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Study Finds Increased Incidence of VTE in Patients with Head and Neck Cancer

Lindsey, Heather

doi: 10.1097/01.COT.0000437965.72890.d3


The overall incidence of venous thromboembolism (VTE) in postsurgery head and neck cancer patients who do not routinely undergo prophylactic anticoagulation may be as high as 13 percent, according to a new study published online ahead of print in JAMA Otolaryngology Head and Neck Surgery ( doi:10.1001/jamaoto.2013.4911 ). Those patients who receive postoperative anticoagulants may have higher bleeding rates.

“Our study indicates that head and neck cancer patients having surgery with an expected hospital stay of more than four days are at increased risk for VTE and should be treated with anticoagulants unless otherwise contraindicated,” said the study's corresponding author, Neil D. Gross, MD, Director of Head and Neck Cancer Clinical Trials at Oregon Health & Science University Knight Cancer Institute and Associate Professor in the Department of Otolaryngology, Head and Neck Surgery at OHSU.

This is also the only prospective study to address the incidence of VTE in head and neck cancer patients, he added.

Asked for her opinion, Genevieve A. Andrews, MD, Assistant Professor of Surgery in the Division of Otolaryngology—Head and Neck Surgery at Penn State Milton S. Hershey Medical Center, said, “Certainly, the incidence rate of 13 percent reported in this study is higher than what's been previously reported.”

Also commenting, Douglas B. Chepeha, MD, MSPH, FRCS(C), Professor and Director of Microvascular Reconstructive Surgery at the University of Michigan Health System, said, “Overall, this article is timely, and increases the awareness of VTE in head and neck cancer patients who may not routinely receive anticoagulation therapy after surgery.





“Venous thromboembolism prophylaxis is very important and does improve clinical care,” he said. “The value outweighs any bleeding risks. It should be a preoperative time-out.”

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Study Details

The researchers (first author was Daniel R. Clayburgh, MD, PhD) conducted a prospective study of 100 consecutive patients undergoing head and neck cancer surgery and who expected to be hospitalized for at least four days. Patients, who had a mean age of 63.5 and a moderate to high risk of VTE (based on the Caprini Venous Thromboembolism Risk Assessment), did not receive routine VTE chemoprophylaxis. Participants underwent a clinical exam and duplex ultrasonography two or three days postsurgery.

Participants with evidence of deep venous thrombosis (DVT) or pulmonary embolism (PE) received therapeutic anticoagulation, while those with superficial VTE underwent repeated ultrasonography examination four to six days after surgery.

At 30 days after surgery, the overall incidence of VTE was 13 percent. Eight percent of patients had clinically significant VTE—including seven patients with DVT and one with PE. Only four of the patients with clinically significant VTEs exhibited symptoms. Screening ultrasound showed that five patients had asymptomatic lower-extremity VTE.

Fourteen percent of study participants received some postoperative anticoagulation therapy, mostly in the intensive care unit.

Overall, eight percent of patients had a bleeding complication. Twenty-nine percent of individuals who received anticoagulants and five percent of those who did not receive these agents had bleeding.

Still, Andrews noted, while the rate of hemorrhagic complications in the study was higher in those with anticoagulation, the study was not designed to evaluate this outcome, and so is not generalizable. More data on complications, therefore, are needed.

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Balancing VTE and Chemoprophylaxis Risk

Balancing the risks of VTE against those of bleeding complications from anticoagulants can be challenging, Chepeha acknowledged. The latter, though, usually are not life-threatening: “They are frustrating, take time to manage, and increase expense, but a thromboembolism can be fatal,” he said.

Generally, cancer patients who undergo surgery are at high risk for VTE, although why this is the case is not entirely understood, said Miriam Lango, MD, Associate Professor in the Department of Surgery, Head and Neck Section, at Fox Chase Cancer Center. In general, patients who are immobilized or must remain in bed are predisposed to developing VTE, but cancer patients are at an increased risk, both after surgery and from other forms of treatment.



VTE is often seen in cancer patients because of a generalized pro-inflammatory state that serves to activate a clotting cascade, Andrews explained. Additionally, undergoing regional and general anesthesia for surgery can produce a condition of venous stasis, and manipulation of soft tissue during surgery can also increase the risk of VTE.

When prophylactic anticoagulants are used to offset VTE risk, postoperative hematoma is usually the most concerning side effect, and although uncommon, skull-based intracranial bleeding is a surgical emergency, Chepeha added.

Andrews said that oncologists are also concerned about hemorrhagic complications such as the risk of airway compromise and bleeding into the brain and orbit, the latter of which can cause blindness.

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Systematically screening or empirically treating high-risk patients such as those included in the study makes sense, Gross said.

However, the Doppler studies used to detect VTE in the paper are not commonly used to screen for asymptomatic VTEs in the postoperative setting, Lango noted. “They picked up a lot of VTE that would not have been detected otherwise,” she said. “The question of whether it makes sense to screen for asymptomatic VTE, and whether it will make a difference and save lives, or cause more patients to have bleeding-related complications is not a question that this study was designed to answer.”

In addition, said Gregory S. Weinstein, MD, FACS, Vice Chair and Professor of the Department of Otorhinolaryngology: Head and Neck Surgery and Co-Director of the Center for Head and Neck Cancer at the University of Pennsylvania Cancer Center, using ultrasound to evaluate patients for thrombosis in their legs is not standard practice: “We don't know what the results mean. What we're trying to avoid is pulmonary embolus.” However, only one patient with VTE detected on ultrasound in the study developed pulmonary embolism, a rate—one percent—that reflects that in other literature, namely a 2012 paper evaluating a national database, he said: Laryngoscope 2012;122:2199-2204.

Treating asymptomatic patients with therapeutic anticoagulation for thrombosis on ultrasound findings to avoid PE may not be warranted, Weinstein continued. In these patients, therapeutic anticoagulation could lead to complications such as hematoma. “We shouldn't be doing this routinely in asymptomatic patients unless we know it is helping them,” he said.

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Lack of Adherence to Guidelines

Gross pointed out that current guidelines from the American College of Chest Physicians and the American Society of Clinical Oncology, which recommended giving all cancer patients VTE chemoprophylaxis, were developed without data that included head and neck cancer patients.

This lack of data, therefore, coupled with the complications associated with anticoagulants, may deter head and neck surgeons from adhering to the guidelines, Andrews said.

The perceived risks of chemoprophylaxis therefore prompt many head and neck surgeons to rely instead on mechanical compression devices and early ambulation, Lango noted. And even the Clayburgh paper found a low rate of symptomatic, clinically significant VTE in head and neck cancer patients postsurgery who did not receive chemoprophylaxis, thereby calling into question whether established guidelines should be broadly applied, she said. “The findings suggest that the incidence of VTE in this population is far less than in patients with gastrointestinal, lung, or gynecologic cancers.”

Still, Andrews noted, while national guidelines aren't specific to head and neck cancer patients, a number of institutional guidelines do address this population. Usually, institutions use a VTE risk factor point system such as the Caprini assessment to determine whether patients should receive prophylaxis, she explained. Patients with only few risk factors generally receive compression devices, but as the risk of VTE increases, chemoprophylaxis is likely.

Weinstein noted, for example, that head and neck cancer patients undergoing surgery at the University of Pennsylvania routinely receive low-dose heparin as VTE prophylaxis. “Our published data of various surgical approaches does not reveal a higher than expected rate of bleeding complications,” he said.

Chepeha said that he and his colleagues often use two interventions for head and neck cancer patients: heparin prophylaxis and a sequential compression device. Prophylaxis should be considered even for biopsies if the patient is on the operating table for more than 15 minutes, he said.

Another way to avoid problems with thrombosis, Weinstein said, is to use more minimally invasive surgery, as with the da Vinci surgical robotic system, which helps to reduce hospital stay. The risk of thrombosis goes down if the patient is up and walking around after two to three days. “Transoral Robotic Surgery, developed at the University of Pennsylvania, allows surgeons in many cases to avoid long complicated free-flap surgery, and patients are usually able to be up and around in a day or two,” he said.



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Next Steps

Further research needs to determine the incidence of VTE in lower-risk head and neck cancer patients having surgery—namely, those hospitalized for fewer than four days, Gross said. Additionally, investigators need to determine prospectively the incidence of bleeding complications with the routine administration of anticoagulation in high-risk head and neck cancer patients having surgery.

A truly randomized trial where half the patients receive prophylaxis and half do not is the next step with research, Chepeha said.

Additionally, a study comparing presurgical screening ultrasound detection of VTE with postsurgical imaging could help to more clearly determine the rate of VTE caused by surgery, Andrews said.

Finally, she concluded, as a specialty, head and neck oncologic surgery needs to work toward establishing guidelines on VTE treatment to improve patient outcomes.

© 2013 by Lippincott Williams & Wilkins, Inc.
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