Spine Cryoablation: Pain Palliation and Local Tumor Control for Vertebral Metastases

Discussion

Painful vertebral column metastatic disease is a substantial cause of morbidity in patients with cancer owing to its high prevalence, the weight-bearing nature of the spine, and close proximity to critical structures, including the nerve roots and spinal cord. Pain from neoplastic bone involvement in the spine is multifactorial and is a consequence of mechanical factors, including direct involvement of spinal nerve roots and mass effect on the nerve roots and spinal cord, biologic factors including osteoclast-mediated proton sensitization of the sensory fibers at the mineralized bone-tumor interface, sensitization or activation of sensory nerve fibers by products directly produced in tumor and tumor stromal cells, and distortion of mechanosensitive fibers following normal mechanical stress due to loss of tensile strength in the bone secondary to cancer.^30⇓–32 Goblirsch et al³² suggested that reduced tumor burden and reduced osteolysis are important for decreased pain following radiation therapy. As with the creation of pain related to osseous metastatic disease, the mechanism of action and therapeutic effects of cryoablation are likely similar and multifactorial; however, they have not been studied.¹⁸

While external beam radiation remains the current standard of care for the management of painful osseous metastases,⁴ percutaneous cryoablation has emerged as a safe and effective treatment option for patients with musculoskeletal tumors, refractory to radiation therapy and systemic palliative therapies including chemotherapy, hormonal therapy, bisphosphonates, and analgesics.^{14⇓⇓⇓⇓⇓⇓⇓⇓–23,30}

The cytotoxic effects of cryoablation are mediated through the formation of intracellular ice crystals during probe-mediated temperature manipulation. The crystals cause denaturation of proteins and shearing of intracellular structures, including cell membrane rupture. A liquid gas, commonly argon, is used to rapidly cool the tip of the cryoprobe, forming an enlarging ice-ball with time followed by a “thawing” phase, commonly achieved with helium gas, resulting in an osmotic gradient.³³ The osmotic gradient causes water to rush into, swell, and then burst the tumor cell, eventually leading to cell hypoxia via indirect ischemic injury.³⁴

Investigators have reported scattered cases of spinal metastases treated with percutaneous cryoablation as part of larger series of patients ablated for extraspinal musculoskeletal metastatic disease or as case series.^{14,18,20,23,26} In 2006, Callstrom et al¹⁴ reported 3 spinal tumors (2 in the sacrum and 1 in the lamina) as part of a 14-patient study managed effectively by cryoablation. As part of a multicenter prospective single-arm clinical trial of 61 patients who underwent image-guided cryoablation for the palliation of painful osseous metastases, Callstrom et al¹⁸ reported 6 spinal tumors (5 in the sacrum and 1 in the vertebral body), which were effectively palliated with significant decreases in pain and subjective improvement in the quality of life at 1, 4, 8, and 24 weeks following the procedure.

Kurup et al²⁰ reported a case series of 6 patients with sacrococcygeal metastases who underwent imaging-guided cryoablation and suggested that cryoablation may be a safe and relatively effective technique for the management of recurrent sacrococcygeal neoplasms for local control or palliation of pain with short-term follow-up. In 2014, Prologo el al²³ reported 2 patients with pedicle lesions as part of larger series of 50 patients with musculoskeletal metastases managed by cryoablation for pain palliation. Subsequently, in 2014, Kurup et al²⁶ reported the utility of motor-evoked potential monitoring during cryoablation of musculoskeletal tumors in 52 patients. The authors reported cryoablation in 27 spine and 3 sacral tumors, which were monitored by motor-evoked potentials. However, the effectiveness of cryoablation for pain palliation and local tumor control was not discussed.²⁶

In a retrospective analysis of data from patients with single vertebral metastasis, Masala et al¹⁹ described the safety and efficacy—through reduced pain (Visual Analog Scale scores) and disability (Oswestry Disability Index)—of cryoablation combined with vertebroplasty for the palliation of painful vertebral metastases, which was at least equivalent to vertebroplasty alone. However, the safety and efficacy of cryoablation as an exclusive treatment approach could not be evaluated because vertebroplasty was performed in all cases.

To our knowledge, this is the first single-center review describing the safety and effectiveness of cryoablation as the exclusive thermal ablation technique for local tumor control and palliation of painful spinal osteoblastic and osteolytic metastatic disease. The present study data suggest that percutaneous cryoablation is safe and effective for vertebral local tumor control and palliation of painful spine metastases. There was statistically significant pain palliation reflected by a substantial decrease in postprocedural NRS scores and analgesic use. Two patients (2 lesions) had persistent but improved pain following cryoablation. Local tumor control, evidenced by no radiographic evidence of active tumor at treated sites, was achieved in 96.7% (30/31 lesions) of lesions on the basis of postprocedural cross-sectional imaging. One patient with sacral metastases did not benefit from the procedure and developed progression of disease despite technically adequate cryoablation.

The safety of the procedure was supported by a lack of major complications and only 2 minor transient complications based on the Society of Interventional Radiology guidelines.²⁹ Thermal protection measures should be implemented in all spine cryoablations to ascertain safety before the procedure. In the current study, these techniques included neuroforaminal thermal monitoring with epidural or neuroforaminal injection of carbon dioxide or warmed 5% dextrose water; thermal isolation of critical abdominal and pelvic soft tissues, including by intraprocedural injection of carbon dioxide; and cutaneous thermal protection by surface application of warm saline during freezing cycles. In addition, intraprocedural motor-evoked potential monitoring was performed during a single ablation performed with the patient under general anesthesia.^26,27

The efficiency of cryoablation for the treatment of osteoblastic spine metastases has not been studied previously. Radiofrequency ablation is rendered ineffective for the treatment of sclerotic metastases due to high impedance levels in attenuated bone. Cryoablation is emerging as an attractive alternative to RFA for palliation of sclerotic metastases. In 2011, de Freitas et al³⁰ reported the effectiveness of cryoablation in a single patient with T9 and sacral osteoblastic metastatic disease. In the current study, 9 osteoblastic vertebral metastases were effectively palliated.

Nerve roots are more vulnerable to potential thermal injury with cryoablation compared with RFA, due to less tissue sensitivity to cold versus heat. This limitation is mitigated by implementation of thermoprotection techniques with the patient under conscious sedation and the use of sensory and motor-evoked potential monitoring with general anesthesia. In addition, posterior central vertebral body lesions are more challenging to access via a transpedicular approach by using straight cryoprobes.

The major limitation of the present study is the single-arm nature of the analysis with no control group and the lack of comparison to other treatment modalities, specifically radiation therapy. Additional limitations of the present study include its retrospective methodology, use of NRS scores for pre- and postprocedural pain assessment versus the more inclusive Brief Pain Inventory, and the relatively small number of palliated tumors.