Evidence-Based Clinical Guidelines for Multidisciplinary Spine Care

Diagnosis and Treatment of Adults with Neoplastic Vertebral Fractures

Recommendations

Interventional Treatment

Interventional Treatment Question 1. What are the criteria/indications/contraindications for vertebral augmentation in patients with neoplastic vertebral fractures?

Interventional Treatment Question 2. How do interventional treatments (augmentation, thermal ablation, radiofrequency ablation and cryoablation) compare to medical treatments in reducing severity and duration of pain and disability in patients with neoplastic vertebral fractures?

Interventional Treatment Question 3. Are there specific characteristics of the fracture or the patient that influence outcomes in patients with neoplastic vertebral fractures undergoing vertebral augmentation?

Interventional Treatment Question 4. What is the risk of treating multiple vertebral levels at one time, for patients with multilevel neoplastic vertebral fractures?

Natural History Question 5. What is the incidence and risk factors for adjacent vertebral body fractures after vertebral augmentation for neoplastic vertebral fractures?

Natural History Question 6. Does the addition of vertebral augmentation to radiation therapy improve outcomes in patients with neoplastic vertebral fractures?

Natural History Question 7. Does the prophylactic use of vertebral augmentation reduce the risk of vertebral fracture after stereotactic radiotherapy for vertebral metastasis?

Natural History Question 8. Does physical therapy after augmentation affect patient outcomes, including pain and function?

Interventional Treatment Question 1: What are the criteria/indications/ contraindications for vertebral augmentation in patients with neoplastic vertebral fractures?

Vertebral augmentation is suggested as a safe and effective procedure in adults with neoplastic vertebral fractures with intractable back pain despite medical management and/or those at risk of vertebral collapse, although caution is recommended because of the potential for cement extrusion.

Grade of Recommendation: B

In a retrospective study, Cianfori et al1 assessed the complications of vertebral augmentation in 48 patients with cortical erosion of the posterior wall undergoing vertebral augmentation for pain palliation and/or stabilization of neoplastic vertebral body lesions. Seventy consecutive levels with cortical erosion of the posterior wall were evaluated. The authors concluded that the “data seem to justify use of vertebral augmentation in patients with intractable pain or those at risk for vertebral collapse.” As a retrospective prognostic study, this paper provides Level II evidence that vertebral augmentation can be safely performed in most adults with NVF with erosion of posterior vertebral wall using the techniques described, but caution should be exercised. For appropriate patients, pretreatment with radiation/ablation is appropriate.

In a retrospective study, Molloy et al2 compared balloon kyphoplasty outcomes in patients with cancer-related vertebral compression fractures with posterior vertebral body wall defect (n=112) versus those without posterior vertebral body wall involvement (n=46). The authors concluded, “<balloon kyphoplasty> [AY1] [CCHM2] can alleviate pain and improve <quality of life> and function in patients with cancer-related <vertebral compression fractures> with <posterior vertebral body wall> defects with no appreciable increase in risk.” As a retrospective prognostic study, this paper provides Level II evidence that vertebral augmentation is a safe and effective procedure using the techniques described for adults with metastatic vertebral fractures who also have posterior vertebral body wall (PVBW) defect with a leakage rate of 31% compared to a 20% leakage rate in those patients without a PVBW defect.

In a retrospective case control study, Hentschel et al3 observed 53 patients with cancer vertebral body fracture who underwent vertebral augmentation, 17 of whom may have had contraindications according to previous literature. They found complications in these 17 patients, but concluded that the procedure was nevertheless safe and effective. This paper provides Level III evidence that adults with NVF may benefit from VA even with potential contraindications to the procedure and that the procedure has a reasonably low rate of cement extravasation using the techniques described in the article.

In a retrospective study, Tancioni et al4 evaluated 11 patients with multiple myeloma with painful vertebral body fractures who underwent vertebroplasty. The authors concluded, “vertebroplasty is a safe and efficient procedure in the treatment of painful vertebral body fractures in patients with multiple myeloma, without potential contraindications, such as fractures of the posterior wall or epidural disease.” The work group downgraded this potential Level II prognostic paper due to small sample size. This paper provides Level III evidence that vertebroplasty may be safe in patients with myeloma and posterior vertebral wall violation or epidural disease as the incidence of leakage is low and most are asymptomatic.

References:

Vertebral augmentation is suggested for the treatment of neoplastic vertebral fractures from multiple myeloma.

Grade of Recommendation: B

In a retrospective study, Huber et al1 examined post-kyphoplasty complications in 76 patients with multiple myeloma. The authors concluded, “By careful interdisciplinary indication setting and a standardized treatment model, kyphoplasty presents a very safe and effective procedure for the treatment of vertebral osteolyses and fractures caused by MM.” As a retrospective prognostic study, the work group concluded that this paper provides Level II evidence that kyphoplasty is a safe and effective procedure for the treatment of vertebral fractures caused by multiple myeloma.

In a retrospective study, Tancioni et al2 evaluated 11 patients with multiple myeloma with painful vertebral body fractures who underwent vertebroplasty. The authors concluded, “Vertebroplasty is a safe and efficient procedure in the treatment of painful vertebral body fractures in patients with multiple myeloma, without potential contraindications, such as fractures of the posterior wall or epidural disease.” The work group downgraded this potential Level II paper due to small sample size. This paper provides Level III evidence that vertebroplasty may be safe in patients with myeloma and posterior vertebral wall violation or epidural disease as the incidence of leakage is low and most are asymptomatic.

References:

There is insufficient evidence to make a recommendation for or against the transoral approach in malignant C2 lesions for vertebral augmentation as a palliative procedure for adults with neoplastic vertebral fractures.

Grade of Recommendation: I

In a prospective study, Anselmetti et al1 analyzed the results of transoral vertebroplasty in 25 patients with malignant painful osteolytic lesions of C2. The authors concluded that, “transoral vertebroplasty is safe, effective, and long-lasting in the treatment of cervical pain resulting from malignant involvement of C2.” This paper provides Level IV evidence that location of the neoplastic fracture in odontoid process is not necessarily a contraindication to augmentation procedure. On the contrary, transoral vertebroplasty is reported to be safe and have good outcomes.

References:

Anselmetti GC, Manca A, Montemurro F, et al. Vertebroplasty using transoral approach in painful malignant involvement of the second cervical vertebra (C2): a single-institution series of 25 patients. Pain Physician. 2012;15(1):35-42. FILE-ALT

FLASK Future Directions for Research

The work group recommends further high-quality studies analyzing specific clinical and radiological criteria to determine eligibility for augmentation procedures.

Interventional Treatment Question 2: How do interventional treatments (augmentation, thermal ablation, radiofrequency ablation, and cryoablation) compare to medical treatments in reducing severity and duration of pain and disability in patients with neoplastic vertebral fractures?

A systematic review of the literature yielded no studies to adequately address the thermal ablation, cryoablation, and radiofrequency ablation components of this question.

Vertebral augmentation is recommended for the improvement of pain and functional outcomes in the treatment of neoplastic vertebral fractures.

Grade of Recommendation: A

Berenson et al1 conducted a multicenter randomized controlled trial to evaluate outcomes of patients with 1-3 painful neoplastic vertebral fractures, comparing patients (n=65) who underwent kyphoplasty versus patients (n=52) who received medical management. The authors concluded, “for painful VCFs in patients with cancer, kyphoplasty is an effective and safe treatment that rapidly reduces pain and improves function.” This paper provides Level I evidence that balloon kyphoplasty improves functional outcomes at 1 month in comparison to medical treatment for neoplastic compression fractures. Although the work group did not downgrade the level of evidence of this paper, they noted that there was significant industry funding, no masking of reviewers, and a high rate of attrition for the 12-month follow-up.

In a prospective randomized control trial study, Yang et al2 evaluated the effect of combined percutaneous vertebroplasty and chemotherapy treatment (n=38) compared to chemotherapy alone (n=38) in patients with multiple-myeloma-associated vertebral fracture. The authors concluded, “Percutaneous vertebroplasty had the characteristics of minimal trauma, easy operation and less complication…(and) can achieve long term analgesic effect, and enhance the spinal stability.” This paper provides Level I evidence that percutaneous vertebroplasty offers better pain relief and functional outcomes than chemotherapy only for neoplastic vertebral fracture that is sustained long term (12 months).

In a retrospective comparative study, Malhotra et al3 compared the outcomes of patients with spinal myeloma treated with balloon kyphoplasty (n=84) versus a thoracolumbar-sacral orthosis (n=99). The authors concluded, “Vertebral augmentation and thoracolumbar bracing improve patient reported outcome scores in patients with spinal myeloma. However, delay in treatment negatively impacts clinical outcome, particularly if managed non-operatively.” This paper provides Level III evidence that more aggressive treatment with balloon kyphoplasty and TLSO in adults with vertebral body fractures secondary to multiple myeloma provided better outcome measure improvement compared to TLSO management alone in adults with less pain or lower SINS scores.

References

FLASK Future Directions for Research

The work group recommends further high-quality studies to determine which patients would benefit most from ablative techniques in adults with neoplastic vertebral body fractures.

Interventional Treatment Question 3: Are there specific characteristics of the fracture or the patient that influence outcomes in patients with neoplastic vertebral fractures undergoing vertebral augmentation?

Vertebral augmentation is suggested to be a safe treatment option with low rate of clinical complications in neoplastic vertebral fractures with cortical wall defects.

Grade of Recommendation: B

In a retrospective case series study, Molloy et al1 compared balloon kyphoplasty outcomes in patients with cancer-related vertebral compression fractures with posterior vertebral body wall involvement (n=112) versus those without posterior vertebral body wall involvement (n=46). The authors concluded that balloon kyphoplasty “can alleviate pain and improve quality of life and function in patients with cancer-related vertebral compression fractures with posterior vertebral body wall defects with no appreciable increase in risk.” This paper provides Level II evidence that balloon kyphoplasty is a safe and effective procedure using the techniques described for adults with neoplastic vertebral fractures who also have posterior vertebral body wall (PVBW) defect with a leakage rate of 31% compared to a 20% leakage rate in those pts without a PVBW defect.

In a retrospective comparative study, Yao et al2 analyzed the risk factors by comparing bone cement leakage rates in patients with vertebral compression fractures caused by multiple myeloma (n=33) or osteoporosis (n=48) treated with percutaneous kyphoplasty. The authors concluded, “compared with osteoporosis, percutaneous kyphoplasty treatment of vertebral compression fractures caused by multiple myeloma is more prone to lead to bone cement leakage.” This paper provides Level II evidence that cortical bone destruction of the vertebral wall in multiple myeloma may predispose to cement leakage after augmentation with no neurological symptoms reported.

In a retrospective case series study, Delpla et al3 evaluated 100 patients who received preventive vertebroplasty for risk of pathological fractures. Of the 215 vertebral metastases studied, 138 were treated and 77 were untreated, resulting in 9 and 16 pathological fractures at the end of follow-up (3.1 years +/- 1.1). The authors concluded, “preventive vertebroplasty is long-term effective for consolidation of vertebral metastases and must be discussed at the early diagnosed. Quality of cement injection matters, suggesting that techniques that improve the quantity and the quality of cement diffusion into the VM must be developed.” This paper provides Level II evidence that SINS score and quality of vertebral filling may affect the risk of fracture after preventive vertebroplasty for NVF.

In a retrospective study, Cianfori et al4 assessed the complications of vertebral augmentation in 48 patients with cortical erosion of the posterior wall undergoing vertebral augmentation for pain palliation and/or stabilization of neoplastic vertebral body lesions. Seventy consecutive levels with cortical erosion of the posterior wall were evaluated. The authors concluded that the “data seem to justify use of vertebral augmentation in patients with intractable pain or those at risk for vertebral collapse.” As a retrospective prognostic study, this paper provides Level II evidence that vertebral augmentation can be safely performed in most adults with NVF with erosion of posterior vertebral wall using the techniques described, but caution should be exercised. For appropriate patients, pre-treatment with radiation/ablation is appropriate.

In a retrospective case control study, Hentschel et al5 observed 53 patients with cancer vertebral body fracture who underwent vertebral augmentation, 17 of whom may have had contraindications according to previous literature. They found complications in these 17 patients, but concluded that the procedure was nevertheless safe and effective. This paper provides Level III evidence that adults with NVF may benefit from VA even with potential contraindications to the procedure and that the procedure has a reasonably low rate of cement extravasation using the techniques described in the article.

References

There is insufficient evidence to make a recommendation for or against the relationship between increasing age and a favorable response to treatment of neoplastic vertebral fractures with vertebral augmentation.

Grade of Recommendation: I

In a retrospective case control study, Jha et al1 reviewed the efficacy of vertebral augmentation in 147 patients with cancer. The authors concluded, “vertebral augmentation provides pain relief for a majority of all compression fractures (osteoporotic and malignant) and metastatic compression fractures. Increasing age may be predictive of pain relief outcomes in metastatic compression fractures. There are special planning, imaging, and technical considerations (eg, needle placement) in using vertebral augmentation to treat cancer patients.” This paper provides Level III evidence that older patients with NVFs undergoing vertebroplasty or kyphoplasty may have a better outcome compared to younger patients with NVFs.

In a retrospective study, Hirsch et al2 evaluated 201 patients with malignant compression fractures who underwent at least one vertebral augmentation (vertebroplasty or kyphoplasty) procedure to identify variables that could influence outcomes. The authors concluded, “In patients who receive both external beam radiation therapy and vertebral augmentation, the sequence in which they are given does not affect pain improvement outcomes.” The work group downgraded this potential Level III paper due to follow-up not being standardized and the diagnostic methods were not described. This paper provides Level IV evidence that in patients with neoplastic vertebral fractures, combination treatment of vertebral augmentation and external beam radiation therapy (EBRT) shows a trend towards positive response with advance age, that is not statistically significant.

References

1. Jha RM, Hirsch AE, Yoo AJ, Ozonoff A, Growney M, Hirsch JA. Palliation of compression fractures in cancer patients by vertebral augmentation: a retrospective analysis. J Neurointerv Surg. 2010;2(3):221-228. doi:10.1136/jnis.2010.002675. FILE-ALT

2. Hirsch AE, Jha RM, Yoo AJ, et al. The use of vertebral augmentation and external beam radiation therapy in the multimodal management of malignant vertebral compression fractures. Pain Physician. 2011;14(5):447-458. doi:10.36076/ppj.2011/14/447. FILE-ALT

FLASK Future Directions for Research

The work group recommends further high-quality studies to determine predictive factors that influence results of vertebral augmentation in patients with neoplastic vertebral fractures.

Interventional Treatment Question 4: What is the risk of treating multiple vertebral levels at one time, for patients with multilevel neoplastic vertebral fractures?

Vertebral augmentation may be considered as a safe treatment of multilevel neoplastic vertebral fractures at one time.

Grade of Recommendation: C

In a retrospective case series study, La Maida et al1 assessed the rate and type of cement leakage after vertebroplasty and kyphoplasty in 14 patients with multiple myeloma vertebral fractures. The authors concluded, “kyphoplasty procedure in these patients is slightly less risky but we suggest doing it with a monopedicular approach.” The work group concluded that this paper provides Level IV evidence that multilevel augmentation has higher risk of cement leakage compared to single level in patients with NVF; however, those were asymptomatic.

In a retrospective case series study, Moulin et al2 evaluated the “safety and efficacy of multilevel thoracolumbar vertebroplasty in the simultaneous treatment of >/=6 painful pathologic compression fractures.” The authors concluded, “Multilevel vertebroplasty for >/=6 pathologic compression fractures is safe and provides significant palliative benefit when performed simultaneously.” The work group concluded that this paper provides Level IV evidence that multi-level vertebroplasty is safe for treatment of neoplastic vertebral fractures with low incidence of complications.

References

FLASK Future Directions for Research

The work group recommends any future studies discussing cement leakage should specify symptomatic vs asymptomatic and should be stratified according to single vs multiple level and tumor type.

Interventional Treatment Question 5: What is the incidence and risk factors for adjacent vertebral body fractures after vertebral augmentation for neoplastic vertebral fractures?

There is insufficient and conflicting evidence to make a recommendation for or against the incidence and risk factors for adjacent vertebral fractures after vertebral augmentation for neoplastic vertebral fractures.

Grade of Recommendation: I

In a retrospective case series study, Kircelli et al1 investigated the clinical results of balloon kyphoplasty for the correction of vertebral deformity from metastatic vertebral compression fractures. The authors concluded that “Balloon kyphoplasty was an effective method to reduce pain, reduce disability, and improve quality of life by eliminating kyphotic deformity in pathological vertebral compression fractures due to vertebral metastases.” This paper provides Level IV evidence that 15.2% of patients with neoplastic vertebral fractures undergoing balloon KP may develop a fracture at an adjacent level.

In a retrospective case series study, Tseng et al2 assessed whether the pain that was induced by spine metastatic tumor was different in spinal metastatic patients before and after vertebroplasty. The authors concluded that “As a treatment option for patients with malignant destruction of the vertebral column, this minimal invasive technique is emerging as one of the most promising new interventional procedures for relieving (or reducing) pain and improving stability.” This paper provides Level IV evidence that adjacent level fracture is an uncommon complication following VP for neoplastic vertebral fractures.

References

FLASK Future Directions for Research

The work group recommends high-quality prospective and longitudinal studies to evaluate the incidence and risk factors for adjacent vertebral body fractures after vertebral augmentation for neoplastic vertebral fractures.

Interventional Treatment Question 6: Does the addition of vertebral augmentation to radiation therapy improve outcomes in patients with neoplastic vertebral fractures?

There is insufficient evidence to make a recommendation for or against the addition of vertebral augmentation to radiation therapy as it relates to outcomes in adults with neoplastic vertebral fractures.

Grade of Recommendation: I

In a prospective case series study, Wardak et al1 aimed to determine neoplastic vertebral fracture pain response and prevention after single-fraction stereotactic ablative radiation therapy (SABR), done conjointly with immediate vertebroplasty, for spine metastases. The authors concluded that “The combined treatment approach was found to be safe and effective after refinement of the vertebroplasty technique.” This paper provides Level IV evidence that the addition of prophylactic VP with spine SABR can improve pain response when compared to historical treatment with EBRT.

References

Wardak Z, Bland R, Ahn C, et al. A Phase 2 Clinical Trial of SABR Followed by Immediate Vertebroplasty for Spine Metastases. Int J Radiat Oncol Biol Phys. 2019;104(1):83-89. doi:10.1016/j.ijrobp.2019.01.072.

FLASK Future Directions for Research

The work group recommends high-quality comparative studies of vertebral augmentation alone to vertebral augmentation with radiation therapy to compare functional improvement and improvements in longevity.

Interventional Treatment Question 7: Does the prophylactic use of vertebral augmentation reduce the risk of vertebral fracture after stereotactic radiotherapy for vertebral metastasis?

A systematic review of the literature yielded no studies to adequately address this question.

FLASK Future Directions for Research

The construction of this question does not provide for a good experimental study. Therefore, the work group does not have any recommendations for future research on this topic.

Interventional Treatment Question 8: Does physical therapy after augmentation affect patient outcomes, including pain and function?

A systematic review of the literature yielded no studies to adequately address this question.

FLASK Future Directions for Research

The work group recommends high-quality studies exploring the role of physical therapy after augmentation in patients with neoplastic vertebral fractures.