Targeted Radiofrequency Ablation of Painful Spinal Metastases in Myeloma

Abstract: Metastasis to bone occurs in the majority of cancers, with the thoracolumbar spine being the most common site of metastasis. Metastatic disease to the spine is a common clinical situation that causes significant morbidity, with tumor deposits potentially causing severe, unremitting pain and reduced mobility. Seventy percent of all myeloma patients have bone pain, and the spine is commonly involved with myeloma deposits. Conventional treatment may be associated with significant side effects. Radiotherapy to metastatic deposits in the spine can achieve pain relief, but this effect may take up to 6 weeks to be achieved, and there is a risk of vertebral body collapse at the treated level. Surgical options include corpectomy, spinal fusion, and fixation, with consequent increased morbidity and mortality and a significant associated economic cost. Use of percutaneous tumor ablation in various body sites has increased over the last few decades. Percutaneous ablation aims to cause necrosis of the tumor and a reduction in tumor load. A commonly used technique is radiofrequency ablation (RFA). The challenge with standard RFA in the vertebral body is proximity to the spinal cord; risks include nerve stimulation, thermal spinal cord injury, and dural and thecal tears with fistula formation. Targeted tumor ablation devices (TRFA) with controlled RF pulses have now been developed, allowing access and navigation within the vertebral body. Real-time feedback of RF energy and cavity creation by tumor debulking with simultaneous cement augmentation provides pain relief as well as spinal stability. This review discusses the indications, contraindications, techniques, and use of TRFA in the treatment of painful spinal metastasis.

Key words: spine, bone metastasis, radiofrequency ablation, interventional radiology

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Metastasis to bone occurs in the majority of cancers, with the thoracolumbar spine being the most common site.¹ Seventy percent of all myeloma patients have bone pain and the spine is commonly involved with myeloma deposits. Metastatic disease to the spine is a common clinical situation that causes significant morbidity, with tumor deposits frequently causing severe, unremitting pain and reduced mobility. 

Conventional treatment options are limited and are associated with significant side effects. In addition to analgesics for symptomatic pain relief, the main treatment options include surgical fixation and conventional external beam radiotherapy. Radiotherapy to metastatic deposits in the spine can achieve pain relief but this effect may take up to 6 weeks to be achieved.² There is also a risk of vertebral body collapse at the treated level.³ The post-radiotherapy vertebral body collapse causes further morbidity, and surgical treatment can be challenging. Surgical options include corpectomy, spinal fusion, and fixation. These are major operations with high associated morbidity and mortality. There is a significant cost to these surgical treatments.⁴

There is a need for less invasive procedures to treat metastatic lesions to the spine. Toward this aim, percutaneous spinal augmentation techniques have been utilized.⁵ Harrington proposed the use of vertebroplasty to treat pain in spinal tumors.⁶ The main issues with a vertebroplasty approach is that the volume of cement that can be instilled is limited. Balloon kyphoplasty was a modification that involves the formation of a cavity within the vertebral body, enabling a theoretical increase in vertebral body height and sufficient cement instillation. However, both kyphoplasty and vertebroplasty do not reduce the size of the tumor and therefore do not affect one of the mechanisms of pain production or account for complications of tumor displacement. 

Percutaneous ablation of tumors in various body sites has increased in prevalence over the last few decades.⁷ The aim of percutaneous ablation is to cause necrosis of the tumor and therefore reduce the tumor size. Several different techniques including laser, ultrasound, alcohol instillation, and heat have been used.⁸ The most popular technique currently used is radiofrequency ablation (RFA). 

Rosenthal et al first reported the use of RFA in treating osteoid osteoma.⁹ The technique has been adapted to treat metastatic disease to the spine. Radiofrequency ablation of spinal tumors utilizes high-frequency alternating current to cause coagulative necrosis of the tumor by frictional heating.¹⁰ The necrosis creates a cavity than can then be filled with polymethylmethacrylate (PMMA) cement, which aids stabilization of the vertebra.¹¹ The mechanism of pain relief is controversial, but it is thought to be due to destruction of the periosteal nociceptors.¹² 

The risks with RFA in the vertebral body, in proximity to the spinal cord, range from nerve stimulation to thermal spinal cord injury to dural and thecal tears with fistula formation. Pleural, peritoneal, vascular, and visceral damage may also occur dependent on the site of intervention. Targeted tumor ablation devices (TRFA) have been developed, allowing access and navigation within the vertebral body with real time feedback of the RF energy and cavity creation by tumor debulking. Instillation of sufficient volumes of high-viscosity cement into cavities overcomes the displacement of tumor. At the same time, it allows biomechanical augmentation of the vertebra. 

INDICATIONS

Metastatic disease to the vertebral column typically presents with severe unremitting pain that is worse with straining and movement. The tumor deposits may also alter the biomechanics of the vertebral column, resulting in an increased risk of vertebral collapse.¹³ Vertebral body collapse can result in sudden worsening of pain as well as the more devastating complication of metastatic spinal cord compression. Patients with severe pain or a localized tumor burden within the vertebral bodies should be considered for RFA.

Pain Relief

The pain related to metastatic deposits to the spine is thought to arise from two different mechanisms. First, the tumor stimulates nociceptors in the periosteum of the vertebra.¹² Second, the tumor produces cytokines that upregulate osteoclastic activity and stimulate pain.¹⁴ The consequences of pain can lead to depression and reduced mobility.¹⁵ The analgesics used to treat pain have their own side effects. Opiates may cause drowsiness and increasing tolerance and nonsteroidal anti-inflammatories may cause gastrointestinal ulceration and renal damage that can be the source of more morbidity. Therefore, reducing pain will reduce the secondary effects of pain and the side effects of analgesic medications.

Stability of the Vertebrae

The presence of tumor within a vertebra weakens the bone by several mechanisms. The tumor produces cytokines and induces cytokine production within the bone that stimulates osteoclastic activity and inhibits osteoblastic activity.¹⁴ The net effect is to reduce bone quality. The second mechanism is the disruption of the normal bone trabeculae and the reduction of the bone matrix, further weakening the bone. The location of the metastatic deposits within the vertebra is important. Lesions found in the anterior third of the vertebral body weaken the vertebra proportionately greater than those found in the posterior third, due to greater craniocaudal loading forces in the anterior third of the vertebra.^16,17 This can lead to weakening and collapse of the vertebra after successful radiotherapy in patients with particularly radiosensitive tumors, such as plasmacytomas and myeloma deposits.

Local Tumor Control

Continued growth of metastatic deposits within a vertebral body can cause local mass effect on adjacent structures such as the cord, nerve roots, and blood vessels. Ablation and debulking of the metastatic tumor can reduce tumor growth.¹⁸ This is particularly important in patients with radiotherapy-resistant tumors. 

AIM OF RADIOFREQUENCY ABLATION PROCEDURE 

Radiofrequency ablation causes coagulative necrosis of metastatic lesions, which results in a reduction in the size of the tumor and the formation of a cavity within the tumor.¹⁹ This may allow an adequate amount of PMMA cement to be instilled into the cavity without clinically significant displacement of the tumor mass. The placement of the cement aids restoration of the biomechanics of the spinal column with a potential reduction in the risk of vertebral body collapse. Radiofrequency ablation of the metastatic lesions has been shown to achieve pain relief within hours of the procedure.²⁰

TECHNICAL ASPECTS OF RADIOFREQUENCY ABLATION PROCEDURES

Preprocedure

Preoperative magnetic resonance imaging of the spine is used to assess the number, size, and location of each metastatic lesion (Figure 1). Each involved vertebra is considered in turn. A plan is made for the direction of insertion of the vertebroplasty cannula. The ablation zones for each vertebra are then planned prior to the procedure. 

There are many bipolar RF devices available on the market, including Coblator (Smith & Nephew), OsteoCool RF Ablation (Medtronic), and STAR Tumor Ablation System (Merit Medical). For the purposes of this review, we describe a general RFA technique. Two different electrode dimensions may be used: a 5 mm/10 mm ablation zone 20 mm in length and two-thirds in height and a 10 mm/15 mm electrode giving a 30 mm length and two-thirds height ablation zone. Full ablation is achieved when the proximal thermocouple reaches 50° C (Figure 2).

Procedure 

Standard technique

Sedation and anesthesia preprocedure is achieved by intravenous midazolam and fentanyl with continuous vital sign monitoring. The RFA approach is a modification of the standard vertebroplasty technique. The vertebroplasty cannulas are inserted under biplane fluoroscopic guidance via a transpedicular approach (Figure 3). The position and trajectory of the cannulas are checked continuously during the procedure. If the lytic metastasis extends into the pedicle and thus cannot be visualized on the fluoroscopic image, then an extrapedicular approach should be considered. The RFA electrode is passed through the vertebroplasty needle and the ablations performed (Figure 4A and 4B). The electrode incorporates the maneuverability and cutting of a curved midline osteotome and allows creation of a track and positioning to target the vertebral lesion, optimally, independent of the trajectory of the pedicular needle. The RFA device has a central radiolucency which should be positioned in the AP view over the spinous process, thereby lying equidistant within the tumor and the vertebral body. On the lateral B plane, the position of the electrode should be in the center of the tumor as planned on the pre-procedural approach (Figure 4A and 4B). It is imperative that the end-plates and pedicles are square on the A and B plane. This is achieved with excellent biplanar radiographic technique using high or continuous frame rate fluoroscopy. 

The main purpose is to produce a predictable ablation zone that is 3:2 length by width. The maneuverable electrode allows ablation of tumor deposits that lie close to the posterior vertebral body cortex, particularly those in the midline, in which treatment was contraindicated in the past, using the nonmaneuverable electrode systems. The RFA is undertaken using a MetaSTAR RF generator (DFINE, Inc.) (Figure 5).

After the insertion of the vertebroplasty needle, a targetable osteotome is passed through to make additional channels within the vertebral bone and tumor. This procedure is particularly required if the metastasis is sclerotic. In addition, a bone drill can be used to create a channel when the bone is sclerotic or compacted due to vertebral plana (Figure 6). This allows the creation of a channel for the insertion of the maneuverable electrode and prevents the electrode from becoming fixed in compacted or sclerotic bone. The maneuverable electrode is passed through the vertebroplasty needle close to the targeted lesion. 

The RF ablation system consists of a navigational bipolar RF electrode.²¹ The two thermocouples are located 10 mm and 15 mm from the center of the ablation zone. The electrode is an articulated 10g metallic catheter that is navigable within the vertebra to enable metastatic lesions to be targeted. There are 2 thermocouples with proximal and distal elements. This enables the temperature both distally and proximally to be monitored, allowing control over the proximal temperature nearest the dura. Ideal ablations would produce a maximal ablation zone of 3 cm x 2 cm when the proximal temperature is maintained around 50° C and distal temperature reaches 60° C (Figure 7). This allows ablations to be performed with a metastatic lesion close to the posterior vertebral cortex as the extent of the ablation temperature can be accurately controlled.

The RF generator continuously displays the temperature of the proximal and distal thermocouples and has an automatic cut-off for a maximal temperature for each thermocouple. There is also a built-in resistance detector that enables the operator to further control the extent of the ablation. The ablation catheter should be cleaned after each burn as the coagulated tissue may block the thermocouple. An average 4 ablations can be performed on each vertebral level for a complete ablation.²¹ Typically, the consequence of the ablation is an oval burn that creates a cavity, allowing better control and a denser cementoplasty (Figure 4C). The PMMA cement can then be instilled into the cavity with less risk of leakage, as in a balloon kyphoplasty. The imaging appearances of the cement fill are also akin to a kyphoplasty rather than a standard vertebroplasty, with a more confluent and homogenous appearance (Figure 4C). The procedure can be performed during and after radiotherapy cycles, without interruptions of these, as the risk of poor wound healing is significantly less than with open surgical procedures.²¹

Postprocedure Care

The 5 mm skin puncture wounds utilized for cannula access vary in number from 2 to 6 depending on the number of vertebrae treated. These are dressed with steristrips and the patient is sent for a spinal CT scan to assess final cement position and ablation zones. After this is reviewed, the patient is mobilized and discharged in approximately 2 hours following the procedure. A review is performed 1 month following the procedure with a final discharge to the referring physician.

Contraindications

The STAR ablation device is contraindicated for the C1 to C7 levels as the size of the devices and the working cannulae are not designed for use in these vertebrae. Due to potential RF incompatibility, existence of pacemakers and other electrical implanted devices is also considered a contraindication. 

COMPLICATIONS

Specific complications of TRFA are related to thermal damage to neural structures. The heat can damage the nerve roots, cauda equine, and spinal cord. The result can be neuropathic pain or paralysis. Cerebrospinal fluid flow in the thecal sac can provide some protection by dissipating the heat to some degree. Inaccurate placement of the electrode can result in nerve stimulation, if adjacent to the neural foramina. Other complications involve the cement installation, including epidural leakage and extension into the segmental veins and pulmonary arterial tree. Complications are also related to the vertebroplasty technique with trauma of needle placement, including hematoma formation, local pain, thorax (pneumothorax and haemothorax), infection (wound or vertebral osteomyelitis), and perforation of the cord or nerve roots, vessels, or dura. 

CONCLUSION

Targeted RFA and cementoplasty of metastatic disease in the spine is a safe and effective treatment that is an adjunct in the treatment of spinal metastases and myeloma deposits. It has the advantage of achieving rapid pain relief and vertebral body stabilization without the need for open surgery. It does not preclude the use of radiotherapy and is an effective alternative to open surgery in patients with radiotherapy-resistant metastases. The review describes indications, contraindications, and technique in the use of TRFA for spinal metastases.

Editor’s note: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no financial relationships or conflicts of interest regarding the content herein.

Manuscript received June 20, 2016; provisional acceptance given June 15, 2016; manuscript accepted August 8, 2016. 

Address for correspondence: Winston J. Rennie, MSc, FRCR. University Hospitals of Leicester, Leicester Royal Infirmary, Infirmary Square, Leicester LE15WW, United Kingdom. Email: winston.rennie@uhl-tr.nhs.uk.

Suggested citation: Street D, Morlese JF, Shah A, Morgan S, Garg M, Rennie WJ. Targeted radiofrequency ablation of painful spinal metastases in myeloma: review of a novel technique. Intervent Oncol 360. 2016;4(12):E201-E210.

Acknowledgements: Special thanks to Mamta Garg MD, FRCP, FRCPath (Hematology), consultant hematologist, chairman of the multidisciplinary meeting where cases were clinically reviewed and referred.

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