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Everything you need to know about Computed Tomography (CT) & CT Scanning


PET/CT Evaluation of Esophageal Cancer: Detection, Staging of Disease, and Monitoring of Response to Therapy

Harpreet K. Pannu MD, Pavni Patel MD, Elliot K. Fishman MD, Richard L. Wahl MD

Introduction

Staging of esophageal cancer requires accurate assessment of regional nodes and detection of disease at distant sites. Relatively noninvasive techniques such as endoscopic ultrasound (EUS) and computed tomography (CT) have limitations such as operator dependence for endoscopy and low sensitivity for nodal spread for CT. Functional imaging with FDG PET (18-F- fluoro-2-deoxyglucose positron emission tomography) is a noninvasive test with potential to more accurately evaluate patients with esophageal cancer. Fused PET-CT scanners provide both metabolic and anatomic information with high accuracy in co-registration of the PET and CT datasets.


Indications for Whole Body FDG PET Imaging in Esophageal Cancer
The indications for whole body FDG PET imaging in esophageal cancer are for the diagnosis, initial staging, and restaging of the disease. These indications are reimbursed by Medicare in the United States. Distant metastases detected on a staging PET scan can affect the decision to perform esophagectomy. In patients who are treated with chemotherapy or radiation, a followup PET scan after therapy is performed to see if there is a reduction in the intensity of tumor activity which suggests response. Finally, local anastomotic and distant recurrences can be detected with PET.

Background

Esophageal cancer is the third most common gastrointestinal cancer [1]. The incidence of esophageal cancer in the United States between 1996 and 2000 was 4.5/100,000 people and the five year survival rate for patients who are candidates for definitive treatment is 5-30% [2]. At presentation, 50% of patients have distant metastases or locally advanced unresectable disease [1].


The incidence of adenocarcinoma has increased and it is now the most common type of esophageal cancer in the US with an incidence of approximately 60% [1-3]. Squamous cell carcinomas were the most common type of esophageal cancer three decades ago and in the early 1990s still predominated in black patients [3]. Adenocarcinoma usually occurs in the distal third of the esophagus and squamous cell carcinoma usually occurs in the middle third of the esophagus.

Anatomy and Routes of Spread

There are initial drainage nodes depending on the site of the primary tumor but disease can also spread longitudinally to other nodal sites. Celiac nodes are seen with 10% of upper third esophageal tumors and 45% of middle third tumors [1]. Cervical nodes are seen with 30% of middle or distal third esophageal tumors.


Local extension occurs to the airway, heart and spine [4]. Hematogenous spread occurs to the liver, lungs, adrenals and bones [4]. Serosal spread occurs to the pleura, peritoneum and pericardium [4].

Staging and Treatment of Esophageal Cancer

Esophageal cancer is staged according to the TNM (tumor, node, metastasis) classification by the American Joint Committee on Cancer (AJCC) [2]. There is a high prevalence of nodal metastases. Nodal spread is seen in 40-50% of T2 cancers and in 80% of T3 and T4 cancers [5]. Thoracoscopy has a high accuracy for nodal disease and T4 lesions but is invasive. Endoscopic ultrasound can assess wall invasion and regional nodes but is operator dependent and technically limited in the setting of high grade stenosis. CT can assess regional nodes and abdominal metastases but nodes are diagnosed as abnormal based on size.

PET Imaging in Staging Esophageal Cancer

PET imaging is usually done with FDG. The primary tumor, malignant nodes and distant metastases can show increased uptake on FDG PET. Intense uptake in the primary tumor can obscure increased uptake in local nodes and limit their detection on PET [6]. Distant metastases that are not obvious on anatomic imaging can be seen on PET [7].


PET imaging may also be performed using carbon-11 choline. C-11 choline is phosphorylated, trapped in the tumor cell and incorporated into the phospholipids of the cell membrane [8]. Combined FDG and C-11 choline PET scans may be helpful for staging of mediastinal nodes.

PET Imaging for Assessing Tumor Response to Therapy

Reduction in activity on FDG PET after therapy suggests response and potentially improved survival. A reduction in activity (SUV = standardized uptake value) compared with an initial scan has been used to distinguish patients responding to therapy from those who are not [16,17]. Histologic regression of tumor is greater, time to recurrence is longer, and survival is greater in responders [16,18]. The 2 year survival was 63% among patients with a less than 60% decrease in SUV and survival was 89% in patients with a greater than 60% decrease in SUV in one study [19]. In the study by Weber et al of 40 patients, a greater than 35% reduction in activity had a 93% sensitivity and a 95% specificity for reponse [16]. In the study by Brucher et al of 27 patients, a > 52% reduction in SUV had a 100% sensitivity and 55% specificity for response [20].

PET Imaging for Detecting Distant Recurrences

In patients who have had an esophagectomy, PET can be positive in cases of an anastomotic recurrence. Although the sensitivity is high, the specificity is only moderate (57%) because of false positive cases in patients who have had dilatation of anastomotic strictures [21]. For the diagnosis of distant recurrences, the sensitivity, specificity and accuracy of PET (80-90%) is similar to anatomic imaging [21].

FDG PET Imaging

In patients who have had an esophagectomy, PET can be positive in cases of an anastomotic recurrence. Although the sensitivity is high, the specificity is only moderate (57%) because of false positive cases in patients who have had dilatation of anastomotic strictures [21]. For the diagnosis of distant recurrences, the sensitivity, specificity and accuracy of PET (80-90%) is similar to anatomic imaging [21].

PET/CT Imaging

The advantage of PETCT is that there is a common table for both scans and there is similar stomach/bladder content for both studies [22]. There is no significant change in body curvature between studies and there is improved alignment of the fused data to within a few mm in 3 translation dimensions and within a few degrees in 3 rotation dimensions [22].


For the technique of the study, patients should fast 4 hours prior to the scan and avoid strenuous activity 1 day prior to the scan [22]. The patient should be interviewed regarding recent surgery/chemotherapy. For the CT portion, they are given 750 mL positive oral contrast 1 hour prior to the study. They are injected with 10-15 mCi of FDG intravenously 1 hour before imaging and asked to void prior to the scan. The scan is acquired from the skull base to the mid thigh level in quiet respiration. CT slices are 4.25 mm thick, with an mA of 80 and kVp of 120. The PET is performed with a 5-10 minute acquisition per imaging level.

Primary Tumor


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Uptake in primary mass of esophageal cancer.
Sagittal CT (a), PET (b) and fused PET-CT (c) images show increased uptake in a thickened proximal esophagus (arrows).

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Uptake in primary mass of esophageal cancer with tumor extending to stomach cardia.
Coronal PET (a), CT (b), and fused PET-CT (c) images show increased uptake in the distal esophagus (arrows). Activity extends to the cardia of the stomach.

 

Metastatic Adenopathy


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Uptake in metastatic chest nodes.
Axial fused PET-CT (a) image shows increased uptake in a thickened esophagus (arrowhead) and in an enlarged aorto-pulmonic window node (arrow). Axial fused PET-CT (b,c) images in a different patient show increased uptake in enlarged supraclavicular nodes and right paratracheal node (arrows).

 


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Uptake in metastatic abdominal node.
Axial CT (a), PET (b) and fused PET-CT (c) images show increased uptake in an enlarged gastrohepatic ligament node (arrow). There is also increased uptake in a liver metastasis (arrowhead).

 


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Uptake in metastatic abdominal nodes.
Coronal CT (a), PET (b) and fused PET-CT (c) images show increased uptake in enlarged para-aortic nodes (arrows). Uptake also seen in chest nodes.

 

Distant Metastases


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Uptake in distant metastases.
Axial CT (a) and fused PET-CT (b) images show mass right lobe of the liver (arrow) which has increased uptake. Increased activity also seen in primary tumor at gastroesophageal junction (arrowhead). Axial CT (c) and fused PET-CT (d) images in a different patient show uptake in the left paraspinal region on the fused image (arrow). Metastatic lesion difficult to appreciate on unenhanced CT. Activity also seen in normal right ureter (arrowhead). Axial CT (e,g) and fused PET-CT (f,h) images show lytic lesions in a left rib and in the thoracic spine (arrows) with increased uptake. Coronal fused PET-CT (i) image shows activity in a small pulmonary metastatic nodule (arrow). Normal activity also seen in the heart.

Response to Therapy


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Response to therapy.
Axial PET (a) image before therapy shows increased uptake in the distal esophagus (arrow). Axial PET (b) image after therapy shows no increased uptake in the esophagus. Increased uptake, however, is present in the left lower lobe (arrowhead) due to radiation pneumonitis. Sagittal fused PETCT (c) image shows increased activity fusing to left lower lobe of the lung. Normal cardiac activity seen in (b) and (c).

 

Pitfalls


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Cancerous vs inflammatory activity in the esophagus.
Axial CT (a) and fused PET-CT (b) images show mild thickening of the distal esophagus and activity that is greatly increased over background (arrows) in a patient with esophageal cancer. Coronal fused PET-CT (c) image in a different patient without esophageal cancer shows linear increased activity in the midesophagus (arrow) secondary to inflammation. This can mimic tumor. Inflammation tends to be more linear while tumor tends to be more focal and intense. CT also may demonstrate a mass in cases of tumor.

 


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Uptake in esophageal cancer and stent.
Axial CT (a) and fused PET-CT (b) images show esophageal stent (arrow) surrounded by tumor (arrowheads). There is increased activity in both the tumor and in the stent. Series of coronal fused PET-CT (c) images from anterior to posterior show increased activity in the stent (arrows) and in the tumor (arrowheads). Stent activity likely due to inflammation. Normal activity also seen in the left kidney and bladder.

 

 


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Uptake in esophageal cancer and stent.
Axial CT (a) and fused PET-CT (b) images show esophageal stent (arrow) surrounded by tumor (arrowheads). There is increased activity in both the tumor and in the stent. Series of coronal fused PET-CT (c) images from anterior to posterior show increased activity in the stent (arrows) and in the tumor (arrowheads). Stent activity likely due to inflammation. Normal activity also seen in the left kidney and bladder.

 


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Uptake in mediastinal nodes secondary to sarcoidosis.
Coronal PET (a) and fused PET-CT (b) images show increased activity in distal esophageal cancer (arrowhead) and in mediastinal nodes (arrows). Activity in mediastinal nodes was due to sarcoidosis and not due to metastatic disease.

 

 

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