KYPHOPLASTY FOR CANCER VERTEBRAL COMPRESSION FRACTURE
Tuesday, February 22, 2011
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Kyphoplasty should be considered an early treatment option for patients with cancer who have symptomatic vertebral compression fractures (VCFs), conclude researchers reporting the first randomized trial in such a patient population.
The results come from the Cancer Patient Fracture Evaluation (CAFE) study, published online February 17 in the Lancet Oncology.
However, an accompanying editorial points out that there are a lot of unanswered questions, and raises the possibility that the benefit seen could be largely a placebo effect.
The trial was funded by Medtronic Spine, which acquired Kyphon, the company that developed the kyphoplasty procedure to improve upon vertebroplasty. Both involve injecting bone cement between cracked vertebrae, but with kyphoplasty, a balloon is first inserted and inflated to increase the space inside the collapsed bone.
The study found that cancer patients with VCFs who underwent kyphoplasty had significantly less pain and disability and significantly better function and quality of life than patients who were treated nonsurgically with standard therapy, including analgesics and bed rest.
"With the results of this new randomized study, there is now clinical evidence of a treatment option for spinal factures in cancer patients," principal investigator James Berenson, MD, from the Institute for Myeloma and Bone Cancer Research in West Hollywood, California, said in a statement.
Previous studies have found that VCFs occur in about 24% of patients with multiple myeloma, 14% with breast cancer, 8% with lung cancer, and 6% with prostate cancer, the authors note.
Could it Be a Placebo Effect?
There are several limitations of the study, including the fact that the randomization was only for 1 month, according to the editorialists.
"This trial leaves unanswered important questions regarding vertebral augmentation in patients with cancer," write David Schiff, MD, and Mary Jensen, MD, from the University of Virginia Health Sciences Center in Charlottesville.
They wonder if vertebroplasty would provide similar benefits in this group of patients, and point out that it costs about a third of what kyphoplasty costs.
"There are no good comparative data of vertebroplasty vs kyphoplasty in malignant VCF," Dr. Schiff told Medscape Medical News.
The editorialists also note that the trial was not blinded, and wonder if the benefit of kyphoplasty could be "primarily a placebo effect."
"I find it hard to believe that it could be a placebo effect," Dr. Berenson responded. "The effects are pretty dramatic," he toldMedscape Medical News. Many of these cancer patients were bed-ridden, yet after the kyphoplasty they were walking and moving around, he said.
There was a significant improvement in function and quality of life, and a significant reduction in disability and in the use of analgesic medications, he pointed out.
Dr. Berenson also explained that he believes it would be unethical to conduct a blinded trial in cancer patients. It was for these reasons that the trial was designed to offer cancer patients who were randomized to the control group a chance to crossover after a month of standard nonsurgical treatment.
Editorialist Dr. Schiff, who is the Harrison Distinguished Professor at the Neuro-Oncology Center at the University of Virginia, toldMedscape Medical News that he agrees with Dr. Berenson "that the benefit of kyphoplasty in CAFE is a large effect."
"However, it would be remiss not to point out that in osteoporotic VCFs, vertebroplasty beats best medical care (unblinded) but does not beat injection with anesthetic but no bone cement," he continued.
Dr. Schiff was referring to 2 trials published in 2009 (N Engl J Med. 2009;361:557-568 and 569-579) that showed a similar benefit from vertebroplasty and sham procedures in patients with osteoporotic spinal fractures. At the time, an accompanying editorial (N Engl J Med. 2009;361:619-621) predicted that those results "may change vertebroplasty from a procedure that is virtually always considered to be successful to one that is considered no better than placebo."
With that in mind, Dr. Schiff commented on the CAFE study: "Thus, without a control arm of injection without bone cement, it is not impossible that the beneficial effect of kyphoplasty in cancer-related VCF could be due in large part to placebo effect."
"One could design a placebo-controlled study that at some defined time point allowed individual patients to be unblended and to crossover to kyphoplasty if originally randomized to the placebo control arm and not experiencing symptom improvement," Dr. Schiff suggested, adding that "this would circumvent ethical concerns."
Benefits From Kyphoplasty
CAFE was an international study conducted in 134 cancer patients who had 1 to 3 painful VCFs. Most of the patients had multiple myeloma or breast cancer, but a few had lung, prostate, or other cancers.
All participants could receive various nonsurgical treatments, including analgesics, bed rest, bracing, physiotherapy, rehabilitation, walking aids, radiation, and other antitumor therapy, at the discretion of the treating physician. Patients with concurrent osteoporosis or bone metastasis could also receive treatment with calcium and vitamin D supplements and antiresorptive or anabolic agents, as necessary.
Approximately half of the patients (n = 68) underwent kyphoplasty; the remainder (n = 60) acted as the control group.
A month later, there were significant differences on several measures between the patients who underwent kyphoplasty and those who did not.
The primary end point was change after 1 month in the Roland-Morris Disability Questionnaire (RDQ) score, which is validated for back-specific physical functioning. Patients who underwent kyphoplasty had a significantly greater change in RDQ score from baseline to 1 month (mean of 17.6 to 9.1; P < .0001) than those who did not (mean of 18.2 to 18.0; P = .83).
There was also a "marked reduction in back pain" and a significant reduction in the use of analgesics (P = .001). Of the patients who were randomized to kyphoplasty, 94% reported using analgesics at baseline, but only 52% were still using them a month after the procedure; there was little change in the control group (85% vs 82%).
Crossover After 1 Month
After a month in the trial, patients in the control group were given a chance to crossover and undergo kyphoplasty; 34 of 52 patients chose to do so. The remaining 18 patients continued with nonsurgical management.
Assessment at 6 months showed that the original kyphoplasty group and the crossover group both had significantly improved RDQ scores, whereas the patients who remained in the control group did not.
For both groups of patients who underwent kyphoplasty, the improvements seen were generally maintained until the final assessment at 12 months, the researchers note.
"Because of the limited improvement in the control group, the results of this study suggest that balloon kyphoplasty should be considered as an early treatment option for patients with cancer who have symptomatic VCFs," they conclude.
Reducing the use of pain medications decreases the risk for drug-related adverse effects and potential for interactions, and improving function reduces the risk for complications related to being bed-ridden, such as deep vein thrombosis, pneumonia, and decubitus ulcers, the researchers point out.
"Thus, a procedure that effectively treats VCFs for patients with cancer might confer clinical and quality-of-life benefits beyond treatment of the fracture itself," they add.
The CAFE study was funded by Medtronic Spine. Dr. Berenson and several coauthors report receiving consulting fees and research funding from Medtronic, and 2 coauthors are employees of the company. Dr. Schiff reports receiving consultancy fees and acting on the advisory board for Genentech. Dr. Jensen reports receiving consultancy fees from Kuros Biotechnology.
Lancet Oncol. Published online February 17, 2011.
The results come from the Cancer Patient Fracture Evaluation (CAFE) study, published online February 17 in the Lancet Oncology.
However, an accompanying editorial points out that there are a lot of unanswered questions, and raises the possibility that the benefit seen could be largely a placebo effect.
The trial was funded by Medtronic Spine, which acquired Kyphon, the company that developed the kyphoplasty procedure to improve upon vertebroplasty. Both involve injecting bone cement between cracked vertebrae, but with kyphoplasty, a balloon is first inserted and inflated to increase the space inside the collapsed bone.
The study found that cancer patients with VCFs who underwent kyphoplasty had significantly less pain and disability and significantly better function and quality of life than patients who were treated nonsurgically with standard therapy, including analgesics and bed rest.
"With the results of this new randomized study, there is now clinical evidence of a treatment option for spinal factures in cancer patients," principal investigator James Berenson, MD, from the Institute for Myeloma and Bone Cancer Research in West Hollywood, California, said in a statement.
Previous studies have found that VCFs occur in about 24% of patients with multiple myeloma, 14% with breast cancer, 8% with lung cancer, and 6% with prostate cancer, the authors note.
Could it Be a Placebo Effect?
There are several limitations of the study, including the fact that the randomization was only for 1 month, according to the editorialists.
"This trial leaves unanswered important questions regarding vertebral augmentation in patients with cancer," write David Schiff, MD, and Mary Jensen, MD, from the University of Virginia Health Sciences Center in Charlottesville.
They wonder if vertebroplasty would provide similar benefits in this group of patients, and point out that it costs about a third of what kyphoplasty costs.
"There are no good comparative data of vertebroplasty vs kyphoplasty in malignant VCF," Dr. Schiff told Medscape Medical News.
The editorialists also note that the trial was not blinded, and wonder if the benefit of kyphoplasty could be "primarily a placebo effect."
"I find it hard to believe that it could be a placebo effect," Dr. Berenson responded. "The effects are pretty dramatic," he toldMedscape Medical News. Many of these cancer patients were bed-ridden, yet after the kyphoplasty they were walking and moving around, he said.
There was a significant improvement in function and quality of life, and a significant reduction in disability and in the use of analgesic medications, he pointed out.
Dr. Berenson also explained that he believes it would be unethical to conduct a blinded trial in cancer patients. It was for these reasons that the trial was designed to offer cancer patients who were randomized to the control group a chance to crossover after a month of standard nonsurgical treatment.
Editorialist Dr. Schiff, who is the Harrison Distinguished Professor at the Neuro-Oncology Center at the University of Virginia, toldMedscape Medical News that he agrees with Dr. Berenson "that the benefit of kyphoplasty in CAFE is a large effect."
"However, it would be remiss not to point out that in osteoporotic VCFs, vertebroplasty beats best medical care (unblinded) but does not beat injection with anesthetic but no bone cement," he continued.
Dr. Schiff was referring to 2 trials published in 2009 (N Engl J Med. 2009;361:557-568 and 569-579) that showed a similar benefit from vertebroplasty and sham procedures in patients with osteoporotic spinal fractures. At the time, an accompanying editorial (N Engl J Med. 2009;361:619-621) predicted that those results "may change vertebroplasty from a procedure that is virtually always considered to be successful to one that is considered no better than placebo."
With that in mind, Dr. Schiff commented on the CAFE study: "Thus, without a control arm of injection without bone cement, it is not impossible that the beneficial effect of kyphoplasty in cancer-related VCF could be due in large part to placebo effect."
"One could design a placebo-controlled study that at some defined time point allowed individual patients to be unblended and to crossover to kyphoplasty if originally randomized to the placebo control arm and not experiencing symptom improvement," Dr. Schiff suggested, adding that "this would circumvent ethical concerns."
Benefits From Kyphoplasty
CAFE was an international study conducted in 134 cancer patients who had 1 to 3 painful VCFs. Most of the patients had multiple myeloma or breast cancer, but a few had lung, prostate, or other cancers.
All participants could receive various nonsurgical treatments, including analgesics, bed rest, bracing, physiotherapy, rehabilitation, walking aids, radiation, and other antitumor therapy, at the discretion of the treating physician. Patients with concurrent osteoporosis or bone metastasis could also receive treatment with calcium and vitamin D supplements and antiresorptive or anabolic agents, as necessary.
Approximately half of the patients (n = 68) underwent kyphoplasty; the remainder (n = 60) acted as the control group.
A month later, there were significant differences on several measures between the patients who underwent kyphoplasty and those who did not.
The primary end point was change after 1 month in the Roland-Morris Disability Questionnaire (RDQ) score, which is validated for back-specific physical functioning. Patients who underwent kyphoplasty had a significantly greater change in RDQ score from baseline to 1 month (mean of 17.6 to 9.1; P < .0001) than those who did not (mean of 18.2 to 18.0; P = .83).
There was also a "marked reduction in back pain" and a significant reduction in the use of analgesics (P = .001). Of the patients who were randomized to kyphoplasty, 94% reported using analgesics at baseline, but only 52% were still using them a month after the procedure; there was little change in the control group (85% vs 82%).
Crossover After 1 Month
After a month in the trial, patients in the control group were given a chance to crossover and undergo kyphoplasty; 34 of 52 patients chose to do so. The remaining 18 patients continued with nonsurgical management.
Assessment at 6 months showed that the original kyphoplasty group and the crossover group both had significantly improved RDQ scores, whereas the patients who remained in the control group did not.
For both groups of patients who underwent kyphoplasty, the improvements seen were generally maintained until the final assessment at 12 months, the researchers note.
"Because of the limited improvement in the control group, the results of this study suggest that balloon kyphoplasty should be considered as an early treatment option for patients with cancer who have symptomatic VCFs," they conclude.
Reducing the use of pain medications decreases the risk for drug-related adverse effects and potential for interactions, and improving function reduces the risk for complications related to being bed-ridden, such as deep vein thrombosis, pneumonia, and decubitus ulcers, the researchers point out.
"Thus, a procedure that effectively treats VCFs for patients with cancer might confer clinical and quality-of-life benefits beyond treatment of the fracture itself," they add.
The CAFE study was funded by Medtronic Spine. Dr. Berenson and several coauthors report receiving consulting fees and research funding from Medtronic, and 2 coauthors are employees of the company. Dr. Schiff reports receiving consultancy fees and acting on the advisory board for Genentech. Dr. Jensen reports receiving consultancy fees from Kuros Biotechnology.
Lancet Oncol. Published online February 17, 2011.
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