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Ann Thorac Surg 1999;68:1133-1136
© 1999 The Society of Thoracic Surgeons

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Original Articles

Evaluation of distant metastases in esophageal cancer: 100 consecutive positron emission tomography scans

^a Section of Thoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA

Address reprint requests to Dr Luketich, Section of Thoracic Surgery, University of Pittsburgh Medical Center, 200 Lothrop St, C-800 PUH, Pittsburgh, PA 15213
e-mail: luketichjd{at}msx.upmc.edu

Presented at the Thirty-fifth Annual Meeting of The Society of Thoracic Surgeons, San Antonio, TX, Jan 25–27, 1999.

	Abstract

Top Abstract Introduction Material and methods Results Comments References

 
Background. Pilot studies suggest positron emission tomography (PET) scanning may be superior to conventional imaging in staging esophageal cancer, especially in the detection of radiographically occult distant metastases. This report summarizes our experience with PET in staging esophageal cancer.

Methods. One hundred consecutive PET scans in 91 patients with esophageal cancer referred for surgery were prospectively collected (1995 to 1998) and compared with computerized tomography (CT) and bone scan. PET images were acquired after injection of 18F-fluorodeoxyglucose and evaluated for abnormal uptake. Minimally invasive surgical staging (MIS) and/or clinical correlation were used to confirm or refute imaging results.

Results. MIS or clinical correlation confirmed 70 distant metastases in 39 cases. PET detected 51 metastases in 27 of 39 cases (69% sensitivity, 93.4% specificity, 84% accuracy) compared with CT, which detected 26 metastases in 18 of 39 cases (46.1% sensitivity, 73.8% specificity, 63% accuracy) (p < 0.01).

Conclusions. PET was more accurate than CT in detecting distant metastases, but was only 69% sensitive compared with minimally invasive staging.

	Introduction

Top Abstract Introduction Material and methods Results Comments References

 
The incidence of adenocarcinoma of the esophagus has been rising at an alarming rate in the U.S. since the mid-1970s [1–3]. Previously, the majority of cases of esophageal cancer were squamous cell neoplasms, but adenocarcinoma is now the most common histology. Definitive information regarding risk factors and etiologies for the rising incidence of adenocarcinoma is not yet available. The most consistent risk factor is chronic esophageal reflux disease, which may lead to Barrett’s esophagus, and in some cases adenocarcinoma.

Conventional approaches to staging esophageal cancer include computerized tomography (CT), bone scans, and endoscopic ultrasound. These modalities have been shown to be inaccurate in detecting small distant metastases and in evaluating locoregional lymph nodes compared with minimally invasive staging [4–6]. However, cost and morbidity are important limitations of laparoscopic and thoracoscopic staging of esophageal cancer. In addition, these procedures do not assess cervical lymph nodes, which may harbor micrometastases in up to 30% of patients with esophageal cancer even when the primary tumor is located in the distal esophagus [7].

Recently, our group [8] and others [9, 10] have reported preliminary data suggesting positron emission tomography (PET) may play a role in staging esophageal cancer. The objective of this study was to report our expanded findings on the use of PET scan in detecting distant metastases in esophageal cancer.

	Material and methods

Top Abstract Introduction Material and methods Results Comments References

 
The patients represented in this series were consecutively referred to the Pittsburgh Cancer Institute at the University of Pittsburgh Cancer Institute for consultation by the Section of Thoracic Surgery between July 1995 and August 1998. Patients with potentially resectable disease based on clinical evaluation, barium esophagram, and CT of the chest and abdomen underwent PET scanning. Other staging modalities used in this study group included endoscopic ultrasound in 75%, minimally invasive surgical staging in 67%, and bone scans in 66%. Patients excluded from the series included those who had biopsy-proven distant disease based on standard noninvasive scanning results and fine needle aspiration, and thus were not candidates for surgical resection.

Positron emission tomography methods
All patients underwent PET scanning at the University of Pittsburgh Medical Center-Presbyterian facility. Scans were performed on either the Siemens/CTI (Knoxville, TN) ECAT ART or HR⁺ tomograph or the newly installed PET/CT combination scanner. Patients were fasted at least 4 hours before scanning. The morning of the PET scan, patients were injected with 6 to 8 mCi of 18-fluorodeoxyglucose (FDG). PET scan was performed approximately 45 minutes after injection to allow sufficient circulation and uptake of tracer. A total of six to eight bed positions were used during scanning, each for approximately 6 minutes, yielding a total scan time of 36 to 48 minutes. The bed positions were overlapped by 4 cm, and whole body, three-dimensional images were reconstructed using the reprojection algorithm of Kinahan and Rogers [11]. The images were smoothed with a Hanning window, cut off at 80% of Nyquist frequency. There was no correction for attenuation or scatter. The PET images were displayed on a monitor in coronal, transverse, and sagittal views. Nuclear medicine-trained physicians analyzed the scans, concentrating on areas of focally increased FDG uptake. CT scans were used as a comparison for anatomic location and correlation.

Statistical analysis
The sensitivity, specificity, and accuracy of PET and CT for identifying distant disease were calculated by comparing the results of each scan with the results of biopsy, minimally invasive surgical staging, surgical resection, or clinical evaluation. Distant metastatic disease included lymph nodes if greater than 10 cm from the primary sit of tumor. A chi-square analysis was performed to assess the significance of the PET results versus the CT results (significance was set at p = 0.01). Kaplan-Meier survival curves were generated to analyze whether the initial PET results were sufficient to stratify survival. A log-rank test was used to assess the significance of this stratification (significance was set at p = 0.01).

	Results

Top Abstract Introduction Material and methods Results Comments References

 
A total of 91 patients were included in the series; nine patients had two PET scans performed at different times, yielding a total of 100 PET scans for study inclusion. Of the 91 patients, 16 were women and 75 were men. The average patient age was 65.5 years (range 39 to 89 years). Of the 100 scans performed, 87 were performed before any surgical treatment. The remaining 13 scans were performed after surgical resection.

Minimally invasive staging or clinical correlation confirmed a total of 70 distant metastases in 39 scans. PET accurately detected 51 of these metastases in 27/39 scans. PET was 69% sensitive for detecting the presence of metastases. Radiographically occult metastatic sites of disease identified by PET scan were liver, 23; lung, 7; bone, 3; adrenal, 1; chest wall, 1; distant lymph nodes (16): mediastinal, 8; axillary, 1; neck, 7. Radiographically occult metastatic sites of disease missed by PET scan and indentified by minimally invasive surgery were liver, 10; lung, 2; pleura, 4; peritoneal, 1; cervical lymph node, 1. Note that all metastatic sites missed by PET scan were less than 1 cm in diameter. Specificity was 93.4%, yielding an overall accuracy of 84%. An example of a false-negative PET scan is shown (Fig 1A). Figure 1B shows the 6-mm liver metastasis found at laparoscopy, which was missed by PET. In 16 cases, the PET scan information led to a decision not to perform esophagectomy. For example, Figure 2 shows a PET scan indicative of distant metastatic disease who had a negative CT scan. False CT, on the other hand, accurately detected 26 metastases in 18 of 39 scans. CT was only 46.1% sensitive for detecting metastases and 73.8% specific, for an overall accuracy of 63%. The difference between PET and CT was statistically significant (p < 0.01). Of the 12 scans where PET was falsely negative, CT was accurate in four (33.3%). Of the 21 scans where CT was falsely negative, PET was accurate in 13 (61.9%). Bone scan was originally included in the comparisons, but it only identified one single metastasis correctly, and was not used in the analysis.

View larger version (71K): [in this window] [in a new window]   Fig 1. (A) False-negative PET scan shows increased focal uptake of tracer only at the site of the primary tumor at the gastro-esophageal junction. (B) In the same patient, laparoscopic staging identified a 6-mm liver metastasis that was not identified by either PET or CT.

View larger version (170K): [in this window] [in a new window]   Fig 2. PET scan showing increased focal uptake at the pleura and paratracheal lymph nodes not identified by CT.

View larger version (15K): [in this window] [in a new window]   Fig 3. Survival based on initial PET scan identification of distant versus local disease only.

	Comments

Top Abstract Introduction Material and methods Results Comments References

PET uses radioactive tracers to detect changes in metabolism between normal tissue and malignant tissue. In most studies to date, 18F-fluorodeoxyglucose has been used to identify sites of increased glucose uptake [12, 13]. Using this approach, PET applications in lung cancer have been reported to detect radiographically occult metastatic disease in up to 15% of patients initially thought to be surgically resectable. Sensitivity for detecting mediastinal lymph node involvement has been 80% to 90%, specificity 85% to 99%, and accuracy as high as 90% [14, 15]. Initial pilot studies by our group and others have shown PET scanning for evaluating lymph node metastases in esophageal cancer has been less accurate, as low as 48% [8]. PET scanning for distant metastatic disease in esophageal cancer has been less frequently reported, but pilot studies suggest that between 10% and 20% of patients may have radiographically occult distant metastatic disease [8–10]. This study confirms previous reports and demonstrated that PET scanning revealed unsuspected metastatic disease in 16% of our patient population. This information was clinically significant and led to nonsurgical treatment approaches for patients with distant metastases.

Sensitivity of PET for detection of distant metastatic disease in this study was 69%, compared with thoracoscopic and laparoscopic staging. The most frequently missed distant metastatic sites by PET included liver and lung, and were usually less than 1 cm in diameter (Table 2). Advances in PET scanning technology could improve the sensitivity of PET for detecting smaller foci of metastatic disease. New tracers, such as C-11 Choline, show promise in the evaluation of locoregional lymph node evaluation [16, 17]. Combination PET/CT scanners will likely improve anatomic localization of uptake in a more precise manner and could lower the costs of separate CT and PET scanning. We are currently evaluating a combination PET/CT scanner developed in our center (by D.W.T.) that performs both scans simultaneously and can superimpose the images. This type of technology provides a more accurate anatomic localization of focal tracer uptake (Fig 4).

View larger version (139K): [in this window] [in a new window]   Fig 4. Example of PET/CT scan in a patient with esophageal cancer primary and local nodal involvement.

	References

Top Abstract Introduction Material and methods Results Comments References

 

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