Treatment strategy and prognosis of spinal glioma

Treatment strategy and prognosis of spinal glioma

Treatment strategy and prognosis of spinal glioma.  2020 China Conference on Oncology (CCO) Neuro-Oncology Committee and Glioma Committee Joint Meeting (graphic summary), Director of Neurosurgery, Beijing Tsinghua Chang Gung Memorial Hospital, Tsinghua University Professor Wang Guihuai gave a report entitled “Tsinghua Chang Gung University’s View: Treatment Strategies and Prognosis of Glioma of the Spinal Cord”.

Professor Wang Guihuai and his team analyzed the clinical data of 308 cases of spinal glioma in the hospital from December 2014 to April 2020, and made a detailed summary, pointing out that the domestic neurosurgery research on spinal glioma is still serious Inadequate status.

Professor Wang Guihuai concluded his speech and pointed out that the incidence of spinal glioma is much lower than that of glioma, and little is known about it. Brain injury can be compensated, but spinal cord injury is difficult to compensate. Therefore, spinal glioma Tumor surgery requires caution; MR suggests diffuse and borderless tumors, the extent of surgical resection and prognosis are controversial, the effect of radiotherapy and chemotherapy is uncertain, and the prognosis of high-grade spinal glioma is extremely poor; MR T2WI shows high signal with border or enhanced scan Glioma of the spinal cord with clear borders should be completely removed with maximum safety. Low-grade gliomas have a good prognosis and ependymomas can be cured; tumor molecular level research is the only way for personalized and precise treatment of spinal gliomas.

The functional anatomy of the spinal cord is full of functions. Compared with the brain, the anterior longitudinal fissure is the same as the posterior longitudinal fissure. The center is gray matter, and the periphery is white matter. Gray matter and white matter alternate. The conduction beams in the brain descend through the spinal cord to various parts of the body or organs, and all functions in the brain They all correspond to the spinal cord. The spinal cord sends sensory information from all parts of the body to the brain at all times. Unfortunately, the imaging structure cannot clarify these problems. Fortunately, the spinal cord is more difficult than the brain. But the important structures of the spinal cord are all concentrated. Except for the basic T1 image and T2 image, MRS can hardly satisfy the diagnosis of spinal cord diseases. The current research on the spinal cord is far from enough.

In the 100-year history of surgical treatment of spinal cord tumors, it has been more than 100 years since the first surgery for spinal cord tumors. The surgical technique is the same as glioma. It is more challenging than brain diseases. Patients with hemisphere resection can still Walking, a slight deviation of the spinal cord may cause paraplegia. Aside from national masters, domestic academician Wang Zhongcheng was engaged in this field in the late 1980s, when brain stem tumors and spinal cord tumors were called “forbidden areas.” In 1994, I followed Academician Wang to study the cervical spinal cord, including medullary tumors. After more than 20 years of experience, I felt that the treatment of spinal glioma was very difficult.

The NCCN guidelines in the United States have hardly changed since 2005. There are borders and no borders. This guide is very simple. MRI of spinal glioma, first, the border is better, of which ependymoma and hair cell astrocytoma are the best. These tumors, if they can Surgery is completely cut off, do not give any room for radiotherapy and chemotherapy. This reflects the technical level and superb skills of the surgeon. If the patient is paralyzed or died after the operation, it will not work. In fact, these cases are WHO Ⅰ, WHO Ⅱ more, WHO Ⅲ There are few levels.

Second, the boundaries of MRI images are unclear and boundless. No matter how many techniques including surgery, radiotherapy and chemotherapy, no matter how many techniques, including metabolism, can not solve this problem. These guidelines have no consensus at all. In glioma of the spinal cord, these are mainly boundless references. The problem is that the microenvironment of the spinal cord is different from that of the brain. The blood vessels supply the brain barrier and the blood spinal cord barrier are different. There are much more microglia than the brain, and molecular MARK is different. The guide is the reference, and the world knows too little about this aspect. There are some cases for you to share later.

Tsinghua Chang Gung-Clinical Data Analysis of 308 Cases of Spinal Glioma

Here are some clinical data of 308 cases of spinal glioma in Tsinghua Chang Gung Memorial Hospital in the past 5 years (December 2014-April 2020), and share with you.

1. Glioma of the spinal cord-preoperative data evaluation and analysis

Spinal cord tumors (also known as intraspinal tumors) and brain tumors, 85% are brain tumors, 15% are spinal cord tumors, each unit is about this ratio; spinal gliomas account for about 1/3 of spinal canal tumors. The previous data stated that gliomas account for 40-50% of brain tumors, while spinal gliomas account for a little bit lower.

There is no difference in gender and age; but there are many symptoms: all functions such as paresthesias, weakness, pain, and urinary disorders may be affected.

In terms of the course of the disease, some gliomas last for half a year and a year, the longest is 10 years, and there are more than ten years and 20 years to come to see the doctor. It is found that the tumor is still growing for more than ten years and no surgery is required.

During the course of the disease, 238 people were misdiagnosed and mistreated, accounting for 77.27%; about 70 people were misdiagnosed and mistreated, accounting for 22.73%, and most of them were mistaken for cervical spondylosis, myelitis, lumbar spondylosis, etc. Or lumbar spondylosis has been diagnosed and treated for many years and has not been found, so prevention is impossible.

The preoperative dysfunction classification. If the tumor is found to be large and can still go to work, the function is obviously light; some patients cannot walk, some patients cannot urinate and urinate, some patients have difficulty breathing, etc. These levels are different. Most are related to the nature of the tumor. Statistics show that WHO Ⅰ level: 128 people accounted for 41.58%, WHO II level: 99 people accounted for 32.14%, WHO III level: 38 people accounted for 12.34%, WHO IV level: 42 people accounted for 13.64%.

Spine deformities before surgery. After the tumor grows, the shape of the spine changes, such as scoliosis, especially in adolescents. The incidence of preoperative conditions accounts for about 18.51%.

Tumor segment and length: The tumor runs through the entire length of the spinal cord, growing from the cervical spinal cord to the vertebral vertebrae, most of which are mainly in the neck, dilated spinal cord, and cervical vertebrae, with very few thoracolumbars.

Preoperative MRI evaluation: At present, the preoperative diagnosis of glioma of the spinal cord is mainly MRI. Unenacted MRI (T2 image) may be more valuable, plus enhanced examination; if inflammatory lesions are suspected, peripheral blood and Cerebrospinal fluid immunological examination can be used for identification, and hormone therapy can be used; if it is not sure that it is inflammation, there is basically no way to diagnose it; if some patients undergo neurological treatment for 3 months, they are still tumors in the neurosurgery assessment. This is an unsolved problem in clinical diagnosis.

[Case] ​​33 years old, male, right upper limb weakness for 2 years, neck pain for 6 months

Preoperative MRI: Spectroscopic and diffusion tensor imaging C2-C7, many abnormal signals, where is the tumor and how to do it? Both DTI and MRS suggest that gliomas may be possible, but MRI is not satisfactory, and metabolism does not provide much information.

2. Glioma of the spinal cord-intraoperative technical evaluation and analysis

Postoperative pathology: In terms of pathological diagnosis in Chang Gung Memorial Hospital, when most patients have problems, it is very difficult to agree on the diagnosis. Glioma may be better, but there are still problems with spinal cord tumors.

Pathological grade: WHO grade II accounts for about 64%, WHO grade I accounts for 16%, and grade III and IV account for less than 20%, so 70-80% are benign tumors, which are not the same as gliomas. A neurosurgeon should do a good job of spinal glioma. The remaining 20% ​​is very difficult and everyone is working on it.

Extent of resection: total resection, subtotal resection, partial removal, biopsy, decompression, etc. This is not a simple description of the operation, but is determined by imaging standards, which are international standards.

In our group of cases, the imaging standard of 98% of the total resection is about 68%, and the subtotal resection is about 20%. Nearly 90% of the two have reached a relatively good surgical record. As the pathology said, there are 80% of spinal gliomas. About% are WHO grade II and I tumors, so the role of surgery is very important.

Intraoperative technique 1: Fluorescence assisted technique

It is a detection method in which the fluorescence signal intensity in a specific area is significantly greater than the surrounding area by injecting a fluorescent color reagent from the outside through the absorption or metabolism of biological tissues. In spinal glioma tumors, the imaging NMR is enhanced, and most of the yellow fluorescence can be reproduced during the operation (95.6%), and of course there are about 10 consistent cases.

【Case】Intraoperative technology 2: Multimodal fusion technology

Intraoperative MRI may be difficult for the spinal cord, including multimodal imaging, intraoperative mobile CT and preoperative MRI fusion, it can accurately locate the tumor, the error is within millimeters, which is more accurate for our surgery to cut the spinal cord. Very good effect, I think, it is no less than the charm of intraoperative NMR.

【Case】Intraoperative technique 3: Neuroelectrophysiological monitoring

Electromyography EMG, somatosensory evoked potentials SSEPs, motor evoked potentials MEPs, etc., if there is no neuroelectrophysiological monitoring, it should be illegal for us to do spinal cord tumor surgery.

• [Case] ​​In this case, the nodular glioma was diffuse before surgery. How much can the tumor be cut? I do near total resection. Intraoperative MEP of extremities suggests deep sensory conduction disorders. During the operation, the MEP of the left upper limb and both lower limbs disappeared completely, and some doctors thought that the operation might be stopped. Can the patient stand immobile, will it stop immediately during the operation? According to our clinical experience, we can continue to do so to completely remove the tumor. The patient’s right lower limb muscle strength was grade IV, left muscle strength was grade III, and limb muscle strength was grade IV 7 days after operation.
• [Case] ​​Hairy cell mucinoid astrocytoma, diffuse type, intraoperative MEP of extremities suggests deep sensory conduction disorder, both lower MEPs are not induced during operation, MEP of left upper limb disappears, and MEP amplitude of right upper limb decreases by more than 50%. Receiving troops? After the operation, the right lower limb muscle strength was grade I, and the rest was normal. 14 days after the operation, the right lower limb muscle strength was grade IV.

These electrophysiological conditions make us rethink, do we rely on electrophysiology or what to decide whether the operation should stop?

Intraoperative technique 4: lamina reduction/internal fixation
Laminectomy, laminectomy, internal fixation, etc., are controversial in spinal and spinal surgery.

We did 308 cases, of which 238 cases of laminoplasty accounted for 77.27%, 57 cases of laminectomy accounted for 18.51%, and 13 cases of partial formation + resection accounted for 4.22%.

In our study, 27 cases of postoperative progressive spinal deformity accounted for about 25.7%. The results of this study were published in the journal JNS-SPINE.

Risk factors for progressive spinal deformity after surgery. Among the related factors, age is the main factor. The younger the age, the more serious; the more surgical segments, the more serious; in addition, those who have been exposed to radiotherapy or undergoing surgery before surgery are prone to deformity, others None of the problems are major.

Can laminoplasty prevent stability? This case is a diffuse astrocytoma, male, 13 years old, with neck pain for more than 4 months, the tumor was subtotal, and the postoperative follow-up for one and two years found that the spine was deformed. Therefore, the laminoplasty is not complete Solve these problems. Over time, it may cause many problems for this patient.

This patient is as tall as me after 5 years. After the operation 5 years ago, the patient now has no dysfunction and can play basketball. If his colleagues think the operation is not good or beautiful, it should be internalized, but the patient cannot accept it. , These issues will be discussed separately.

Laminectomy + spinal fixation-glioblastoma: This male, 15 years old, has neck pain and left upper limb itching for 2 months. If there is a problem before the operation, it is undoubtedly fixed directly, and the stability problem is solved soon after the operation.

Of the 308 cases, tumor resection accounted for 300 cases, and 8 cases were resection + internal fixation. But some internal fixation is controversial.

3. Glioma of the spinal cord-evaluation and analysis of the effect of postoperative adjuvant treatment

For low-grade gliomas, during our follow-up for 5 years, most of the patients were still alive. About 5 cases of first-level and second-level gliomas died. The main reason was respiratory dysfunction.

During the 5-year follow-up for high-grade gliomas, the survival rate is probably less than 30%. This is very scary.

The average survival time is about one year in the surgical treatment group, and about 14 months after surgery plus radiotherapy and chemotherapy. Surgery for high-grade gliomas seems to have no effect. Obviously, expanding excision may also be a false proposition.

There are also oligodendroastrocytomas. We have seen that the tumor is nearly completely resected. The postoperative follow-up was very good for the first three years. After the third year, it was found that the tumor recurred. It is recommended that patients with radiotherapy and chemotherapy are not willing to do it; follow-up for 3 years To 6 and a half years, follow up once every six months, the tumor is basically gone, no radiotherapy, no chemotherapy, just physical exercise. In April 2020, the patient sent a photo showing that the oligoastrocytoma has recurred, but the tumor can die out or is called autophagy, which cannot be explained.

There are still many things we don’t know after glioma.

4. Spinal glioma-molecular pathology and immunotherapy

According to the new WHO classification of central nervous system tumors, glioma has entered the era of molecular pathology. In the 2016-WHO new classification, the content of molecular genetic diagnosis includes histological diagnosis, histological analysis, molecular genetic information, etc.

There are differences between brain and spinal cord research. We are doing various molecular Marks. It seems that there is no change, and we can’t find out what is going on in the spinal cord.

Immunotherapy of GBM: Immunotherapy of glioma, Tsinghua-Chang Gung Medical-Industry Research: Research on Immunochemical Synergistic Therapy of GBM. Interferon is an immunomodulator enhancer, which is very useful in anti-tumor enhancement, and is also used in other clinical systems. We see a small protein. When the protein and interferon are combined, it is liquid at 4° and becomes milk at 30°. After surgical removal of the tumor, it is directly sprinkled in the tumor cavity, which can enhance immunity. Features. Animal experiments have shown that the residual tumor can be reduced, and the effect of temozolomide is better. Can this medicine be used like this? We are currently doing clinical trials soon, and this medicine has brought us great encouragement.

In other respects, we have also done some clinical experimental studies, and internationally, but in general, there are not many people with glioma of the spinal cord. Electric field therapy, the NCCN guidelines of the United States seem very attractive, and I very much hope that our colleagues will strengthen research in this area.

5. Summary

The incidence of spinal glioma is much lower than that of brain glioma, and little is known about it. Brain injury can be compensated, but spinal cord injury is difficult to compensate. Therefore, surgery for intramedullary glioma requires caution. MR suggests diffuse and borderless tumors. The degree of surgical resection and prognosis are controversial. The effect of radiotherapy and chemotherapy is determined. High-grade spinal glioma has a very poor prognosis. Glioma of the spinal cord on the MR T1 enhanced image or the obvious signal on the T2 image by the border should be completely removed with the greatest safety. Low-grade glioma has a good prognosis and ependymoma can be cured. Tumor molecular level research is the only way for personalized and precise treatment of spinal glioma.

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