Metastatic lesions that spread to the spine can cause severe pain, spinal fractures, and neurological problems due to nerve root and spine compression by the tumour mass . Several treatment alternatives for spinal metastases including radiotherapy, chemotherapy, isotopic therapy, bisphosphonate therapy, pharmacotherapy, RFA, and palliative surgery can be used . The choice of treatment depends on the histopathology of the primary tumour, neurological function before treatment, number of involved vertebrae, vertebral level, site of the osteolytic lesions in the spinal body, degree of intraspinal diffusion, disease severity, and the patient’s general condition.
Narcotic analgesics are the first-line pharmacotherapy for pain control in patients with metastatic lesions; however, they can cause extreme drowsiness, constipation and nausea. Previous studies have reported that palliative radiotherapy is highly beneficial in alleviating metastasis-related pain [13,14]. However, a 57% recurrence rate (of pain) was reported 15 weeks after the end of radiotherapy . Approximately 40% of patients did not benefit from a second round of radiotherapy . Reconstruction surgeries such as surgical decompression, pedicular screws, and corpectomy-cage placement can be performed in patients whose life expectancy exceeds 6 months . However, the complication rate is as high as 20-40%, and systemic complications such as surgical wound area infection, pneumonia, and urinary tract infections were observed in several patients [12,16,17].
Pain is the most common finding in patients with spinal metastasis, with a consequential reduction in mobility and deterioration in the QoL. Approximately 30-50% of patients with cancer experience pain, and excruciating pain disrupts the QoL in 75-90% of patients with advanced-stage cancer . Bone metastasis-related pain is triggered by osseous destruction induced by osteoclasts, which are the principal bone resorption cells of the body . Biochemical factors and cytokines released from the periosteum and tumour cells also contribute to osseous destruction . The pain caused by vertebral involvement is dull and stable and progressively increases, exacerbated by movement of the extremities [15,19]. Radiation and/or chemotherapy, surgery, and use of opioids and other analgesics are common for pain control in patients with spinal metastasis . However, the QoL is extremely poor owing to intolerable pain in these patients. All patients in our study had a history of increasing analgesic use at least 2 months before the procedure.
Callstrom reported that pain in daily life decreased at a rate of 0% 4 weeks after RFA in patients with bone metastasis . While Goetz reported that analgesics use decreased significantly6 months after treatment in 41 of 43 patients treated with RFA . Zhao determined a significant reduction in analgesics use 6 months after the implementation of RFA in 34 patients with metastases .
In our study, tramadol hydrochloride was discontinued 48 h after the procedure in groups 1 and 2, while the need for tenoxicam, another analgesic used at the end of the first week, significantly decreased. Group 1 patients had increased pain at the 3-month follow-up, and analgesic use increased before the procedure. This situation was attributed to the increase in the degree of collapse in the affected vertebra.
VP has also been reported to facilitate safe and rapid pain reduction in patients with cancer with spine involvement and increased patients’ ability to walk and perform daily activities . The skeleton is stabilized with the application of VP after RFA, thus preventing periosteal deformation and pain . RFA and PMM injection can be combined to reduce pain and improve the QoL. The advantage of performing RFA before PMM injection is increased control for PMM distribution, which can be useful in posteriorly located lesions . Moreover, the spread and displacement of tumour cells are prevented by the ablation shell barrier, which is applied during RFA. RFA can also cause intravertebral venous plexus thrombosis, and subsequently reduce the risk of PMM leakage. Liu et al. reported that the combination of RFA, a minimally invasive intervention used for treating metastatic spine lesions, with percutaneous VP was particularly beneficial in reducing the incidence of fracture, risk of pain and surgery, and improving the QoL .
Lane reported a reduction inthe pain scores in some patients treated with combined RFA and VP . Gronemeyer reported a significant reduction in pain and disability in patients treated with RFA and VP . In our study, 16 patients underwent PMM injection into the vertebrae with metastatic lesions after successful RFA.
The reported rate of serious complications for percutaneous VP is low (<10%); however, one study reported a PMM leakage rate of 81% visualised using CT . Barragan-Campos reported 42 cases of PMM leakage cases from amongst 159 percutaneous VP procedures ; however, only 2 patients had serious complications. Furthermore, Nakatsuka reported that 4 patients developed hemiplegia and radiculopathy after RFA+VP, which was performed under CT fluoroscopy guidance . In our study, PMM leakage occurred in 4 (25%) of 16 patients who underwent VP, but no serious complications were observed (Figure 2).
All the aforementioned complications occur in cases where the tumour invades the vertebral cortex, and consequently, VP is contraindicated in these patients . On the other hand, the combined procedure is safe in patients without posterior cortex and pedicular invasion. Shimony et al.  reported their successfully performing VP in patients with metastasis-related compression fractures but without posterior cortical deterioration, and successful pain control in 82% of patients, without any serious complications. Our study protocol achieved a successful pain control rate exceeding 80% 6 months postoperatively.
Goetz reported a reduction of at least 2 points in the pain scores in 95% of patients after RFA treatment . The reduction in pain levels was the highest in the first week, with a rate of 41%, with significant reductions in the opioid requirement in the 8thand 12thweeks . In our study, significant improvement was observed in patients with refractory pain caused by spinal metastasis. According to the VAS assessment, the mean decrease in pain was 3.3 points after 72 h, 5.3 points in the 1stweek, 5.7 points in the 1stmonth, and 6.7 points in the 6thmonth.
Limitations of the present study include the small sample population, lack of a control group, and short-term follow-up. The patients were followed-up for an average period of 6 months after the procedure, which was insufficient to determine long-term pain control and recurrence rates. Long-term follow-ups are required to determine the rate of recurrence and long-term survival. However, it was difficult to follow-up this patient population for longer durations owing to the progression to terminal cancer stages, characterised by metastases to different organs. Future multi-centre studies are required to improve RFA effects, expand the scope of its application for tumours or metastases, and reduce possible complications.