The first-ever clinical classification of metastatic spinal malignancies serves as a vital reference to surgical management:a retrospective case-control study

doi:10.21203/rs.3.rs-2971720/v1

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The first-ever clinical classification of metastatic spinal malignancies serves as a vital reference to surgical management:a retrospective case-control study

https://doi.org/10.21203/rs.3.rs-2971720/v1

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Background: It is commonly accepted that Surgical treatment is an essential component of the comprehensive treatment of metastatic spinal malignancies. However, Up until now, the clinical classification of metastatic spinal malignancies has not been well-structured.

Methods: After IRB approval, 86 patients with metastatic spinal malignancies who underwent therapy at the Second Hospital of Shanxi Medical University between January 2014 and March 2020 were adopted. According to the vascular distribution, stability of vertebrae and the degree of nerve compression, osteolytic metastatic spinal tumors can be classified into five types. 20 of them who did not receive segmental arterial embolization was set as a control group. The standard group included 24 patients who received segmental arterial embolization on both sides of the diseased vertebrae. 42 patients were included in the intervention group after receiving responsible arterial embolization. Surgical intervention was performed within 24 hours following an embolization.

Results: In comparison with the control and standard groups, the intervention group presented unique advantages in terms of bleeding volume (p＜0.001), operating time (p＜0.001), and local recurrence rate within 12 months (p＜0.006).

Conclusion: The promising surgical intervention strategies can be developed according to the new clinical classification of metastatic spinal malignancies.

Metastatic spinal malignancy

Clinical classification

Offending arterial embolization

Surgical intervention

Several kinds of cancers can easily metastasize to the spine through hematogenous spread, causing metastatic spinal malignancies^[1]. Generally speaking, local hematogenous dissemination, lymphatic dissemination, or implantation metastases are no longer present in metastatic spinal malignancies, which are typically locally infiltrative in growth^[2]. Metastatic spinal malignancies are commonly osteolytic, destabilizing the spine and compressing the spinal cord and nerve roots^[3]. The purpose of the surgical procedure is to relieve pain, reestablish the spinal stability, release the compression of spinal cord and nerves, and quickly make patients regain the self-care ability^[4].

As we all know, the Enneking, Tomita, and WBB scores can often offer surgical therapy guidelines for primary spinal tumors^{[5, 6]}. Although the ESCC (epidural spinal cord compression) scale can be used to assess the level of spinal cord compression brought on by metastatic spinal malignancy, the specific classification of metastatic spinal malignancy has not been described. In clinical settings, doctors may choose to perform preoperative angiography on the tumor supply arteries of metastatic spinal malignancies to carry out vascular embolization at the appropriate blood supply sites. Additionally, preoperative imaging of the tumor supply arteries can help assess the degree of tumor erosion as hematogenous spread is the primary way that the primary tumor metastasizes to the vertebral body. In this study, to help surgeons make accurate surgical decisions, we developed a specific clinical classification based on the characteristics of the blood supply to metastatic spinal malignancies. Also, the potential of employing the classification to guide surgical plan is evaluated.

2.1. Patients

The clinical and radiological data of patients with metastatic spinal tumors who underwent surgical treatment in the Second Hospital of Shanxi Medical University from January 2014 to March 2020 were collected for retrospective analysis. 86 patients were finally included in this study. The general systemic condition, degree of spinal cord compression (ESCC score) and spinal instability (SINS score) of patients were assessed to determine the surgical intervention.

2.2. Vertebral Zone Division of Metastatic Spinal Malignancies

The vertebrae was divided into three sections (section 1, 2 and 3) according to the vertebral vascular distribution (Fig. 1). Section 1 refers to the vertebral body including 2/3 of the anterior vertebral body (Zone ①) and 1/3 of the posterior vertebral body (Zone ②) (Fig. 2). The anterior vertebral body is supplied by the epiphyseal artery, periosteal artery, and epiphyseal reticular artery from the segmental artery. The posterior vertebral body is supplied by the nutrient artery from the anterior branch of the spinal canal artery, which derives from the spinal branch of the segmental artery posterior branch. Section 2 consists of the isthmus of the vertebral pedicle, vertebral pedicle, articular process and transverse process. The posterior branch of the segmental artery sends out dorsal branches and transverse branches. Then the dorsal branch sends out superior articular, inferior articular and interarticular branches to supply blood for the superior and inferior articular process, pedicle isthmus, and vertebral pedicle. The transverse branch sends out the anterior transverse process artery and supplies blood for the transverse process. Section 3 is composed of the vertebral plate and spinous process. The posterior branch of segmental artery sends out spinal branches and then forms posterior branches of the vertebral canal, which supplies blood for vertebral plate and spinous process.

2.3. Vertebral Classification of Metastatic Spinal Malignancies

According to the vascular distribution, stability of vertebrae, and the degree of nerve compression, osteolytic metastatic spinal tumors can be classified into five types. Type I refers to tumors mainly located in the vertebral body, consisting of Ia (tumors localized in the vertebral body) and Ib (tumors breaking through the posterior wall of the vertebral body). Type Ib can be further divided into Ib① and Ib②. Type II refers to the tumors located in the vertebral pedicle, superior and inferior articular process, and transverse processes, which can be classified into type IIa (tumors localized within the bone cortex) and type IIb (tumors breaking into the spinal canal through the bone cortex). Type III indicates the tumors located in the vertebral plate and spinous process, including IIIa (tumors localized within the bone cortex) and IIIb (tumors breaking through the bone cortex). Type IV a complex of type I, II and III, includes type IVa and IVb. Type IVa is a combination of Type I and II (tumors located in the lateral anterior of vertebrae) while type IVb is a composite of Type II and III (tumors located in the posterolateral of vertebrae). Tumors of type I, II and III occur together and grow from multiple directions into the spinal canal is classified as type V (Fig. 3)

2.4 Surgical strategy

The sites of tumors were determined based on the vascular distribution in the vertebra of metastatic spinal malignancies and preoperative imaging data. The embolization and angiography of offending arteries that fed the tumors were performed. There are several strategies for embolization. One is the embolization of the blood supply to the vertebral arch, which requires embolization of the posterior artery emanating from the segmental artery. The whole-spine blood supply was embolized for mixed tumors affecting all parts of the vertebra. Embolization was not performed on segmental arteries which supply the spinal cord. The flow during particulate embolization was determined by roadmap and angiography. At the end of the embolization, tumor vessels were completely checked by the final series of angiography, and hemostasis was performed with the coil. After embolization, injections at the superior or inferior level to the embolized segment were performed to show relieved redness and swelling in tumors and reduced additional collateral branches.

Within 24 hours after embolization, cytoreductive surgery, and reconstruction were performed. Based on the vertebral classification of metastatic spinal malignancies, there were four types of surgical interventions. 1) type I, curettage and reconstruction of tumors in the anterior vertebral plate of the posterior vertebral canal, 2) type II, curettage and reconstruction of tumors in the lateral vertebral plate of the posterior vertebral canal, 3) type III, curettage and reconstruction of tumors in the posterior vertebral plate of the posterior vertebral canal, and 4) type IV and V, curettage, and reconstruction of surrounding tumors in the posterior spinal canal.

2.5. Statistical Methods

Categorical data were compared using Chi-squared analysis and mean values in the different treatment groups were compared using t-tests. The SPSS software (IBM SPSS Statistics for Windows, version 24.0; IBM Corp., Armonk, NY, USA) was used for statistical analysis. p < 0.05 was considered significant difference.

3.1 General Data of Patients

The mean age of patients in these three groups was 64.4 ± 11.2, 59.4 ± 11.1, and 57.5 ± 10.2, respectively (p = 0.065). Forty-six patients were male, and the remaining 40 were female. The lesion was located in the thoracic vertebrae in 35 patients and in the lumbar vertebrae in the other 51 patients. There was no significant difference in demographic data such as age, gender, and primary cancer among the three groups. No significant difference was found in the revised ESCC score and SINS (ESCC score: p = 0.356; SINS = 11.2 ± 2.9, 12.7 ± 2.3, 11.6 ± 3.2, respectively. (p = 0.260)). There was no significant difference in the procedure options for patients who underwent tumor curettage among the three groups (p = 0.859) (Table 1).

3.2 Clinical classification of included patients

The 86 patients included in the study were clinically categorized preoperatively based on the cross-sectional CT and MRI examinations of spinal tumors, as shown in Table 2.

3.3. Sites of Tumor Occurrence in Vertebrae and Offending Arterial Embolization

24 patients with metastatic spinal malignancies, who underwent embolization for the bilateral segmental arteries of the diseased vertebrae, were included in the standard group. The intervention group concluded the patients that received offending arterial by embolizing with coils and gelatin sponge particles. According to the preoperative CT and MRI examinations of spinal tumors in the transverse section, metastatic spinal malignancies were divided into three groups. The specific subgroups and related intraoperative embolization are shown in Table 3. Specific cases of intraoperative embolization are shown in Fig. 4.

3.4 Comparison of surgical outcomes

There were significant differences in bleeding volume and operation time among the three groups (p < 0.001). And significant differences were observed in the local recurrence within one year after the operation among the three groups (p = 0.006) (Table 4).

The advancements in medication, radiotherapy, and surgical techniques have significantly enhanced the survival rate, functional status, and overall quality of life for cancer patients. Over time, the approach to treating patients with spinal metastases has shifted regarding the role of surgery. When it comes to treating metastatic spinal malignancies, the surgical approach taken is dependent on various factors such as the patient's overall health and the location and quantity of metastases. As an additional form of treatment, surgical procedures are progressively being utilized for patients with metastatic spinal tumors^[7]. When selecting a surgical treatment plan, it is important to consider methods that are less invasive and allow for faster postoperative recovery. This not only improves the patient's quality of life and reduces pain, but also provides systemic benefits for their overall treatment. Therefore, a simple operative approach should be chosen^[8]. Radical surgery cannot be achieved for metastatic spinal malignancies, regardless of the surgical method chosen^[9]. However, before the operation, based on CT data of metastatic spinal malignancies, the feeding offending vessels of the diseased vertebrae can be analyzed, arteries to be effectively embolized preoperatively can be planned, embolization time can be shortened, and the use of embolization materials can be reduced so that feeding vessels can be rapidly embolized, the bleeding volume during and after the operation can be effectively reduced, and the procedure cost can be saved^[10].

Tumors in the spine are distinct from those found in other areas of the body. The bone structure of the spinal column is mainly divided into the vertebral body and the vertebral arch. Compared with primary spinal malignancies, the incidence of metastatic spinal malignancies is relatively higher. Metastatic spinal malignancies destroy the bony structure of the vertebra, causing spinal instability^[11]. The spine possesses unique physiological structures that have limited blood supply, including endplates, intervertebral discs, anterior and posterior longitudinal ligaments, and fasciae of the surrounding muscular tissues. When metastatic spinal tumors are present, the tumor cells typically spread within the vertebra until the bony structure is destroyed, leading to pathological fractures. The tumor tissue then expands into the surrounding soft tissue and grows in an infiltrating manner, forming a tumor envelope that compresses the spinal cord and nerve roots, causing pain and paralysis. According to the location and direction of tumor growth, the tumors occurring in the vertebral bone grow into the spinal canal, towards the anterior (a), posterior (p), and lateral (t) directions of the spinal cord, respectively (Fig. 5)^[12]. Some reasons for surgery are when the spinal cord is compressed within the spine or when the nerve roots outside of the spine are compressed. Depending on the particularity of the spinal structure, intralesional excision is always required to preserve important nerve and vascular structures and reduce the incidence of complications. Decompression surgery based on this special anatomy can guide the method of cytoreductive surgery^[13]. The scope of cytoreductive surgery should be consistent with the location of tumor occurrence, and other adjuvant therapies should be combined postoperatively.

Before a surgery to treat diseased vertebrae, there are two primary ways to block blood supply. The first involves obstructing blood flow to the vertebral body by directly embolizing the main branch of the segmental artery. The second method involves obstructing blood flow to the vertebral arch by embolizing the posterior branch of the segmental artery. The segmental artery on the right side of the vertebral body travels around it, as the thoracic and abdominal aorta is situated on the left. This artery gives rise to several nutrient arteries of the anterior and lateral vertebral bodies, posterior branches of the right vertebral arch, and right intercostal arteries at the middle point. Therefore, if the right anterior 2/3 vertebral body and the right side of the vertebral arch are invaded by tumors, embolization can be performed through the right segmental artery; if lesions only occur in the right vertebral arch, embolization can be performed through the posterior branches of the right segmental artery; the left anterior 1/3 vertebral body is supplied by the left segmental artery, and the left vertebral arch is supplied by the posterior branch of the left segmental artery, so it can be embolized through the same approach after lesion occurs^[14]. Prior to the surgery, imaging data can be used to determine the zoning and classification of metastatic spinal malignancies, which serves as a preoperative guide for the location of arterial embolization. CT scans, which provide high density resolution, are advantageous in observing bone destruction, particularly in detecting early mild bone destruction and destruction of facet joints of the vertebral arch. However, it is inferior to MRI in visualizing early-stage bone marrow infiltration. Enhanced CT can show the artery course and bone morphology (Fig. 6).

Studies have shown that successful embolization of the offending vessel can significantly reduce blood supply to the tumor and minimize perioperative bleeding, as indicated by preoperative angiography of the affected vertebrae^{[15, 16]}. A successful preoperative embolization of the affected artery can minimize harm to other structures in the spine due to loss of blood supply, as well as prevent complications related to nerve damage.It was discovered that there is no involvement of the intervertebral disc. This may due to the fact that intervertebral disc has avascular structures, making it less accessible for the tumor thrombus. Meanwhile, the transparent cartilage of the endplate caan potentially act as a protective barrier against the invasion of cancer tissue.

Our study also have certain limitations. In order to examine the efficacy of clinical surgical treatment for metastatic spinal tumors, we conducted preoperative angiography which revealed a thinner inferior feeding artery. Moreover, the embolization materials and embolization technology, with certain limitations, cannot reach the level required by this study, and currently, only the closest origin of the above-mentioned artery can be embolized. Because of the limited number of patients and brief follow-up period, it is not feasible to establish a correlation between the current treatment approach and survival or local recurrence rate over an extended postoperative duration. Additionally, it is challenging to determine the precise therapeutic impact of preoperative arterial embolization, combined with curettage in the arterial supply region, on spinal metastases.

The clinical classification of metastatic spinal malignancies has some significance for the preoperative classification evaluation and surgical treatment plan of patients and may be considered as the new standard of surgical surgery for metastatic spinal malignancies.

IRB Institutional Review Board

WBB Weinstein-Boriani-Biagini

ESCC Epidural Spinal Cord Compression

SINS Spinal Instability Neoplastic Score

SPSS Statistical Product and Service Solutions

CT Computer Tomography

MRI Magnetic Resonance Imaging

Ethics approval and consent to participate

This study was approved by the institutional review committee of the Second Hospital of Shanxi Medical University.

Consent for publication

Not applicable.

Availability of data and materials

All data generated or analysed during this study are included in this published article.

Competing interests

The authors declare that they have no competing interests.

Funding

This work was supported by the National Natural Science Foundation of China (Grant Number 81902273).

Authors' contributions

BJJ and LJ contributed to data collection, analysis and interpretation; LJ and YWZ contributed to manuscript preparation and editing; WYS contributed to revision of the manuscript; LZ and FY were involved in supervision. All authors read and approved the final manuscript.

Acknowledgements

Not applicable.

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Table 1 Tumor location of metastatic spinal malignancy.

	Tumor Location
	Ib	IIb	IIIb	IV	V
Primary Cancer
Renal Cancer 12	6	1	1	3	1
Thyroid Cancer 3	1	1		1
Breast Cancer 13	5	3	1	4
Lung Cancer 38	16	8	2	10	2
Prostate Cancer 7	4	1		2
Hepatic Cancer 3	4	1		2
Colon Cancer 1	1
Gastric Cancer 2		1		1
Esophageal Cancer 1				1
Bile Duct Cancer 1		1
Pancreatic Cancer 1	1
Cervical Cancer 3	2	1
Bladder Cancer 1		1

Table 2 Characteristics of patients in different groups.

Groups	Non-embolization Group		Embolization Group	Offending Embolization Group		P-Value
Number of Cases	20		24	42
Gender					0.179
Male	12		13	21
Female	8		11	21
Age (Years)	64.4±11.2		59.4±11.1	57.5±10.2		0.065
SINS	11.2±2.9		12.7±2.3	11.6±3.2		0.260
ESCC Grade					0.356
1		3	1	8
2		8	7	15
3		9	16	19
Primary Cancer Renal Cancer 12 Thyroid Cancer 3 Breast Cancer 13 Lung Cancer 38 Prostate Cancer 7 Hepatic Cancer 3 Colon Cancer 1 Gastric Cancer 2 Esophageal Cancer 1 Bile Duct Cancer 1 Pancreatic Cancer 1 Cervical Cancer 3 Bladder Cancer 1		2 1 12 3 1 1	6 1 4 7 2 1 1 1 1	4 2 8 19 2 1 1 1 1 2 1
Affected Part of Vertebra
Thoracic Vertebra		2	14	19
Lumbar Vertebra		18	10	23
Surgical Methods						0.859
1	4		5	7
2	5		7	15
3	3		6	6
4	8		6	14

Table 3 Sites of tumor occurrence in vertebrae and offending arterial embolization.

Tumor Location

The Location of Offending Arterial Embolization

Ib②, IIIb

IIb

Ib①, IV, V

Spinal Branches

Dorsal and Transverse Branches

Segmental Arteries

Primary Cancer

Renal Cancer 4

Thyroid Cancer 2

Breast Cancer 8

Lung Cancer 19

Prostate Cancer 2

Liver Cancer 1

Gastric Cancer 1

Bile Duct Cancer 1

Pancreatic Cancer 1

Cervical Cancer 2

Bladder Cancer 1

Table 4 Comparison of patients’ characteristics during and after surgery among groups.

Surgical Methods	Non-embolization Group	Embolization Group	Offending Embolization Group	P-Value
Bleeding Volume	4113.9±1537.0	1476.5±371.2	836.9±270.6	<0.001
Operation Time	263.4±33.9	233.5±38.0	184.9±30.4	<0.001
Recurrence within 1 Year				0.006
Recurrence	13	8	10
No Recurrence	7	16	32

No competing interests reported.

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You are reading this latest preprint version

The first-ever clinical classification of metastatic spinal malignancies serves as a vital reference to surgical management:a retrospective case-control study

Status:

Version 1

Abstract

Figures

1. Introduction

2. Materials and Methods

2.1. Patients

2.2. Vertebral Zone Division of Metastatic Spinal Malignancies

2.3. Vertebral Classification of Metastatic Spinal Malignancies

2.4 Surgical strategy

2.5. Statistical Methods

3. Results

3.1 General Data of Patients

3.2 Clinical classification of included patients

3.3. Sites of Tumor Occurrence in Vertebrae and Offending Arterial Embolization

3.4 Comparison of surgical outcomes

4. Discussion

5. Conclusions

Abbreviations

Declarations

References

Tables

Additional Declarations

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