Download Venous thromboembolism in patients with head and neck cancer

ORIGINAL ARTICLE
Venous thromboembolism in patients with head and neck cancer after surgery
Leo Thai, BS, Kate McCarn, MD, William Stott, BS, Tammara Watts, MD, Mark K. Wax, MD, Peter E. Andersen, MD, Neil D. Gross, MD*
Department of Otolaryngology–Head and Neck Surgery, Oregon Health and Science University, Portland, Oregon.
Accepted 3 November 2011
Published online 2 February 2012 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/hed.22920
ABSTRACT: Background. The purpose of this study was to report the
incidence of venous thromboembolism (VTE) in patients with head and
neck cancer after surgery.
Methods. This was a single-institution, retrospective cohort: 134
patients underwent resection and simultaneous microvascular
reconstruction. The primary endpoint was identification of confirmed or
suspicious VTE within 30 days of surgery.
Results. Two subjects (1.4%) with confirmed VTE (1 pulmonary
embolism, 1 deep venous thrombosis) and 6 subjects (4.4%) with
suspicious VTE (1 acute respiratory failure, 1 sudden cardiac arrest, and
4 cases of leg edema without imaging) were identified. The strongest
predictors of possible VTE were prior VTE (p ¼ .004; odds ratio [OR],
Venous thromboembolism (VTE) is a potentially lifethreatening condition that includes both deep venous
thrombosis (DVT) and pulmonary embolism (PE).
Patients with cancer are at increased risk of developing a
VTE. Cancer increases the risk of VTE by 4- to 6-fold.1,2
A prothrombic state is also augmented in the surgical setting. Therefore, patients with cancer undergoing major
surgery are considered particularly high risk for VTE.
Patients with cancer undergoing surgery have a 2-fold
risk of developing postoperative VTE compared with
patients without cancer undergoing similar procedures.1,3
The morbidity associated with VTE is substantial, ranging
from chronic leg swelling to pulmonary embolism. In
some cases, VTE can be fatal. In fact, VTE was recently
reported to be the most common cause of death in the
postoperative period among patients with cancer.4
In accord with current criteria, most patients with head
and neck cancer who have surgery are presumed to be
high risk for developing VTE.3,5 This is especially true
for patients undergoing simultaneous microvascular free
tissue transfer reconstruction after resection. The majority
of patients with head and neck cancer presenting for
oncologic resection and free tissue transfer reconstruction
have commonly identified risk factors for VTE, notably
*Corresponding author: N. D. Gross, Department of Otolaryngology–Head and
Neck Surgery, Oregon Health and Science University, Portland, Oregon. E-mail:
[email protected]
This work was presented at the 2010 American Head and Neck Society Research
Workshop in Washington, DC, October 30, 2010.
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HEAD & NECK—DOI 10.1002/HED
JANUARY 2013
25.11; 95% confidence interval [CI], 1.13–556.40), red cell transfusion
(p ¼ .009; OR, 1.80; 95% CI, 1.16–2.80), high body mass index (p ¼
.015, OR, 1.29, 95% CI, 1.05–1.58), and older age (p ¼ .046; OR, 1.10;
95% CI, 1.00–1.19).
Conclusion. The incidence of VTE in patients with head and neck cancer
after resection and microvascular reconstruction ranged from 1.4% to
C 2012 Wiley Periodicals, Inc. Head Neck 35: 4–9, 2013
5.8%. V
KEY WORDS: venous thromboembolism, deep venous thrombosis,
pulmonary embolism, squamous cell carcinoma, surgery
advanced cancer stage, older age, and prolonged surgery
time.
Surprisingly, there have been few data to quantify the
risk of VTE among patients with head and neck cancer
undergoing surgery. The primary purpose of our study
was to report the incidence of VTE in patients with head
and neck cancer after resection and microvascular reconstruction. In addition, we aimed to identify potential risk
factors for developing VTE for patients with head and
neck cancer and to explore the impact of VTE on
survival.
MATERIALS AND METHODS
Subjects
This retrospective study included patients with head
and neck cancer treated at Oregon Health and Science
University (OHSU) between 2007 and 2009. The study
was designed to include patients at highest risk for VTE
according to current guidelines for patients with cancer.5,6
Therefore, the study was restricted to patients with malignant disease undergoing a surgical procedure lasting >4
hours. These patients are automatically considered high
risk for VTE regardless of other factors including age
and comorbidities. The study was further restricted to
patients whose surgery included microvascular free-tissue
transfer reconstruction to maximize the period for detection of VTE in a high-acuity setting. All patients who
undergo microvascular reconstruction at our institution
are hospitalized for a minimum of 5 days. All patients
included in the study were treated in accord with our
institution’s standard of care, including intraoperative
VTE
sequential compression devices (SCDs) and early ambulation. The conduct of this study was approved by the Institutional Review Board at OHSU.
It was hypothesized that the risk of VTE could vary by
the timing of cancer treatment.7–9 Therefore, study
patients were separated into 2 groups: (1) active head and
neck cancer cases (active cancer group) and (2) patients
previously treated for head and neck cancer (prior cancer
group). The active cancer group included previously
untreated patients as well as patients with recurrent or
second primary disease. All active patients with cancer
were treated surgically with curative intent and planned
microvascular reconstruction. The prior cancer group
included previously treated patients with head and neck
cancer, with no evidence of disease, undergoing secondary reconstruction. This group included patients treated
for failed primary reconstruction or for complications
from prior treatments (eg, osteoradionecrosis of the
mandible).
Exposure
Potential risk factors for VTE were identified by a thorough review of the current literature prior to abstracting
the electronic medical record (Table 1). All established
risk factors for VTE were included, such as advanced
age, estrogen therapy, prior VTE, comorbidity, chemoradiation, prolonged operative time, and postoperative
immobilization.7,10–12 The comorbid conditions specifically analyzed in our study were diabetes mellitus, atrial fibrillation, chronic obstructive pulmonary disease, and peripheral vascular disease. In addition, we also examined
obesity (body mass index [BMI]), red cell transfusion, free
tissue transfer donor site tourniquet time, and infection, all
of which have been reported as potential risk factors for
VTE.11,13 Finally, a Caprini risk assessment was performed
retrospectively for all cases, to allow for comparison of
results to a validated risk stratification tool.14
Data collection
We systematically reviewed relevant notes within the
electronic medical record to fulfill all desired data fields.
Demographic and clinicopathologic data were retrieved
from documents including: history and physical examination notes, anesthesia notes, pathology reports, imaging
reports, cancer staging forms, operative reports, hospital
progress notes, discharge summaries, and outpatient clinic
notes.
Ambulation time was defined as the first postoperative
day the patient was noted to be ambulating by the healthcare team (physician, medical student, nurse, or physical
therapist). Ambulation was defined as the independent or
assisted ambulatory movement of the patient beyond the
bedside or the first nonevaluative day of physical therapy.
Daily hospital progress notes were reviewed to identify
any reports of leg swelling. All imaging reports were
reviewed to determine which patients had a lower extremity ultrasound Doppler and/or spiral CT examination. Discharge summary notes were reviewed for evidence of
anticoagulation prescriptions and for orders for outpatient
physical therapy. Follow-up data were collected at the
dates closest to a 2-week and 1-month follow-up period.
AFTER HEAD AND NECK CANCER SURGERY
TABLE 1. Patient characteristics.
Active
cancer group
Variable
Total patients, N
134
Total cases, n
139
Age, y
Mean
65.4
SD
15.9
Sex
Male
82 (59%)
Female
57 (41%)
Smoking status
Never
44 (32%)
Active
43 (31%)
Quit
52 (37%)
Body mass index
Mean
25.6
SD
5.3
VTE: prior VTE history
7 (5%)
Comorbidities
DM
21 (15%)
Atrial fibrillation
17 (12%)
COPD
22 (16%)
PVD
14 (10%)
Histology
Squamous cell carcinoma 106 (76%)
Basal cell carcinoma
6 (4%)
Melanoma
5 (4%)
Adenocarcinoma
5 (4%)
Adenoid cystic carcinoma
3 (2%)
Other
13 (9%)
Medication use
ASA
32 (23%)
Estrogen
1 (1%)
Prior therapy
Chemotherapy
13 (9%)
Radiation therapy
51 (37%)
Prior
cancer group
p value
26
32
—
.78
64.5
15.2
.60
21 (66%)
11 (34%)
.005
5 (16%)
5 (16%)
22 (68%)
.07
23.6
4.9
0
.42
0
2 (6%)
3 (9%)
3 (9%)
.04
.51
.51
1.00
.88
23 (72%)
1 (3%)
1 (3%)
0
2 (6%)
5 (16%)
9 (28%)
3 (9%)
.70
.02
9 (28%)
28 (88%)
.10
<.001
Abbreviations: SD, standard deviation; VTE, venous thromboembolism; DM, diabetes mellitus;
COPD, chronic obstructive pulmonary disease; PVD, peripheral vascular disease; ASA,
aspirin.
Progress notes were reviewed for findings suggestive of
VTE, including postoperative leg edema, leg pain, and respiratory distress. Disease status at last follow-up was
confirmed for all patients, including cause of death as applicable. All deaths were confirmed by cross-referencing
with the Social Security Death Index database.
Endpoints
The primary endpoint of the study was possible VTE,
which included patients with confirmed VTE or findings
suspicious for VTE. Confirmed VTE was defined as either a deep venous thrombosis (DVT) or pulmonary embolism (PE), confirmed by diagnostic imaging. Lower extremity venous duplex ultrasound was used to confirm
DVT. Spiral CT and or pulmonary angiography were
used to confirm PE. Suspicious VTE was defined as history or examination findings suspicious for VTE but without conclusive diagnostic imaging.
Statistical analysis
VTE incidence was assessed for the period between the
date of the surgery and 30 days after hospital discharge.
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THAI ET AL.
The risk models were constructed using only data from
the active cancer group since these patients are at greatest
risk of VTE. Univariate analyses were performed for the
active group using risk factors as the time-independent
covariant (ie, preoperative and postoperative patient variables) and possible VTE as the time-dependent outcome.
Categorical variables were analyzed using the chi-square
test for independence and assessing for association with
the Spearman correlation coefficient. Continuous variables were analyzed using univariate logistic regression
analysis. Covariates in the analysis with a value of p < .3
were considered candidates for subsequent multivariate
analysis. In the multivariate analysis, we used stepwise
backward logistic regression analysis to determine the
odds ratio (OR) of VTE 30 days of surgery for each
qualified covariant. To assess for the strength of the multivariate model, we performed the Omnibus Tests of
Model Coefficients. All analyses were performed in SPSS
version 15 (SPSS Inc., Chicago, IL). A 2-tailed value of
p < .05 was considered statistically significant for all
analyses.
RESULTS
Patient characteristics, procedures, and perioperative
findings
There were 134 patients with head and neck cancer in
the study who underwent a total of 139 procedures (prior
cancer group had 26 patients in 32 cases). At the time of
surgery, the average patient age was 65.4 years, and 59%
were male. As shown in Table 1, the active cancer and
prior cancer groups were similar in several important
ways. There was no significant difference between groups
with respect to age (p ¼ .78), sex (p ¼ .60), or histology
(p ¼ .88). There was no difference between groups for
comorbidities. There were some notable differences
between the active cancer and prior cancer groups. For
example, active patients with cancer were more likely
to be smokers (p ¼ .14) and have diabetes mellitus (p ¼
.04). Prior patients with cancer were more likely to be on
estrogen replacement therapy (p ¼ .02) and to have a
prior history of radiation therapy (p .001) (Table 1).
Procedures and perioperative events are summarized in
Table 2. Overall operative time and free tissue transfer
tourniquet time were similar between groups. The distribution of free tissue transfer donor sites was also similar.
It is worthwhile to note that there were substantially
more fibular osteocutaneous free tissue transfer reconstructions for the prior cancer group compared with the
active cancer group (28% vs 0%). There was no significant difference in the use of intraoperative (p ¼ 1.00) or
postoperative (p ¼ .76) heparin between groups. However, active patients with cancer were more likely to
receive postoperative aspirin compared with prior patients
with cancer (43% vs 19%, p ¼ .02). The overall complication rate, ambulation time, and length of stay were similar between the 2 groups (Table 2). The median followup for active patients with cancer was 8.4 months (range,
0.4–23.5 months).
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TABLE 2. Procedures and perioperative findings.
Outcome
Total cases, n
Operative time, h
Mean
SD
Free-tissue donor site
Radial forearm
Anterolateral thigh
Fibula osteocutaneous
Rectus musculocutaneous
Latissimus dorsi
musculocutaneous
Jejunum
Other
Tourniquet time, min
Mean
SD
Anticoagulation
Intraoperative heparin
Postoperative heparin
Postoperative aspirin
Complications
Pulmonary embolism
Respiratory failure
Cardiac arrest
Anoxic brain injury
Recipient site infection
Other
Ambulation time, d
Mean
SD
Length of stay, d
Mean
SD
Active cancer Prior
group
cancer group p value
139
32
8.2
2.3
7.2
3.0
—
.57
.61
60 (43%)
26 (19%)
15 (11%)
13 (9%)
12 (9%)
12 (38%)
5 (16%)
9 (28%)
2 (6%)
1 (3%)
6 (4%)
7 (6%)
0
3 (9%)
15.0
20.0
22.0
23.0
.12
11 (8%)
24 (17%)
60 (43%)
2 (6%)
4 (13%)
6 (19%)
1 (0.72%)
1 (0.72%)
1 (0.72%)
1 (0.72%)
7 (5%)
4 (3%)
0
0
0
0
4 (13%)
2 (6%)
15.0
20.0
22.0
23.0
10.1
10.0
10.6
7.9
1.00
.76
.02
.85
.07
.20
Abbreviation: SD, standard deviation.
Possible (confirmed and suspicious) venous
thromboembolism
During a follow-up of 30 days, there were 2 cases of
confirmed VTE, yielding a minimum incidence of 1.4%
(Table 3). One patient was confirmed to have a fatal PE
2 days after discharge from the hospital. Another active
patient with cancer was discovered to have a DVT; that
patient was successfully treated without further sequelae.
Given that a retrospective study design is likely to
underestimate the true incidence of VTE, we also
included suspicious cases. There were 6 cases suspicious
for VTE during the 30-day follow-up period. One patient
suffered from fatal sudden respiratory failure and another
patient suffered from fatal sudden cardiac arrest, although
an autopsy was not performed in either case. Therefore,
VTE could not be excluded as the cause of death. In
addition, 4 patients presented to the clinic in follow-up
with unilateral lower extremity swelling reported in the
electronic medical record. No further workup was ordered
in these cases. Likewise, no known sequelae were documented. Two of the patients with leg swelling had
received a fibula free-transfer reconstruction. However, in
each of these cases the leg swelling was documented in
the nonoperative leg. Therefore, a total of 8 possible
VTE
AFTER HEAD AND NECK CANCER SURGERY
TABLE 3. VTE outcomes.
Outcome
Total cases, n
Confirmed
PE
DVT
Suspicious
Respiratory failure
Cardiac arrest
Leg edema
Possible total
Active cancer group
Prior cancer group
139
32
1
1
0
0
1
1
4
8 (5.8%)
0
0
2
2 (6.3%)
Abbreviations: VTE, venous thromboembolism; PE, pulmonary embolism; DVT, deep venous
thrombosis.
cases (5.8%) of VTE were documented from the active
cancer group (Table 3).
In comparison, the prior cancer group did not have any
cases of confirmed VTE (Table 3). However, 2 cases
(6.3%) were identified during the 30-day follow-up periods that were suspicious for VTE. In each of these cases,
new-onset unilateral leg edema was noted during the postoperative clinic visit in the nonoperative leg. These
patients did not undergo further workup or empiric treatment for DVT. The rationale for this was not documented
in the medical record.
A Caprini risk assessment was performed retrospectively for all active cancer cases (Figure 1). The 2
patients with confirmed VTE had a mean Caprini score
of 13.0 (PE patient ¼ 16, DVT patient ¼ 10). The 6
patients with suspicious VTE had a mean Caprini score
of 12.8. The remaining patients with no history suggestive
of VTE had a mean Caprini score of 10.5. All groups had
mean scores well above the threshold to be considered at
highest risk for DVT (Caprini score 5). There was no
statistically significant difference in Caprini scores
between groups.
Univariable and multivariable analyses for active cancer
group
Using univariable analyses, a prior history of VTE (phi
¼ 0.40, p ¼ .0005), increased BMI (OR ¼ 1.19, p ¼
.006), and red cell transfusion (OR ¼ 1.31, p ¼ .004)
were positively associated with possible (confirmed and
suspicious) VTE. For patients that received anticoagulation in the postoperative period, univariable analysis
showed a significant protection against possible VTE with
heparin (p ¼ .041), but not with aspirin (ASA, p ¼ 1.00).
However, in the multivariable analysis the protective
advantage of heparin did not reach significance (p ¼ .85).
Of note, the use of SCDs after surgery was not associated
with reduced risk of possible VTE.
The final multivariate model included length of hospital
stay, age, BMI, red cell transfusion, and a prior history of
VTE (Table 4). Short length of stay was associated with
a slightly decreased risk of possible VTE, but this did not
reach statistical significance (OR ¼ 0.89, p ¼ .15). Conversely, increased age and BMI were associated with an
increased risk of possible VTE by 10% and 29%, respectively. Increased red cell transfusion was associated with
an 80% increased relative risk of possible VTE (p ¼
FIGURE 1. Comparison of Caprini risk assessment scores
between patients with confirmed, suspicious, and no venous
thromboembolism (VTE). There was no statistically significant
difference between groups. Patients with a Caprini score 5
(represented by the dotted line) are considered to be at highest
risk for deep venous thrombosis (DVT).
.009). The factor most strongly associated with possible
VTE was a prior history of VTE, which increased the relative risk 25-fold (p ¼ .041).
DISCUSSION
Risk factors for VTE are well known and include primary site of tumor, comorbid conditions (obesity, infection, pulmonary disease, renal disease), older age, immobilization, previous history of VTE, active chemotherapy
or hormonal therapy, and recent major surgical intervention.6,15 Patients with cancer undergoing surgery are considered to be at greatest risk of VTE and a significant
proportion of patients with cancer undergoing surgery are
affected by VTE. It has been estimated that patients with
cancer undergoing surgery have a 2-fold increase in postoperative DVT and a 3-fold increase in fatal PE compared with patients without cancer who undergo similar
operations.16,17 The most effective methods for preventing
VTE are also well known and include early ambulation,
mechanical compression devices, and pharmacologic
thromboprophylaxis.
There is an increasing national imperative to better
address the risk of VTE among patients with cancer
undergoing surgery. This is reflected in recent guidelines
from the American College of Chest Physicians (ACCP)
and the American Society of Clinical Oncology (ASCO),
recommending that patients with cancer undergoing surgery receive medical prophylaxis for up to 1 month after
surgery.5,6,15 For patients with cancer who are undergoing
major surgery, ACCP recommendations include routine
TABLE 4. Multivariant analysis for active cancer group
Variable
Odds ratio
Length of stay
Age
BMI
Red cell transfusion
VTE (prior)
0.89
1.10
1.29
1.80
25.11
95% CI
p value
0.75–1.04
1.00–1.19
1.05–1.58
1.16–2.79
1.13–556.39
.15
.046
.015
.009
.041
Abbreviations: CI, confidence interval; BMI, body mass index; VTE, venous thromboembolism.
HEAD & NECK—DOI 10.1002/HED
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THAI ET AL.
thromboprophylaxis with low-molecular-weight heparin
(LMWH) or fondaparinux. For patients with cancer with
additional risk for VTE (eg, history of VTE, advanced
age) the recommendation is to use LMWH or fondaparinux in combination with mechanical methods such as
SCDs. Aspirin alone is not recommended for thromboprophylaxis in any patient groups. Similarly, ASCO recommendations suggest that all patients with cancer undergoing major surgical intervention for malignant disease
be considered for thromboprophylaxis with pharmacologic and optional mechanical methods, reserving the former only if there is risk of active bleeding.
There are many studies that investigate the risk of VTE
after surgery for patients with colon, prostate, and breast
cancer.1,4,6,8 Yet, there are scant data regarding the risk
of VTE for patients with head and neck cancer undergoing surgery. A prior large retrospective study that
included all otolaryngologic procedures performed at a
single institution showed a very low incidence of VTE
(0.3%). The incidence of VTE in that study was 0.6% for
patients with head and neck cancer.18 Another similar retrospective study of general otolaryngology patients
showed an incidence of 0.15%.19 It is speculated by some
that patients with head and neck cancer may be at low
risk of VTE after surgery because of the relatively superficial nature of dissection and postoperative early ambulation compared with other oncologic procedures. There is
also a concern that routine prophylactic anticoagulation
will increase the risk of postoperative hematoma, which
can compromise flap viability. Thus, currently few head
and neck surgeons routinely prescribe anticoagulation after
resection and microvascular reconstruction despite national
guidelines for patients with general oncologic surgery.
The most robust data to date regarding the risk of VTE
among patients with head and neck cancer undergoing
extensive resection and reconstruction were presented by
Chen and colleagues.20 In that study, the authors compared symptomatic VTE and PE incidence after oncologic
surgery with reconstruction for patients with head and
neck cancer to patients with non–head and neck cancer.
They found that the incidence of symptomatic VTE or
PE was low (0.75%). Interestingly, they reported that the
incidence of symptomatic VTE was greater for patients
with head and neck cancer (0.31% DVT, 0.44% PE) than
that for patients with non–head and neck cancer (0.008%
DVT, 0.09% PE). It is worth noting that all patients in
the study received routine LMWH for VTE prophylaxis.
Current methods to risk-stratify patients with head and
neck cancer for possible VTE are imperfect. The most
widely used risk assessment tool was developed by Caprini.14 The Caprini risk assessment tool was first used
nearly 30 years ago and has been updated periodically
since then. With this model, approximately 40 risk factors
are listed, with weights of 1 to 5 points each. The total
risk factor score is then used to group patients into 1 of 4
categories (low, moderate, high, and highest risk), each
with a recommended prophylactic regimen. The Caprini
risk assessment tool has been validated in retrospective
studies for use in patients needing elective general surgery and modified for use in patients needing plastic surgery.21 Most recently, it has been correlated with proven
30-day VTE incidence in a prospective study of 1470
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general surgery patients.22 In our study, a Caprini risk
assessment was performed retrospectively for all active
cancer cases. In accord with our inclusion criteria, all
patients included in this study were classified at highest
risk of DVT by a Caprini risk assessment (score 5).
We found no significant difference in mean Caprini
scores between patients classified as confirmed, suspicious, or no VTE (Figure 1). Therefore, the Caprini risk
assessment tool was unable to accurately risk-stratify our
patients. To our knowledge this is the only study to evaluate the use of the Caprini risk assessment tool specifically in patients with head and neck cancer after resection
and microvascular reconstruction. It is possible that our
sample size was too small for the model to discriminate
between VTE and non-VTE patients. Therefore, the clinical utility of the Caprini risk assessment tool for patients
with head and neck cancer having surgery has yet to be
fully elucidated.
In this study, we aimed to better define the incidence
of VTE in patients with head and neck cancer after resection and microvascular reconstruction. It was postulated
that these patients would be at greatest risk of VTE
because of the increased length of surgery and hospitalization and the lack of routine anticoagulation. We found
that 5.8% of our patients with active cancer developed a
possible (confirmed and suspicious) VTE. It is important
to note that only 2 cases (1.4%) with active cancer were
proven radiographically, and therefore classified as confirmed VTE. The majority of possible VTE cases were
classified as suspicious because imaging confirmation
was not available. For example, 2 patients died outside of
the hospital from sudden respiratory failure or sudden
cardiac arrest within 30 days of surgery and were classified as suspicious VTE. We speculated that there could
be a difference between patients with active cancer and
patients with prior cancer with respect to risk of VTE.
Therefore, we compared the groups for baseline differences and VTE outcome. Despite differences between
groups, including baseline smoking status, estrogen use,
and postoperative aspirin use, the rate of possible VTE
was similar for patients with active cancer and prior cancer. Three patients in our study died as a direct result of
a possible VTE. It is interesting that all of these cases
occurred in the active cancer group.
Our findings suggest that the incidence of VTE among
patients with head and neck cancer after resection and
microvascular reconstruction may be higher than previously reported. Even if we excluded suspicious cases, our
confirmed VTE incidence of 1.4% is still above the range
of incidences previously reported for head and neck cancer.18–20 The clinical significance of this finding is yet to
be determined, especially since the patients included in
our study did not receive routine anticoagulation. Our
confirmed VTE incidence is lower than the incidence
reported for most patients who had non–head and neck
oncologic surgery, where prophylaxis is routinely used.
For example, the incidence of VTE has been reported to
be 2.8% in general surgery, 2.0% in gynecologic surgery,
and 0.87% in urologic surgery.4 These relatively low
VTE incidences were achieved in the setting of routine
use of perioperative LMWH, including nearly a third of
study patients receiving postdischarge prophylaxis.
VTE
In this study we also aimed to identify potential risk
factors for developing VTE for patients with head and
neck cancer. We found increased age, increased BMI, red
cell transfusion, and prior history of VTE to be significant
predictors of possible VTE on multivariate analyses. Of
these, a prior history of VTE showed the greatest risk
(25-fold). Our results appear in line with the identified
risk factors identified in other studies.4,6,11 For example,
prior history of VTE is a well-known risk factor for subsequent VTE because many of the factors that contribute
to VTE are chronic in nature. Recurrence of VTE is
greatest within the first few months after a thrombotic
episode, but has been reported to be as high as 22% over
5 years.23 Patients with VTE are at increased risk of recurrence and death after treatment.24 Therefore, the importance of prior VTE in risk-stratifying patients cannot
be overstated. Interestingly, we found red cell transfusion
to be associated with possible VTE for patients with head
and neck cancer undergoing surgery. Although red cell
transfusion is not included in many VTE risk factor
assessments, it has been associated with increased risk of
VTE after resection of colorectal cancer.25
There are limitations to the current study. We took
great effort to carefully review the medical record notes
to identify classic symptoms of DVT in our patients in
the perioperative period. However, our results depend on
the accuracy of the medical records. Thus, there is the
potential for recall bias. Patients with subclinical DVT
were not identified. Only patients who were symptomatic
and hospitalized were investigated with imaging. Therefore, it is possible that our results are an underestimation
of the true VTE incidence. Autopsy studies have demonstrated that the incidence of VTE in patients with cancer
can be as high as 50%, with clinically confirmed cases
ranging between 4% and 20%.26 We included suspicious
VTE cases into our analysis to partially account for this
possibility. It is possible that our decision to include suspicious cases overestimates the true incidence. Therefore,
we have presented the data as a range, to provide the best
estimate of the true incidence of VTE in our cohort.
There are 2 possible interpretations of our findings: (1)
the true incidence of VTE among patients with head and
neck cancer surgery is low even without prophylactic
anticoagulation or (2) the true incidence of VTE among
patients with head and neck cancer surgery is
underestimated.
Our findings suggest that a retrospective study design
is inadequate to accurately define the true incidence of
VTE among patients with head and neck cancer having
surgery. We report an incidence that ranges from a minimum of 1.4% (confirmed VTE) to a maximum of 5.8%
(confirmed and suspicious VTE). Thus, our data are not
compelling enough at this point to modify our current
VTE prophylaxis strategies. We cannot recommend routine VTE prophylaxis with LWMH without further
investigation to characterize the risk:benefit ratio, especially in the context of microvascular reconstruction.
AFTER HEAD AND NECK CANCER SURGERY
Therefore, we have initiated a prospective observational
study to elucidate a more accurate VTE incidence
among patients with head and neck cancer after surgery.
REFERENCES
1. Behranwala KA, Williamson RC. Cancer-associated venous thrombosis in
the surgical setting. Ann Surg 2009;249:366–375.
2. Lee AY. Epidemiology and management of venous thromboembolism in
patients with cancer. Thromb Res 2003;110:167–172.
3. Prandoni P, Piccioli A, Girolami A. Cancer and venous thromboembolism:
an overview. Haematologica 1999;84:437–445.
4. Agnelli G, Bolis G, Capussotti L, et al. A clinical outcome-based prospective study on venous thromboembolism after cancer surgery: the @RISTOS Project. Ann Surg 2006;243:89–95.
5. Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133:381S–453S.
6. Lyman GH, Khorana AA, Falanga A, et al. American Society of Clinical
Oncology guideline: recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer. J Clin Oncol 2007;25:
5490–5505.
7. Blom JW, Doggen CJ, Osanto S, Rosendaal FR. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. J Am Med Assoc 2005;
293:715–722.
8. Chew HK, Wun T, Harvey D, Zhou H, White RH. Incidence of venous
thromboembolism and its effect on survival among patients with common
cancers. Arch Intern Med 2006;166:458–464.
9. Sallah S, Wan JY, Nguyen NP. Venous thrombosis in patients with solid
tumors: determination of frequency and characteristics. Thromb Haemost
2002;87:575–579.
10. Reeves D, Liu CY. Retrospective evaluation of venous thromboembolism
prophylaxis in the adult cancer population. J Oncol Pharm Pract 2010;16:
27–31.
11. Sousou T, Khorana AA. New insights into cancer-associated thrombosis.
Arterioscler Thromb Vasc Biol 2009;29:316–320.
12. Sud R, Khorana AA. Cancer-associated thrombosis: risk factors, candidate
biomarkers and a risk model. Thromb Res 2009;123 (Suppl 4):S18–S21.
13. White RH, Zhou H, Gage BF. Effect of age on the incidence of venous
thromboembolism after major surgery. J Thromb Haemost 2004;2:
1327–1333.
14. Caprini JA. Risk assessment as a guide for the prevention of the many faces of
venous thromboembolism. Am J Surg 2010;199:S3–S10.
15. Mandala M, Falanga A, Roila F. Venous thromboembolism in cancer
patients: ESMO Clinical Practice Guidelines for the management. Ann
Oncol 2010;21 (Suppl 5):v274–v276.
16. Gallus AS. Prevention of post-operative deep leg vein thrombosis in
patients with cancer. Thromb Haemost 1997;78:126–132.
17. Huber O, Bounameaux H, Borst F, Rohner A. Postoperative pulmonary
embolism after hospital discharge. An underestimated risk. Arch Surg
1992;127:310–313.
18. Moreano EH, Hutchison JL, McCulloch TM, et al. Incidence of deep venous thrombosis and pulmonary embolism in otolaryngology–head and
neck surgery. Otolaryngol Head Neck Surg 1998;118:777–784.
19. Lee J, Alexander A, Higgins K, Geerts W. The Sunnybrook experience:
review of deep vein thrombosis and pulmonary embolism in otolaryngology. J Otolaryngol Head Neck Surg 2008;37:547–551.
20. Chen CM, Disa JJ, Cordeiro PG, et al. The incidence of venous thromboembolism after oncologic head and neck reconstruction. Ann Plast Surg
2008;60:476–479.
21. Davison SP, Venturi ML, Attinger CE, Baker SB, Spear SL. Prevention of
venous thromboembolism in the plastic surgery patient. Plast Reconstr
Surg 2004;114:43E–51E.
22. Bahl V, Hu HM, Henke PK, et al. A validation study of a retrospective venous thromboembolism risk scoring method. Ann Surg 2010;251:344–350.
23. Hansson PO, Sorbo J, Eriksson H. Recurrent venous thromboembolism after deep vein thrombosis: incidence and risk factors. Arch Intern Med
2000;160:769–774.
24. Andresen MS, Sandven I, Brunborg C, et al. Mortality and recurrence after
treatment of VTE: long term follow-up of patients with good life-expectancy. Thrombosis Res 2011;127:540–546.
25. Nilsson KR, Berenholtz SM, Garrett-Mayer E, et al. Association between
venous thromboembolism and perioperative allogeneic transfusion. Arch
Surg 2007;142:126–132.
26. Gomes MP, Deitcher SR. Diagnosis of venous thromboembolic disease in
cancer patients. Oncology (Williston Park) 2003;17: 126–135, 139.
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