Glioma, especially malignant glioma, is very dangerous and the treatment effect is not ideal, and the five-year survival rate of World Health Organization (WHO) grade IV glioma is only 9 or 8% as reported in the literature. Recently, with the development of evidence-based medicine, the individualized treatment of tumors has received more and more attention. This paper reviews the importance of establishing and developing a comprehensive treatment system for glioma by evaluating the effects of individualized surgery, radiotherapy, chemotherapy, and biotherapy. 1. Medical history and individualized neuroimaging assessment: The medical history should include age, important signs and symptoms, previous treatment (the type of pathology and relevant important biological markers of the last surgery, details of surgery and radiotherapy for recurrence), etc. This information is important for planning an individualized and comprehensive treatment strategy. In addition to conventional MRI, multivoxel magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI), diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), and functional MRI should be performed if available. PWI imaging is used to determine the relative cerebral blood flow (rCBV) in tumors in relation to tumor biological behavior and patient survival by measuring the relative cerebral blood flow (rCBV) in tumors. Most low-grade gliomas have rCBV values greater than normal brain tissue (1, 5), and higher rCBV values tend to indicate more aggressive tumors. Individualized surgical plan to maximize the protection of brain function and maximize tumor resection: Recently, more and more studies have shown that the degree of tumor resection is an independent prognostic factor, and resection of 99% of high-grade malignant gliomas, supplemented with radiotherapy after surgery, significantly prolongs the survival of patients compared with the control group (evidence-based medicine level I, the same below). There have been three opinions on the management of low-grade gliomas: early surgical resection, biopsy, and follow-up observation. With the finding that low-grade gliomas have a high heterogeneity and variability, with a mean of 17% to 73% of tumors escalating histologically in 2,1 to 10,1 years. Maximum safe resection of the tumor helps to prolong the time to recurrence and evolution to high-grade glioma in low-grade gliomas (Class II evidence). Therefore, early surgical intervention has been recently advocated. In addition, preoperative assessment of high-risk factors facilitates the physician to make appropriate treatment choices. These high-risk factors include: patient age >40 years, tumor invasion of language areas, KPS ≤80, tumor ≥4 cm, and growth rate >8 mm per year. There are several techniques that can serve the purpose of individualized surgery for maximum safe resection: (1) DTI, fMRI and MRS: In the past, surgery was based on surgeon’s experience to determine the tumor boundary. As a result, the functional nerve structures were often mistakenly injured in the pursuit of the extent of tumor resection, resulting in postoperative neurological dysfunction of the patient (limb paralysis, aphasia); or excessive tumor tissue was left behind for fear of damaging the nerve structures. Subcortical conduction tracts and functional cortex can now be identified according to DTI and fMRI, respectively. The tumor infiltration zone can be determined according to the choline peak/N-acetylaspartate peak (CHO/NAA) ratio in MRS, so as to achieve the removal of the tumor as much as possible under the premise of protecting the function and creating favorable conditions for subsequent treatment. (2) Electrophysiological monitoring: Although with the emergence and application of noninvasive imaging of functional brain structures, these structures have changed from invisible to visible, improving surgical safety, fMRI is not a direct detection of excitable neurons because it uses blood oxygen saturation level detection (BOLD) to reflect the excitable brain layers with increased local blood flow. fMRI localized functional cortex has some correlation with the real functional cortex, but there is a difference of several millimeters in the actual measurement. The commercial software currently used for DTI is a single volume, which does not show the complete conduction bundle, and because of the effects of intraoperative brain displacement, preoperative DTI alone is not yet reliable for determining subcortical conductance. Therefore, electrophysiological monitoring remains the gold standard for intraoperative determination of functional brain structures. It includes evoked potential (sensory and motor) monitoring and direct current stimulation. In our experience, electrophysiological monitoring should be used in combination with fMRI and DTI to complement each other. For surgery in the speech area, arousal anesthesia should also be added and electrophysiological testing should be performed to localize the speech cortex in the area suggested by fMRI. Since low-grade gliomas have a higher incidence of epilepsy than high-grade gliomas, intraoperative exploration of tumor peripheral tissues for epileptic waves and corresponding resection can be of great benefit to the control of epilepsy in these long-term survivors, especially drug-refractory epilepsy; (3) navigation and intraoperative MRI: the application of navigation technology has elevated neurosurgery from relying on subjective physician judgment to objective and scientific quantification. Points (1) and (2) above are techniques applied in combination with navigation techniques, which have been proven to be effective and more reliable in clinical practice. However, due to the cranial cavity opening, cerebrospinal fluid loss and tumor removal during craniotomy, brain shift (or drift) will occur, which will affect the accuracy of applying preoperative imaging data for navigation, resulting in interference with the goal of maximum tumor removal and protection of neurological function. The best solution to this problem is the application of intraoperative MRI, which can both scan and collect image data in real time as needed intraoperatively and also navigate in real time, and is currently the best surgical weapon for the treatment of glioma. 3. Molecular markers of glioma: Because of the obvious heterogeneity of glioma, as many specimens as possible should be retained intraoperatively for routine pathology and molecular marker examination. Although stereotactic biopsy can obtain specimens for diagnostic purposes, there is a certain amount of diagnostic error. In addition to HE staining of paraffin sections for conventional pathology, various immunohistochemical and other tests should be added, among which MGMT, 1p19q and IDH have important clinical significance. (1) MGMT detection: MGMT gene is a DNA damage repair gene, which has a very important position in the individualized treatment of glioma because it can predict the sensitivity to radiotherapy and chemotherapy. Although it can be detected by immunohistochemical methods, which are easy to perform, MGMT is also widely expressed in normal neurons, glial cells, lymphocytes, erythrocytes and vascular endothelial cells, which affects its accuracy. A more reliable method is to detect the level of MGMT promoter CpG island methylation, i.e. MSPCR method. (2) 1p19q: Heterozygous deletion of chromosome 1p/19q is a molecular genetic feature of mesenchymal oligodendroglioma (level I evidence), and these patients with combined deletion of chromosome 1p 19q have a significantly higher response rate to PCV chemotherapy regimens than those without 1p 19q deletion (100% vs. 23%-31%) and a better prognosis. However, the effect on glioblastoma and astrocytoma is unknown. Although the use of PCV regimen for glioma chemotherapy of oligodendroglial origin is more frequently reported, TMZ is also valued because of its low side effects, and our experience has also revealed that PC regimen can be used if TMZ is ineffective for those with combined deletions (Figure 3). Methods for detecting 1p/19q heterozygous deletion include polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH), which can be carried out in hospitals that are in a position to do so. (3) IDH1 and IDH2 mutation detection: IDH1/IDH2 mutations are present in most WHO II and III and secondary gliomas, suggesting that IDH1/IDH2 plays an important role in the initiation phase of glioma development. The IDH1/IDH2 mutation is currently used as a diagnostic bioindicator to distinguish hairy cell astrocytoma from diffuse astrocytoma and primary GBM from secondary GBM, and sometimes as a prognostic bioindicator: patients with glioma expressing the IDH1/IDH2 mutation have a better prognosis than those who retain the wild-type gene and are sensitive to radiotherapy and chemotherapy (e.g. temozolomide). ). The IDH1 and IDH2 variants can be detected by PCR or immunohistochemistry. Due to the convenience of detection, IDH1 has been used as a common molecular diagnostic index for glioma. A large randomized controlled study (RCT) by Stupp et al. found that temozolomide (TMZ) combined with radiotherapy prolonged the median survival time of patients by 2 or 5 months compared with radiotherapy alone, while the proportion of 2-year survivors increased by 16% (Class I evidence). However, although early postoperative radiotherapy for low-grade gliomas may prolong 5-year PFS, not only the overall survival time of patients is not prolonged, but also there is an increase in cognitive dysfunction at a later stage. Therefore, many scholars now propose that for patients with low-grade glioma without high-risk prognostic factors, postoperative radiotherapy can be implemented without early radiotherapy and only when tumor progression occurs. For patients with multiple high-risk factors, early postoperative radiotherapy is still recommended. In addition, radiotherapy doses of 45-54 Gy are generally appropriate for low-grade gliomas. Indications for chemotherapy in low-grade gliomas: recurrence after surgery and radiotherapy (level II evidence); large postoperative residual or unresectable tumors with recent 1p19 deletion (level II evidence). Recently, tumor genetic mapping engineering (TCGA) can classify European and American primary GBM into 4 subtypes, each with different signaling pathways, different prognosis and drug sensitivity, which undoubtedly advances the process of individualized glioma treatment. It is important to genotype glioma in China to find and establish individualized treatment with Chinese characteristics. Immunotherapy among biological therapies is an emerging therapeutic tool. Recently, foreign scholars selected 14 human HLA-A24-restricted antigenic peptides related to glioma, including EGFR/EGFRvIII, EZH2, MRP3, Lck, and SART, and prepared personalized antigenic peptide vaccines for the treatment of 12 patients with recurrent or progressive glioblastoma (10 of which were insensitive to temozolomide chemotherapy), and the results confirmed the safety and feasibility of this method . The preliminary results of the phase I clinical trial of human glioma stem cell-like antigen-sensitized dendritic cells at Shanghai Huashan Hospital suggest that this approach is safe and feasible, and that the combination of chemotherapy can prolong the survival of patients. However, how to prepare efficient antigen and overcome the microenvironment of local immune escape of tumor requires continuous follow-up of clinical and basic research. 5. Glioma follow-up database: Glioma follow-up is very important and requires a dedicated person to summarize all the above information into a database (named “Glioma Case Database” by Shanghai Huashan Hospital) and follow up according to the specific situation. A complete follow-up database combined with a tissue bank will not only help identify more prognostic/predictive factors, but also better serve clinical trials; ultimately benefiting patients and the next generation of young physicians.