Clinical Outcomes of Isolated Distal Deep Vein Thrombosis Associated with Cancer: The Cleveland Clinic Experience
Authors: Poudel Shyam K. , Jia Xuefei , Park Deborah Y. , Wilks Mailey Lynn , Pinkava Vicki , O'Brien Meghan , Tripp Barbara , Song Jung-Min , McCrae Keith R. , Khorana Alok A. , Angelini Dana E. 
Published: October 2019

Abstract
Introduction:
Although a randomized trial showed no difference in progression of VTE in patients with isolated distal deep vein thrombosis (IDDVT) treated with anticoagulation vs. serial ultrasound monitoring, cancer patients were excluded from this study and remain a high risk population. Furthermore, studies to evaluate the long-term clinical outcomes of IDDVT in cancer patients have been limited. Here we report patient outcomes from our experience in treating cancer-associated IDDVT.
Methods:
We evaluated a prospective cohort of patients referred to our centralized cancer-associated thrombosis (CAT) clinic at the Cleveland Clinic Taussig Cancer Institute from 8/2014-5/2018. We evaluated clinical characteristics, anticoagulation prescription, venous thromboembolism (VTE) recurrence rate, major bleeding, hospital admission, and overall survival in patients diagnosed with IDDVT compared to those with proximal events. Statistical methods included t-tests, chi-squared tests, Cox model and competing risks model where appropriate. Multivariable analysis was performed to identify risk factors associated with overall survival and recurrence rate.
Results:
Data from 1100 patients were included in the analysis. After excluding upper extremity DVT, a total of 302 (27.5%) VTE events were diagnosed, 122 (40.4%) of which were IDDVT. Of patients diagnosed with IDDVT, 14 (11.7%) had a history of prior VTE and 48 (55.8%) had documented stage 4 cancer (see table 1). Low molecular weight heparin (LMWH) was the most commonly prescribed anticoagulant (50.8%) followed by rivaroxaban (35.2%). Seven patients (5.7%) did not receive anticoagulation due to contraindication. Proximal events were seen more often in males vs. females (110/180 (61.1%) vs. 70/180 (38.9%), p=0.027 and in those with stage 4 disease vs. stage 0-3 (95/120 (79.2%) vs. 25/120 (20.8%), p=0.001. Rate of VTE recurrence (see figure 2) in patients initially diagnosed with IDDVT was similar to the rate of VTE recurrence in proximal DVT or pulmonary embolism (PE), with 1-year incident rate of 12.7% and 8%, respectively, (HR 1.31, 95% CI, 0.54 - 3.15, p= 0.55). There was no difference in rate of major bleeding 6 months after the initial event between patients with IDDVT and proximal events, 4/17 (23.5%) vs. 7/30 (23.3%), respectively, p=1.0. There was no difference in subsequent hospital admission between those with IDDVT and proximal events 48/122 (39.3%) vs. 73/175 (41.7%), respectively, p=0.77. After multivariable analysis, there was no difference in overall survival between IDDVT vs. proximal events HR 1.43 (95% CI 0.88-2.32), p=0.15 (see figure 1). Overall survival was negatively impacted in patients with stage 4 disease, hematologic malignancy, male gender, and symptomatic VTE.
Discussion:
This study demonstrates that cancer patients with IDDVT have a similar rate of VTE recurrence, subsequent hospital admission, rate of major bleeding, and overall survival compared to those with proximal events. These findings, if validated, suggest that treatment of cancer-associated IDDVT should mirror treatment of proximal events.

Disclosures
Khorana: Janssen: Consultancy; Bayer: Consultancy; Pfizer: Consultancy; Sanofi: Consultancy.