Current Status and Prospects of Radiofrequency Thermal Ablation in Bone Tumor Treatment
Radiofrequency ablation (RFA) is a rapidly developing non-vascular interventional technique in recent years, especially in the minimally invasive treatment of tumors. The ions in the tumor tissues around the electrode vibrate and generate frictional heat, causing thermal damage and coagulation necrosis in the tumor tissues around the electrode to achieve the effect of killing tumor cells, which is widely used in solid tumors such as liver tumors [1].
The complexity of spinal anatomy makes the surgical treatment of spinal tumors difficult. In recent years, some scholars have explored the application of image-guided radiofrequency technology to the treatment of some spinal tumors with good results, which provides a new way for the minimally invasive treatment of spinal tumors. This article summarizes the progress of radiofrequency ablation technology in the treatment of spinal tumors in recent years and discusses the application of radiofrequency ablation technology in the treatment of osteoid osteoma of the spine, palliative treatment of osteolytic metastatic carcinoma of the spine, treatment of multiple recurrent refractory primary spinal tumors and intraoperative adjuvant treatment of spinal tumors.
1.Radiofrequency ablation technology applied to osteoid osteoma of the spine
The main clinical manifestation of spinal osteoid osteoma is pain and restriction of daily activities, and the tumor is composed of nucleus and peripheral reactive bone. The main goal of treatment is to relieve clinical symptoms and prevent recurrence. Surgical scraping or en bloc resection is the main treatment method for this tumor [2]. In recent years, radiofrequency ablation technique has been applied to osteoid osteoma of the spine, and its characteristics such as less trauma, rapid pain relief and similar recurrence rate as surgical treatment have led to its wide application.
et al [3] applied RFA technique for the first time to treat a case of spinal osteoid osteoma with tumor located in the L4 adnexa using Radionics RFG-6 system with a set temperature of 85°C and ablation time of 4 minutes; this patient had significant pain relief and no recurrence on imaging at 16 months of follow-up.
Dupuy et al [4] applied Radionics RFG system to treat one case of T11 arch-like osteoma with a setting temperature of 90°C and an ablation time of 6 minutes, and the pain was completely relieved after the procedure, and CT examination showed that the tumor had healed at 8 months of follow-up. The authors concluded that the reactive bone and intact cortical bone around the tumor nucleus can effectively block the heat transfer into the spinal canal, while the intraventricular plexus and cerebrospinal fluid circulation in the spinal canal can take away part of the heat and prevent thermal injury to the spinal cord. At the same time, it is proposed that the nucleus of osteoid osteoma is generally less than 12 mm, and the tumor can be ablated well by using ordinary monopolar radiofrequency electrodes. cove et al [5] reported in 2000 that the Radionics radiofrequency system was applied to treat 2 patients with L3 vertebral plate and transverse process osteoid osteoma with a setting temperature of 90℃ and ablation time of 4 minutes, with no operational complications and no recurrence of pain relief for 2 years of follow-up. Hadjipavlou et al [6] reported in 2003 two patients with osteoid osteoma of the spine treated with RFA, one at the superior L4 synovial process and one at the T9 pedicle, using the Radionics system with a set temperature of 90°C and an ablation time of 4 minutes, with no significant complications and no recurrence of pain disappearance at 2.5 to 3 years of follow-up. Samaha et al [7] reported in 2005 that RFA treated three cases of osteoid osteoma of the spine adjacent to nerve roots and spinal cord structures in three cases, one case located at the posterior edge of the T8 vertebral body separated from the spinal canal by only a thin layer of bone, one case located at the superior C6 articular eminence, immediately adjacent to the C7 nerve root, and one case located at the superior L5 articular eminence, immediately adjacent to the L4 nerve root. The radiofrequency temperature was set at 90°C, and the ablation time was 4 minutes. No obvious neurological impairment was observed, and the symptoms disappeared with no recurrence of the tumor during the follow-up period of 8 months to 2 years, suggesting that RFA treatment is also safe and effective for osteoid osteoma immediately adjacent to neurospinal structures.
Vanderschueren [8] reported in 2009 that 24 patients with cumulative spinal osteoid osteoma received a total of 28 RF treatments, which is the largest reported case so far. 24 patients were followed up for an average of 72 months, and 16 patients had tumors adjacent to spinal nerve structures (less than 1 cm from the spinal nerve roots), and a 5-mm RF electrode was used to set the RF temperature at 90 degrees and the RF time at 4 minutes. The success rate of the first radiofrequency treatment was 79%, and the patients who had recurrence or poor efficacy after radiofrequency ablation were treated with ablation again, and the overall success rate of radiofrequency was 96%. The authors concluded that RFA is safe and reliable for osteoid osteoma of the spine, and that re-ablation can still achieve satisfactory results in recurrent cases, but surgery is still recommended for those who show neurospinal compression or whose tumor margins are within 2 mm of the spinal nerve roots.
Most authors agree that radiofrequency ablation can achieve the same results as surgery for osteoid osteoma. Rosenthal [9] et al. reported a controlled study of 68 cases of osteoid osteoma of the extremities treated with open surgery and 33 patients treated with radiofrequency ablation, and the average follow-up for the radiofrequency ablation group was 3.4 years, with a recurrence rate of about 12%, which was comparable to that of open surgery. This author reported in 2003 that 271 patients with osteoid osteoma treated with radiofrequency ablation 126 patients who received more than 2 years of follow-up had 89% symptom remission rate and 91% symptom remission rate in primary patients, and only 2 cases of operation-related complications occurred, 1 case of cellulitis and 1 case of sympathetic dystrophy. Radiofrequency treatment of osteoid osteoma is considered to be a safe and efficient minimally invasive method suitable for the treatment of most osteoid osteomas [10]. However, osteoid osteoma accumulated in the spine is relatively rare, accounting for only about 10% of cases, the literature reports fewer cases, the lack of randomized controlled studies with surgical treatment, and because of the proximity of the spinal nerve, there is a possibility of thermal damage to nerve tissue, in recent years some scholars have done a lot of useful exploration on the prevention of thermal damage to the spinal nerve during radiofrequency, Vanderschueren [8] summarized 24 cases of spinal osteoid osteoma radiofrequency Vanderschueren [8] summarized the experience of 24 cases of spinal osteoid osteoma with radiofrequency radius of 5 mm that the non-circulating water-cooled radiofrequency electrode could better control the ablation range, reduce the unnecessary ablation area, and prevent the possibility of thermal injury to the nerve spinal cord by excessive ablation range. Klass [11] reported that in seven patients with spinal osteoid osteoma treated with radiofrequency, the ablation process was performed by continuous warm saline perfusion to the paramedian nerve root and epidural to prevent spinal nerve thermal injury. At the outlet, 10 ml of normal temperature saline was injected through the 26G cannula before the start of RF to distribute it around the nerve root and the adjacent epidural space to start ablation, and the injection was repeated every 30 seconds to prevent neurospinal thermal injury. After the operation, 1-3 ml of 0.5% bupivacaine was injected through a 26G cannula with a view to relieving the neurogenic symptoms. And 7 patients were treated with this method without complications of neurothermal injury. Compared with traditional surgical resection, radiofrequency ablation has the advantages of safety, high efficiency and few complications in the treatment of osteoid osteoma [8, 10], but the long-term efficacy needs to be further verified [8].
2. Radiofrequency ablation technology applied to the palliative treatment of osteolytic spinal metastases
Spinal bone metastases are the most common spinal tumor, and pain is the most common first symptom, accounting for about 90-95% of patients. The pain caused by metastases is often severe and unbearable seriously affecting the quality of patients’ daily life, so relieving pain and improving long-term survival are equally important goals [12]. Some patients are not sensitive to conventional radiotherapy for pain relief, and such patients are often unable to increase the dose of radiotherapy. The side effects of high-dose opioid analgesics often greatly affect the quality of patient survival. In recent years, some scholars have applied radiofrequency ablation to the palliative analgesic treatment of spinal metastases, and some authors have combined radiofrequency ablation and vertebroplasty (PVP) for the treatment of advanced spinal metastases to relieve patients’ pain and improve their survival quality. The posterior border of the vertebral body was cortically intact and radiofrequency ablation time was set at 12 minutes under local anesthesia combined with basic anesthesia using Radionics 3cm Cool-Tip radiofrequency electrode. The authors pointed out that the intact bone cortex and cancellous bone between the tumor and spinal cord can effectively prevent the heat transfer during the RF process, and RF treatment is relatively safe for those with intact bone cortex at the posterior edge of the vertebral body.Gronemeyer et al [13] reported 10 cases of spinal metastases treated with CT-guided RF ablation, operated under simple local anesthesia, applying the temperature control mode of RITA multipolar RF electrode, setting the temperature The average follow-up was 5.8 months, and the pain relief was assessed by VAS score. 90% of the patients had significant pain relief, with an average pain reduction rate of 74.4%, and the Frankel score remained the same in 9 cases and improved in 1 case compared with the preoperative period. No tumor regrowth was seen in the ablated area. The authors concluded that radiofrequency ablation is a safe and effective minimally invasive treatment for unresectable spinal tumors that are not sensitive to radiotherapy, and suggested for the first time that radiofrequency ablation combined with vertebroplasty could have a synergistic effect on pain relief. 2003 Schaefer et al [20] first reported a case of phase I radiofrequency ablation combined with L3 vertebral metastasis of renal cell carcinoma, using the RF3000 radiofrequency ablation system from RadioTherapeutics, with impedance control mode under general anesthesia, and the energy gradually increased from 40w, rising 10w every 3 minutes until the impedance rose to 45 ohms and the current could not further The patient’s pain was completely relieved and he left the hospital after 24h without any restriction in daily activities and no signs of nerve damage. The authors concluded that radiofrequency destroyed the blood vessels of the tumor and increased tissue homogeneity in the radiofrequency area, which facilitated the distribution of bone cement and prevented leakage of bone cement or entry into the drainage vein. Nakatasuk et al [14] reported 17 patients with 23 malignant bone tumor lesions treated by radiofrequency ablation combined with vertebroplasty, 17 of which involved spinal lesions, 2 of which invaded the posterior wall of the vertebral body and 13 invaded the pedicle. The patient complained of radiological pain, and the operation was stopped immediately to prevent nerve injury. The success rate of postoperative technique was 96% (22/23), one osteogenic lesion failed to place radiofrequency electrodes, and the VAS score of 13 patients complaining of pain decreased from an average of 8.4 preoperatively to 1.1 at 1 week postoperatively. MRI showed that the postoperative tumor necrosis rate ranged from 14% to 100% (71% ± 24%), and there was a significant difference in the necrosis rate between tumors smaller or larger than 5 cm (78% ± 23%: 59% ± 22%). Five patients had recurrence of pain, two had in situ tumor growth, three had new metastases, and six died during follow-up within one year. four patients had nerve damage during radiofrequency treatment (three had cortical destruction at the posterior margin of the vertebral body and one had invasion of the pedicle), three patients improved after treatment, and one had persistent symptoms. The authors concluded that the release of heat during cement sclerosis had a synergistic effect on radiofrequency thermal ablation, and that the recurrence of pain due to in situ tumor regrowth in two patients, both with tumor diameters greater than 5 cm, suggested that radiofrequency treatment of large tumors (diameter greater than 5 cm) was inadequate and that radiofrequency ablation was not indicated for the treatment of osseous bone tumors. The risk of neurothermal injury due to radiofrequency ablation in cases with vertebral cortical damage or tumors adjacent to spinal nerve root structures is great.Toyota et al [15] reported 17 patients with painful bone metastases with 23 lesions treated by radiofrequency ablation combined with vertebroplasty, among which 8 lesions involved the spine, using Radionics Cool-Tip radiofrequency electrodes, operated under general anesthesia, with a starting power of 50W, rising 10W per minute until the current could not flow further. Pain relief was 100% with no significant complications. This author proposed that radiofrequency for patients with incomplete posterior wall of vertebral body should avoid radiofrequency of tumor tissue in the posterior wall region of vertebral body to prevent the occurrence of neuromuscular thermal injury, and also believed that the tumor tissue impedance of high-dose chemotherapy patients is large, which makes it difficult to reach the expected temperature of radiofrequency and the ablation effect is poor. 50% survival rate of this group of patients in one year suggests that radiofrequency ablation is helpful to control tumor-related pain to improve patients’ quality of life, but it has no significant effect on The authors also believed that the combination of vertebroplasty cement sclerosis and heat generation had a synergistic effect on radiofrequency thermal ablation, while the cement strengthened the stability of the spine to prevent pathological fractures and improved the quality of life of patients. der Linden et al [16] reported 12 cases of spinal tumors with vertebral body posterior wall rupture treated with radiofrequency combined with vertebroplasty. The authors selected 12 patients with osteolytic bone destruction in the cervicothoracic and lumbar spine who were older than 18 years old, with two lesions or less, and whose previous treatment was ineffective, and whose destruction was accompanied by pain caused by vertebral posterior wall breakdown or pathological fracture. The RITA multi-polar radiofrequency electrode and Radionics cool-tip radiofrequency electrode were used. The output power of RITA system was set at 150W, the temperature was set at 100℃, the ablation time was 10 minutes, and if the patient complained of pain, the ablation time was extended by 10℃, and if the electrode temperature was lower than 60℃ after the ablation, the ablation time was extended by 5 minutes. If the temperature of the radiofrequency head is lower than 60 ℃, the ablation is extended for 5 minutes, and then the other side of the arch is ablated by the same procedure. The pain relief rate was 92% at one week after the procedure. only 6 patients were followed up after 3 months, the other 6 died of primary disease in 4 cases and 2 cases were lost to follow-up. No significant complications occurred. The authors concluded that none of the 12 patients with posterior wall injury had significant neuromuscular injury for the following reasons: 1, the rate of spinal canal encroachment in the enrolled patients was controlled to less than one-third, and only 3 of the 12 patients had intradural encroachment; 2, technical reasons, awake anesthesia can obtain direct feedback from patients, and patients with pain sensation are prevented from nerve injury by reducing radiofrequency temperature and energy; 3, avoiding the use of RF near the spinal cord and nerve root region.Nakatsuka et al [17] reported 10 cases of radiofrequency treatment for painful spinal tumors under real-time temperature-controlled monitoring in the spinal canal. For 10 patients with spinal tumors within 1 cm of the spinal cord for which radiotherapy and chemotherapy surgical methods were ineffective, radiofrequency ablation was used, using basic anesthesia with local anesthesia and Cool-Tip radiofrequency electrodes, while another thermometric electrocouple with a temperature probe was placed into the epidural space between the tumor and the dura through a 21G puncture needle to monitor the temperature change of the epidural space in real time, and the temperature exceeding 45°C was The ablation will be stopped immediately if the temperature exceeds 45℃. In 9 patients, the monitored temperature did not exceed 45℃, and in 1 patient, RF treatment was stopped immediately after reaching 45℃, but the intradural temperature eventually reached 48℃ and showed transient spinal cord damage, which was relieved after 2 days of conservative treatment. The VAS score decreased from 7.5 ± 2.7 to 2.7 ± 2 at 1 week after surgery, and all patients died after 4.5 ± 1.3 months of follow-up. 1 patient had a recurrence of pain and 2 patients had new lesions causing pain. 6 of 10 patients had the temperature-controlled probe mistakenly inserted into the subarachnoid space, suggesting that the placement of the temperature-controlled probe in the epidural space is meaningful to prevent thermal injury to the spinal cord during ablation, but it is difficult to operate.
It is now generally believed that the pain relief principles of radiofrequency ablation for painful bone metastases are as follows: 1) destruction of tumor margins and subperiosteal nerve endings; 2) ablation of tumor to reduce tumor secreted cytokines; 3) stabilization of spinal structure to reduce the chance of pathological fracture and destruction of intraosseous microstructure [1]. For unresectable osteolytic bone metastases that cause significant pain, radiofrequency ablation therapy can rapidly relieve patients’ pain and improve their quality of life [1, 5, 13-17]. However, although radiofrequency ablation has obvious effects on local tumor control, it has little significance in improving long-term survival of patients [16, 17]. And some scholars [18, 19] believe that the extent of tumor ablation is not necessarily related to pain relief. Radiofrequency treatment of tumors with posterior wall breach and arch root invasion has the risk of damaging the spinal cord and nerve roots, which is considered contraindicated by some scholars [1], and some scholars believe that maximum tumor ablation can be achieved under intracanal temperature monitoring [17]. The application of radiofrequency ablation alone for the treatment of osteolytic metastases of the spine in combination with vertebroplasty lacks randomized controlled studies.
3. Application of radiofrequency ablation technology to recurrent refractory primary spinal tumors
The complexity of spinal anatomy and the proximity of important structures such as spinal nerve roots often lead to incomplete surgical resection, and some junctional or low-grade malignant primary spinal tumors are less sensitive to radiotherapy and have a higher recurrence rate.
Chordoma is the most common primary spinal malignancy, and surgical resection combined with radiotherapy or proton radiotherapy is commonly used, but the extremely high rate of local recurrence and the difficulty of reoperation after multiple surgeries make the treatment of this disease very difficult. The tumor recurred and increased progressively after postoperative radiotherapy. The patient was treated with radiofrequency ablation under basic anesthesia combined with local anesthesia using Cool-Tip radiofrequency electrodes. The authors suggested that radiofrequency ablation is a minimally invasive treatment option in addition to conventional surgery and radiotherapy for chordoma that causes significant pain and rapid growth.Anis et al [21] reported two cases of recurrent sacral chordoma treated with radiofrequency ablation. One patient was unable to relieve the pain with 120 mg/d of oral morphine, so radiofrequency ablation under general anesthesia was used and the patient left the hospital after 48 hours of observation. The patient’s MRI follow-up revealed no regrowth of the tumor in the RF region, but the tumor in the non-RF region was still growing rapidly. Radiofrequency ablation is a safe and efficient minimally invasive treatment option for recurrent spinal primary tumors that are difficult to resect and insensitive to radiotherapy [20, 21].
4. Adjunctive application of radiofrequency ablation technology in spinal tumor surgery
Li Haomiao and Gasbarrini [24] reported 11 cases of spinal metastases treated with radiofrequency ablation followed by tumor curettage. The single ablation time was set at 12 minutes, power 150w, and upper temperature limit 100℃. The dural sac and nerve roots were fully exposed in the posterior approach first, and the radiofrequency electrode was placed to the lesion via the arch under X-ray guidance, and the radiofrequency ablation was performed under a large amount of saline flushing of the dura and nerve roots. The authors believe that tumor tissue consolidation and vascular occlusion after radiofrequency ablation can reduce bleeding during the scraping process and improve the completeness and safety of tumor removal.
5. Risk of neurospinal cord thermal injury during radiofrequency ablation of spinal tumors
Froese et al [22] proposed that the ED50 value of spinal cord thermal injury in mice was 10.8 min at 45°C through radiofrequency thermal injury experiments on the spinal cord of mice. Dupuy et al [3] confirmed that the temperature transfer in the vertebral body during RF ablation was much lower than that in the paravertebral muscles. 48°C, 41°C and 39°C, 84°C, 62°C and 58°C (p<0.01) were detected in the vertebral body and paravertebral muscles at 5 mm, 10 mm and 15 mm from the RF electrode, respectively. It is believed that cancellous bone can effectively reduce the heat transfer in RF, and the intact bone cortex is a good isolator of heat. It is also believed that the abundant epidural venous plexus and unobstructed cerebrospinal fluid circulation can take away some of the heat, further reducing the temperature of the epidural space. Radiofrequency treatment that ensures the intact cancellous bone and bone cortical structures between the tumor tissue and the spinal canal will be safe. According to some scholars, radiofrequency ablation will be safe and reliable to ensure that the tumor edge is more than a certain distance from the neurospinal cord tissue and the bone cortex is intact. goetz et al [1] believed that radiofrequency ablation can be performed only when the tumor edge is more than 1 cm from the spinal cord according to 43 cases of radiofrequency ablation of painful bone metastases, but in clinical practice, most spinal metastases are accompanied by invasion of the posterior wall of the vertebral body or the spinal canal. For example, short-acting intravenous anesthesia midazolam and fentanyl are used in combination with local infiltration anesthesia to ensure that the patient is awake and receives good analgesia during the operation, and if the patient complains of radiating pain and numbness and other signs of neurothermal injury during the radiofrequency process, the ablation process is stopped immediately or the ablation energy is reduced to avoid ablation of tumors adjacent to the spinal nerve tissue. As mentioned above, some scholars have also used temperature monitoring electrodes around the RF area [17] or interventional perfusion methods to reduce the temperature of the neurospinal structures around the RF target tissues [11], which has achieved good results.
6.Summary and outlook
Although there is a potential risk of thermal injury to the spinal cord, it is believed that with the advancement of technology and equipment, radiofrequency ablation will have a greater application in the field of comprehensive treatment of spinal tumors. It is believed that with the progress of technology and equipment, radiofrequency ablation will have a greater prospect of application in the field of comprehensive treatment of spinal tumors.