32 Vertebro/Kyphoplasty for Metastatic Spine Fractures

Justin E. Costello and Troy A. Hutchins

Abstract

The management of spinal osseous metastatic disease requires a multidisciplinary approach. For painful uncomplicated osseous metastases to the spine, radiation therapy remains the treatment of choice for palliative treatment. However, there are limitations and potential complications of radiation therapy. Pain relief from external beam radiation is often a delayed response. ¹ Also, patients who receive radiation therapy to a preexisting pathologic fracture or vertebral segment that has had prior radiation are at higher risk for developing a new compression fracture at that level. ² Newer ablative radiation therapy techniques (stereotactic body radiation therapy) are also associated with a higher risk of subsequent vertebral compression fracture. ³ In selected patients with osseous metastatic disease, percutaneous vertebral augmentation (PVA), with or without adjunctive tumor control interventions, may be an appropriate treatment choice and can offer advantages compared to radiation therapy alone. Therefore, it is important for the neurointer-ventionalist to understand the current literature regarding the use of PVA for treatment of pathologic compression fractures, as well as its limitations and potential complications.

Key words

vertebroplasty – kyphoplasty – spine radiofrequency ablation – spinal metastases – multiple myeloma

32 Vertebro/Kyphoplasty for Metastatic Spine Fractures

32.1 Goals

Review the literature regarding the basic understanding of percutaneous vertebral augmentation (PVA) for metastatic lesions, emphasizing indications, contraindications, and potential complications.
Critically analyze the literature regarding the efficacy of PVA for spinal osseous metastases.
Understand when PVA is most appropriate in the setting of painful vertebral metastases.
Review current literature regarding use of PVA combined with radiation therapy or radiofrequency ablation (RFA).
Review the current literature pertaining to PVA for high-risk patients.

32.2 Case Example

32.2.1 History of Present Illness

A 62-year-old Caucasian male is referred for evaluation of a new painful LI compression fracture. He has a history of multiple osseous metastases in the setting of advanced renal cell carcinoma, diagnosed a few years prior. He has received previous palliative external beam radiation to the lumber spine. The patient has been pain-free until 2 weeks prior, when he experienced sudden lower back pain while bending forward. Subsequent lumbar spine imaging revealed a new LI compression fracture. His pain was rated as 8 out of 10 in severity and interfered with his activities of daily living. The patient attempted conservative therapy, including bracing and opioids, without relief of symptoms. He denies any lower extremity radicular symptoms, weakness, or saddle anesthesia.

Past medical history: COPD, knee osteoarthritis. No history of bleeding disorders.

Past surgical history: Bilateral total knee replacement.

Family history: Noncontributory.

Social history: Quit smoking 15 years prior; 10 pack/year smoking history.

Review of systems: As per the above.

Neurological examination: The patient is focally tender to palpation over the midline lower back, near the LI level. Otherwise, unremarkable.

Imaging studies: See Fig. 32.1a-d. In this figure, sagittal computed tomography (CT) and sagittal Tl, T2, and short tau inversion recovery (STIR) magnetic resonance (MR) images of the lumbar spine demonstrate an LI compression fracture with 60% vertebral body height loss and an underlying osteolytic lesion on CT. High signal is seen on STIR images, consistent with acute marrow edema. There is no retropulsed fragmentation or vertebral cortical destruction. There are mild degenerative changes of the lumbar spine without evidence of high-grade spinal canal stenosis or nerve root impingement.

32.2.2 Treatment Plan

After review of potential risks and benefits, the patient elected to undergo treatment of the LI compression with PVA and RFA. The LI vertebral body was accessed via left unipediculate approach (Fig. 32.2a, b). An RFA probe was then advanced into the LI vertebral body and RFA was performed (Fig. 32.2c). The RFA probe was removed and replaced with a vertebroplasty needle. Subsequent injection of polymethylmethacrylate (PMMA) shows adequate filling of the LI vertebral body without evidence of cement leak (Fig. 32.2d).

32.2.3 Follow-up

The patient did well after the LI vertebroplasty and RFA procedure. He reported an immediate decrease in pain following treatment. Follow-up MR imaging 6 months after the procedure reveals no progression of the LI fracture or tumor progression. The patient remained without lower back pain at time of the 6-month follow-up examination.

32.3 Case Summary

What are the key indications and contraindications that should be assessed in this patient prior to performing PVA?
1. Osteolytic vertebral lesion:
  
  In the setting of osseous metastatic disease, CT is an important imaging modality for patient preassessment. CT should demonstrate an osteolytic vertebral lesion, ⁴ typically with associated vertebral height loss. The vertebral cortex should also be evaluated for evidence of cortical destruction or fracture instability. MRI is additionally recommended as part of the patient preassessment. ⁵ Vertebral marrow edema on STIR sequences (Fig. 32.1c) indicates that the compression fracture is acute and MRI may better delineate epidural or foraminal tumor extension. Comparison with prior imaging is also important to help determine fracture acuity.
2. Pain must be attributed to the osteolytic vertebral fracture:
  
  As described in the previous chapter, patient selection is essential. ⁵ ^, ⁶ ^, ⁷ Patients with metastatic disease may have back pain from multiple sources and physical examination should localize symptoms to the vertebral treatment level.
  
  Pain levels should be severe enough to impair activities of daily living and new radicular symptoms should not be present. Pain severity score, impact on activities of daily living, clinical examination, and failed conservative management should be documented prior to treatment.
3. Absolute contraindications:
  
  Absolute contraindications for PVA include irreversible coagulopathy, allergy to cement or contrast agent, and active infection, including local cellulitis, discitis-osteomy-elitis, epidural abscess, or systemic infection. ⁴ PVA should be postponed in patients with a fever or suspected sepsis.
4. Relative contraindications:
  
  Advanced vertebral collapse is a relative contraindication to PVA. ⁴ At least 25% vertebral height is usually required to safely perform PVA. Purely osteoblastic lesions are also a relative contraindication, due to limitations in vertebral access and cement distribution within the vertebral body. Vertebral lesions with posterior cortex breakthrough, unstable fractures, and fractures causing neurologic symptoms should generally not be treated with PVA. ⁴ However, with highly skilled neurointerventionalists, these are not considered absolute contraindications (see section below regarding high-risk patients). Finally, patients who are unable to lie prone are usually not candidates for PVA.

What are the most common complications of vertebral augmentation in the setting of osseous metastases?

The overall complication rate is higher with PVA for metastatic compression fractures compared to osteoporotic compression fractures, estimated at approximately 10% (1-3% with osteoporotic compression fractures). ⁸ This increase in morbidity may be related to destruction of the vertebral body or medical condition of the cancer patient; however, most of these complications are minor or transient. ⁵
1. Cement leakage:
  
  As with osteoporotic vertebral compression fractures (VCFs), cement leakage is the most common complication following PVA for metastatic VCFs. ⁹ Similarly, the majority of cement leaks are of no clinical significance, including disc cement leaks, which, although controversial, ¹⁰ ^, ¹¹ ^, ¹² ^, ¹³ have been recently shown to not increase risk for adjacent-level vertebral fractures. ¹⁴
  
  Cement leaks can also occur in the epidural space, neural foramina, paravertebral veins, or vertebral venous plexus, where there is a higher incidence of clinically relevant complications. The overall rate of symptomatic neurologic compromise following PVA for metastatic compression fracture is < 2%, ⁴ and potentially higher in patients with vertebral cortical destruction. To minimize this risk, bone cement filling must be performed slowly and carefully monitored with real-time fluoroscopy. If foraminal cement material is encountered in the polymerization phase, targeted foraminal saline injection may be of benefit to prevent radiculopathy secondary to heating. ¹⁵ Cement pulmonary embolism is common following PVA, occurring in 3.5 to 23% of osteoporotic VCFs, ¹⁶ with theoretical higher incidence with metastatic compression fractures due to tumor vascularity. The majority of cement pulmonary emboli are incidentally discovered on follow-up chest imaging and asymptomatic. No specific treatment is recommended for these patients, other than clinical follow-up. ¹⁶ Less than 1% of cement pulmonary emboli will be central or symptomatic (Fig. 32.3c). ⁷ ^, ¹⁶ In these patients, therapy is recommended according to current thrombotic pulmonary embolism treatment guidelines. ¹⁶
2. Other complications:
  
  Other potential complications are reported to occur at <1%, including infection, significant hemorrhage, allergic reaction, fracture, symptomatic hemothorax or pneumothorax, and death. ⁴ During PVA, intravenous antibiotic prophylaxis is recommended for immunocompromised patients; however, there is no consensus for antibiotic administration in immunocompetent patients. ¹

Under fluoroscopic guidance, how should the vertebral body be accessed for injection ofPMMA cement material in this patient?

In this patient, the best method for vertebral access is by transpedicular approach (Fig. 32.4a). Transpedicular access allows for the easiest recognition of anatomic landmarks and reduces the risk of nerve injury or cement leak. ⁵ ^, ⁸ Often this is performed by bilateral transpedicular access; however, Kim et al ¹⁷ have demonstrated similar efficacy and safety using a unipediculate approach. If the pedicle is infiltrated with tumor or is too small, parapedicular or posterolateral approaches (Fig. 32.4b-c) can be used, though these may be associated with higher risk of paraspinous hematoma, pneumothorax, or foraminal cement leak. ⁵ Also, in the cervical spine, an anterolateral approach is used to avoid injury to the carotid or jugular vasculature.

What is the difference between kyphoplasty and vertebro-plasty techniques, and does one confer benefits over the other in this patient?

Both vertebroplasty and kyphoplasty involve similar percutaneous vertebral access using trocar systems; however, in kyphoplasty, balloon-assisted cavities are created prior to cement injection. Clinical outcomes are similar for patients treated with vertebroplasty or kyphoplasty. A recent systematic review by Sadeghi-Naini et al ¹⁸ concluded that there were no clear benefits of vertebroplasty versus kyphoplasty in the setting of metastatic vertebral lesions; thus, treatment method is typically based upon operator experience and preference. Several studies have reported improved vertebral height restoration using kyphoplasty (versus vertebroplasty) ¹⁹ ^, ²⁰ ^, ²¹ ; however, this has not been shown to be clinically significant. Prior literature also mentions the need for general anesthesia when performing kyphoplasty, but these procedures are routinely performed with local anesthetic and conscious sedation. ⁸

Based on prior literature, is PVA effective for pain control in patients with a pathologic compression fracture?

Vertebroplasty and kyphoplasty have been shown to rapidly alleviate pain secondary to VCFs with underlying osseous metastatic disease. ⁹ The body of evidence for PVA treatment of pathologic compression fractures is mostly based upon observational studies. Numerous single-arm prospective and retrospective studies have demonstrated decreased pain intensity from baseline following either vertebroplasty or kyphoplasty for compression fractures related to multiple myeloma or other metastatic cancers. ²² ^, ²³ ^, ²⁴ ^, ²⁵ ^, ²⁶ ^, ²⁷ ^, ²⁸ ^, ²⁹ ^, ³⁰ ^, ³¹ ^, ³² ^, ³³ ^, ³⁴ A statistically significant decrease in pain severity has been reported in 70 to 92% of patients, ⁴ with pain severity assessed at 12 hours up to 3 years following PVA ²² ^, ²³ ^, ²⁴ ^, ²⁵ ^, ²⁶ ^, ²⁷ ^, ²⁸ ^, ²⁹ ^, ³⁰ ^, ³¹ ^, ³² ^, ³³ ^, ³⁴ ^, ³⁵ ^, ³⁶

A multicenter randomized controlled trial was published by Berenson et al ³⁵ in 2011. In this study, there was a statistically significant reduction in pain severity scores in patients who received kyphoplasty compared to nonsurgical management of painful VCFs due to underlying metastatic disease. Similar results were reported in a smaller randomized controlled trial by Yang et al ³⁶ in 2012 assessing vertebroplasty for painful multiple myeloma metastases, with pain relief lasting up to 3 years in the PVA treatment group.

Does the current literature support combined treatment approaches with vertebral augmentation?

Local tumor control is an important consideration in patients presenting with a VCF secondary to osseous metastatic disease. Most commonly, this is achieved through radiation therapy and/or systemic chemotherapy. Other methods for local tumor control are also available, including percutaneous RFA.
1. PVA and radiation therapy:
  
  Studies assessing the use of PVA and palliative external beam radiation therapy (EBRT) are limited. To date, there are no randomized controlled trials assessing the combined efficacy or optimal timing of EBRT with PVA. Should EBRT be performed before or after PVA? What time interval is ideal for EBRT before or following PVA? The current data behind these questions is unclear at this time. In a retrospective cohort study by Kasperk et al, ³⁷ pain intensity scores at 1-month and 1-year follow-ups were similar for patients treated with PVA or palliative EBRT in the setting of painful multiple myeloma compression fractures. In addition, both PVA and EBRT were significantly better at pain control compared to systemic chemotherapy alone. Another prospective study by Qian et al ³⁸ demonstrated rapid and sustained (24-hour and up to 2-year follow-up assessment) decrease in pain intensity scores with kyphoplasty followed by EBRT (external radiation was performed 1-2 weeks after kyphoplasty).
  
  Stereotactic body radiation therapy (SBRT) involves multiple radiation beams at different angles and delivers ablative radiation doses to the tumor. SBRT to the spine is associated with higher risk of VCF following treatment, with reported risk of 0.7 to 40.5%. ³⁹ In a recent systematic review, the overall risk of VCF following SBRT was estimated to be approximately 14%. ³ This systematic review also determined risk factors for VCF following SBRT, including tumor size, osteolytic disease, and preexisting compression deformity. ³ In a retrospective study by Gerszten et al, ⁴⁰ kyphoplasty performed prior to SBRT was found to be effective in patients with preexisting VCFs. However, this treatment strategy has not become common practice and no further studies have assessed the efficacy of PVA prior to spinal SBRT.
  
  In recent consensus guidelines by the American Society of Therapeutic Radiology and Oncology (ASTRO), ⁴¹ ^, ⁴² kyphoplasty and vertebroplasty are recognized as potentially useful treatments for osteolytic metastases. However, ASTRO emphasizes that PVA does not obviate the need for external beam radiation. They also suggest that additional prospective trials are needed to better define patients who would benefit from treatment with PVA, and if so, how those procedures should be best sequenced with EBRT.
2. PVA and RFA:
  
  While it is common practice to perform RFA prior to PVA, data to support RFA efficacy are limited. To date, one randomized controlled study has been published with use of PVA and RFA. In this study by Orgera et al, ⁴³ RFA with PVA was shown to be effective and safe, but without additional pain control benefit when compared to PVA alone in the setting of painful multiple myeloma metastases. Local tumor control was not assessed in this study.
  
  Several additional observational studies ⁴⁴ ^, ⁴⁵ ^, ⁴⁶ ^, ⁴⁷ ^, ⁴⁸ have shown that RFA is safe and may be effective for local tumor control in nonmultiple myeloma vertebral metastases; however, this has yet to be validated with a randomized controlled study. Regarding pain control for nonmultiple myeloma metastases, several observational studies have reported excellent reduction in pain scores following RFA; however, these results are obscured by concurrent treatment with PVA.
  
  One current, ongoing multicenter prospective trial, the STAART study, ⁴⁹ has begun to assess the effectiveness of RFA with PVA for the treatment of painful pathologic vertebral fractures in patients who have failed radiation therapy (group 1) or who are radiation naive (group 2). Preliminary results from this study are promising, with nearly 80% of patients demonstrating adequate pain and local tumor control, as well as no major complications related to RFA.
3. Other methods of percutaneous local tumor control: Multiple other adjunctive percutaneous local tumor control therapies are available for use, including microwave ablation, cryoablation, alcohol ablation, laser photocoagulation, radiofrequency ionization, and brachytherapy. In general, these techniques are less commonly used as compared to RFA, and not well assessed in the literature. There have been a few small randomized studies assessing the efficacy of PVA with ¹²⁵I brachytherapy. In their first study, Yang et al ⁵⁰ reported statistically improved pain scores at 6-month follow-up for PVA plus brachytherapy (mean visual analog score [VAS] pain intensity 2.3) versus PVA alone (mean VAS pain intensity 5.4) for treatment of mixed spinal metastases. However, local tumor control was not statistically different between the two groups. In a subsequent study, Yang et al ⁵¹ reported statistically improved pain scores for PVA plus brachytherapy compared to external beam radiation, with interval clinical follow-ups over a 1-year period. Also, the EBRT group did not show a pain response until 1 month after treatment.

In high-risk patients (neurologic symptoms, posterior vertebral wall defect, spinal canal compromise, or cervical compression fractures), is there a role for vertebral augmentation?

Multiple small observational studies have demonstrated that vertebroplasty and kyphoplasty can be safely performed in high-risk patients. In a systematic review published in 2016, ⁹ a review of 14 studies evaluating vertebroplasty for compression fractures with posterior wall defects or spinal canal compromise reported 22 major complications (4.1%). No major complications were reported in 2 small observational studies (45 patients) for kyphoplasty performed for similar indications.

Cervical PVA can also be safely performed; however, it does require modified approaches for vertebral access (anterolateral or transoral). Two observational studies, 1 a multicenter study, reported no major complications following cervical vertebroplasty (97 total patients). ⁹