 Score = 1 Score = 0 Score = 1 PET M0 disease M1 disease ≤60 mL >60 mL Maximum score = 2 Score = 0 Score = 1 Score = 0 Score = 1
CT, computed tomography; PET, position emission tomography.
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Accuracy of PET-CT Compared to PET in a Lesion-Based Analysis of Distant Metastatic Sites
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Table 5
Accuracy of PET-CT Compared to PET (reviewed side by side with CT) in Identifying Metastatic Sites Based on a Visual Analysis
PET-CT PET Distant Metastatic Sites Visual Analysis Visual Analysis Sensitivity 79% (36/45) 65% (29/45) Specificity 97% (38/39) 94% (37/39) PPV 97% (36/37) 94% (29/31) NPV 81% (38/47) 70 % (37/53) Accuracy 88% (74/84) 78% (66/84)
CT, computed tomography; NPV, negative predictive value; PET, position emission tomography; PPV, positive predictive value.
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Tumor Volume Predicts Overall Survival
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Discussion
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