Patients who undergo intramedullary nailing to stabilize bone fractures caused by cancer metastases have an increased risk for venous thromboembolism (VTE) following surgery and may need more than the usual amount of preventive anticoagulants, according to a study in The Journal of Bone & Joint Surgery (2015;97:1503-1511).
“The study describes what should be a shift in the way orthopedic surgeons and oncologists who are seeing patients with bone lesions think,” said the senior author, John A. Abraham, MD, Associate Professor of Orthopedic Surgery and Radiation Oncology at the Sidney Kimmel Medical College at Thomas Jefferson University, Director of the Jefferson Sarcoma and Bone Tumor Center, and an orthopedic surgeon specializing in orthopedic oncology at the Rothman Institute at Jefferson.
Orthopedic surgeons usually treat metastatic disease in the long bones in the same manner, no matter what type of primary cancer is present, he explained. The new findings, however, emphasize the importance of multidisciplinary care, with orthopedic, medical, and radiation oncologists all part of the treatment team, giving input on the best management of the patient with a skeletal lesion.
Asked for her perspective, Jane Carleton, MD, Associate Chief of Clinical Affairs at Monter Cancer Center and Assistant Professor of Medicine at Hofstra-North Shore LIJ School of Medicine, agreed: “This study illustrates how oncologists need to be tailoring and optimizing the use of anticoagulants in this patient population. It also demonstrates that oncologists should not be afraid to anticoagulate.”
The Jefferson team—first author is Brandon Shallop, MD—retrospectively reviewed the database records of 287 patients with metastatic bone cancer. These individuals had 336 impending or pathologic bone fractures that were stabilized with intramedullary nailing between February 2001 and April 2013.
The types of anticoagulants patients received included low-molecular weight heparin, warfarin, aspirin, fondaparinux, and heparin; some individuals did not receive any anticoagulation.
Of the 336 operations, 24 VTE events (about 7%) were reported in the first 90 days after surgery. Thirteen (4%) were pulmonary embolism (PE), and 11 (3%) were deep vein thrombosis (DVT).
The investigators also found a low incidence of wound complications (3.3%) that required reoperations or antibiotics. None of the patients with VTE had wound complications, and there did not appear to be a correlation between the type of anticoagulant and the rate of wound complications.
A total of 66 percent of patients who developed VTE by 90 days after surgery also had a primary cancer of the lung. Additionally, statistical analyses found a significantly increased VTE risk in patients with primary lung cancer histology.
Patients who did not receive radiation therapy after surgery had a slightly decreased risk of developing VTE, which approached statistical significance, the team reported. And after an analysis of anticoagulant use, investigators did not identify a significant relationship between the use of any of the specific anticoagulants studied and the development of DVT, PE, or VTE.
Also asked his opinion, Jeffrey M. Farma, MD, FACS, Surgical Oncology Fellowship Director and Co-Director of the Cutaneous Oncology Program at Fox Chase Cancer Center, said via email that the research illustrates the importance of identifying high-risk groups of cancer patients who may need improved detection and prevention of VTE, either with preoperative anticoagulation, prolonged postoperative anticoagulation, or utilization of newer agents.
The rate of VTE in this study was not surprising, given that VTE is more common in cancer patients and is also more common in individuals undergoing orthopedic procedures, said Helen K. Chew, MD, FACP, Professor of Medicine in the Division of Hematology and Oncology and Director of The Joe Sullivan Hematology and Oncology Program at UC Davis Comprehensive Cancer Center. “These [study] patients had two separate risks.”
Carleton said that while oncologists certainly know that the risk of VTE increases with radiation therapy and chemotherapy, the paper demonstrates that intramedullary nailing also increases the risk. “If you have a patient with lung cancer who is having surgery and undergoing adjuvant radiation, risk factors are stacking up,” she said.
Chew cautioned that when assessing patient risk, the study findings need to be interpreted with some consideration. For example, the study population mostly consisted of individuals with lung cancer and metastatic disease, “so it wasn't surprising that they had the greatest amount of VTE.”
In addition, while the investigators noted that the results regarding radiation therapy approached clinical significance, she said that she and her colleagues, who research VTE incidence in cancer patients, have more stringent standards than a P value of 0.05 as cut-off in their analyses of prior databases with many variables. Still, the findings in the study related to radiation therapy may be hypothesis generating, she said.
Overall, when assessing risk, oncologists should work closely with orthopedic surgeons to ensure that patients are receiving anticoagulation and are monitored afterward, and together, these specialists need to balance postoperative bleeding and VTE risks.
Farma also called for the development of standardized protocols and guidelines to manage such patients.
Questions Surrounding Anticoagulation
Abraham noted that although two weeks of anticoagulation therapy as VTE prophylaxis is usually the standard of care after intramedullary nailing, that is based on experience with routine cases of fracture, not higher-risk patients with cancer and pathologic fractures. Therefore, rather than evaluating patient database records within the two-week mark, the team extended the time frame to three months post-surgery based on other published data suggesting that VTEs can occur much later.
“And indeed, at three months, we still found a number of events,” he said. “If we used a two-week postoperative period as the study period, we would have missed nearly half the VTE events captured in this study.”
Additionally, the low incidence of postoperative wounds may mean that the more aggressive use of anticoagulants is a possibility, according to the study authors.
Carleton said that oncologists may now want to consider prescribing these medications for longer periods of time in carefully selected patients.
Chew said that you can't really argue for giving these patients more anticoagulation without having clinical evidence: “We have to know the doses they were taking and whether they were compliant.” Because the study was retrospective, these factors can't be confirmed.
Abraham added that another question the study raises is that while low-molecular-weight heparin is often favored for VTE prevention, the data did not show any differences between this agent and the other types of anticoagulants used with respect to VTE outcomes. Notably, 11 percent of the patients who did not receive any postoperative anticoagulant therapy had about the same risk of VTE as those who did, suggesting that current regimens of postoperative anticoagulation do very little to reduce the risk.
Patient education is also key, said Carol Mackenzie Jackson, PhD, PA-C, a physician assistant in the surgical services at Cancer Treatment Centers of America in Philadelphia. Jackson and her colleagues are closely evaluating VTE risk in an interdisciplinary manner to help improve patient surveillance.
She said that because anticoagulation may not be enough to help reduce risk, patients need to understand the importance of being mobile after surgery: “The very purpose of bone fixation is to enable patients with advanced disease to avoid immobility, which puts them at even greater risk for blood clots. When we use femoral rods here, patients are up and walking the next day. Being immobile is a negative.”
In the hospital, patients may work with a physical therapist to improve mobility. Once home, they are encouraged to move and to return to their daily activities as much as possible, she explained.
Abraham said that he and his colleagues are now planning a large nationwide, multicenter clinical trial of different anticoagulants used at various doses and durations in cancer patients with bone metastases who are undergoing the nailing procedure to help clarify the ideal postoperative anticoagulation regimen.
Research also needs to determine why none of the drugs in the current study were able to substantially reduce VTE risk. “Even though many may think low-molecular weight heparin is the best option, there's no real proof of that, and there may be a better agent available” he said.
Carleton summed up: “Optimizing anticoagulation for patients who have undergone intramedullary nailing for metastatic bone lesions remains a challenge, and more data is needed to determine the optimal dose and duration of therapy. Because the study showed a very low rate of wound complications with anticoagulation, there is clearly room to study more aggressive anticoagulation regimens.”