I. Overview of glioma
Gliomas are named after the glial cells from which they originate. Glial cells form the supporting tissue of the brain and can be described as holding nerve cells (neurons) together like “jelly”. Gliomas are the most common tumors of the brain and spinal cord, accounting for more than 60% of all primary brain tumors. In the brain, neurogliomas often occur within the cerebral hemispheres (located in the upper part of the brain), but may also affect other brain regions, especially the optic nerve, brainstem, and cerebellum.
There are three types of glial cells – astrocytes, ventricular meningeal cells, nuclear oligodendrocytes – and gliomas can originate from any of these cells. The most common type of glial cell is the astrocyte, and tumors derived from this cell are called astrocytomas.
Gliomas can progress from a low grade to a higher grade, or they can recur after surgery and become a higher grade tumor, or they can start out as a high grade tumor. The term “high-grade glioma” includes both mesenchymal astrocytoma and glioblastoma multiforme.
Mesenchymal astrocytomas account for 22% of all gliomas, and astrocytomas arise from glial cells called “astrocytes” (star-shaped supporting cells in the brain). They can be found anywhere in the central nervous system (CNS), including the brain and spinal cord, but the most common site is the frontal lobe. Interstitial astrocytoma (AA) is a grade III astrocytoma. “Mesenchymal” means that the cancer cells have characteristics of rapid division and do not resemble normal cells or have little resemblance to them.
Glioblastoma multiforme (GBM) is a grade IV astrocytoma. It accounts for 52% of all brain gliomas and is the most common type of brain tumor in adults. This type of tumor contains extremely aggressive cells that can rapidly invade surrounding tissues. It usually originates in the cerebral hemispheres, but can also be seen in any other part of the central nervous system.
II. Possible Symptoms
Brain tumors usually invade or extend into normal brain tissue, and the pressure of their growth may cause symptoms such as nausea, seizures, vomiting, dizziness or weakness of the upper and lower extremities. These symptoms may be related to the occupancy of the tumor itself or to the swelling (edema) in the area surrounding the tumor. The same – individual may present with many different types of symptoms, or may be asymptomatic for a long time, or have only mild symptoms.
Common symptoms may include symptoms of high cranial pressure such as headache and vomiting, or changes in higher intelligence such as decreased intelligence and speech difficulties. Tumors located in functional areas may also cause symptoms such as hyperalgesia, limb weakness, and hemiparesis. Epilepsy is often the only manifestation of low-grade glioma.
Treatment of glioma
At present, the treatment for glioma at home and abroad is surgery, radiotherapy and chemotherapy.
(A) Surgery
Glioma is a common intracranial malignant tumor, which is characterized by infiltrative growth, unclear boundary and easy recurrence, and is the most common primary tumor in the skull. The surgical treatment of glioma in functional brain area is a difficult problem in neurosurgery clinical work. Maximizing the removal of lesions while protecting normal brain function as much as possible, while preserving neurological function to a large extent and avoiding postoperative neurological deficit, which not only improves the quality of postoperative survival of patients, but also can obtain satisfactory long-term prognosis, is the highest goal of surgical treatment of glioma.
1. Surgical purpose.
Surgical resection is the most critical first step in the comprehensive treatment strategy of glioma. The main purposes of surgery include: so the therapeutic purpose of surgery can only be limited to the following five aspects
(1) To clarify the pathological diagnosis;
②reduce the tumor volume to decrease the number of tumor cells.
③Improve the symptoms and relieve the high cranial pressure symptoms;
④Prolonging life and creating the opportunity for other comprehensive treatments to follow;
⑤ Obtain tumor cell kinetic information to provide the basis for finding effective treatment.
2. Surgical concept change.
With the progress of society and the improvement of people’s quality of life, there is a new change in the international philosophy of surgical treatment for glioma, that is, from the past priority of “Maximal Resection” to “Maximal Safety”. “This is to ensure the removal of the tumor while maintaining the neurological integrity and better quality of life of the patient.
3.Application of new surgical techniques
(1) Preoperative precise tumor localization
The CT and MRI should be read carefully, and the coronal suture and cerebral gyrus morphological signs shown by MRI should be used to locate the tumor as accurately as possible. According to the location of the tumor, the corresponding cortical approach should be adopted.
(2)fMRI
The recently developed blood oxygen level-dependent technique is the basis for the application of fMRI. fMRI can perform functional analysis of the human brain under safe and non-invasive conditions, and its high temporal and spatial resolution can non-invasively display the relationship between the tumor and functional areas, which helps to select the best surgical plan or pathway.
(3) Diffusion tensor imaging (DTI)
If preoperative imaging techniques can localize subcortical pathways, it can avoid postoperative neurological deficits as well as provide a better understanding of the pathways between functional areas. While the aforementioned functional neuroimaging cannot localize white matter fiber tracts, DTI can show specific white matter fiber tracts in the living brain by measuring the diffusion process of water molecules to evaluate the biological tissue structure and physiological state, and can clarify the spatial anatomical relationship between the tumor and adjacent white matter fiber tracts, thus assisting in the development of surgical plans and assessment of patient prognosis.
(4) Intraoperative arousal anesthesia technique
This technique is used in neurosurgery to wake up the patient intraoperatively and perform microsurgery to completely remove the lesion in the awake state, using nerve block and target-controlled infusion (TCI). After the lesion is removed, general anesthesia is restored, and hemostasis and cranial closure are performed. In the surgical treatment of lesions in functional areas of the brain, the difficulty of localization is a problem frequently encountered by neurosurgeons. Maximizing the removal of lesions while maximizing the protection of normal brain function is a key issue that is difficult to master during the surgical operation, which is also related to the quality of the patient’s survival after surgery.
(5) Neuronavigation technology and intraoperative imaging technology
Glioma is the most common intracranial tumor with infiltrative growth, which is difficult to be removed by conventional surgery. The emergence and development of neuronavigation technology in recent years has provided us with a precise, convenient, safe and effective surgical method, which greatly improves the rate of complete resection of lesions and surgical safety. It can be said that the application of neuronavigation system is an important symbol of the development of neurosurgery from microsurgery to microinvasive surgery.
(6) Intraoperative functional localization techniques
The central sulcus has always been the anatomical boundary that delineates the cortical sensory and motor areas. Using the property that the proprioceptive evoked potentials are phase-inverted in the central area, it is a very reliable and practical method to identify the boundaries of the sensory and motor cortical functional areas during surgery.
(7) Intraoperative ultrasound
Intraoperative ultrasound can accurately localize the lesion and functional area, and clearly determine the tumor size, boundary, location, and relationship with the surrounding brain tissue and blood vessels. This greatly improves the surgical quality and surgical effect of functional area glioma and improves the postoperative survival and survival quality of patients.
(II) Radiotherapy
Radiotherapy is the routine treatment for almost all types of glioma, but the efficacy is evaluated differently, except for medulloblastoma which is highly sensitive to radiotherapy and ventricular meningioma which is moderately sensitive, other types also have some effect on radiotherapy. X-knife and γ-knife are in the category of radiation therapy, but the treatment scope is limited by the location, size and sensitivity of the tumor to radiation, and it is believed that glioma, especially malignant astrocytic grade III-IV or glioblastoma, is not suitable for γ-knife treatment.
Radiotherapy can kill or inhibit residual tumor cells and prolong survival; external radiation therapy has become the standard treatment for malignant glioma. In recent years, multiple dose fractionation methods, multiple radiotherapy modalities (three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), intra-stromal brachytherapy and stereotactic surgery) and the application of new radiotherapy equipment have improved the effectiveness of radiotherapy. Simultaneous temozolomide (TMZ) radiotherapy combined with adjuvant chemotherapy has become the standard of care for newly diagnosed GBM.
The US NCCN guidelines recommend a total radiotherapy dose of 60 Gy for malignant glioma, split into 1.8-2 Gy/dose. Patients aged >70 years who require assistance in life may be treated with a reduced dose of radiation therapy: 15 fractions of 40Gy or 28 fractions of 50Gy. Whole brain radiotherapy and gamma knife radiotherapy are not recommended.
(C) Chemotherapy
In principle, it is used for malignant tumors, but the efficacy of chemotherapeutic drugs is still unsatisfactory due to the limitation of blood-brain barrier and toxic side effects of drugs, and the efficiency of commonly used BCNU, CCNU and VM-26 is about 30%. In recent years, with the application of emerging chemotherapeutic drugs such as temozolomide and avastin, the treatment effect of high-grade glioma has been improved.
The 2012 edition of the Guidelines for the Diagnosis and Treatment of Glioma in China recommends newly diagnosed GBM (WHO grade IV): TMZ synchronized radiotherapy combined with adjuvant chemotherapy is strongly recommended: the whole course of radiotherapy should be synchronized with chemotherapy, oral TMZ 75 mg/m2 for 42 days. After 4 weeks of radiotherapy, adjuvant TMZ treatment at 150 mg/m2 for 5 days is recommended for a course of 28 days, and if well tolerated, it will be increased to 200 mg/m2 in subsequent chemotherapy courses.
ACNU (or other alkylating agents BCNU, CCNU) in combination with VM26 can also be used according to the actual situation in China: ACNU (or other alkylating agents BCNU, CCNU) 90 mg/m2, D1, VM-26 60 mg/m2, D1-3, 4-6 weeks in 1 cycle, 4-6 courses. Newly diagnosed mesenchymal glioma (WHO grade III): recommended radiotherapy combined with TMZ (same as GBM) or nitrosoureas: PCV regimen (lomustine + methylbenzhydryl + vincristine); nitrosoureas, such as ACNU regimen.
(iv) Other treatments.
Gene therapy, immunotherapy, molecular chemotherapy, etc., are mostly in the research stage and their efficacy is not yet certain.
New therapeutic tools include.
(1) Development of new drugs to block more than 1 cell proliferation signaling pathway.
(2) Overcoming the resistance of current chemotherapeutic drugs.
(3) Targeted therapies, such as the vascular endothelial growth factor (VEGF) antibody bevacizumab (bevacizumab).
(4) Ongoing research on the efficacy of tumor stem cell therapy, which will reduce patient mortality through new drug cocktail therapies targeting important molecular pathways by 2020, offering new hope for patients and physicians.