Brain cancer is a form of tumor that originates in the central nervous system (CNS), which comprises the brain and spinal cord.1 There are 2 main types of brain tumors: primary brain tumors and secondary brain tumors. A primary brain tumor occurs in the CNS, while a secondary brain tumor originates in another part of the body and spreads to the brain or spinal cord.2

Glioma is the general term that is used to describe malignant primary brain tumors, which include astrocytomas, ependymomas, oligodendrogliomas, glioblastomas, and mixed gliomas.3 These aggressive tumors commonly occur in the CNS and account for 80% of all malignant primary brain tumors.4-6 Despite recent advances in the management of brain cancer, primary brain tumors are difficult to treat and are associated with a 5-year survival rate of approximately 35%.7

Glioblastoma multiforme (GBM) is the most malignant and frequently diagnosed primary brain tumor, accounting for more than 60% of all brain cancer diagnoses in adults.8 More than two-thirds of patients who are diagnosed with GBM will die within 2 years of diagnosis.9

Colored computed tomographic (CT) imaging of the brain demonstrating glioblastoma, which is the most aggressive form of brain cancer.
Figure 1. Colored computed tomographic (CT) imaging of the brain demonstrating glioblastoma, which is the most aggressive form of brain cancer. Credit: Getty Images.

Most brain tumors are not associated with any specific risk factors, and in most cases, the underlying cause cannot be determined. However, certain factors can increase the risk of developing brain tumors, including age, gender, chemical exposure, family history, exposure to certain microbes and allergens, electromagnetic fields, and ionizing radiation.10

The most common environmental risk factor for brain cancer is exposure to moderate to high doses of ionizing radiation, such as radiation therapy for the treatment of other conditions or cancers (eg, leukemia).11 Children who receive low- to moderate-range radiation treatment to the head or brain have an increased risk of developing a brain tumor during adulthood.12

According to the American Cancer Society (ACS), the risk of developing radiation-induced tumors due to imaging tests (eg, radiographs, computed tomography [CT] scans) is low.13 These types of tests involve lower levels of radiation than what patients are exposed to for radiation treatments, which means the potential risk from radiation exposure during imaging tests is minimal.14

Additional risk factors contributing to the development of brain tumors include a family history of genetic disorders, such as tuberous sclerosis, Von Hippel-Lindau syndrome, Li-Fraumeni syndrome, Turcot syndrome, and neurofibromatosis type 1 (NF1) and type 2 (NF2).15 NF1 is also known as von Recklinghausen disease.

Brain Cancer Treatment

Brain cancer treatment involves the collaborative efforts of a multidisciplinary team that creates a management plan that involves different types of therapies. The team may include neuro-oncologists, primary care providers, nurses, nurse practitioners, physician assistants, neurosurgeons, rehabilitation specialists, and other health professionals. The standard treatment plan often involves surgery (resection) to remove all or most of the tumor. If necessary, the surgery is followed by chemotherapy or radiation therapy to eliminate any cancer cells that may still be present in the CNS. Recurrent brain cancer following surgery requires additional therapy (eg, targeted drug therapy, electric field therapy).

Brain cancer is often detected due to the symptoms the tumor causes. A tumor may be low grade or high grade, depending on its appearance and growth rate.16 Some patients who have small, low-grade tumors may be initially asymptomatic. As low-grade tumors grow slowly and are less likely to metastasize, physical symptoms may not develop right away. It may take years before a low-grade tumor causes symptoms that lead to a diagnosis. Large, high-grade tumors develop quickly and grow rapidly over several weeks or months. High-grade tumors are also associated with the rapid onset of different symptoms.

The most common symptoms of a brain tumor include:

  • Headaches
  • Seizures
  • Severe fatigue
  • Nausea and vomiting
  • Cognitive impairment
  • Muscle weakness
  • Coordination issues
  • Sensory disturbances
  •  Vision problems

Low- and high-grade tumors are further graded from 1 to 4 based on how normal or abnormal the cancer cells appear under a microscope.17 Low-grade tumors are often grades 1 and 2, and high-grade tumors are mostly grades 3 and 4.

Grading of Brain Tumors

  • Grade 1 tumors, such as pilocytic astrocytomas, may be relatively benign and grow slowly over time. The cancer cells are well differentiated, meaning that they have a normal appearance. Grade 1 tumors are treated with surgery. However, recurrent tumors may necessitate additional treatment, such as radiation therapy.  
  • Grade 2 tumors, such as diffuse astrocytomas and oligodendrogliomas, grow slowly but may gradually invade healthy tissue. The cancer cells are moderately differentiated, and this type of cancer can also be treated with surgery. For some patients, the tumors recur at a higher grade, which warrants additional therapy.
  • Grade 3 tumors, such as anaplastic astrocytomas, grow quickly and invade nearby tissue. The cancer cells are poorly differentiated and have an abnormal appearance. In addition to surgery, treatment for grade 3 tumors may involve a combination of therapies.
  • Grade 4 brain tumors grow rapidly, metastasize quickly, and are often diagnosed as glioblastomas. The cancer cells display a high degree of undifferentiation, and this form of cancer is the most difficult to treat.

Treatments for Brain Cancer

Standard treatments for malignant primary brain tumors include the following:

  • Surgery
  • Radiation therapy
  • Chemotherapy
  • Targeted therapy 
  • Electric field therapy


For most brain tumors, surgery (resection) is performed by a neurosurgeon to remove the tumor from the brain and confirm the brain cancer diagnosis. If a brain tumor is suspected, a magnetic resonance imaging (MRI) scan will be ordered, as the images provide an efficient delineation of tumors. High-grade tumors and brain metastases enhance on an MRI scan; low-grade tumors do not enhance.

If the results of the MRI confirm the presence of a low-grade tumor, the standard treatment is resection.18 The MRI images provide an indication of whether all or part of the tumor can be removed through one of the following surgical procedures:

  • Gross total resection. This procedure is performed to remove all or the majority of the tumor. The more tumor tissue that is removed, the better the prognosis. Tumor resection also relieves intracranial pressure or treats additional symptoms that are hard to manage, such as seizures.
  • Subtotal resection. A subtotal (or partial) resection may be performed when the whole tumor cannot be removed. However, enough tumor tissue must be removed to preserve the patient’s functionality and quality of life. A subsequent resection may be necessary to remove the remainder of the tumor.19
  • Stereotactic biopsy. This is the standard procedure for a brain tumor in an area not amenable to resection, and recurrence may occur due to the partial resection. Following the biopsy, another MRI will be performed to assess the extent of tumor resection.20
  • Open biopsy. This is a major surgical procedure in which a craniotomy is performed to gain access to the tumor prior to its removal. Similar to a resection, the majority of the tumor is removed during an open biopsy if amenable.

To achieve safe resection with minimal surgical morbidity, the National Comprehensive Cancer Network (NCCN) recommends the use of neuro-navigation systems, including21:

  • Preoperative functional MRI
  • Intraoperative MRI or CT
  • Intraoperative mapping techniques
  • Awake craniotomy
  • Motor and/or speech mapping
  • Diffusion tensor imaging-based fiber tracking
  • Intraoperative ultrasonography
  • Frameless stereotactic navigation
  • Fluorescence-guided resection with 5-aminolevulinic acid (5-ALA)

Low-grade tumors often have well-defined borders that allow for gross total resection, but the tumor resection margin may be unclear, even with neuro-navigation guidance. In some cases, removal of tumor tissue near the resection margin may not be feasible, and invasive cancer (eg, glioma) cells and tissue from high-grade tumors may remain in the brain following resection.

Nearly all high-grade tumors recur, but re-resection at the time of recurrence may improve the outcome for select patients.22 However, tumor development in critical brain areas, large tumor volume (>50 cm3), and a poor Karnofsky performance status (KPS) score are associated with unfavorable re-resection outcomes.23

To determine the extent of resection for gliomas and other types of brain tumors, a postoperative brain MRI scan should be performed within 48 hours of surgery. In addition, postoperative spine MRI should be deferred by at least 2 to 3 weeks to avoid visualization of postsurgical artifacts. Follow-up brain MRI scans should be performed at regular intervals following treatment, with increased frequency in the event of clinical changes, such as neurologic deterioration or the development of seizures, to determine the next course of treatment.

Radiation Therapy

Radiation therapy (RT) is commonly used to treat both completely resected and partially resected brain tumors. This form of therapy induces cancer cell apoptosis and radiation-induced reproductive failure (mitosis inhibition).24 Depending on the type of brain cancer, radiation will be administered directly to the tumor and surrounding tissue, where cancer cells may also be present.

Postoperative RT is beneficial for improving local control and survival in patients with newly diagnosed high-grade brain tumors. The standard dose of 60 Gy in 30 to 33 fractions of 1.8 to 2.0 Gy increases the median overall survival (OS) from 3-5 months to 8-10 months for patients diagnosed with GBM.25 Sufficient radiation doses maximize survival rates, but dose escalation above 60 Gy is unfavorable.26

The following types of RT are used to treat specific types of brain cancer:

  • External beam radiation therapy (EBRT). This form of RT is most frequently used to treat malignant primary brain tumors, such as gliomas. EBRT is administered within a limited field that penetrates the tumor or surgical cavity and a small margin of adjacent brain tissue.
  • Conformal radiation therapy (CRT). This technique includes 3-dimensional conformal radiation therapy (3D-CRT) and intensity-modulated radiation therapy (IMRT), which are recommended for focal brain irradiation. IMRT provides better sparing of critical brain areas and dosimetric target coverage than 3D-CRT.27
  • Stereotactic radiosurgery (SRS). This procedure is also known as stereotactic body RT (SBRT) and it allows precise, high-dose delivery in 1 or 2 fractions that minimizes exposure of the spinal cord and other vital organs. SRS is frequently recommended for pre-irradiated patients.28
  • Fractionated stereotactic radiation therapy (FSRT). This form of RT combines the high-dose gradients and small treatment margins of SRS. FSRT is generally considered if a patient is a poor candidate for treatment with SRS due to toxicity concerns, the tumor measures ≥3 cm in diameter, if the tumor is near an eloquent or critical structure, or if the proximity of the brain tumor would lead to dose bridging in a single-fraction SRS treatment.29
Administration of stereotactic radiotherapy for brain cancer.
Figure 2. Administration of stereotactic radiotherapy for brain cancer. Credit: Getty Images.


Chemotherapy is the standard form of treatment for newly diagnosed or recurrent malignant primary brain tumors (grades 2 to 4).30 The mechanisms of action for chemotherapy include apoptosis, senescence, autophagy, and autophagic cell death induction. Chemotherapy drugs that are used to treat brain cancer include the following:

  • Temozolomide
  • Carmustine (BCNU)
  • Carboplatin
  • Cisplatin
  • Etoposide
  • Irinotecan
  • Methotrexate
  • Procarbazine
  • Lomustine (CCNU)
  • Vincristine   

Effective chemotherapy agents must cross the blood-brain barrier (BBB) to penetrate the cancer. Certain drugs, such as temozolomide and nitrosoureas (eg, carmustine and lomustine), have small molecular sizes and high lipid solubility, allowing these agents to achieve efficient BBB penetration and high concentrations in brain tumors. Drug delivery can be further improved through continuous infusion methods or by bypassing the BBB with biodegradable wafers. A limited number of chemotherapy agents, such as cytosine arabinoside and methotrexate, can be administered directly through intrathecal injection but have not demonstrated consistent efficacy in brain tumors.31 

Temozolomide or the combination of procarbazine, lomustine, and vincristine (PCV) is commonly used to treat newly diagnosed, low-grade (2) tumors and high-grade brain tumors (grades 3 to 4), as well as recurrent tumors.32 Treatment with temozolomide is more effective than radiotherapy alone for newly diagnosed and recurrent glioblastoma. Due to better tolerance, temozolomide is frequently administered instead of nitrosourea-containing chemotherapy agents (eg, PCV). However, PCV is more effective than nitrosourea single-agent use in patients with anaplastic astrocytoma and anaplastic oligodendroglioma. Other chemotherapy agents — including carboplatin, cisplatin, etoposide, procarbazine, and irinotecan — may be used as second- or third-line treatments.

Dosing Regimens

The following dosing regimens are in accordance with the Full Prescribing Information, Indications and Usage Information, in accordance with the US Food and Drug Administration (FDA) and the NCCN Clinical Practice Guidelines in Oncology.21


Patients with refractory anaplastic astrocytoma. The initial dose of temozolomide is 150 mg/m2 orally, administered once daily for 5 consecutive days per 28-day treatment cycle. In adult patients, the temozolomide dose is increased to 200 mg/m2/d for 5 consecutive days per 28-day treatment cycle if both the nadir and day of dosing (day 29, day 1 of next cycle) absolute neutrophil counts (ANC) are greater than or equal to 1.5 x 109/L (1500/µL) and both the nadir and day 29, day 1 of next cycle platelet counts are greater than or equal to 100 x 109/L (100,000/µL).

A complete blood count is obtained on day 22 (21 days after the first dose) of treatment and weekly until the ANC is above 1.5 x 109/L (1500/µL) and the platelet count exceeds 100 x 109/L (100,000/µL). The next cycle of temozolomide does not begin until the ANC and platelet count exceed these levels. If the ANC falls below 1.0 x 109/L (1000/µL) or if the platelet count is less than 50 x 109/L (50,000/µL) during any cycle, the dose for the next cycle is reduced by 50 mg/m2. For patients who are unable to tolerate a dosage of 100 mg/m2 per day, temozolomide is permanently discontinued.

Patients with newly diagnosed GBM. The concomitant-phase treatment schedule entails the administration of temozolomide orally at 75 mg/m2 daily for 42 days concomitant with focal RT (60 Gy administered in 30 fractions), followed by maintenance temozolomide for 6 cycles. Dose reductions are not recommended. However, dose interruptions may occur based on patient tolerance. The dose of temozolomide is continued throughout the 42-day concomitant period up to 49 days if all of the following conditions are met: an absolute neutrophil count greater than or equal to 1.5 x 109/L, a platelet count greater than or equal to 100 x 109/L, and nonhematologic adverse reactions of grade 1 or less (with the exception of alopecia, nausea, and vomiting).

During treatment, a complete blood count is obtained weekly. Temozolomide dosing may be interrupted or discontinued during the concomitant phase as per the criteria established for toxicity as noted above (ANC and platelet count). Prophylaxis for Pneumocystis pneumonia is necessary during the concomitant administration of temozolomide and RT and is continued in patients who develop lymphocytopenia until resolution to grade 1 or less.

The maintenance phase treatment schedule is 4 weeks after completing the temozolomide and RT phase, at which time temozolomide is administered for an additional 6 cycles. The dosage in cycle 1 (maintenance treatment phase) is 150 mg/m2 once daily for 5 days, followed by 23 days without treatment. At the start of cycle 2, the dose of temozolomide is increased to 200 mg/m2 if the nonhematologic adverse reactions for cycle 1 are grade 2 or less (with the exception of alopecia, nausea, and vomiting), ANC is greater than or equal to 1.5 x 109/L, and the platelet count is greater than or equal to 100 x 109/L. If the dose is not increased at cycle 2, it should not be increased in subsequent cycles.

The dosage is maintained at 200 mg/m2 per day for the first 5 days of each subsequent cycle, except if toxicity occurs. During treatment, a complete blood count is obtained on day 22 (21 days after the first dose) and then weekly until the ANC is above 1.5 x 109/L (1500/µL) and the platelet count exceeds 100 x 109/L (100,000/µL). The next cycle of temozolomide does not begin until the ANC and platelet count exceed these levels. Dose reduction during the next cycle is based on the lowest blood counts and worst nonhematologic adverse reactions experienced during the previous cycle.


Patients with malignant glioma, GBM, medulloblastoma, astrocytoma, ependymoma, and brain metastases. For carmustine injection, the treatment regimen is 150 to 200 mg/m2 intravenously (IV) over at least 2 hours, repeated every 6 weeks. The dose is not repeated until blood counts recover, as demonstrated by a leukocyte count greater than 4000 cells/mm3, ANC greater than 1000 cells/mm3, and a platelet count greater than 100,000 cells/mm3, and no sooner than every 6 weeks.

Carmustine injection may be administered as a single dose or divided into daily doses on 2 consecutive days (eg, 75 to 100 mg/m2 IV daily on days 1 and 2). Lower doses are recommended when carmustine injection is administered in combination with other myelosuppressive drugs or in patients with depleted bone marrow reserves. Patients are premedicated with antiemetic agents prior to each dose.

Patients with newly diagnosed and recurrent high-grade glioma. Carmustine implantable wafers are an adjunct to surgery and RT and an adjunct to surgery in patients with recurrent GBM. The implantable wafer dosage is 61.6 mg (8 x 7.7-mg wafers), implanted intracranially in the resected cavity once. Fewer than 8 wafers can be placed in the cavity if it is not large enough to accommodate 8 wafers. The wafers may slightly overlap, and wafers that break in half may also be implanted in the cavity. Wafers that break into more than 2 pieces are discarded.

Nitrosourea-Containing Agents


Patients with recurrent brain tumors, primary and metastatic. The recommended dose of lomustine is 110 to 130 mg/m2, with a maximum dose of 200 mg, taken as a single oral dose every 6 weeks. Doses are rounded to the nearest 5 mg. For patients with compromised bone marrow function, the dose is reduced to 100 mg/m2 to be taken every 6 weeks. The dose is also reduced accordingly when lomustine is used in combination with other myelosuppressive drugs. After combined chemoradiotherapy with temozolomide, the maximum recommended dose of lomustine is 110 mg/m2 to be taken every 6 weeks.

Lomustine may also be administered as a combination regimen: procarbazine, lomustine, and vincristine (PCV). The 6-week PCV combination treatment consists of lomustine 110 mg/m2 on day 1, procarbazine 60 mg/m2 on days 8 through 21, and IV vincristine 1.4 mg/m2 to a maximum dose of 2 mg on days 8 and 29.

One of the main side effects of lomustine is cumulative bone marrow suppression and late nadir onset at 4 to 6 weeks. Therefore, nitrosourea-containing agents are administered in 6- to 8-week cycles. Additional side effects, such as nausea, vomiting, and hepatotoxicity, warrant the use of a prophylactic 5HT3 antagonist.

Targeted Therapy

Targeted therapy is distinct from chemotherapy in that it is directed against tumoral features such as tumor-specific markers, altered metabolic and signaling pathways, tumor vasculature, and the tumor microenvironment.33 The efficiency of targeted therapy involves key factors that include target identification, detecting and developing an antibody or small molecule against the target, and relevant clinical trials. In 2009, bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), was granted approval by the FDA for the treatment of recurrent GBM.34 

The treatment regimen for bevacizumab is 10 mg/kg IV every 2 weeks. This chemotherapy agent is only administered as an IV infusion and is not administered as an IV push or bolus. Bevacizumab is not initiated until at least 28 days following surgery, after the surgical incision has fully healed. The first infusion is administered over 90 minutes. The second infusion is administered over 60 minutes if the first infusion is tolerated. Subsequent infusions are administered over 30 minutes if the 60-minute infusion is tolerated. However, bevacizumab has not demonstrated consistent benefit in OS in newly diagnosed or recurrent GBM. Therefore, bevacizumab is combined with RT and other chemotherapies.

Additional agents that target VEGF receptor (VEGFR) include vatalanib, cediranib, cabozanitib, and pazopanib. Varying response rates among patients with GBM have been reported with these agents, demonstrating the benefit of combined therapy (eg, with chemotherapy).

Alternating Electric Field Therapy

Alternating electric field therapy, also known as tumor treating fields (TT fields), is an approved treatment for recurrent GBM that disrupts brain tumor cell mitosis. Exposure of cancer cells to the TT fields leads to membrane blebbing, the disruption of microtubule spindle elements, and chromosomal order following mitosis.35 Investigators have reported a 1-year survival rate of approximately 20% with TT fields for recurrent GBM, which indicates that alternating electric field therapy has an equivalent efficacy when compared with chemotherapy with bevacizumab.36

Monitoring Complications of Treatment for Brain Cancer


The most common complications following surgery for brain cancer are postoperative pulmonary hematomas (7%) and hemorrhages (6%), of which a small percentage require intervention.37 These types of complications are major causes of morbidity and mortality following intracranial surgery. Different factors have been correlated with the occurrence of postoperative complications. The most critical are perioperative factors, such as the inability to achieve hemostasis, as well as intraoperative factors, such as the occurrence of hypertension, severe bleeding, and disseminated intravascular coagulation (DIC).

Preoperative factors that increase the risk of surgical complications include older age, pre-existing hypertension, and hematologic abnormalities (eg, thrombocytopenia and coagulation abnormalities). Certain types of tumors — such as glomus tumors, meningiomas, and high-grade gliomas — have been associated with an increased frequency in the development of postoperative hematomas or hemorrhages, particularly following SRS.

Unless an immediate postoperative CT scan is standard procedure, most postoperative complications (eg, hemorrhages) are suspected based on clinical symptoms, including failure to recover from anesthesia, the development of focal neurologic deficits, or the deterioration in sensorium. Postoperative hemorrhages can be subdural hematomas, epidural hematomas, or tumor bed hematomas. Although most postoperative hemorrhages are located in the primary surgical region, remote-site hemorrhages may develop in subdural, epidural, subarachnoid, and intraparenchymal locations or in different areas.

When clinically necessary, repeat surgery may improve mortality, but the neurologic deficits are less likely to improve completely, which may lead to more significant morbidity. Preventive strategies include maintaining perioperative and postoperative normotension and achieving meticulous hemostasis through the use of bipolar coagulation and commercially available topical hemostats. Preventing and managing coagulation complications helps reduce the incidence of postoperative hematoma and hemorrhage.

Radiation Therapy

Radiation-induced side effects include alopecia, fatigue, headache, cognitive deficits, blurry vision, skin changes, nausea, vomiting, wound-healing abnormalities, and necrosis. Given the established impact of RT on wound healing, intervals of 1 to 3 weeks between resection and subsequent RT are recommended. Necrotic tissue can be resected to help restore blood flow and promote healing. Hyperbaric oxygen treatment also promotes tissue healing. 



Complications that are associated with temozolomide include alopecia, nausea, vomiting, fatigue, constipation, headache, convulsions, and anorexia. Toxicity may also lead to noncumulative myelosuppression. Patients should be evaluated regularly through the monitoring of blood counts.


Carmustine administered via IV is contraindicated in patients with a history of hypersensitivity to this drug or any of its components. Anemia, aseptic meningitis, bone marrow suppression, infection, bleeding, neutropenia, leukopenia, thrombocytopenia, carmustine implant migration, and subsequent obstructive hydrocephalus have been reported following implantation of carmustine wafers. If an area larger than the diameter of a wafer exists preoperatively, it should be closed prior to wafer implantation. Patients should also be monitored for signs of obstructive hydrocephalus.

Nitrosourea-Containing Agents

Nitrosourea-containing agents may cause myelosuppression that can lead to bleeding and fatal infections. Myelosuppression associated with lomustine is dose related, delayed, cumulative, and often occurs 4 to 6 weeks following drug administration. Patient blood counts should be monitored for at least 6 weeks after each dose, and lomustine should not be administered more frequently than in 6-week intervals. The lomustine dose should be adjusted based on nadir blood counts from the previous dose.21

Additional side effects that are specific to PCV chemotherapy include loss of appetite, vincristine-associated peripheral neurotoxicity, symptoms of malaise (eg, fatigue), and weight loss. Myelosuppression due to PCV treatment is more prominent than that of lomustine treatment alone. Pregnancy and lactation are contraindications to treatment with nitrosurea-containing agents.21

Targeted Therapy

The most frequently reported adverse events reported with bevacizumab treatment include headache, fatigue, infection, hypertension, diarrhea, epistaxis, hemorrhage, thromboembolic events, wound-healing complications, proteinuria, and gastrointestinal perforation.21 Safety data indicate that adverse events appear in a dose-dependent manner. In addition, certain toxicities are associated with the presence of risk factors.

To reduce the occurrence of treatment complications, preventive measures should be taken, including comprehensive screening for risk factors and appropriate selection of candidates for bevacizumab treatment. This involves a meticulous evaluation of the risk-benefit ratio.

Alternating Electric Field Therapy

Grade 1 or 2 scalp irritation is the most common complication associated with TT fields therapy. Shifting the arrays slightly during treatment and applying topical corticosteroids can minimize this irritation. Compared with chemotherapy, TT field therapy is associated with fewer complications such as hematologic toxicity, constipation, appetite loss, fatigue, diarrhea, nausea, pain, and vomiting.

Management of Cancer Progression and Recurrence

Follow-up for brain cancer progression and recurrence involves MRI or CT imaging within 1 to 3 months post-treatment, followed by every 3 to 4 months for 1 year, then as clinically indicated depending on sustained remission or the re-emergence of symptoms.21 Upon the detection of tumor progression or recurrence, the recommended management plan is based on the previous treatment.

Patients who previously underwent prior RT or surgery and adjuvant RT may consider re-irradiation or repeated surgery. Stereotactic RT may also be appropriate for select patients. Clinicians should allow 6 months or more between treatments, depending on the tolerance of the spinal cord and its nerve roots. The subsequent dose of RT should be limited to no more than 10 Gy near the surface of the spinal cord. Radioablation (augmentation) may be used as clinically indicated for painful lesions.


Numerous guidelines are available to assist with clinical decision-making for patients with brain cancer.


  1. Advances in brain and spinal cord tumor research. National Cancer Institute. Updated July 12, 2022. Accessed May 29, 2023.
  2. What are adult brain and spinal cord tumors? American Cancer Society. Updated May 5, 2020. Accessed May 29, 2023.
  3. Hanif F, Muzaffar K, Perveen K, Malhi SM, Simjee SU. Glioblastoma multiforme: a review of its epidemiology and pathogenesis through clinical presentation and treatment. Asian Pac J Cancer Prev. 2017;18(1):3-9. doi:10.22034/APJCP.2017.18.1.3
  4. Schwartzbaum JA, Fisher JL, Aldape KD, Wrensch M. Epidemiology and molecular pathology of glioma. Nat Clin Pract Neurol. 2006;2:494-503. doi:10.1038/ncpneuro0289
  5. Agnihotri S, Burrell KE, Wolf A, et al. Glioblastoma, a brief review of history, molecular genetics, animal models and novel therapeutic strategies. Arch Immunol Ther Exp (Warsz). 2013;61(1):25-41. doi:10.1007/s00005-012-0203-0
  6. Messali A, Villacorta R, Hay JW. A review of the economic burden of glioblastoma and the cost effectiveness of pharmacologic treatments. Pharmacoeconomics. 2014;32(12):1201-1212. doi:10.1007/s40273-014-0198-y
  7. Brain tumor facts. National Brain Tumor Society. Updated 2022. Accessed May 29, 2023.
  8. Rock K, McArdle O, Forde P, et al. A clinical review of treatment outcomes in glioblastoma multiforme – the validation in a non-trial population of the results of a randomized phase III clinical trial: Has a more radical approach improved survival? Br J Radiol. 2014;85(1017):729-733. doi:10.1259/bjr/83796755
  9. Aldape K, Brindle KM, Chesler L, et al. Challenges to curing primary brain tumors. Nat Rev Clin Oncol. 2019;16:509-520. doi:10.1038/s41571-019-0177-5
  10. American Society of Clinical Oncology. Brain tumor: risk factors. Updated September, 2021. Accessed May 29, 2023.
  11. Braganza MZ, Kitahara CM, de Gonzalez AB, Inskip PD, Johnson KJ, Rajaraman P. Ionizing radiation and the risk of brain and central nervous system tumors: a systematic review. Neuro Oncol. 2012;14(11):1316-1324. doi:10.1093/neuonc/nos208
  12. Goshen Y, Stark B, Kornreich L, Michowiz S, Feinmesser M, Yaniv I. High incidence of meningioma in cranial irradiated survivors of childhood acute lymphoblastic leukemia. Pediatr Blood Cancer. 2007;49(3):294-297. doi:10.1002/pbc.21153
  13. Do x-rays and gamma rays cause cancer? American Cancer Society. November 20, 2022. Accessed May 29, 2023.
  14. Ron E. Cancer risks from medical radiation. Health Phys. 2003;85(1):47-59. doi:10.1097/00004032-200307000-00011
  15. Blumenthal DT, Cannon-Albright LA. Familiality in brain tumors. Neurology. 2008;71(13):1015-1020. doi:10.1212/01.wnl.0000326597.60605.27
  16. Momeni F, Abedi-Firouzjah R, Farshidfar Z, et al. Differentiating between low- and high-grade glioma tumors measuring apparent diffusion coefficient values in various regions of the brain. Oman Med J. 2021;36(2):e251. doi:10.5001/omj.2021.59
  17. Tumor grade. National Cancer Institute. Updated August 2, 2022. Accessed May 30, 2023.
  18. Kim YZ, Kim C-Y, Lim DH. The overview of practical guidelines for gliomas by KSNO, NCCN, and EANO. Brain Tumor Res Treat. 2022;10(2):83-93. doi:10.14791/btrt.2022.0001
  19. Coburger J, Segovia von Riehm J, Ganslandt O, Wirtz CR, Renovanz M. Is there an indication for intraoperative MRI in subtotal resection of glioblastoma? A multicenter retrospective comparative analysis. World Neurosurg. 2018;110:e389-e397. Doi:10.1016/j.wneu.2017.11.015
  20. Iijima K, Hirato M, Miyagishima T, et al. Microrecording and image-guided stereotactic biopsy of deep-seated brain tumors. J Neurosurg. 2015;123(4):978-988. Doi:10.3171/2014.10.JNS14963
  21. NCCN Guidelines: Central Nervous System Cancers. Version 2.2021. National Comprehensive Cancer Network. Updated 2021. Accessed May 30, 2023.
  22. Barker FG II, Chang SM, Gutin PH, et al. Survival and functional status after resection of recurrent glioblastoma multiforme. Neurosurgery. 1998;42(4):709-720. doi:10.1097/00006123-199804000-00013 
  23. Park JK, Hodges T, Arko L, et al. Scale to predict survival after surgery for recurrent glioblastoma multiforme. J Clin Oncol. 2010;28(24):3838-3843. doi:10.1200/JCO.2010.30.0582
  24. Wu Q, Allouch A, Martins I, et al. Modulating both tumor cell death and innate immunity is essential for improving radiation therapy effectiveness. Front Immunol. 2017;8:613. doi:10.3389/fimmu.2017.00613
  25. Walker MD, Green SB, Byar DP, et al. Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery. N Engl J Med. 1980;303(23):1323-1329. doi:10.1056/NEJM198012043032303
  26. Wee CW. Radiotherapy for newly diagnosed glioblastoma in the elderly: what is the standard? Brain Tumor Res Treat. 2022;10(1):12-21. doi:10.14791/btrt.2022.10.e34
  27. Ding M, Newman F, Chen C, Stuhr K, Gaspar LE. Dosimetric comparison between 3DCRT and IMRT using different multileaf collimators in the treatment of brain tumors. Med Dosim. 2009;34(1):1-8. doi:10.1016/j.meddos.2007.04.001
  28. Redmond KJ, Robertson S, Lo SS, et al. Consensus contouring guidelines for postoperative stereotactic body radiation therapy for metastatic solid tumor malignancies to the spine. Int J Radiat Oncol Biol Phys. 2017;97(1):64-74. Doi:10.1016/j.ijrobp.2016.09.014
  29. Marcrom SR, McDonald AM, Thompson JW, et al. Fractionated stereotactic radiation therapy for intact brain metastases. Adv Radiat Oncol. 2017;2(4):564-571. Doi:10.1016%2Fj.adro.2017.07.006
  30. Taal W, Bromberg JEC, van den Bent MJ. Chemotherapy in glioma. CNS Oncol. 2015;4(3):179-192. Doi:10.2217%2Fcns.15.2
  31. Rampling R, James A, Papanastassiou V. The present and future management of malignant brain tumors: surgery, radiotherapy, chemotherapy. J Neurol Neurosurg Psychiatry. 2004;75(Suppl 2):24-30. doi:10.1136/jnnp.2004.040535
  32. Cairncross JG, Ueki K, Zlatescu M, et al. Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J Ntl Cancer Inst. 1998;90(19):1473-1479. doi:10.1093/jnci/90.19.1473
  33. Wang H, Xu T, Jiang Y, et al. The challenges and the promise of molecular targeted therapy in malignant gliomas. Neoplasia. 2015;17(3):239-255. doi:10.1016/j.neo.2015.02.002
  34. Cohen MH, Shen YL, Keegan P, Pazdur R. FDA drug approval summary: bevacizumab (Avastin®) as treatment of recurrent glioblastoma multiforme. Oncologist. 2009;14(11):1131-1138. doi:10.1634/theoncologist.2009-0121
  35. Swanson KD, Lok E, Wong ET. An overview of alternating electric fields therapy (NovoTTF therapy) for the treatment of malignant glioma. Curr Neurol Neurosci Rep. 2016;16(1):8. Doi:10.1007/s11910-015-0606-5
  36. Stupp R, Wong ET, Kanner AA, et al. NovoTTF-100A versus physician’s choice chemotherapy in recurrent glioblastoma: a randomized phase III trial of a novel treatment modality. Eur J Cancer. 2012;48(14):2192-2202. doi:10.1016/j.ejca.2012.04.011
  37. Patil CG, Lad SP, Santarelli J, Boakye M. National inpatient complications and outcomes after surgery for spinal metastasis from 1993-2002. Cancer. 2007;110(3):625-630. doi:10.1002/cncr.22819

Author Bio

Takeesha Roland-Jenkins, PhD, is a psychologist, writer, editor, and educator with many years of experience working in the mental health and medical arena. She earned her doctorate in general psychology from Grand Canyon University in 2018. Her writing has been published in the Journal of Instructional Research, as well as by Brain Blogger, Between Us Clinic, Consultant 360, BrainMass, and The Good Men Project, among others. Her subject areas cover a wide variety of topics that pertain to psychology, mental health, general health and fitness, dietary supplementation, ethnicity-related backlash, and own-group conformity pressure, to name a few.