**8. Inferior Vena Cava (IVC) filters in cancer patients**

Treatment of VTE typically includes initial anticoagulation with unfractionated heparin, LMWH or a pentasaccharide like fondaparinux, (Buller et al., 2004) along with vitamin K antagonists like warfarin. Occasionally, specific clinical situations present in which the risk of PE is very high or systemic anticoagulation might be associated with high risk of bleeding; in these instances, IVC filters are utilized to provide mechanical thromboprophylaxis to prevent PE, the life-threatening complication of VTE. Such filters are inserted using a relatively noninvasive technique to maintain central flow. Thanks to newer technology, the IVC filters are becoming a very attractive option and can function with anticoagulation to optimize the prophylaxis strategy. Inferior Vena Cava filters are usually utilized in many clinical situations detailed in table-2 (Schwarz et al., 1996; Saour et al., 2009).

However, many of such indications are subjective and consensus might occasionally be difficult to reach. In a community-based study, researchers at McMaster University reviewed 1547 local county residents with confirmed diagnosis of acute VTE and without a prior IVC filter. Following the VTE, 203 (13.1%) patients had an IVC filter placed. In reviewing the indications for IVC filter placement, panel members unanimously agreed that the use of IVC filter was appropriate in 51% of the cases and inappropriate in 26%; no consensus was reached in the remaining 23% of the cases (Spencer et al., 2010).

The clinical benefit of IVC filter placement was addressed in one prospective trial (the PREPIC study) in which 400 patients with proximal DVT who were at risk for PE, were randomized to receive IVC filter (200 patients) or no filter (200 patients). Both groups were anticoagulated with LMWH or unfractionated heparin. At day 12, two (1.1%) patients assigned to receive filters, as compared with nine (4.8%) patients assigned to receive no filters, had symptomatic or asymptomatic PE (odds ratio, 0.22; 95 percent confidence interval, 0.05 to 0.90). However, at two years, 37 (20.8%) patients assigned to the filter group,

Several clinical trials have addressed the issue of VTE prophylaxis in such patients. One study showed a benefit in reducing VTE events when low fixed-dose warfarin (1mg/day) was used for prophylaxis (Bern et al., 1990). However, two subsequent clinical trials failed to

Low molecular weight heparin was also tried in two large, double-blind clinical trials (Verso et al., 2005; Karthaus et al., 2006). The first trial failed to show beneficial effect of enoxaparin when used at a dose of 40 mg once daily versus placebo in a group of 385 cancer patients with CVC (Verso et al., 2005). In the second trial, dalteparin at 5,000 units once daily was tested against placebo in 439 cancer patients who were receiving chemotherapy through such catheters; clinically relevant VTE occurred in 3.7% and 3.4% in the dalteparin and placebo recipients, respectively (Karthaus et al., 2006). Nadroparin, another LMWH, showed no advantage when tested against low fixed dose of warfarin (1 mg/day) in a small

Given the results of these studies, thromboprophylaxis with anticoagulants for patients with

Treatment of VTE typically includes initial anticoagulation with unfractionated heparin, LMWH or a pentasaccharide like fondaparinux, (Buller et al., 2004) along with vitamin K antagonists like warfarin. Occasionally, specific clinical situations present in which the risk of PE is very high or systemic anticoagulation might be associated with high risk of bleeding; in these instances, IVC filters are utilized to provide mechanical thromboprophylaxis to prevent PE, the life-threatening complication of VTE. Such filters are inserted using a relatively noninvasive technique to maintain central flow. Thanks to newer technology, the IVC filters are becoming a very attractive option and can function with anticoagulation to optimize the prophylaxis strategy. Inferior Vena Cava filters are usually utilized in many clinical situations detailed in table-2 (Schwarz et al., 1996; Saour et al.,

However, many of such indications are subjective and consensus might occasionally be difficult to reach. In a community-based study, researchers at McMaster University reviewed 1547 local county residents with confirmed diagnosis of acute VTE and without a prior IVC filter. Following the VTE, 203 (13.1%) patients had an IVC filter placed. In reviewing the indications for IVC filter placement, panel members unanimously agreed that the use of IVC filter was appropriate in 51% of the cases and inappropriate in 26%; no

The clinical benefit of IVC filter placement was addressed in one prospective trial (the PREPIC study) in which 400 patients with proximal DVT who were at risk for PE, were randomized to receive IVC filter (200 patients) or no filter (200 patients). Both groups were anticoagulated with LMWH or unfractionated heparin. At day 12, two (1.1%) patients assigned to receive filters, as compared with nine (4.8%) patients assigned to receive no filters, had symptomatic or asymptomatic PE (odds ratio, 0.22; 95 percent confidence interval, 0.05 to 0.90). However, at two years, 37 (20.8%) patients assigned to the filter group,

consensus was reached in the remaining 23% of the cases (Spencer et al., 2010).

show any benefit [Heaton et al., 2002: Couban et al., 2005).

central venous catheters is not recommended.

2009).

**8. Inferior Vena Cava (IVC) filters in cancer patients** 

randomized trial that involved 45 evaluable patients (Mismetti et al., 2003).

as compared with 21 (11.6%) patients assigned to the no-filter group, had recurrent DVT (odds ratio, 1.87; 95% CI, 1.10 to 3.20) ( Decousus et al., 1998). This study was updated 8 years later; patients with IVC filters experienced a greater cumulative incidence of symptomatic DVT (35.7%versus 27.5%; HR 1.52, CI 1.02 to 2.27; *P* = 0.042), but significantly fewer symptomatic pulmonary emboli (6.2%versus 15.1%; HR 0.37, CI 0.17 to 0.79; *P* = 0.008) (The PREPIC Study Group, 2005). The conclusion from this long-term follow-up was similar to the original report; that is, with an IVC filter there is an equivalent trade-off of fewer PE at the cost of more DVTs. There was no difference in long-term morbidity or mortality in both groups.


IVC: Inferior Vena Cava, GI: Gastrointestinal, GU: Genitourinary, GYN: Gynecological, CNS: Central Nervous System, VTE: Venous Thromboembolism

Table 2. Indications for IVC filter placement

Given the lack of long term benefits of IVC filters; temporary, retrievable filters had gained increasing interest. Many different retrievable filters had recently received approval for temporary insertion. Recent data suggest that the use of these filters may be associated with low rates of PE and insertion complications (Imberti & Prisco, 2008). Nevertheless; no randomized clinical trials have been performed. In one large retrospective study that included 252 evaluable patients who had retrievable filter placed for different indications; only 47 filters were successfully retrieved yielding a retrieval rate of 18.7% ( Dabbagh et al., 2010). Similar or higher retrieval rates were reported by others (Mismetti et al., 2007).

Regardless of the type of the filter placed, the most recent American Colleague of Chest Physicians (ACCP) guidelines recommend systemic anticoagulation, when possible, even with the filter in place (Kearon et al., 2008).

Cancer itself, or its treatment, might result in certain clinical complications that make systemic anticoagulation very risky (Abdel-Razeq et al., 2011). Venous thromboembolic disease is a frequent complication in patients with intracranial malignancies. Many of the primary brain tumors like gliomas or secondary metastatic tumors to the brain are either bulky or very vascular thus increasing the risk of bleeding with or without systemic anticoagulation (Ruff & Posner, 1983). Brain metastases from melanoma, choriocarcinoma, thyroid carcinoma, and renal cell carcinoma have particularly high propensities for

Venous Thromboembolism Prophylaxis in Cancer Patients 121

primarily by the malignant process (Schunn et al., 2006). Researchers at M.D. Anderson Cancer center concluded, in a study that included 308 cancer patients with VTE and IVC filters, that such filters are safe and effective in preventing PE-related deaths in selected patients with cancer. However, patients with a history of DVT and bleeding or advanced

Despite its proven efficacy, VTE prophylaxis in cancer patients is clearly underutilized. Strategies to improve prophylaxis rate in such high risk patients are highly needed (Abdel-Razeq, 2010). Establishment of "VTE prophylaxis multidisciplinary team" addressing this issue supported by hospital administration might help. Recently, many health advocacy groups and policy makers are paying more attention to VTE prophylaxis. The National Quality Forum (NQF) recently endorsed strict VTE risk assessment evaluation for each patient upon admission and regularly thereafter (National Quality Forum (NQF), 2011). Additionally, the Joint Commission has recently approved new measure sets that included VTE prophylaxis; this standard mandates that a VTE prophylaxis method is in place within 24 hours of hospital admission, otherwise, a risk assessment and contraindications for prophylaxis should be documented for each and every hospitalized medical or surgical patient (The Joint Commission Manual for Performance Improvement Measures, 2011). Recently, Maynard and Stein (2011) have published their experience and recommendations following their extensive efforts to better utilize VTE prophylaxis in high-risk patients. Such

disease had the lowest survival after IVC filter placement (Wallace et al., 2004).

recommendations are worth careful attention and are summarized in table-3.

**Support by hospital administration for better VTE prophylaxis initiative. Establishment of VTE Prophylaxis "Multidisciplinary Team"; this team should:** 

Report regularly to hospital administration or a "Quality Council".

Provide clear link between risk level and prophylaxis choice. Provide guidance to manage patients with contraindications. **Continuous education and training of all health care providers.** 

Table 3. Strategies to improve VTE prophylaxis in high risk cancer patients.

Simple, yet efficient in daily use; two to three VTE risk levels are enough!

In conclusion, though published guidelines are somewhat different; hospitalized cancer patients, in the absence of bleeding or absolute contraindications, should be considered for thromboprophylaxis. Certain cancers, like Multiple Myeloma when treated with drugs like thalidomide or other immune modulators may benefit from prophylaxis. However, current guidelines do not recommend prophylaxis for ambulatory cancer patients or patients with

Extended thromboprophylaxis with LMWH (21-28days) should be considered in cancer

Standardize the process of providing VTE prophylaxis

Facilitates implementation of guidelines.

patients undergoing major pelvic/abdominal surgeries.

Audit and monitor outcomes.

**Better guidelines:** 

central venous catheter.

**9. Conclusions and future directions** 

spontaneous hemorrhage while metastatic tumors from sites like lung and breast are less likely to bleed spontaneously (Mandybur, 1993). However, not all patients with intracranial malignancies are at higher risk of bleeding with anticoagulation. Complication rate of IVC filters in patients with brain tumors is higher than commonly perceived and may outweigh the risk of anticoagulation. Researchers at Brigham and Women's Hospital in Boston reviewed the records of 49 patients with intracranial malignancies and venous thromboembolic disease to determine the effectiveness and complications resulting from systemic anticoagulation or IVC filter placement. Of the 42 patients received IVC filters, a strikingly high percentage (62%) developed one or more complications; 12% developed recurrent PE, while 57% developed filter thrombosis, recurrent DVT, or post-phlebitic syndrome. These complications severely reduced the quality of life of affected patients. Only 15 (31%) patients were treated with anticoagulation, and seven of these received it because of continued thromboembolic disease. None of these 15 patients had proven hemorrhagic complications (Levin et al., 1993).

Many recent studies questioned the need to insert IVC filters in cancer patients particularly those with advanced-stage disease whose survival is short and prevention of PE may be of little clinical benefit and could be a poor utilization of resources. In one retrospective study performed to determine the clinical benefit of IVC filter placement in patients with malignancy, 116 patients who had such filters inserted were included. Ninety one (78%) patients had stage IV disease, 42 (46%) of them died of cancer within 6 weeks and only16 (14%) were alive at one year (Jarrett et al., 2002).

The benefits of IVC filter placement on overall survival, as measured from the time of VTE was addressed in a recent retrospective study that examined 206 consecutive cancer patients with VTE. Patients were classified into 3 treatment groups: anticoagulation-only (n= 62), IVC filter-only (n=77), or combination of both IVC filter and anticoagulation (n=67). Median overall survival was significantly greater in patients treated with anticoagulation (13 months) compared with those treated with IVC filters (2 months) or combination of both (3.25 months; *P* < 0.0002). IVC patients were at 1.9 times more risk of death than anticoagulation only (hazard ratio=0.528; 95% confidence interval=0.374 to .745). Multivariate analysis revealed that performance status and type of thrombus were not confounders and had no effect on overall survival (Barginear et al., 2009).

In another study, the survival benefit of IVC filters in patients with late-stage malignancy was evaluated in a group of 5,970 patients who were treated with a primary diagnosis of malignancy at a tertiary care facility. Retrospective analysis identified 55 consecutive patients with stage III or IV malignant disease and VTE who received IVC filters. In a case control study, 16 patients with VTE but without IVC filter were matched for age, sex, type of malignancy, and stage of disease. Filter placement prevented PE in 52 (94.5%) patients, however, four (7.3%) of patients had complications related to the procedure; 13 (23.6%) patients with late-stage cancer survived less than 30 days following placement of the filter; another 13 (23.6%) patients of this group, however, survived more than one year. Ambulatory status differed significantly (*P* = 0.01) between these two subgroups. Authors concluded that IVC filter placement conferred no survival benefit compared to the control group and that the survival of such patients with advanced-stage cancer was limited

spontaneous hemorrhage while metastatic tumors from sites like lung and breast are less likely to bleed spontaneously (Mandybur, 1993). However, not all patients with intracranial malignancies are at higher risk of bleeding with anticoagulation. Complication rate of IVC filters in patients with brain tumors is higher than commonly perceived and may outweigh the risk of anticoagulation. Researchers at Brigham and Women's Hospital in Boston reviewed the records of 49 patients with intracranial malignancies and venous thromboembolic disease to determine the effectiveness and complications resulting from systemic anticoagulation or IVC filter placement. Of the 42 patients received IVC filters, a strikingly high percentage (62%) developed one or more complications; 12% developed recurrent PE, while 57% developed filter thrombosis, recurrent DVT, or post-phlebitic syndrome. These complications severely reduced the quality of life of affected patients. Only 15 (31%) patients were treated with anticoagulation, and seven of these received it because of continued thromboembolic disease. None of these 15 patients had proven hemorrhagic

Many recent studies questioned the need to insert IVC filters in cancer patients particularly those with advanced-stage disease whose survival is short and prevention of PE may be of little clinical benefit and could be a poor utilization of resources. In one retrospective study performed to determine the clinical benefit of IVC filter placement in patients with malignancy, 116 patients who had such filters inserted were included. Ninety one (78%) patients had stage IV disease, 42 (46%) of them died of cancer within 6 weeks and only16

The benefits of IVC filter placement on overall survival, as measured from the time of VTE was addressed in a recent retrospective study that examined 206 consecutive cancer patients with VTE. Patients were classified into 3 treatment groups: anticoagulation-only (n= 62), IVC filter-only (n=77), or combination of both IVC filter and anticoagulation (n=67). Median overall survival was significantly greater in patients treated with anticoagulation (13 months) compared with those treated with IVC filters (2 months) or combination of both (3.25 months; *P* < 0.0002). IVC patients were at 1.9 times more risk of death than anticoagulation only (hazard ratio=0.528; 95% confidence interval=0.374 to .745). Multivariate analysis revealed that performance status and type of thrombus were not

In another study, the survival benefit of IVC filters in patients with late-stage malignancy was evaluated in a group of 5,970 patients who were treated with a primary diagnosis of malignancy at a tertiary care facility. Retrospective analysis identified 55 consecutive patients with stage III or IV malignant disease and VTE who received IVC filters. In a case control study, 16 patients with VTE but without IVC filter were matched for age, sex, type of malignancy, and stage of disease. Filter placement prevented PE in 52 (94.5%) patients, however, four (7.3%) of patients had complications related to the procedure; 13 (23.6%) patients with late-stage cancer survived less than 30 days following placement of the filter; another 13 (23.6%) patients of this group, however, survived more than one year. Ambulatory status differed significantly (*P* = 0.01) between these two subgroups. Authors concluded that IVC filter placement conferred no survival benefit compared to the control group and that the survival of such patients with advanced-stage cancer was limited

confounders and had no effect on overall survival (Barginear et al., 2009).

complications (Levin et al., 1993).

(14%) were alive at one year (Jarrett et al., 2002).

primarily by the malignant process (Schunn et al., 2006). Researchers at M.D. Anderson Cancer center concluded, in a study that included 308 cancer patients with VTE and IVC filters, that such filters are safe and effective in preventing PE-related deaths in selected patients with cancer. However, patients with a history of DVT and bleeding or advanced disease had the lowest survival after IVC filter placement (Wallace et al., 2004).
