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1 Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York
Ave., New York, NY 10021.
2 Weill Medical College of Cornell University, 1300 York Ave., New York, NY
10021.
3 Present address: Department of Radiology, Danbury Hospital, 24 Hospital Ave.,
Danbury, CT 06810.
Received February 22, 2002;
accepted after revision April 22, 2002.
Presented at the annual meeting of the American Roentgen Ray Society,
Seattle, April—May 2001.
Abstract
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MATERIALS AND METHODS. We reviewed the radiology report for each CT angiogram that was obtained for clinically suspected pulmonary embolism at our institution (a tertiary cancer center) during a 25-month period. The radiology information system was then searched for any additional confirmatory radiologic examinations performed within 2 days after a negative finding on CT angiography. Medical records were reviewed to determine whether anticoagulation therapy was started or continued despite a negative finding on CT angiography.
RESULTS. Two hundred seventy-six CT angiograms were obtained in 260 oncology patients who were clinically suspected of having pulmonary embolism. The findings from 203 CT angiograms (74%) were interpreted as negative; 56 (20%), as positive; and 17 (6%), as equivocal for pulmonary embolism. Fifty-eight patients (21%) with negative findings on CT angiography subsequently underwent additional imaging, the results of which were potentially clinically important in 6% of the patients. Six patients began to receive and two continued to undergo anticoagulation therapy despite negative findings on CT angiography; three of the six patients received anticoagulation for new-onset atrial fibrillation.
CONCLUSION. Negative results of CT angiography for pulmonary embolism did not deter referring physicians from ordering other confirmatory imaging tests in 21% of patients in a high-risk oncologic population. Those additional tests rarely revealed results that might have been clinically important.
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Ventilation—perfusion scanning remains the first-line examination at many institutions, although CT angiography has been increasingly performed in patients suspected of having a pulmonary embolism. Although many clinicians readily accept a diagnosis of pulmonary embolism obtained with CT angiography, others are hesitant to accept a negative result as a definitive answer and will order additional studies to confirm the negative findings. The prevalence of a subsequent pulmonary embolism after negative findings on CT angiogrphy is low (1%), similar to that after findings of a normal or low-probability ventilation—perfusion scan [5].
Oncology patients are at an increased risk of venous thromboembolism, which is the second most common cause of death in patients with clinically overt cancer and which may be the first clinical manifestation of an occult cancer [6]. In addition to the increased risk of thromboembolic disease from a malignancy, oncology patients undergoing surgery are also placed at an increased risk by the surgical procedure, especially gynecologic surgery. Because of these concerns, we undertook this study to determine the frequency and types of additional imaging examinations that were performed immediately after a negative finding for pulmonary embolism on CT angiography in a high-risk oncologic population. We also sought to determine what percentage of these patients began to receive or continued to undergo anticoagulation therapy despite negative findings on CT angiography. Our study did not attempt to determine the diagnostic accuracy of CT angiography because recent studies have shown sensitivities and specificities for pulmonary embolism of more than 90% [1, 2, 7].
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Medical records were reviewed to determine whether anticoagulation therapy was started or continued after a negative finding on CT angiography.
Our institutional review board performed a post hoc assessment of our study and stated that it would have been considered exempt research had it been initially reviewed.
CT Angiographic Technique
All CT angiograms were obtained on a Light-Speed QX/i or HiSpeed CT/i
(General Electric Medical Systems, Milwaukee, WI) scanner. Contrast-enhanced
helical CT of the pulmonary arteries was performed from 1 cm above the level
of the aortic arch to the level of the inferior pulmonary veins. Scans were
acquired in a caudocephalad direction from the level of the inferior pulmonary
veins with the patient supine in suspended inspiration. Two scanning protocols
were selected, depending on the scanner used. A total volume of 150 mL of
nonionic contrast material was injected IV at a rate of 3 mL/sec (HiSpeed
CT/i) or 4 mL/sec (LightSpeed QX/i) through an 18-gauge IV needle.
Scanning on the HiSpeed CT/i was performed with 3-mm collimation at a pitch of 1.6:1 with a 30-sec delay from injection to scanning. The scans were retrospectively reconstructed at 1-mm intervals with a field of view of 25 mm. The remainder of the chest, including the lung apices and bases, was scanned with 7-mm collimation.
Scanning on the LightSpeed QX/i was performed with 2.5-mm collimation and reconstructed with a 1.25-mm overlap at HiSpeed 15 with a 25-sec injection-to-scanning delay. The remainder of the chest was scanned with 7.5-mm collimation.
All images were interpreted on a PACS (picture archiving and communication system) workstation.
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A subsequent study was performed in 58 (21%) of 203 patients after negative findings on CT angiogrphy. Seventeen patients (8%) underwent ventilation—perfusion scanning within 2 days (mean, 0.6 days) after CT angiography, and 30 patients (15%) underwent one (n = 26) or two (n = 4) follow-up sonographic examinations within 2 days (mean, 0.7 days) after CT angiography. Ten patients underwent both ventilation—perfusion scanning and extremity sonography. One other patient underwent pulmonary angiography within 2 days after CT angiography; the finding from that angiogram was negative (Fig. 1). The additional examination results were potentially clinically important in 12 (6%) of the 203 scans: high-probability (n = 2) and intermediate-probability (n = 3) on ventilation—perfusion scanning and deep venous thrombosis (n = 7) on lower extremity sonography.
In the 17 patients with negative findings on CT angiography who underwent only subsequent ventilation—perfusion scanning, the ventilation—perfusion scans were of high, intermediate, or low probability for pulmonary embolism in two, two, and 12 patients, respectively, and the findings from one other ventilation—perfusion scan was normal. Of the two patients with high-probability ventilation—perfusion scans, one was treated with anticoagulation therapy and the other was not treated with anticoagulation or filter placement because of improvement in the patient's clinical symptoms. One of two patients with intermediate-probability ventilation—perfusion scans was given anticoagulation therapy, and the other had an inferior vena cava filter placed. Eleven of the 12 patients with low-probability ventilation—perfusion scans did not receive treatment for pulmonary embolism; the other patient was placed on anticoagulation therapy because of high clinical suspicion despite these negative examination results. No treatment was initiated for the patient with a normal finding on the ventilation—perfusion scan.
Of the 10 patients who underwent ventilation—perfusion scanning and sonography, both studies were negative in seven patients, sonography was positive for lower extremity thrombus in two, and ventilation—perfusion scanning was of intermediate probability in one. Treatment with anticoagulation therapy was begun only in the patients with lower extremity thrombus. These treatment decisions were based on the combination of clinical suspicion and the information obtained from the three imaging studies (CT angiography, ventilation—perfusion scanning, and sonography).
Of the 17 CT angiograms interpreted as equivocal, eight were interpreted as possibly positive and nine as possibly negative for pulmonary embolism. These interpretations were limited by suboptimal contrast bolus, respiratory motion, or other artifacts. Of the eight patients with a possibly positive finding on CT angiography, six underwent follow-up sonography or ventilation—perfusion scanning; in only one patient did the results from these additional studies change patient management. This patient had an intermediate-probability ventilation—perfusion scan and a sonogram that was positive for lower extremity thrombus, and the patient was subsequently treated with anticoagulation therapy. Of the nine patients with a possibly negative finding on CT angiography, two underwent follow-up ventilation—perfusion scanning; the results did not lead to any patient being subsequently treated with anticoagulation therapy (Fig. 1). Nine patients underwent no further follow-up scanning and received no anticoagulation therapy; two of these patients remain alive 2 years later, and the seven others died within 3 months from their advanced metastatic cancers (no autopsy of the lungs was performed).
A review of the medical records of the 187 patients with a negative finding on CT angiography revealed that two patients (1%) were continued on anticoagulation therapy that had been initiated before CT angiography. One of these patients had an intermediate-probability ventilation—perfusion scan and the other received anticoagulation therapy for an upper extremity deep venous thrombus diagnosed at another institution before admission. Six patients (3%) were placed on anticoagulation therapy after a negative finding on CT angiography. Three patients were given anticoagulation therapy because of a high clinical suspicion for clinically presumptive pulmonary embolism (although one of these patients had a negative finding on sonography), another had a low-probability ventilation—perfusion scan, and the third had an intermediate-probability ventilation—perfusion scan. The remaining three patients had no further imaging; they developed atrial fibrillation during their hospitalization and were therefore placed on anticoagulation therapy.
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As for most diagnostic tests, clinicians have more confidence in a CT angiogram that is positive for pulmonary embolism than in a CT angiogram that is interpreted as negative. Clinicians may order additional radiologic tests or initiate treatment for pulmonary embolism on clinical grounds when findings on CT angiography are negative. Garg et al. [8] and Goodman et al. [5] recently reported a 99% negative predictive value for CT angiography, higher than the 89% reported by Remy-Jardin et al. [9] in 1996. These more recent results were likely better because of interval improvement in CT equipment and greater experience of interpreters in the late 1990s. One reason for the lack of confidence in a negative CT angiogram is the possibility of a missed subsegmental embolus, although the clinical relevance of such small peripheral emboli in the absence of a central embolus is uncertain [10, 11]. However, a normal finding on CT angiography is as reliable as a normal findings on a lung scan in excluding a diagnosis of pulmonary embolism [10]. In fact, CT can be more useful than ventilation—perfusion scanning because CT often provides an alternate diagnosis to explain the patient's signs and symptoms [8, 12].
The use of thinner collimation (2-3 mm) with single-detector CT has been shown to improve detectability of pulmonary embolism [13]. Multidetector CT scans with even thinner (1.0-1.25 mm) collimation and shorter scanning times may further improve pulmonary embolism detectability. Interpreting images in the cine mode on a PACS workstation improves detection of small pulmonary nodules [14]; this process may also improve pulmonary embolism detectability. All our studies were interpreted in the cine mode on a PACS workstation.
CT venography has been shown to have a high sensitivity (97%) and specificity (100%) for femoropopliteal deep venous thrombus [15]. Combining CT venography and CT angiography allows concurrent evaluation for pulmonary embolism and deep venous thrombus in a single imaging study without additional IV contrast administration. Because pulmonary embolism and deep venous thrombus are two different aspects of the same disease, this combined examination may be a valuable addition to the initial diagnostic algorithm. Further studies assessing clinical impact and cost-effectiveness are needed to evaluate whether this method would be an appropriate alternative to CT angiography alone.
Although many clinicians believe that the more information they have about their patients, the better they can care for them, in fact the search for maximum information is neither practically sound nor logically defensible. It is hard for some to accept the notion that the quest for diagnostic certainty can be carried too far [16]. Not only is absolute certainty unattainable, but as certainty is approached the incremental informational yield of subsequent diagnostic procedures approaches zero. Such diagnostic overkill can lead to a false sense of accomplishment by the accumulation of supposedly accurate and precise test results, some of which will be false-positive and some, false-negative [17]. A cascade of tests, some with potential for morbidity or mortality, may be initiated when an initial test result is abnormal or ambiguous. Despite the limitations of diagnostic procedures, many physicians continue to test excessively, partly because of their discomfort with uncertainty [16] and their desire to minimize a perceived malpractice risk.
One limitation of our study is that it is a retrospective analysis. We reviewed CT angiography reports, additional imaging reports, and medical records without reinterpreting the actual imaging studies. This methodology was chosen to study our actual clinical practice. Some patients may have undergone further examinations or therapy elsewhere that was not reflected in our medical records. Also, different results may have been obtained if our protocol had included routine CT of the lower extremities as part of CT angiography.
Like others, we believe that CT angiography should be the initial imaging examination performed for evaluation of clinically suspected pulmonary embolism [5, 18] in patients with known radiographically evident pulmonary disease or in hospitalized patients because of their greater likelihood of confounding pulmonary abnormalities. No further imaging is needed if the CT angiographic results are negative or positive for pulmonary embolus; if the results are equivocal, we recommend immediate ventilation—perfusion scanning or repeated CT angiography within 24 hr.
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