Radiofrequency Tumor Ablation with Vertebroplasty for the Treatment of Spine Metastases

47 Radiofrequency Tumor Ablation with Vertebroplasty for the Treatment of Spine Metastases

Anthony A. Turk and Daniel K. Fahim

Abstract

Radiofrequency tumor ablation, combined with vertebroplasty, is a relatively new tool in the minimally invasive treatment of metastatic disease involving the thoracic and lumbar spine. This percutaneous, outpatient procedure can contribute to local oncological control and provide nearly instantaneous and dramatic pain relief of painful pathological fractures involving the spine secondary to metastatic disease.

Keywords: radiofrequency ablation, metastatic disease, pathological fracture, vertebroplasty

47.1 Introduction to Spine Metastases

The skeleton is the third most common site of tumor metastasis after lung and liver, with the spine most frequently involved. There have been progressively more diagnoses of spine metastases in recent years, primarily due to the development of newer imaging modalities, as well as improvements in systemic treatments. As medical techniques have advanced and patient survival periods have increased, postmortem studies indicate that, depending on the primary cancer, 30 to 90% of patients with terminal cancer have metastatic spinal tumors.¹^,²^,³

Metastatic tumors are estimated to be 20 times more frequent than primary spine tumors.⁴ Although metastatic disease to the spine can occur at any age, it is most common between the ages of 40 and 70. In addition, men are more afflicted by spine metastases⁵^,⁶; however, this may be attributed to the higher incidence of prostate cancer relative to breast cancer (both of which commonly metastasize to the spine). Spine metastases arise in the thoracic region 70% of the time, followed by the lumbar and then cervical spine.⁷^,⁸ Spinal metastases from a tumor can spread via the arterial system, Batson’s venous plexus, cerebrospinal fluid, or direct extension from paraspinous disease. The posterior vertebral body is the initial site of involvement in two-thirds of cases, with the posterior elements being involved typically later and seldom in isolation. Spinal metastases are extradural in 94 to 98% of patients, predominantly arising in the vertebral column and secondarily extending into the epidural space. Intradural metastases are exceedingly rare with only 0.5% occurring in the intradural/intramedullary compartment.⁹^,¹⁰

The most common presentation of metastatic spine tumors is back pain. The pain associated with spine metastases is due to either direct tumor progression and subsequent destruction or biomechanical weakness from bone loss.¹¹ Tumor-related pain is predominantly nocturnal or early morning pain and generally improves with activity throughout the day. It may be caused by inflammatory mediators or tumor stretching the periosteum of the vertebral body.¹² Mechanical pain results from a structural abnormality of the spine, such as a pathologic vertebral compression fracture (VCF) resulting in instability. This pain is movement-related and may be exacerbated by sitting or standing, which increases the axial load on the spine. The incidence of VCF is estimated to be 24, 14, 6, and 8% among patients with multiple myeloma and breast, prostate, and lung cancers, respectively.¹³^,¹⁴ Additionally, most untreated metastatic spine tumors eventually cause neurological deficits at the terminal stage.

It must be understood that VCFs secondary to cancer are much different than osteoporotic fractures. Osteoporotic VCF is a relatively benign condition with spontaneous healing occurring in approximately 33% of patients.¹⁴ The probability of selfhealing is less likely in cancer patients because of the increased rate of bone loss from tumor osteolysis, chemotherapy, steroid treatment, and poor nutrition. It is clear spinal metastases are a significant source of morbidity for an increasingly large number of patients. Early diagnosis and aggressive intervention of spinal metastases are essential to minimize the consequences and maximize patient quality of life.

47.2 Current Treatment Options for Spine Metastases

Current treatment options of spinal metastases are typically palliative rather than curative, with the following goals:

• Relieving pain.

• Preventing development of pathological fractures.

• Retaining mobility.

• Preserving neurological function.

These options include radiotherapy, surgery, chemotherapy, and radiosurgery. The decision-making paradigm for treatment of patients with spine metastases is beyond the scope of this chapter. It is important to note that, thus far, there has been minimal use of percutaneous procedures to treat the actual neoplastic disease, but rather only consequences of the tumor such as utilization of vertebroplasty or kyphoplasty for the treatment of VCFs.

Radiation therapy (RT) is extremely effective in alleviating tumor-associated pain. It is generally the first line of treatment. This is appropriate when the patient has multiple metastatic lesions in the spine, no compromise of the structural integrity of the spine, and no neurological deficits. Mechanical instability pain involving the spine does not respond well to radiation treatment. Radiculopathic pain associated with nerve root compression secondary to a metastatic tumor responds to radiation treatment only if the tumor is radiosensitive and decreases in size in response to radiotherapy. Approximately 90% of patients experience at least minimal relief of tumor-related pain, with 54 to 66% obtaining complete relief.¹¹^,¹⁵ The mechanism of pain relief by RT is still unclear, although it is thought to be related to tumor shrinkage or to depressed cytokine production by inflammatory cells surrounding the tumor cell.¹⁶^,¹⁷

Unfortunately, the benefits of pain relief and tumor control provided by RT are not able to control mechanical pain associated with a fracture. In fact, RT has been shown to increase the risk of developing VCF in some studies.¹⁴ High doses of radiation can damage collagen, which compromises the integrity of bone.¹⁸ At high doses, degradation of the collagen matrix might occur via the breaking of peptide bonds in the collagen backbone.¹⁹ Ultimately, exposure to radiation progressively degrades the strength, ductility, and durability of bone tissue.²⁰ The risk of vertebral body fractures has become even more evident with the increasing use of stereotactic radiosurgery for the treatment of patients with solitary or oligometastatic disease involving the spine.²¹^,²²^,²³^,²⁴^,²⁵

Because pain relief by RT may take weeks and restabilization months, if it occurs at all, less invasive techniques such as kyphoplasty or vertebroplasty are important adjuncts for the treatment of patients with spine metastases who may be experiencing mechanical back pain or have associated VCFs. Percutaneous kyphoplasty is a fluoroscopically guided procedure that, unlike vertebroplasty, involves percutaneous insertion of a balloon that creates a cavity, followed by intravertebral infusion of polymethyl methacrylate (PMMA). An advantage of kyphoplasty and vertebroplasty is they can be used to treat both benign and metastatic lesions. Furthermore, these vertebral augmentation procedures (VAPs) are associated with short surgical times and low morbidity while also providing spine stabilization and immediate pain reduction.²⁶^,²⁷

Despite the variety of treatment options available, approximately one-third of patients remain inadequately relieved. Even analgesic medications may be insufficient or cause adverse reactions.²⁸ In light of this evidence, it is clear there is great need for a superior treatment option. Spinal metastases must be recognized as a complex condition requiring integrated multistep and multidisciplinary care. Therefore, successful cancer treatment should consist of a combination of surgery, chemotherapy, and irradiation. Thermoablative procedures such as radiofrequency ablation (RFA), laser-induced thermotherapy, and cryoablation are established treatment options for soft-tissue tumors. In particular, RFA has received increased attention as an effective, minimally invasive treatment for various benign and malignant tumors. Recent technological advances have allowed this technology to be applied to the spine.²⁹^,³⁰^,³¹

47.2.1 Radiofrequency Ablation

RFA uses thermal energy generated from a high-frequency alternating current to destroy tissue surrounding an electrode, resulting in coagulative necrosis of tissue from high temperatures. This typically involves a percutaneous transpedicular approach to access the affected vertebral body ( Fig. 47.1). Optimal tissue destruction occurs between 50 and 90 °C.³² The radius of the ablation zone is dependent on the tissue temperature and time the tissue is maintained at that temperature. Accurate temperature measurements are vital to ensure proper tumor ablation and also to minimize unintended tissue damage. Thermal destruction of pain-sensitive nerve fibers ceases transmission of pain signals. Tumor cell necrosis has also been implicated in decreasing the cytokine-mediated pain pathways involving interleukins and tumor necrosis factor.³³ RFA also delays tumor progression to the sensitive periosteum.³⁴^,³⁵ The combination of these mechanisms leads to rapid decrease in pain that can provide long-lasting relief.

RFA is a relatively new method for the treatment of spine tumors. It was initially introduced for the treatment of osteoid osteoma²⁹ and then became an important tool in the treatment of metastatic liver, renal, and lung tumors.³⁰^,³⁶^,³⁷^,³⁸ RFA is now approved by the U.S. Food and Drug Administration for the treatment of spinal metastases, which often include unresectable spinal tumors unresponsive to chemotherapy and RT. It has the advantage of being able to destroy a tumor without requiring its removal and can be used in patients who are otherwise poor surgical candidates. RFA can be performed under conscious sedation and local anesthesia and has the advantage of allowing the operator to control the size of the ablation using image guidance.³⁹ Up to 80% of patients reported a decrease in their analgesic medication use at some time during their follow-up period after treatment of painful osteolytic metastases.⁴⁰^,⁴¹

Fig. 47.1 Artist’s depiction of the radiofrequency ablation process. (a) After gaining access into the vertebral body through the pedicle (in this case the left pedicle), the radiofrequency ablation probe is targeted into the vertebral body lesion. (b) Depiction of the ablation beginning (shows as a darker region within the vertebral body lesion). (c) Completion of the ablation to involve the entire metastatic lesion and withdrawal of the radiofrequency probe. (Reproduced with permission from Merit Medical.)

Data show that a clinically and statistically significant reduction in spinal pain is usually achieved within 6 weeks following RFA, which decreases further at 6 months and is maintained at that level for an extended period of time.⁴² RFA is not only effective, but also highly predictable and therefore a feasible technique for destroying tumors adjacent to vulnerable structures. The use of multiple temperature measuring centers allows for real-time measuring of spinal canal temperatures and consequently a more precise ablation zone.⁴³ The use of two active thermocouples is known as bipolar RFA ( Fig. 47.2).

In summary, RFA may prevent or delay tumor progression and the risk for fracture, thereby delaying or preventing the effects of metastases to the spine. Several studies have confirmed it is feasible, safe, and effective for treating neoplastic disease. However, RFA alone does not address the issue of mechanical instability due to bone loss, and therefore should be coupled with a cement augmentation procedure such as vertebroplasty.

47.2.2 Vertebroplasty

Vertebroplasty consists of a radiologically guided percutaneous injection of PMMA (“surgical cement”) into a vertebral body to provide mechanical stability. It can be used to treat benign lesions such as osteoporotic fractures or malignancies such as spine metastases.⁴⁴^,⁴⁵ It is particularly useful to treat VCFs secondary to spine metastases because it provides mechanical stability where bone weakness is a source of severe back pain. Unlike kyphoplasty, vertebroplasty does not use an expandable balloon to create a cavity and restore vertebral height prior to injection of PMMA. However, recent studies found no correlation between restoration of vertebral height and pain relief.⁴⁶ Nonetheless, vertebroplasty has been effective for reducing mechanical pain in the spine.

Vertebroplasty is a particularly attractive option for patients with metastatic disease who are poor surgical candidates, have limited survival, or have recurrent disease and have received maximal spinal RT. One study reported 94% of patients experienced improvement in pain after undergoing the procedure.⁴⁵ The improvement was stable in 73% of patients at 6 months and 65% at 1 year.⁴⁵ Other studies showed that 97% of patients with osteolytic metastases or myeloma had partial or complete pain control within 6 to 72 hours.⁴⁷

The benefits of vertebroplasty include a minimally invasive approach, outpatient care, immediate pain relief, opportunity for biopsy, and possible antitumor effects.¹⁴ Patients can also resume anticoagulation therapy, chemotherapy, and RT on the first postoperative day.

The physiological mechanisms of this analgesic effect are not perfectly understood, possibly due to the stabilization of microfractures by the PMMA or destruction of pain fibers on contact with the cement, through the exothermic reaction generated during its polymerization.⁴⁸ One study contends the mechanical effect takes precedence over the thermal effect since no histological lesions of intraosseous nerve fibers were seen on contact with PMMA injected into the vertebrae of rabbits.⁴⁹ In agreement, another report found identical analgesic efficacy in three groups of patients treated with cements with very different peak polymerization temperatures.⁵⁰

Vertebroplasty is well documented to be a safe, feasible, and effective method for pain reduction due to bone instability, but it is neither a curative therapy nor an anticancer treatment when used as a sole intervention. In order to achieve optimal outcomes in patients with spinal metastases, vertebroplasty is coupled with RFA. RFA treats the neoplastic disease and vertebroplasty provides stabilization while preventing progression to fracture. This is also a suitable combination because the transpedicular approach of RFA allows for easier access to the vertebral body during cement augmentation.