Application of Separation Surgery Combined with Radiofrequency Ablation and Bone Cement Strengthening in Thoracolumbar Metastasis

Abstract

The spine is a common site for metastatic tumors, with 5%-10% of patients developing epidural spinal cord compression (ESCC), which significantly reduces their quality of life and accelerates the process of death. When total en-bloc spondylectomy (TES) radical surgery does not achieve the desired tumor control, palliative care remains the primary treatment option. Traditional laminar decompression or partial tumor resection can only relieve local compression. Although the surgical trauma and complications are less, these methods cannot effectively address tumor recurrence and secondary compression. Therefore, separation surgery combined with radiofrequency ablation and bone cement strengthening was used to treat thoracolumbar metastatic tumors, aiming to achieve good clinical results. In this protocol, the steps and key points of separation surgery combined with radiofrequency ablation and bone cement reinforcement for thoracolumbar metastatic tumors are introduced in detail. Meanwhile, the clinical data of 67 cases of thoracolumbar metastatic tumors in our hospital meeting the inclusion criteria were retrospectively analyzed. Different treatment methods divided the patients into two groups: separation surgery combined with radiofrequency ablation and bone cement strengthening (group A, 33 cases) and the radiotherapy group (group B, 34 cases). All patients were evaluated using improved Tokuhashi, Tomita, SINS, and ESCC scores before treatment. VAS score, Frankel grading, and Karnofsky scores during different periods of the two treatments were compared to assess the clinical outcomes. Studies have shown that separation surgery combined with radiofrequency ablation and bone cement strengthening can significantly reduce pain, promote neurological function recovery, enhance mobility, and improve quality of life in treating thoracolumbar metastatic tumors.

Introduction

With the development of precision medicine, the survival rate of patients with malignant tumors has gradually increased, and the incidence of bone metastasis has also risen significantly. Spinal metastasis is the most common occurrence in patients with malignant tumors, accounting for approximately 60%-70%. Among these, 5%-10% of patients will suffer from epidural spinal cord compression (ESCC)^1,2, which can result in bone-related events, such as localized pain, hypercalcemia, spinal instability, pathological fractures, spinal cord and nerve root compression, and other clinical symptoms. About 50% of patients will suffer from neurological dysfunction³, which dramatically reduces their quality of life and accelerates death.

The diagnosis and treatment of spinal metastases require multidisciplinary collaboration. Treatment of the primary tumor is fundamental, and surgical intervention plays a vital role in managing spinal metastases. The objectives of surgical treatment are to relieve pain, rebuild spinal stability, improve neurological function, control local tumor lesions, enhance the patient's quality of life, provide conditions for further treatments such as radiotherapy, chemotherapy, and immunotherapy, and even prolong life⁴. Conventional laminectomy or partial tumor resection only relieves local compression. Although the surgical trauma is minor and the incidence of surgical complications is low, these methods cannot effectively address tumor recurrence and secondary compression⁵.

Separation surgery involves performing a 360° annular decompression around the compressed spinal dura mater to ensure a safe gap of about 5-8 mm between the spinal dura mater and the tumor tissue for radiotherapy. Bone cement is used to separate the anterior affected vertebra, tumor body, and dura mater. Several clinical studies have shown^6,7,8,9 that separation surgery combined with stereotactic radiotherapy has achieved satisfactory clinical efficacy in treating spinal metastatic tumors. However, there are issues such as significant surgical trauma, excessive bleeding, and re-progression of vertebral tumors after resection, which affect its therapeutic efficacy.

In clinical practice, our team observed that during separation surgery for spinal metastases, patients were prone to local progression of vertebral tumors and recurrent nerve compression symptoms while waiting for the incision to heal for subsequent radiotherapy. Radiofrequency ablation (RFA) is a minimally invasive treatment method widely used in clinical tumor hyperthermia. It uses biological heat generated during friction and ion collision to kill local tumor cells and coagulate the surrounding vascular tissues to form a reaction zone, thus destroying their blood supply¹⁰.

Therefore, separation surgery combined with radiofrequency ablation and bone cement reinforcement was used to treat thoracolumbar metastatic tumors. In this technical report, the steps and key points of separation surgery combined with radiofrequency ablation and bone cement reinforcement for thoracolumbar metastatic tumors are described in detail. Additionally, the clinical data of 67 patients with thoracolumbar metastases who met the inclusion criteria and were admitted to the General Hospital of Ningxia Medical University from January 2019 to January 2023 were retrospectively analyzed. These patients were categorized into two groups based on the different treatment approaches. The clinical efficacy of separation surgery combined with radiofrequency ablation and bone cement strengthening (group A, 33 cases) and the radiation therapy group (group B, 34 cases) in thoracolumbar metastatic tumors was evaluated using various observation indicators. This analysis provides a basis for selecting clinical treatment methods for spinal metastatic tumors.

A retrospective analysis was performed on 67 patients with thoracolumbar metastases who met the inclusion criteria and were admitted to our hospital from January 2019 to January 2023. The patients were divided into two groups based on different treatment methods: separation surgery combined with radiofrequency ablation and bone cement strengthening (group A, 33 cases) and the radiotherapy group (group B, 34 cases). The two groups were evaluated for age, gender, primary tumor, time of primary tumor occurrence, affected vertebral body, ESCC score, SINS score, Tomita score, and Tokuhashi score⁴. There was no statistical significance (P > 0.05) in these variables, indicating that the clinical baseline data were consistent between the two groups (Table 1).

Protocol

This study was conducted in accordance with the principles of the Declaration of Helsinki, and the study protocol was approved by the Institutional Review Board (IRB). All patients and guardians provided written informed consent. Inclusion criteria: (1) Thoracolumbar metastatic tumor confirmed by preoperative imaging and puncture biopsy; (2) ESCC classification of spinal cord compression greater than 1a; (3) Expected survival time of the patients ≥3 months as assessed by the modified Tokuhashi score and Tomita score⁴. Exclusion criteria: (1) Primary spinal tumors; (2) Patients with poor general condition or severe medical diseases who could not tolerate general anesthesia and surgery; (3) Patients with poor adherence and incomplete clinical data. The reagents and equipment used are listed in the Table of Materials.

1. Preoperative preparation

1. Perform the diagnosis of thoracolumbar metastasis through preoperative imaging, H&E staining, and immunohistochemical staining¹¹, as shown in Figure 1.
   NOTE: H&E staining and immunohistochemical staining for CK7, TTF-1, Ki67, CKpan, and P40 were carried out according to the standard operating procedure¹¹.
2. Use preoperative X-ray, CT, and MRI to evaluate the lesion site and fully understand the anatomy of local spinal lesions and adjacent segments, as shown in Figure 2.
3. Before surgery, perform an electrocardiogram, SPECT/CT, and chest CT (Figure 3), and exclude patients with contraindications for surgery and anesthesia.
   NOTE: Patients and their families should be fully informed of surgery-related risks and complications before surgery, and surgery-related consent should be signed.

2. Treatment procedure

1. Surgical process for separation surgery combined with radiofrequency ablation and bone cement strengthening
   1. Incision and exposure: Use C-arm fluoroscopy to locate the affected vertebra. Make a 10 cm longitudinal incision, cut through the subcutaneous and lumbar dorsal fascia using the posterior median incision, and push the paravertebral muscles to both sides to reveal the spinous process, lamina, articular process, and transverse process of the upper and lower vertebrae centered on the affected vertebra, as shown in Figure 4A.
   2. Pedicle screw implantation: Locate the pedicle screw insertion position of the upper and lower two vertebrae of the affected vertebrae using the transversal-midpoint method¹², and screw in the pedicle screw sequentially by drilling, tapping, and probing the wall (Figure 4B).
      NOTE: The screw's position was verified satisfactorily using C-arm fluoroscopy. For osteoporosis or micro-metastatic lesions in the upper and lower vertebrae of the affected vertebrae, 1.5-2 mL of bone cement was injected through the pedicle screw channel to strengthen the vertebrae.
   3. Radiofrequency ablation: Remove the vertebral lamina and bilateral facet joints of the compression segment using an ultrasonic bone knife and establish a working pathway through the pedicle approach of the affected vertebra.
      1. Connect the radiofrequency ablation instrument and radiofrequency needle, and insert the radiofrequency needle into the lesion of the affected vertebra. Set the bare area of the electrode needle at 1-1.5 cm according to the tumor size and vertebral body size.
      2. Perform radiofrequency ablation for 10-15 min, maintaining the radiofrequency central temperature at 80-100 °C, as shown in Figure 4B.
         NOTE: The radiofrequency time was adjusted according to intraoperative conditions.
   4. Cement reinforcement of the affected vertebra: Push the bone cement into the vertebra about 3-4 mL under fluoroscopy via the established working pathway in step 3.1.3, as shown in Figure 4C,D.
      NOTE: The bone cement that did not enter the vertebral canal was satisfactory.
   5. Separation surgery: Expose the anterior part of the spinal dura mater through the pedicle approach, and carefully remove the tumor tissue attached to the dorsal and ventral sides of the dura mater.
      1. Remove the adjacent intervertebral disc and posterior longitudinal ligament above and below the affected vertebra, and remove part of the vertebra using an ultrasonic bone knife to reach the filled bone cement.
      2. Perform 360° annular decompression around the spinal cord to ensure a safe gap of more than 5 mm between the dura mater and tumor tissue, as shown in Figure 4E.
2. Radiotherapy procedure
   1. According to the location and scope of the spinal metastatic tumor, perform an enhanced CT scan to locate the tumor and map the target area with an MRI. Apply a three-dimensional planning design to ensure that the tumor receives a sufficient radiation dose while protecting the spinal cord and other vital organs.
      NOTE: The target area includes the metastatic vertebral body, bilateral pedicle, spinous process, and transverse process, and the external expansion of 0.5 cm forms a Planning Target Volume (PTV). Use Volumetric Modulated Arc Therapy (VMAT) with 6 MV-X beams¹², as shown in Figure 5. 8 Gy per session can also be given to patients with a poor general condition, difficulty in mobility, in multiple rounds of radiotherapy, or with a short life expectancy. For single bone metastases with good prognoses, such as breast cancer and prostate cancer, if the primary tumor is well controlled, stereotactic radiotherapy or intensity-modulated radiotherapy technology should be used whenever possible, as it can effectively increase the local radiation dose and improve the tumor control rate.

3. Postoperative management

1. Administer antibiotic prophylaxis within 24 h after surgery. Monitor the patient's vital signs, as well as the sensation and movement of both lower limbs. Follow-up with X-rays after surgery, as shown in Figure 6.
   NOTE: If the drainage volume is less than 50 mL, remove the drainage tube. One week after the operation, wear a thoracolumbar fixation brace for ground movement and focus on functional exercises during bed rest to prevent complications.

4. Statistical analysis

1. Analyze the data using SPSS software. Describe measurement data that meet the normal distribution using means ± standard deviation.
2. Conduct a one-way analysis of variance to compare measurement data between groups. Use the Kruskal-Wallis H non-parametric test for data that do not meet the normal distribution.
3. Express counting data as rates (%) and compare them between groups using the Chi-square test. Consider a p-value of <0.05 as statistically significant.

Representative Results

This study aimed to investigate the efficacy of combining separation surgery with radiofrequency ablation and radiotherapy in treating thoracolumbar metastatic tumors. The representative images of the treatment procedure, as well as pre- and postoperative evaluation, are presented in Figure 1, Figure 2, Figure 3, Figure 4, Figure 5, and Figure 6 (for details, refer to the protocol steps).

Outcome evaluation
VAS scores¹³ before treatment, at 1 week, 1 month, and 3 months after treatment, as well as Frankel Grade and Karnofsky scores¹² before treatment, at 1 month after treatment, and during the last follow-up, were compared to evaluate the clinical effects of the two treatments.

Clinical outcome
All patients were followed up for 14.05 ± 5.21 months (from 6-24 months). No complications related to radiofrequency ablation or bone cement leakage occurred in group A. The operative time was 250.97 min ± 77.85 min, and the blood loss was 700 mL ± 342.67 mL.

The VAS scores did not show a significant difference between the two groups prior to treatment (P > 0.05). The VAS scores of group A before treatment and at 1 week, 1 month, and 3 months after treatment were significantly decreased, with a statistically significant difference compared to group B (P < 0.01). There was no statistically significant difference in VAS scores between group B before treatment and 1 week after treatment (t = 1.538, P = 0.129), indicating that this surgical treatment can significantly improve the pain symptoms of patients with spinal metastases, whereas radiotherapy cannot rapidly improve the pain symptoms of patients (Table 2).

The neurological function of both groups recovered to varying degrees during the follow-up (see Table 3). One month after treatment, the proportion of patients whose Frankel grading improved from low to high was 27 out of 33 in group A and 7 out of 34 in group B. At the last follow-up, the proportion of patients whose Frankel grading improved from low to high was 33 out of 33 in group A and 18 out of 34 in group B. There was a statistically significant difference between group A and group B at 1 month after the operation (χ² = 25.119, P = 0.000). There was also a statistically significant difference between group A and group B at the last follow-up (χ² = 17.895, P = 0.000), indicating that the neurological function of patients undergoing surgical treatment was significantly better than that of patients undergoing radiotherapy.

There was no significant difference in KPS scores between the two groups before treatment (P > 0.05). The KPS scores of group A significantly increased at 1 week, 1 month, 3 months, and the last follow-up after treatment, with a statistically significant difference compared to group B (P < 0.01) (see Table 4).

Figure 1: Representative preoperative puncture pathology. (A) Representative bone tissue and hyperplastic fibrous tissue showing epithelial malignant tumor, which was consistent with metastatic adenocarcinoma in combination with immunohistochemical results. (B) Immunohistochemical results: carcinoma tissue CK7 (+), TTF-1 (-), Ki67 (index about 70%), CKpan (+), and 40 (-). Magnification: 200x. Please click here to view a larger version of this figure.

Figure 2: Preoperative imaging data. (A,B) Representative X-ray, suggesting wedge-shaped changes in lumbar 2 vertebrae. (C,D) Preoperative CT images (C, sagittal, D, axial) demonstrating bone destruction and pathological fracture of the second lumbar vertebrae. (E,F) Lumbar MRI T1 (E, sagittal) showed low-signal and wedge-shaped vertebral changes in the second lumbar vertebrae. Lumbar MRI T2 (F, sagittal)showed high signals, indicating a fresh fracture in the second lumbar vertebrae. (G,H) Lumbar MRI T2 (axial) showed high signals, and the spinal cord was compressed. L2 represents the second lumbar vertebrum. Please click here to view a larger version of this figure.

Figure 3: Preoperative routine examinations. (A) Normal electrocardiogram. (B) SPECT/CT showed newly active bone salt metabolism in the lumbar 2 vertebrae, and the right iliac bone was considered bone metastases, including pathological fractures in the second lumbar vertebra. L2 represents the second lumbar vertebrum. (C) Chest CT examination of lung cancer. Oval dashed lines represent lung cancer lesion sites. Please click here to view a larger version of this figure.

Figure 4: Surgical process. (A) The exposure of the intraoperative incision. (B) Pedicle screw implantation and radiofrequency ablation. (C,D) Cement reinforcement of the affected vertebra. (E) Separation surgery. L2 represents the second lumbar vertebrum. Please click here to view a larger version of this figure.

Figure 5: Planning of radiation therapy. (A) Target area design and planning before radiotherapy. (B) Different radiation doses in other regions of lumbar metastatic carcinoma. (C) Other directions of radiation therapy in the different areas of lumbar metastatic carcinoma. Please click here to view a larger version of this figure.

Figure 6: Postoperative imaging. (A,B) X-ray indicated that the internal fixation position was perfect, the bone cement filling was satisfactory, and the decompression was thorough. L2 represents the second lumbar vertebrum. Please click here to view a larger version of this figure.

Table 1: Comparison of general data between the two groups. Please click here to download this Table.

Table 2: Comparison of VAS scores before and after treatment among the two groups. Please click here to download this Table.

Table 3: Comparison of Frankel grading before and after treatment in the two groups of patients. Please click here to download this Table.

Table 4: Comparison of KPS scores before and after treatment in the two groups of patients. Please click here to download this Table.

Discussion

Although the Tokuhashi score, Tomita score, SINS score, and ESCC score provide a solid evidence-based medical basis for selecting surgical treatment for patients with spinal metastatic tumors, developing an individualized and accurate treatment plan for patients remains a complex problem. Multidisciplinary comprehensive treatment methods are used, including traditional open surgery, minimally invasive surgery, radiotherapy, chemotherapy, and immunotherapy. Roy A. Patchell et al.¹⁴ designed a randomized, multi-center, non-double-blind study showing that for patients with spinal cord compression caused by spinal metastatic tumors, direct decompression combined with postoperative radiotherapy is superior to radiotherapy alone. Traditional laminectomy or partial tumor resection only relieves local compression. Although surgical trauma is minor and the incidence of surgical complications is low, relapse often occurs due to an insufficient radiotherapy dose to protect the spinal cord from postoperative radiotherapy¹⁵, significantly reducing the chance of surgery after recurrence. Therefore, some scholars have proposed the concept of separation surgery to achieve the advantages of the above two surgical methods¹³.

Separation surgery can effectively decompress the spinal cord while retaining sufficient space for adequate postoperative radiotherapy, ensuring not only the complete resection of the local tumor but also minimizing the occurrence of postoperative complications. Postoperative radiotherapy is necessary for the treatment of spinal metastases. For radiotherapy-sensitive metastases, it has an excellent effect. However, for metastatic tumors such as liver cancer and non-small cell carcinoma, conventional radiotherapy has a control rate of only about 30%. Studies¹⁶ reported that approximately 75% of patients will have an incomplete pain response during radiotherapy. Only 10-20 weeks after the completion of radiotherapy, the alleviation will be presented to the greatest extent, which is challenging to ensure the analgesic effect for patients with low life expectancy.

Radiofrequency ablation (RFA) combined with vertebroplasty provides better stability and pain relief for the affected vertebrae with spinal tumors¹⁷. In the treatment of patients with spinal metastatic tumors involving cortical damage at the vertebral posterior margin or spinal cord compression, RFA can create space in the affected vertebra instead of simply compressing the lesion tissue of the vertebra. This space facilitates the entry of bone cement, and there is a specific interval between the bone cement and the posterior cortex of the vertebra, thus reducing the complications of bone cement leakage¹⁸. However, it cannot effectively relieve spinal nerve compression, and its clinical benefit is limited¹⁹.

Separation surgery combined with RFA and bone cement strengthening has obvious advantages in treating spinal metastases. Firstly, radiofrequency ablation can locally coagulate tumor microvessels through thermal ablation, which helps reduce blood vessel density and intraoperative bleeding, shortens surgery time, and effectively relieves postoperative pain symptoms in patients²⁰. In this study, the VAS scores of group A were significantly lower than those of group B at 1 week, 1 month, and 3 months after treatment, indicating that separation surgery combined with radiofrequency ablation and bone cement strengthening can significantly improve the pain symptoms of patients with spinal metastases. Additionally, there was a statistically significant difference in the recovery of neurological function between group A and group B at 1 month after treatment and at the last follow-up, indicating that patients treated with surgery had significantly better neurological function compared to those treated with radiotherapy.

KPS scores are mainly used to evaluate patients' functional abilities, and lower scores indicate worse health status. This study showed a statistically significant difference in KPS scores between group A and group B at 1 week, 3 months after treatment, and at the last follow-up. This may be because radiofrequency ablation combined with bone cement can destroy nerve fibers in the surgical area, reduce the lesion, and decrease the production of inflammatory factors, thus achieving better pain relief and improving the quality of life²¹.

The procedure includes the following key steps: (1) Intraoperative electrophysiological testing is required for all patients during surgery; (2) Two groups of pedicle screws must be implanted in the upper and lower vertebrae of the affected vertebra. If the upper and lower vertebrae have osteoporosis or small metastatic lesions, 1.5-2 mL of bone cement should be injected through the pedicle screw channel to strengthen the vertebrae or using bone cement screws to enhance the biomechanical strength of the pedicle screws; (3) Radiofrequency ablation is performed first, followed by using bone cement to strengthen the vertebra through radiofrequency channels. The radiofrequency range is determined according to the size of the lesion before surgery, and temperature changes around the spinal cord are monitored during radiofrequency ablation; (4) During the separation surgery process, 360° annular decompression of the spinal cord must be performed to ensure a safe gap of more than 5 mm between the dura mater and tumor tissue.

The interval between surgery and radiotherapy for spinal metastases should be more than 2 weeks to allow for incision healing²². In this study, patients in group A had no local tumor progression while waiting for postoperative radiotherapy. In terms of inhibiting tumor progression, separation surgery combined with radiofrequency ablation and bone cement strengthening therapy was more advantageous. The authors consider the reasons for preoperative tumor progression as follows: (1) A long interval of chemotherapy in the operative area; (2) Close correlation with the primary tumor's characteristics; (3) Failure to completely meet the standard of separation surgery during the operation; (4) Patients often have overly optimistic expectations for pain and symptom relief, recovery, and prognosis after spinal metastases surgery or advanced cancer treatment²³.

However, separation surgery combined with radiofrequency ablation and bone cement strengthening has achieved satisfactory clinical results in the treatment of thoracolumbar metastatic tumors. Nevertheless, we must acknowledge that there are still some limitations in this study: (1) This study is a retrospective clinical study with a low level of evidence; (2) It is a single-center study with a small sample size; (3) The primary tumor heterogeneity among patients with spinal metastases is large, which further increases the heterogeneity of the study; (4) Patients with spinal metastases have shorter survival and shorter follow-up time. Therefore, designing a prospective, multi-center, large-sample, randomized controlled study is needed to further elucidate the results of this study.

Materials

Name	Company	Catalog Number	Comments
Bone cement	Tecres S.P.A	1230
CArm Xmedical equipment	Siemens Healthcare	Cios Spin
CT machine	Siemens Healthcare	SOMATOM Force
MRI machine	Siemens Healthcare	MAGNETOM Terra
Pedicle screws	Shandong Weigao Medical Equipment Co., LTD	Premier-6.6mm*45mm
Radio-frequency ablation instrument	Mianyang Leading Electronic Technology Co.,ltd.	LDRF-120S
Radiofrequency ablation needle	Mianyang Leading Electronic Technology Co.,ltd.	RFDJ03
Radiofrequency Ablation Needle	Varian Clinac	IX
Ultrasonic Osteotome System	Misonix INC	MXB-10
X-ray machine	Philips Investment Co., LTD. Medical system	XR/a