Farmer, Sara A.

Abstract Background: Active cancer is an independent predictor of recurrent venous thromboembolism (VTE; hazard ratio=2.2–4.2). However, whether the risk of VTE recurrence among active cancer patients can be further stratified by tumor site or presence of metastases is uncertain. Objectives: To estimate and compare the cumulative incidence of VTE recurrence by tumor site and presence of metastases among active cancer patients with incident VTE. Study Design and Population: Retrospective cohort study of Olmsted County, MN residents with active cancer who lived >1 day after a first-lifetime deep vein thrombosis or pulmonary embolism over the 35-year period, 1966–2000 (n=418). 25 patients with oral (6), bone (1), skin (4), soft tissue (3), eye (1) and other/unknown (10) were excluded, leaving 393 remaining patients. Measurements: Baseline demographic and clinical characteristics, tumor site, presence and location of tumor metastases, and date of first recurrent VTE. Tumor site and metastases were tested as potential predictors of time-to-recurrent VTE using the Cox proportional hazards model. Results: 114 of 393 patients with active cancer developed recurrent VTE over 764 person-years of follow-up. The cumulative incidence of recurrent VTE at seven, 30, 90, and 180 days, 1, 5, and 10 years was 1.9%, 10.3%, 18.3%, 22.3%, 28.7%, 44.5%, and 53.5%, respectively. After adjusting for age and gender, tumor site was an independent predictor of first VTE recurrence (p<0.01). The hazard of VTE recurrence was over 2-fold higher for lung cancer patients compared to the lowest recurrence group (kidney, bladder and other genitourinary cancer; HR=2.04, 95% CI: 0.88, 4.70, p=0.096), and the hazard for brain and pancreatic cancer was nearly 2-fold higher (HR=1.9 for each, p=0.22, 0.24, respectively). The hazard of recurrence among hematological; breast and ovarian; gastric, colon, and liver; and prostate cancer patients did not differ significantly from the lowest recurrence group. Univariately, the presence of metastases at cancer diagnosis was not associated with recurrent VTE (HR=1.16; 95% CI: 0.79, 1.69, p=0.45). Conclusions: Tumor site is an independent predictor of VTE recurrence after adjusting for age and gender. In particular, lung, brain and pancreatic cancer patients have the highest risk for recurrence and these patients should be considered for secondary prophylaxis. Disease severity, as reflected by metastatic disease at cancer diagnosis, is not a predictor of recurrence.

Abstract Background: While several uncommon disorders (e.g., myeloproliferative diseases, connective tissue disease, etc.) have been suggested as potential risk factors for VTE, the independence and magnitude of any risk is uncertain. Objective: To test uncommon characteristics as potential independent risk factors for VTE, and estimate the magnitude of risk for each. Methods: Using the resources of the Rochester Epidemiology Project, we identified all incident cases of deep vein thrombosis and pulmonary embolism over the 6-year period, 1992–1997. For each objectively confirmed case (n=562), we identified up to two Olmsted County residents without VTE who most closely matched a case on age, gender, and medical record number (n=755). Because medical record numbers are assigned sequentially, such matching assures a similar duration of medical follow-up. For all cases and controls, we reviewed the complete medical records in the community for over 125 baseline characteristics which were tested for an association with VTE using conditional logistic regression. Results: The mean ± SD (range) ages for cases and controls were 65.71 ± 18.85 (0–102) and 64.90 ± 18.66 (0–102) years, respectively, and 55.5% were female. Novel univariate risk factors for incident VTE included former tobacco smoker, ischemic heart disease, valvular heart disease, chronic lung disease, all-cause pulmonary hypertension, chronic renal disease, myeloproliferative disorders, any infection, femoral artery catheterization (angiography or percutaneous intervention), ICU admission and angiotensin converting enzyme (ACE) inhibitor therapy. Among infections, septicemia, pneumonia, and ENT, cardiovascular, GI, urinary tract and skin/soft tissue infections were univariately associated with VTE; reproductive tract infection was not. Diabetes mellitus, hyperlipidemia, lipid-lowering drugs (including statins), inflammatory bowel disease, asthma, connective tissue disease, and influenza were not univariately associated with VTE, and beta-blocker therapy was not protective. A multivariate analysis will test these characteristics as potential independent VTE risk factors. Conclusions: Several novel characteristics are univariately associated with VTE. Such novel characteristics may provide new insights into VTE mechanisms if, upon further analysis, these characteristics are independent VTE risk factors.

Abstract Background: Hematological cancer patients are at an increased risk for VTE (RR range = 12–32). However, whether VTE risk among such patients can be further stratified is uncertain. Objective: To test hematological cancer type, stage, stage progression and chemotherapy as potential risk factors for VTE among active hematological cancer patients after controlling for other previously-identified VTE risk factors. Methods: Using the resources of the Rochester Epidemiology Project, Mayo Clinic Master Diagnostic Index and Mayo Clinic Tumor Registry, we identified all Olmsted County, MN residents with active hematological cancer over the 28-year period, 1973–2000. From this prevalence cohort, we identified 86 patients with no prior VTE (controls) who were matched on age and date of hematological cancer diagnosis to 86 hematological cancer patients with incident VTE over the same time frame (cases). For all cases and controls, we reviewed the complete medical records in the community for baseline and hematological cancer-related characteristics. Hematological cancers were re-staged at the dates of the cancer and VTE diagnosis. We tested these characteristics as potential risk factors for VTE in active hematological cancer using conditional logistic regression. Results: In an initial multivariate analysis that included body mass index (BMI), hospitalization, and any infection or central venous catheter placement within 90 days prior to the VTE event, VTE was significantly associated with hospitalization (OR=6.70; p<0.001), and marginally associated with any infection (OR=2.18; p=0.09). After adjusting for the above variables, chemotherapy administered within the preceding 90 days was significantly associated with VTE (OR=4.25; p=0.02), while stage progression was marginally associated (OR=4.79; p=0.10). Compared to all other hematological cancer types, acute leukemia (OR=5.95; p=0.01) and non-Hodgkin’s lymphoma (OR=2.61; p=0.01) were associated with VTE. However, after adjusting for BMI, hospitalization, any infection and central venous catheter, only non-Hodgkin’s lymphoma was independently associated with VTE (OR=3.79, p=0.009), while acute leukemia was not (OR=2.66, p=0.35). Conclusions: Hematological cancer type (in particular, non-Hodgkin’s lymphoma and possibly acute leukemia), recent hospitalization, recent chemotherapy, and possibly stage progression and recent infection, are risk factors for VTE among patients with active hematological cancer.