Prevalence and Significance of Asymptomatic Venous Thromboembolic Disease Found on Oncologic Staging CT

Carmel G. Cronin; Derek G. Lohan; Maccon Keane; Clare Roche; Joseph M. Murphy

Disclosures

Am J Roentgenol. 2007;189(1):162-170. 

In This Article

Discussion

Prompt diagnosis of DVT and PE is essential because both can recur and can have fatal sequelae, thereby affecting morbidity and survival. PE is a fatal complication of DVT from which more than 100,000 people die annually.[1] More than 90% of PEs arise from lower extremity DVT.[2] The cumulated venous thromboembolism recurrence rate is 14% for unilateral proximal DVT and 13.2% for bilateral proximal DVTs. The adjusted survival rate in patients with unilateral proximal DVT is 72% and 65% for those with bilateral proximal DVTs.[20]

Patients with cancer and thrombosis have a lower survival rate than those with cancer without thrombosis. Sørensen et al.[21] found that the 1-year survival rate for cancer patients with thrombosis was 12% compared with 36% in control patients (i.e., cancer patients without venous thromboembolism) (p < 0.001). This high mortality was thought to reflect deaths due to both thromboembolism and a more aggressive course of malignancies associated with venous thromboembolism.[21] Patients with cancer have a four- to eightfold higher risk of dying after an acute thrombotic event than patients without cancer.[10,22]

Evidence suggests that the absolute risk of venous thromboembolism depends on the tumor type, the stage or extent of the cancer, and treatment with antineoplastic agents. We confirmed some of these factors in our study. We found a clinically and statistically significant increased prevalence of PE and DVT in inpatients and in those with advanced stage disease. We found a clinical but not statistically significant increased risk of venous thromboembolism in those undergoing treatment.

The most common malignancies associated with thrombosis are those of the breast, colon, and lung, reflecting the prevalence of these malignancies in the general population. When data were adjusted for disease prevalence, the cancers most strongly associated with thrombotic complications are those of the pancreas, ovary, and brain.[23] In our patient group, iliofemoral DVT was most frequent in patients with breast cancer, lymphoma, and ovarian cancer. PE was most frequently found in patients with breast cancer, lymphoma, and melanoma. However, on analysis we found no statistical difference in the association of venous thromboembolism with cancer type (hematologic, solid organ, or breast). This may be secondary to the inadequate population size.

The diagnosis of venous thromboembolism continues to be a challenge. Venous thromboembolism often has no specific clinical presentation, can be asymptomatic, can masquerade as other illnesses, and may go undiagnosed. The significance of subsegmental emboli, the role of anticoagulation therapy, and whether the risks of anticoagulation outweigh the benefits in the different PE patient subgroups are other controversial, unsolved areas of study. Advances in radiologic technologies have resulted in improved radiologic diagnosis and identification of incidental DVTs and PEs in asymptomatic patients. Occult PE is a well-recognized clinical entity, and it is believed that most PEs that are fatal are not suspected clinically and are not treated.[24,25] However, the significance and clinical outcome of patients with asymptomatic DVT and those with asymptomatic PE diagnosed incidentally are not yet known.

In previous studies, incidental PEs were detected in 1-1.5% of patients scanned using single-detector CT and IV contrast material.[11,26] Both of these studies found a higher rate of PEs in a subgroup of cancer patients than in those with other risk factors such as trauma, surgery, congestive cardiac failure, and immobilization. Gosselin et al.[11] and Winston et al.[26] also found a higher rate of PEs among inpatients of between 2% and 5%. From their subgroup analyses, Winston et al. found a PE prevalence of 9% in inpatients with malignancies. Sebastian and Paddon[14] found a prevalence of 2.6% in oncology patients, but they did not perform subgroup analysis by cancer type or cancer stage or by whether patients were inpatients or outpatients. Gladish et al.[12] found a PE prevalence of 4% in oncology patients (6% in oncology inpatients). Storto et al.[13] found a prevalence of 3.4-4% in inpatients with malignancy and 0.9% in outpatients with malignancy. These results are similar to our finding of an overall prevalence of 3.3% in outpatients and 6.8% in inpatients.

To our knowledge, no long-term survival studies of patients with an incidentally detected DVT or PE have been reported in the literature. Engelke et al.[27] in a recent retrospective study found that those with an incidentally diagnosed and undetected PE at the time of scanning, despite failure to treat, had a benign prognosis. Their results concurred with those of Schultz et al.[28] in their review of untreated PEs in trauma patients. However, the PEs in both of these studies were of low intrapulmonary clot burden (Engelke et al.) or were minor PEs (Schultz et al.). These retrospective trials were also limited by small patient numbers, and both groups of investigators recommended further assessment. Low intrapulmonary clot burden and minor PEs are also in keeping with the current dilemma regarding the clinical importance and risk versus benefit of anticoagulation therapy for treatment of small subsegmental emboli discovered at MDCT.[29,30,31] In our group, we found significant clot burden and in each case the clot was located in the lobar or segmental branches.

The prevalence of IVC, iliac, and iliofemoral DVTs has not been reported to date. We found an overall incidental finding of iliofemoral DVT in 6.8% of patients. Iliofemoral DVT was found in 10% of the inpatient group, most of whom had advanced stage malignancy. An incidental finding of DVT in this patient group is important because 8.7% (2/23) with an asymptomatic DVT and PE subsequently had a more significant symptomatic PE diagnosed on CT pulmonary angiography within 8 weeks. Another 8.7% (2/23) of patients with an asymptomatic DVT (one of whom also had an asymptomatic PE) had clinically symptomatic PEs requiring Greenfield filter insertion within 6 weeks of imaging.

Limitations

A limitation of staging CT as a means of venous thromboembolism assessment versus CT pulmonary angiography is collimation size. In 1992, Remy-Jardin et al.[32] used 5- or 10-mm helical CT, which is similar to the collimation that we used. They found a high sensitivity and specificity (80-100%) for detection of central PEs. This scanning method was noted to be less sensitive for the detection of segmental and subsegmental PEs than other diagnostic techniques.[32,33] Therefore, subsegmental PEs may be missed on staging CT. However, currently a smaller collimation size in staging CT is now standard practice, which would almost certainly increase the sensitivity and specificity for the detection of subsegmental PEs. Gladish et al.[12] used a collimation of 3.75 mm. However, as we stated earlier, the appropriate management of subsegmental PEs incidentally detected is currently controversial. Eyer et al.[34] in a retrospective review of clinicians' responses to radiologists' reports of isolated subsegmental PE using MDCT found that the patients received anticoagulation therapy more often than not. In those patients who did not receive anticoagulation therapy for subsegmental PEs, no recurrent PE was identified on follow-up.[34]

Other limitations of our study besides collimation size include the retrospective method of data collection and the lack of upper extremity venous evaluation. Excluding nondiagnostic scans due to inadequate vessel opacification may lead to the failure to diagnose a DVT or PE. Nevertheless, these findings are significant and important. Attention should be paid to these areas on review of staging CT.

Conclusion

We have shown that cancer patients have a significantly increased rate of incidental venous thromboembolism (iliofemoral DVT and PE) on staging CT scans than the general population. Thromboembolism was seen more frequently in inpatients (RR of DVT, PE, venous thromboembolic disease = 1.6, 2.1, 1.4, respectively) and in those with advanced stage disease (RR of DVT, PE, venous thromboembolic disease = 2.2, 1.8, 2.0). Therefore, a high index of suspicion and vigilance and dedicated assessment for thromboembolism are recommended while interpreting all scans of oncologic patients regardless of cancer stage. Staging CT of the thorax, abdomen, and pelvis provides a single examination that allows both the pulmonary arterial system and the pelvic and lower extremity venous system to be evaluated, therefore offering an important diagnostic opportunity.

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