What is glioma?
Glioma is a malignant tumor originating from glial cells and is the most common intracranial tumor, accounting for the first place of intracranial tumors (about 50%). The incidence of glioma is 3-10/100,000, accounting for 1%-3% of systemic malignant tumors, and the average survival period for surgery plus radiotherapy is only 8-11 months. In 1998, the World Health Organization announced that malignant glioma was the second cause of death for patients under 34 years of age and the third cause of death for patients between 35 and 54 years of age, ranked in order of mortality. Globally, malignant gliomas relentlessly claim the precious lives of 180,000 to 600,000 young and middle-aged people each year.
What are the types of glioma pathology?
There are four pathological types of glioma: astrocytoma, oligodendroglioma, ventricular meningioma, and mixed glioma.
Gliomas can be broadly classified according to the degree of differentiation (malignancy) – grade I: benign, mostly with long cell cycle and slow growth, such as astrocytoma and oligodendroglioma; grade II-III: also called mesenchymal astrocytoma or mesenchymal oligodendroglioma, with more or less active cells in the tumor; grade IV: most malignant, such as glioblastoma The prognosis is extremely poor.
The malignancy of gliomas often changes, for example, if a grade I astrocytoma recurs after surgery, it may be found to be a mesenchymal astrocytoma or glioblastoma when operated on again.
Gliomas are more common in males than in females, especially in glioblastoma multiforme and medulloblastoma. Most gliomas are seen between the ages of 20-50, with a peak at 30-50 years of age, and another small peak in children around 10 years of age.
Modern neuroscience can predict the growth rate, aggressiveness, and sensitivity to radiotherapy by examining tumor-specific proteins or gene expression (e.g. EGFR, P53, 1p19q, MGMT, etc.) through immunohistochemistry.
What are the characteristics of glioma?
Most of them grow in situ and recur in situ. Few of them metastasize or spread within the skull or central nervous system (brain, spinal cord), and few cases metastasize outside the central nervous system.
Malignant gliomas (mesenchymal or glioblastoma) grow rapidly and the cell cycle of active cells is often only a few days, that is, 100,000 active glioma cells today will become 200,000 a few days later, so usually the most malignant glioblastomas have an average survival of only one year, many only a few months, even after surgery and radiotherapy.
Glioma cells have an immune escape capability that makes it difficult for the body to naturally produce specific killer cells and antibodies against them, thus effectively circumventing the suppression and clearance by the body’s immune system.
What are the clinical symptoms of glioma?
The general symptoms are increased intracranial pressure, headache, vomiting, optic nerve papillary edema, visual field changes, epilepsy, diplopia, cranial enlargement (in children) and changes in vital signs.
Local symptoms vary according to the location of tumor growth
(1) Cerebral hemispheric astrocytoma: About 1/3 of patients have epilepsy as the first symptom and about 60% of patients have epilepsy.
(2) Cerebellar astrocytoma: ataxia of the affected limb, clumsy movement, unstable holding, low muscle tone and tendon reflex, etc.
(3) Thalamic astrocytoma: light paralysis, sensory impairment and hemiplegia, ataxia and choreiform movements of the affected limb, psychiatric disorders, endocrine disorders, ipsilateral blindness on the healthy side, upward visual impairment and hearing impairment, etc.
(4) Optic nerve astrocytoma: The main manifestations are visual impairment and abnormal eye position.
(5) Third ventricular astrocytoma: Patients with obstructive hydrocephalus often present with severe episodic headache, sudden loss of consciousness, mental disorders, and memory loss.
(6) Brainstem astrocytoma: Central tumors often show eye movement disorders, pontine tumors show limited eye abduction, facial nerve and trigeminal nerve involvement, medullary tumors often show swallowing disorders and changes in vital signs.
Glioblastoma: The tumor is highly malignant and has a short course. Most of the tumors are diagnosed within 3 months from the onset of symptoms to the time of consultation. 33% of the patients have seizures and 20% of the patients have psychiatric symptoms such as apathy, dementia and mental retardation.
Oligodendroglioma and mesenchymal (malignant) oligodendroglioma: epilepsy is often the first symptom, psychiatric symptoms are mainly emotional abnormalities and dementia, invasion of motor and sensory areas may produce hemiparesis, hemianesthesia and aphasia, etc. High cranial pressure symptoms appear later.
What imaging tests are currently available to diagnose glioma?
CT and magnetic resonance imaging (MRI) are the main tools to diagnose glioma. They can not only determine the location, size and number of tumors, but also infer the pathological nature of tumors based on imaging characteristics.
Functional MRI (fMRI) can not only infer the benignity and malignancy of tumors by observing their blood volume, but also assist surgeons in planning surgery to avoid functional areas adjacent to tumors.
Magnetic resonance angiography (MRA) and X-ray digital subtraction (DSA) can show the blood supply to the tumor and the relationship between the tumor and large arteries and veins. Positron emission tomography (PET-CT) and fMRI can also make a differential diagnosis of tumor recurrence and necrotic foci after surgery. Magnetic resonance spectroscopy (MRS) can distinguish tumors from inflammatory and demyelinating lesions, and even different types of gliomas for preoperative histological diagnosis. Magnetoencephalography can be applied to the localization of glioma secondary to epileptic foci and the localization of functional brain areas around epileptic foci; intraoperative cortical electroencephalography has guiding significance for resection of tumor and epileptic foci and protection of important functional brain areas.
What are the common treatment methods for glioma at present?
Surgical treatment: Surgical resection mainly achieves to reduce the number of glioma cells, alleviate the symptoms of the tumor, and temporarily reduce the intracranial pressure. Based on the growth characteristics of glioma, it is theoretically impossible to completely remove the tumor, and some tumors growing in important areas such as the brainstem are not operable at all.
(1) To clarify the pathological diagnosis;
(2) To reduce the volume of tumor and decrease the number of tumor cells;
(3) To improve the symptoms and relieve the high cranial pressure symptoms;
(4) prolonging life and creating an opportunity for subsequent comprehensive treatment;
(5) To obtain information on tumor cell kinetics to provide a basis for finding effective treatment.
Radiation therapy: Radiation therapy is the routine treatment for almost all types of glioma, but the efficacy of radiation therapy has been evaluated differently, except for medulloblastoma, which is highly sensitive to radiation therapy, and ventricular meningioma, which is moderately sensitive, but all other types are not sensitive to radiation therapy, and it has been observed that the prognosis of radiation therapy and non-radiation therapy is the same. X-knife and γ-knife are in the category of radiation therapy, but the treatment scope is limited by the location of the tumor, the size of the tumor (generally limited to less than 3 cm) and the sensitivity of the tumor to radiation, and currently it is considered that glioma, especially malignant astrocytic grade III-IV or glioblastoma, is not suitable for γ-knife treatment.
Chemotherapy: In principle, it is used for malignant tumors, but the efficacy of chemotherapeutic drugs is not yet certain because they are limited to the blood-brain barrier and the toxic side effects of drugs, and the efficiency of commonly used BCNU, CCNU and VM-26 is less than 30%. New chemotherapeutic drugs include temozolomide capsules.
Cellular immunotherapy:Cellular immunotherapy has the efficacy of preventing recurrence and metastasis while not causing pain to patients. Cellular immunotherapy has given new hope to brain tumor patients. Cellular immunotherapy is to extract some immune cells from the patient’s body, and then carry out a series of operations such as “culture, induction, and activation” in vitro, so that their anti-tumor activity is greatly improved, and then infuse these anti-tumor effector cells, which are originally from the patient’s own body and activated in vitro, back into the patient’s body. The tumor treatment or prevention of tumor recurrence can be achieved by infusing the tumor cells back into the patient’s body, allowing this specially trained “special force” to kill the tumor cells and at the same time stimulate the body’s own immune protection mechanism and enhance the ability of the immune system.
Molecular targeted specific immunotoxin therapy: Targeted toxin, also known as immunotoxin or cytotoxin, is a cellular molecule that binds to specific antigens or receptors on the surface of tumor cells or tumor vascular endothelial cells, such as epidermal growth factor receptor, transferrin receptor, interleukin-13 or interleukin-4 receptor, and its toxin components can kill tumor cells [2]. Antibodies for the treatment of malignant tumors have gradually evolved from murine-derived and chimeric antibodies to humanized antibodies [2]. Almost all cytotoxins used in clinical trials have the toxin part of the molecule modified from bacterial or plant toxins, while the cellular recognition part, i.e. the targeting part, is replaced by antibodies or carriers.
Chinese medicine treatment: conservative treatment with Chinese herbal medicine can reduce clinical symptoms and prolong the life span of patients by regulating yin and yang, qi and blood, and the functions of the internal organs, and by tonifying deficiency and dipping actuality. Chinese medicine can help post-operative recovery and improve side effects caused by radiotherapy, such as nausea, vomiting, loss of appetite, hair loss, rough and flaky skin, insomnia or drowsiness, and help patients complete the course of radiotherapy and achieve the expected results.
What is individualized treatment for glioma?
According to the patient’s general condition, age, tumor site, nature and characteristics of glioma will be taken into various integrated treatment methods: namely, postoperative intratumoral interstitial chemotherapy, postoperative intratumoral brachytherapy, postoperative transcerebral arterial interventional chemotherapy, simple transcerebral arterial interventional chemotherapy in non-high cranial pressure state, immune-guided radiotherapy, interstitial fluid radiotherapy of tumor tissue, high-dose chemotherapy supported by peripheral blood hematopoietic stem cells and other new technologies.
Why should we pay attention to the comprehensive treatment of glioma?
Malignant glioma cells are a cunning and tenacious enemy with three major functions of their own: immune evasion function, rapid replication function and self-damage repair function. Only by overcoming, suppressing and defeating these functions is it possible to cure the disease. Although radiotherapy is effective for some of them, unfortunately, it is often unable to completely kill those tumor cells that are in hypoxic state or G0 stage, which means the chance of killing all remaining tumor cells by radiotherapy alone is very low. However, theoretically, as long as there is one tumor cell left, and it can receive sufficient blood and oxygen supply, a new tumor can be created from scratch.
On the one hand, comprehensive treatment improves and optimizes traditional surgery and radiotherapy techniques, and on the other hand, it adds many new treatment items and measures, which effectively make up for the loopholes and shortcomings of traditional treatment methods, and provides an all-round, continuous, three-dimensional, siege type comprehensive treatment system to ensure that no tumor cell is missed. It has been proven that the correct application of comprehensive treatment can greatly improve the cure rate and survival of malignant glioma.
What to pay attention to the recurrence of glioma?
Whether the tumor grows again: Strictly speaking, tumor recurrence and tumor regrowth are defined differently. The former refers to the tumor that has been completely removed by surgery and then grows again in the skull; the latter refers to the tumor that has been partially removed by surgery but still remains in the skull and then grows again. In this case, the number of review is more than that of the former, and the number of review and interval time depends on the specific situation, and should be reviewed in time when clinical discomfort or aggravation of existing symptoms occurs. If the tumor recurs, the majority of the patients will be treated in a timely manner.
Whether the tumor recurs or not: Most of the patients’ tumors will not recur after complete resection, but there are still individual cases of tumor regrowth, and the growth site is usually in the original tumor site. Generally, the tumor will be reviewed 1-2 times in the first year after surgery, and if there are no clinical symptoms and imaging abnormalities, the number of reviews will be gradually reduced. If the tumor recurs, you can consider another surgery.
In addition, special attention should be paid to distinguish whether it is tumor recurrence or radiation brain necrosis, which can be largely judged by further examination of PET-CT. Understand the patient’s physical condition: Some gliomas show many functional and organ changes in human body after surgery.