Clinical Prediction Rule for VTE Recurrence Risk in Cancer Patients

Zosia Chustecka

December 06, 2010

December 6, 2010 — Cancer patients are known to be at increased risk for venous thromboembolism (VTE); once they develop a clot, they are treated with long-term anticoagulants to prevent a recurrence.

Current guidelines recommend 6 months of therapy with low-molecular-weight heparin (LMWH), and suggest that anticoagulation therapy be continued as long as the cancer is active.

But do all cancer patients who have had a VTE need to be treated this way?

Perhaps not, suggest data from a new study presented here at the American Society of Hematology (ASH) 52nd Annual Meeting.

The study, presented by Martha Louzada, BSc, MD, a hematologist at the University of Western Ontario, in London, Ontario, demonstrated for the first time that cancer patients with VTE vary in their risk for VTE recurrence. Using a new scoring system, Dr. Louzada and colleagues identified factors that predicted patients who were at low risk for VTE recurrence (4.5%) and those who were at high risk (19.7%).

"We had thought from clinical practice that [there was a difference], but we were able to show independent predictors," she told Medscape Medical News.

"This is important as it is a first step in demonstrating that such a heterogenous population varies in terms of VTE recurrence risk," she explained, adding that it opens up the possibility of tailoring treatment accordingly.

In the future, a cancer patient with VTE can be assessed using this scoring system, she said in an interview. Patients who are identified as being at high risk for recurrent VTE can be given more aggressive treatment, and those identified as low risk can be given less intensive anticoagulation therapy, or perhaps none at all, she suggested.

"It will enable physicians to better tailor their treatment," she said.

After hearing the presentation, a delegate commented that this would be a "major paradigm shift," because currently all cancer patients with VTE are treated similarly. However, he noted that the model is not ready yet for clinical use.

Dr. Louzada had emphasized that the scoring system was developed on the basis of retrospective data, and it needs validation in a prospective study, which is already planned, she said.

A Good First Step

Approached for comment, incoming ASH president J. Evan Sadler, MD, PhD, agreed that this model is not ready yet for clinical practice, but said it was a "good first step."

"We already know that the risk varies among cancer patients, and we know some of the risk factors. What we don't know is how to take into account that risk and modify our therapy accordingly," said Dr. Sadler, who is professor of medicine in the hematology department at Washington University, in St. Louis, Missouri.

This study is a good first step toward a clinically feasible scoring system to stratify cancer patients who have already had a clot according to their risk of having a VTE recurrence, Dr. Sadler noted.

Another expert was more enthusiastic about the research. David Kuter, MD, PhD, head of hematology at Massachusetts General Hospital, Boston, told Medscape Medical News that the model "is potentially useful to physicians." He added that "it needs to be validated in a prospective clinical trial, but it is halfway to being a good proposal."

Dr. Kuter pointed out that the model was developed by the same group (senior author was Phil Wells, MD, from The Ottawa Hospital in Ontario) that developed the Wells criteria for deep vein thrombosis and pulmonary embolism, which have been "widely accepted." This latest study is based on the same approach, he added.

New Scoring System

To developed the scoring system, Dr. Louzada and colleagues reviewed the charts of 543 cancer patients with VTE followed from 2002 to 2004 and in 2007 and 2008 at the Thrombosis Unit at The Ottawa Hospital.

During the first period (2002 to 2004), most of the patients were taking oral vitamin K antagonists, usually warfarin; during the second study period (2007 and 2008), most were receiving subcutaneous LMWH, Dr. Louzada reported.

This reflects a change in practice, which was incorporated into treatment guidelines after the publication of the CLOT study in the New England Journal of Medicine (2003;349:146-153), she explained. The CLOT study showed that LMWH halves the risk for a VTE recurrence, compared with oral vitamin K antagonists (9% vs 17%, a 52% reduction).

However, Dr. Louzada reported that she and her colleagues found no significant difference in risk reduction between the 2 anticoagulant approaches.

Overall, 10.1% of patients developed a second clot during the first 6 months of anticoagulant therapy. The rate was 10.5% among patients receiving LMWH (36 of 343 patients) and 9.5% among those receiving oral vitamin K antagonists (19 of 200 patients).

A multivariate analysis of the data identified independent risk factors. Being female, having the primary tumor site in the lung, and having a history of VTE all increased the risk for VTE recurrence. In the new scoring system, each of these was allocated 1 point. Breast cancer and stage 1 disease appeared to have a lower risk, and these were each allocated –1 point.

However, during the discussion that followed the presentation, a delegate questioned the fact that being female increased the risk for VTE recurrence among cancer patients with VTE, because in the general population, it is males that are at higher risk. Dr. Louzada said she had no explanation for this observation. Another delegate asked about hematologic malignancies. Dr. Louzada said these appear to lower the risk, but the number of patients was so small, they decided not to include this as an independent risk factor.

The researchers calculated the points for each patient, and then calculated the frequency of VTE recurrence in each patient group.

VTE Recurrence Rate According to the Sum of Points in the Model

Sum of Points Patients (n) VTE Recurrence (n) Frequency of VTE Recurrence (%)
–3 0 0 0.0
–2 33 0 0.0
–1 24 1 4.2
0 215 10 4.7
1 218 34 15.6
2 49 9 18.4
3 4 1 25.0

Patients scoring –3 to 0 are at low risk for VTE recurrence, and patients scoring from 1 to 3 are at high risk, Dr. Louzada explained.

In this patient cohort, 48% were calculated to be at low risk (a rate for VTE recurrence below 5%).

In an interview with Medscape Medical News, Dr. Kuter noted that "5% is a threshold. Below this level of risk, we wouldn't ordinarily put a patient on anticoagulation therapy." Hence, the data from this study suggest that nearly half of cancer patients with a VTE would not need anticoagulation, or could be treated with less intensive regimens, he said.

The model also identifies patients who are at very high risk for VTE recurrence, and it could be feasible to intensify anticoagulation therapy in this population, he noted.

However, Dr. Sadler pointed out that more intensive anticoagulation would also increase the risk for major bleeding, and cancer patients who are on chemotherapy are already at increased risk of bleeding because of adverse effects such as thrombocytopenia. Also, he said, there are currently no data to show that intensifying the anticoagulation regimen results in a reduction in the risk for VTE recurrence.

Dr. Louzada has disclosed no relevant financial relationships.

American Society of Hematology (ASH) 52nd Annual Meeting: Abstract 475. Presented December 6, 2010.


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