Chapter 6 Discussion
6.2 Incidence Rate of VTE among Cancer Patients
Given the relatively low incidence rate of various types of cancer and VTE among
Asian population, a large cohort study is needed to estimate the incidence rate of VTE
across different cancer types. Use of Taiwan NHI research database has been proved to
be a powerful data source for epidemiological studies of rare diseases.91-94 Using the
NHI research database, we examined the incidence, risk factors and clinical
characteristics of VTE among patients with different cancer types over a period of 9
years.
Two definitions of VTE were adopted in our study. To verify the accuracy of
diagnosis, VTE (definition 2) was based on both the VTE diagnosis codes and
management of VTE during the hospital stay. This definition was similar to the outcome
definition used in the population-based studies of Lee et al.10 and Jang et al.8, which
used Taiwan and Korea NHI databases as data source to explore the epidemiology of
VTE among the general population. However, cancer patients have more thrombosis at
unusual sites than the general population, such as thrombosis of upper extremities, vena
cava, and splanchnic veins.55 The application of anticoagulants has not been confirmed
in these situations.75 Some cancer patients who diagnosed with thrombosis of upper
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extremities, splanchnic veins, and other unspecified site may not receive anticoagulant
treatment. Therefore, patients with thrombosis at unusual sites might not be included as
VTE cases according to definition 2. To avoid serious underestimation of the incidence
rate of VTE among cancer patients, we defined VTE event as hospitalization with any
diagnosis of VTE in the inpatient medical claims (definition 1). We use two outcome
definitions in our study to provide a crude incidence rate of VTE which included
accidentally detected VTE and clinical symptomatic VTE.
In our study, 1.1% to 3.2% of all newly diagnosed cancer patients were hospitalized
for VTE events. The incidence rate of VTE (definition 1 and definition 2) were 9.88 per
1,000 person-years (range, 1.0-68.2 per 1,000 person-years) and 3.35 per 1,000
person-years (range, 0.0-16.0 per 1,000 person-years), respectively (Table 5.1 and 5.2).
The incidence rate of VTE is 21- to 62- folds among cancer patients than the general
population (15.9 per 100,000 person-years).10 Malignancy alone was reported to be
associated with 4-folds increased risk of VTE and the use of chemotherapy increased
the risk to 6.5-folds. Meanwhile, surgery and hospital admission were associated with
21-folds and 8-folds increased risk of VTE, respectively.34 There is convincing evidence
that the risk of VTE increases in proportion to the number of predisposing factors.32,33
Taken together, these conditions may contribute to the high incidence rate of VTE
among cancer patients.
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The higher incidence rate of VTE in our study may also be partially explained by
the differences in the outcome definition and studied year in different studies. For
example, Lee et al.10 did not include diagnosis of phlebitis and thrombophlebitis
(ICD9-CM codes 451.xx) in their study and they only included patients with VTE
events between 2001 and 2002. In contrast, we used more recent data, including patients
with VTE events between 2001 and 2009. In addition, ICD9-CM codes of VTE used in
our study included 451.xx-453.xx.
Incidence rates of VTE among Asian cancer patients have been studied in certain
types of cancer associated with higher risk of VTE, including colorectal cancer
(4.5%),15 gastric cancer (3.5%),14 advanced pancreatic cancer (5.3%),12 diffuse large B
cell lymphoma (10.6%),16 multiple myeloma (3.9%),13 and cholangiocarcinoma
(3.7%)18 (Table 2.9). Our reported rates are lower than the rates reported in previously
disease-specific studies among Asian population.12-16,18 Data sources used in our study
and previous studies may result in these differences. All existing studies used medical
records database as data source and most of them defined outcomes as objectively
confirmed VTE events (including accidentally detected VTE). In our study, some
accidentally detected VTE during imaging studies for assessment of tumor status or
other diseases might not be recorded in the NHI claim-based databases.
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The inclusion criteria of patients in different studies might be another contributing
factor. Koh et al.13 only included patients with multiple myeloma who receiving
thalidomide therapy and Oh et al.12 only included patients with unresectable advanced
pancreatic cancer in their studies. In the study of Yokoyama et al.16, 72% of patients had
stage III/IV diffuse large B cell lymphoma. More advanced stage diseases among their
study populations and the use of thalidomide therapy can explain the higher incidence
rate of VTE compared with our study. In patients with multiple myeloma, VTE rates of
28% had been reported in patients treated with thalidomide-based chemotherapy
regimens.80
The incidence of VTE varies in different ethnic populations. Risk of developing
VTE is reported to be significantly lower among Asian populations than Caucasian
populations.22,26,27 Among Caucasian patients with cancer, the estimated incidence rate
of VTE ranges from 0.6% to 12.1% (Table 2.3 and 2.4).47-54 In our study, the incidence
rate of VTE (definition 2) (1.1%) is about 2-folds lower than that reported in study in
Denmark (1.8%) using administrative database52 and 4-folds lower than another study
in USA (4.0%) using discharge database of the University HealthSystem Consortium as
data source.51 The incidence rate of VTE (definition 1) (3.2%) was similar to the rate
reported by Khorana et al. among Asians/Pacific Islanders patients in 2007 (3.3%).51 In
general, the incidence rates of VTE in Asian populations were lower than existing
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studies among Caucasian populations.
The rates of VTE (definition 2) varied with various malignancies from 0.5 per
1,000 patient-years in patients with thyroid cancer to 16.0 per 1,000 patient-years in
patients with pancreas cancer (Table 5.2). We found that pancreas cancer, lung cancer,
liver cancer, multiple myeloma, and sarcoma were associated with higher rates of VTE,
which are consistent with other researches.49,51,52,54
Pancreas cancer and multiple
myeloma have been associated with high risk of VTE.49,51,52 Higher VTE risks in
patients with lung and liver cancer were also found in our study.
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