1.Preface
Gliomas are the most common tumors of the central nervous system (CNS), with malignant ones (2007 WHO Classification of Tumors of the Central Nervous System, grades III and IV) being the most common. Although the prognosis of malignant glioma in CNS depends on various factors and diagnostic and treatment measures, the survival is generally 2-3 years for grade III and about 1 year for grade IV (e.g., glioblastoma). Recently, guidelines or recommendations on the management of glioma have been developed in Europe and the United States, which are helpful to standardize and improve the diagnosis and treatment of CNS glioma. For this reason, the Tumor Specialized Group of the Neurosurgery Branch of the Chinese Medical Association took the lead in organizing relevant experts in China to consult with multiple people on a particular issue according to the “CONSORT” and “AGREE” procedures to assess the quality of evidence in the literature and reach recommendations. The level of recommendation.
After repeated discussions and modifications, the “Chinese Consensus on the Diagnosis and Treatment of CNS Malignant Glioma” (hereinafter referred to as “Consensus”) was formulated for the reference and application of clinical practitioners, hoping to help standardize and promote the diagnosis and treatment of CNS malignant glioma in China and better serve patients. It is hoped that it will help standardize and promote the diagnosis and treatment of CNS malignant glioma in China, and better serve the patients and their families. Dong Fang, Department of Radiotherapy, Gansu Cancer Hospital
Glioma is a tumor originating from glial cells and is the most common primary intracranial tumor. Gliomas are classified into grade I-IV in WHO central nervous system tumor classification, and grade III and IV are malignant gliomas, accounting for 77.5% of all gliomas. In the past 30 years, the incidence of primary malignant brain tumors has been increasing year by year, with an annual growth rate of about 1.2%, especially in the elderly population. It is generally believed that the occurrence of malignant glioma is the result of the interaction of genetic factors within the body and external environmental factors, but the specific pathogenesis is unknown.
The clinical manifestations of glioma include symptoms and signs of increased intracranial pressure and neurological deficits. At present, malignant glioma is mainly diagnosed by MRI and CT imaging, and the pathological diagnosis is clarified by tumor resection or biopsy, and the research of pathological diagnosis at molecular and genetic levels is gradually advanced. The treatment of malignant glioma adopts a comprehensive treatment based on surgery combined with radiotherapy and chemotherapy.
Surgery advocates safe and maximal tumor removal, and the application of functional MRI, intraoperative MRI, and neuronavigation technologies has facilitated this purpose. Radiotherapy can kill or inhibit residual tumor cells and prolong survival. Temozolomide (TMZ) synchronized radiotherapy combined with adjuvant chemotherapy has become the standard regimen for newly diagnosed glioblastoma (GBM).
2.Diagnosis of malignant glioma
The clinical manifestations of malignant glioma are not specific and are dominated by neurological deficits with symptoms of increased intracranial pressure. MRI is usually a mixed signal lesion with isosignal or low signal in T1WI and inhomogeneous high signal in T2WI, accompanied by hemorrhage, necrosis or cystic degeneration, peritumoral edema and significant occupational effect. The tumor often spreads along the white matter fiber bundle. CT scan shows heterogeneous density with hemorrhage, necrosis or cystic lesion, peritumor edema and occupying effect are obvious. Enhancement shows significant heterogeneous enhancement, irregular or ring-like enhancement.
MRI special function tests (MRS, PWI, DWI, DTI), PET and SPECT are recommended, mainly for differential diagnosis, preoperative assessment and outcome evaluation.
3.Pathological diagnosis and biological markers of malignant glioma
The pathological diagnosis and grading of malignant glioma are strongly recommended in strict accordance with the 2007 WHO Classification of Tumors of the Central Nervous System. In order to match the treatment, efficacy observation and prognosis of glioma patients, it is strongly recommended that hospitals at all levels carry out selective molecular biological markers such as GFAP, Olig2, EMA, p53, MGMT, Ki67 and 1p/19q LOH according to the actual situation.
4.Surgical treatment of malignant glioma
It is strongly recommended that for primary high-grade (WHO grade III-IV) or low-grade (WHO grade II) gliomas confined to the lobes of the brain, maximum safe resection of the tumor should be pursued. Based on the swelling infiltrative growth pattern and blood supply characteristics of glioma, microscopic neurosurgical techniques are recommended to make anatomical resection along the white matter fiber bundle course of the tumor margin with the cerebral sulcus and cerebral gyrus as the boundary to obtain maximum tumor resection with minimal tissue and neurological function damage and clear histopathological diagnosis.
For.
(1) diffuse infiltrative growth of the dominant hemisphere, the
(2) lesions invading bilateral hemispheres, and
(3) elderly patients (>65 years of age), (4) patients with preoperative neurological disease
(4) poor preoperative neurological status (KPS <70), (5) deep intracerebral brain lesions
(5) malignant glioma in deep brain or brainstem sites.
(6) Gliomatosis, partial tumor resection, open biopsy, or stereotactic (or navigated) puncture biopsy are recommended as appropriate. Partial tumor resection offers a higher survival advantage than biopsy alone. Biopsy is mainly applied to lesions that are adjacent to functional cortical areas or deep in location and cannot be removed clinically. Biopsy mainly includes stereotactic (or under navigation) biopsy and open surgical biopsy. Stereotactic (or guided) biopsy is indicated for lesions that are more deeply located, whereas craniotomy is indicated for lesions that are superficially located or close to the functional cortex.
Review of MRI in the early postoperative period (<72 hours) is strongly recommended to assess the extent of glioma resection using quantitative volumetric analysis of preoperative and postoperative imaging. The T1WI-enhanced scan of MRI for high-grade gliomas is currently recognized as the "gold standard" for diagnostic imaging; T2WI or FAIR sequence images of MRI are recommended for low-grade gliomas. In units where MRI review is not available, it is recommended to review CT in the early postoperative period (<72 hours).
In order to achieve maximum safe resection of malignant gliomas, the following new techniques of image-guided surgery are recommended: conventional neuronavigation, functional neuronavigation, intraoperative neurophysiological monitoring techniques (e.g., functional cortical localization and subcortical stimulation of nerve conduction bundles), intraoperative MRI real-time imaging ( intraoperative imaging) neuronavigation. We can recommend: fluoroscopy-guided microsurgery, intraoperative ultrasound imaging for real-time localization.
5. Principles of radiation therapy for malignant glioma (WHO III-IV)
It is recommended to start radiotherapy as soon as possible about 2-4 weeks after surgery. External irradiation with conventional segmentation (1.8-2.0Gy/dose, 5 times/week) of 6-10MV X-rays is strongly recommended, with a total standard radiotherapy dose of 54-60Gy and 30-33 segments (Class I evidence). There is no benefit from increasing the dose of tumor irradiation within a certain dose range. Increased doses of brachytherapy and changes in segmentation modality have no effect on survival. Fractionated stereotactic radiotherapy (FSRT)/stereotactic radiosurgery (SRS) is indicated for push volume after conventional external irradiation or as one of the treatment modalities of choice for recurrent tumors, and this treatment is advantageous for smaller tumors. X- or Y-blade is not recommended as the preferred treatment modality after surgery for malignant gliomas.
Although GBM may be widely disseminated, local radiotherapy is still recommended. Current imaging techniques do not allow determination of the true borders of the tumor, and therefore all tumors and associated edema shown on imaging should be integrated and extensively bordered sufficiently when determining the target area for radiotherapy. It is recommended that for enhanced high-grade gliomas, the initial clinical target volume (CTV) is the enhanced tumor plus abnormalities shown on FLAIR images or T2 images with approximately 2 cm of outgrowth, and that only 2 cm outside the enhanced tumor is included in the field reduction push. multifield irradiation with 3D planned design is recommended. Compared with conventional radiotherapy, 3D conformal radiotherapy provides better protection of normal brain tissue.
For GBM, TMZ 75 mg/m2 chemotherapy with concurrent radiotherapy is strongly recommended, followed by 6 cycles of TMZ adjuvant chemotherapy. Application of temozolomide during and after radiotherapy significantly prolonged patient survival, and this treatment was most pronounced in patients with methylation of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter (see chemotherapy section.) Phase I/II trials have initially shown a role for TMZ in the treatment of WHO grade III tumors, but there are no relevant trials for grade III tumors. Therefore, TMZ 75 mg/m2 chemotherapy with concurrent radiotherapy can be recommended.
Pseudoprogression refers to the appearance of cool tumor progression on imaging after radiotherapy or radiochemotherapy, which is related to the dose of radiotherapy and not to tumor progression. The incidence of pseudoprogression is significantly higher in patients with low expression of MGMT than in those with high expression, and the incidence of pseudoprogression increases after TMZ synchronized radiotherapy/chemotherapy, and the time of pseudoprogression appears earlier. If only imaging manifestation, patients without clinical symptoms can be followed up and observed; when the enhanced lesion increases in a short period of time and cannot be identified by imaging (MRS, PET/CT), biopsy or surgery should be performed.
6. Chemotherapy for newly diagnosed malignant glioma
For newly diagnosed GBM, TMZ synchronous 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. Four weeks after the end of radiotherapy, adjuvant TMZ treatment, 150 mg/m2 for 5 days, 28 days as a course of treatment, if well tolerated, then increase the dose to 200 mg/m2 in subsequent courses of chemotherapy, 6 courses of adjuvant TMZ chemotherapy are recommended. TMZ for patients with malignant glioma has the following benefits: prolonged survival time; prolonged tumor progression-free period; no significant negative impact on quality of life ;lower incidence of early adverse events. Those with GBM who are not eligible for TMZ recommend ACNU (or other alkylating agents BCNU, CCNU) 90 mg/m2, D1, VM-26 60 mg/m2, D1-3, 1 cycle in 4-6 weeks, 4-6 courses of treatment for GBM.
Newly diagnosed mesenchymal glioma (WHO grade III): recommended radiotherapy combined with temozolomide (same as glioblastoma multiforme) or application of nitrosoureas chemotherapeutic agents: PCV regimen (lomustine + methylbenzylhydrazine + vincristine): 8 weeks as a course of treatment, not more than 6 courses. Oral lomustine (CCNU) 110 mg/ m2, D1; daily oral methylbenzylhydrazine (PCB) 60 mg/ m2, D8-21; intravenous administration of vincristine (VCR) 1.4 mg/ m2 (maximum dose is 2 mg), D8, D29. ACNU regimen (see above).
A biodegradable polymer (Gliadel Wafer, Guilford, USA) containing carmustine (BCNU) implanted in the local tumor cavity showed a survival benefit in patients with newly diagnosed malignant glioma in a randomized controlled phase III clinical trial (Level I evidence). The safety and efficacy of this transplantation tablet has not been reported for the national population as it is not yet available in China. Due to the lack of results from large-scale randomized controlled studies and the high cost and technical requirements, the promotion of arterial chemotherapy and adjuvant autologous bone marrow transplantation is not recommended at this time. It is recommended that immunohistochemical detection of MGMT protein or methylation PCR of the MGMT gene promoter be carried out as soon as possible in units that are in a position to do so, in order to better individualize chemotherapy for malignant gliomas. Patients with mesenchymal oligodendroglioma and mesenchymal oligodendro-astrocytoma with combined deletion of chromosome 1p 19q are not only sensitive to chemotherapy, but also have significantly longer survival. Targeted therapy represented by bevacizumab is currently under investigation.
7.Follow-up of malignant glioma and treatment of recurrence
Regular follow-up with MRI examination is highly recommended. MRI examination should be performed 2-6 weeks after radiotherapy and every 2-4 months for the next 2-3 years, and every 3-6 months after 3 years. For patients with recurrence, it should be considered according to the site of recurrence, tumor size, intracranial pressure and the patient’s basic condition. For local recurrence, reoperation is recommended; for patients who are not suitable for reoperation, radiation therapy and/or chemotherapy may be recommended; for those who are not suitable for reirradiation if they have received previous radiation therapy, chemotherapy is recommended; for those who have failed chemotherapy, a change in chemotherapy regimen and/or investigational therapy including molecular targeted therapy is recommended. For diffuse or multifocal recurrence, chemotherapy and/or investigational therapy including molecular targeted therapy is recommended. For patients with advanced disease, symptomatic supportive therapy is recommended.