neurologic disorders
Gliomas
Treatment of Gliomas
Surgical excision Radiation therapy Chemotherapy for some types Treatment involves surgery, radiation therapy, and chemotherapy to reduce tumor mass. Safely excising as much tumor as possible (without unduly damaging areas of eloquent brain [areas that subserve functions such as speech and motor function]) prolongs survival and improves neurologic function. After surgery, patients receive a full tumor dose of radiation therapy (60 Gy over 6 weeks); ideally, conformal radiation therapy, which targets the tumor and spares normal brain tissue, is used. For glioblastomas, chemotherapy withtemozolomideis now routinely given with radiation therapy. The dose is 75/mg/m2/day for 42 days (including weekend days when radiation is skipped) Then 150 mg/m2 orally once a day for 5 days a month during the next month Followed by 200 mg/m2 orally once a day for 5 days a month in subsequent months for a total of 6 to 12 months /sulfamethoxazole 800 mg/160 mg is given 3 times a week to prevent Pneumocystis jirovecii Pneumonia . Patients receiving chemotherapy require a complete blood count (CBC) at varying intervals. Implantation of chemotherapy wafers during surgical resection may be appropriate for some patients. may be appropriate for some patients. Tumor-treating fields interfere with glioblastoma mitosis and organelle assembly by delivering alternating electric fields to the scalp. In one randomized clinical trial, tumor-treating fields appeared to improve survival in patients with glioblastoma ( Treatment references ). Investigational therapies (eg, stereotactic radiosurgery, new chemotherapeutic drugs, gene or immune therapy) should also be considered. Clinical trials of numerous immune checkpoint inhibitors, in particular of CTLA4- and PD1-dependent immune modulation, are underway. After conventional multimodal treatment, the survival rate for patients with glioblastomas is about 50% at 1 year, 25% at 2 years, and 10 to 15% at 5 years. Prognosis is better in the following cases: Patients are<45 years. Histology is that of anaplastic astrocytoma or a lower-grade tumor (rather than glioblastoma). Initial excision improves neurologic function and leaves minimal or no residual tumor. Tumors have theIDH1mutation. MGMT (methylguanine-methyltransferase) promoter methylation is present. With standard treatment, the median survival time is about 30 months for patients with anaplastic astrocytoma and about 15 months for patients with glioblastoma. A wide range of clinical trials, in particular those including a number of investigational immunotherapy and immune checkpoint inhibitors, are being done. Ongoing and recently completed trials are referenced inclinicaltrials.gov. Maximal safe surgical resection is indicated for low-grade astrocytomas and oligodendrogliomas. After complete resection in patients < 40, observation may be considered. For other patients, radiation therapy plus adjuvant chemotherapy prolongs survival ( Treatment references ). Median survival ranges from 1 to 2 years in high-risk patients (without theIDH1mutation, with incomplete resection) to > 10 years in those with favorable prognostic factors. In high-risk patients, malignancy is likely to progress further. mutation in a histone protein; epigenetic strategies that modify DNA and DNA-associated proteins in the cell to change gene expression are being studied ( Treatment references ). Patients with the Biopsy with genetic analysis, cerebrospinal fluid sampling, and craniospinal imaging should be used to stage ependymomas and to assess their spread in the central nervous system. Treatment of ependymomas includes maximal safe surgical resection for unifocal disease or symptomatic tumors. For higher-grade tumors, radiation therapy can be directed locally or include the entire craniospinal axis depending on how far the tumor has spread. The role of chemotherapy is not well defined. Prognosis varies with tumor location, genetics and stage ( Treatment references ). In general, with treatment, overall 5-year survival rate is about 50%; however, for patients with no residual tumor, the 5-year survival rate is > 70%. 1.Stupp R, Taillibert S, Kanner A, et al: Effect of tumor-treating fields plus maintenancetemozolomidevs maintenancetemozolomidealone on survival in patients with glioblastoma: A randomized clinical trial.JAMA318 (23):2306–2316, 2017. doi: 10.1001/jama.2017.18718 2.Buckner JC, Shaw EG, Pugh SL, et al: Radiation plusprocarbazine, CCNU, andvincristinein low-grade glioma.N Engl J Med374 (14):1344-1355, 2016. doi: 10.1056/NEJMoa1500925 3.Miklja Z, Pasternak A, Stallard S, et al: Molecular profiling and targeted therapy in pediatric gliomas: Review and consensus recommendations.Neuro Oncol21:968–980, 2019. 4.Pajtler K, Mack S, Ramaswamy V, et al: The current consensus on the clinical management of intracranial ependymoma and its distinct molecular variants.Neuropathologica133:5–12, 2017. doi: 10.1007/s00401-016-1643-0 