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Genomics of brain tumor imaging.

Brain Tumors in Children | Neurology

Neuroimaging Clin N Am ; Imaging genomics in gliomas. Cancer J ; Glioblastoma multiforme: A review of where we have been and where we are going. Expert Opin Investig Drugs ; Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature ; Olar A, Aldape KD. Using the molecular classification of glioblastoma to inform personalized treatment.

J Pathol ; Curr Neurol Neurosci Rep ; New developments in the pathogenesis and therapeutic targeting of the IDH1 mutation in glioma. Int J Med Sci ; Genetics of glioblastoma: A window into its imaging and histopathologic variability. Radiographics ; Smits M, van den Bent MJ. Imaging correlates of adult glioma genotypes. Radiology ; Glioblastoma, a brief review of history, molecular genetics, animal models and novel therapeutic strategies. Arch Immunol Ther Exp Warsz ; Waddington CH.

The epigenotype Int J Epidemiol ; Ohgaki H, Kleihues P. The definition of primary and secondary glioblastoma. Clin Cancer Res ; An integrated genomic analysis of human glioblastoma multiforme. Science ; Can morphological MRI differentiate between primary central nervous system lymphoma and glioblastom? Cancer Imaging ; Differentiation between glioblastoma multiforme and primary cerebral lymphoma: Additional benefits of quantitative diffusion-weighted MR imaging.

PLoS One ;e Primary brain tumours in adults. Lancet ; Diffusion tensor imaging for glioma grading: Analysis of fiber density index. Basic Clin Neurosci ; Apilot study of pre-operative motor dysfunction from gliomas in the region of corticospinal tract: Evaluation with diffusion tensor imaging.

Shan W, Wang XL. The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above. The Prognostic Factors subsection was extensively revised. Added American Joint Committee on Cancer as reference 2. Revised text to state that treatment options for patients with low-grade gliomas are not as clear as in the case of high-grade tumors and include observation, postoperative radiation therapy, and chemotherapy with temozolomide.

Added text about the EORTC [ NCT ] trial, which randomly assigned patients with low-grade glioma and at least one high-risk feature to receive either radiation therapy or temozolomide chemotherapy. Radiation therapy consisted of conformal treatment; chemotherapy was dose-dense oral temozolomide. There was no significant difference in progression-free survival or health-related quality of life cited Baumert et al.

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Brain & Central Nervous System Cancer

Search term. Risk Factors Few definitive observations have been made about environmental or occupational causes of primary CNS tumors. Clinical Features The clinical presentation of various brain tumors is best appreciated by considering the relationship of signs and symptoms to anatomy. Diagnostic Evaluation All brain tumors, whether primary, metastatic, malignant, or benign, must be differentiated from other space-occupying lesions that can have similar clinical presentations, such as abscesses, arteriovenous malformations, and infarctions.

CT is superior for detecting calcifications, skull lesions, and hyperacute hemorrhages bleeding less than 24 hours old and helps direct differential diagnosis and immediate management. MRI has superior soft-tissue resolution.

Types of Benign Brain Tumors

MRI can better detect isodense lesions, tumor enhancements, and associated findings such as edema, all phases of hemorrhagic states except hyperacute , and infarctions. High-quality MRI is the diagnostic study of choice in the evaluation of intramedullary and extramedullary spinal cord lesions. Biopsy Biopsy confirmation to corroborate the suspected diagnosis of a primary brain tumor is critical, whether before surgery by needle biopsy or at the time of surgical resection.

Prognostic Factors Several genetic alterations have emerged in recent years as powerful prognostic factors in diffuse glioma astrocytoma, oligodendroglioma, mixed glioma, and glioblastoma , and these alterations may guide patient management. Patients with wild-type IDH tumors had the worst prognosis independent of treatment type. Atlanta, Ga: American Cancer Society, Available online. Last accessed June 7, Bethesda, Md: National Cancer Institute, Also available online. Last accessed February 22, Last accessed February 1, J Neurooncol 43 3 : , Lancet : , Kleihues P, Cavenee WK, eds.

Neuroimaging Clin N Am 13 2 : , x-xi, Ricci PE: Imaging of adult brain tumors. Neuroimaging Clin N Am 9 4 : , Lancet Oncol 17 11 : , Earlier attempts to develop a TNM-based classification were dropped for the following reasons:[ 2 ] Tumor size T is less relevant than are tumor histology and location. Metastatic spread M rarely applies because most patients with CNS neoplasms do not live long enough to develop metastatic disease. WHO grade I includes lesions with low proliferative potential, a frequently discrete nature, and the possibility of cure following surgical resection alone.

WHO grade II includes lesions that are generally infiltrating and low in mitotic activity but recur more frequently than do grade I malignant tumors after local therapy. Some tumor types tend to progress to higher grades of malignancy. WHO grade III includes lesions with histologic evidence of malignancy, including nuclear atypia and increased mitotic activity. These lesions have anaplastic histology and infiltrative capacity. They are usually treated with aggressive adjuvant therapy. WHO grade IV includes lesions that are mitotically active, necrosis prone, and generally associated with a rapid preoperative and postoperative progression and fatal outcomes.

The lesions are usually treated with aggressive adjuvant therapy. Table 1. Brain and Spinal Cord. New York, NY: Springer, , pp. Brain Pathol 3 3 : , Acta Neuropathol 2 : , Brain Pathol 19 3 : , J Clin Invest 5 : , Cancer Res 68 21 : , PLoS One 6 3 : e, PLoS One 4 11 : e, Science : , N Engl J Med 8 : , Neurology 73 21 : , J Clin Oncol 27 25 : , Acta Neuropathol 6 : , Acta Neuropathol 4 : , Cancer Res 66 20 : , J Neuropathol Exp Neurol 70 2 : , Brain Pathol 20 1 : , Surgery For most types of CNS tumors in most locations, complete or near-complete surgical removal is generally attempted, within the constraints of preserving neurologic function and the patient's underlying health.

The primary goals of surgical resection include the following:[ 4 ] To establish a histologic diagnosis. To reduce intracranial pressure by removing as much tumor as is safely possible to preserve neurological function. Resection proceeds until either the magnetic resonance imaging MRI signal abnormality being used to monitor the extent of surgery is completely removed or subtle neurologic dysfunction appears e. When the tumor is located in or near language centers in the cortex, intraoperative language mapping can be performed by electrode discharge-induced speech arrest while the patient is asked to count or read.

Large-volume hospitals had lower in-hospital mortality rates after craniotomies for primary brain tumors odds ratio [OR], 0. Although there was no specific sharp threshold in all-cause mortality outcomes between low-volume hospitals and high-volume hospitals, craniotomy-associated in-hospital mortality was 4.

High-volume surgeons had lower in-hospital patient mortality rates after craniotomy OR, 0.

Types of Brain Tumors

Radiation therapy High-grade tumors Radiation therapy has a major role in the treatment of patients with high-grade gliomas. Evidence postoperative radiation therapy [PORT] : A systematic review and meta-analysis of five randomized trials plus one trial with allocation by birth date comparing PORT with no radiation therapy showed a statistically significant survival advantage with radiation risk ratio, 0.

A randomized trial comparing 60 Gy in 30 fractions over 6 weeks with 45 Gy in 25 fractions over 4 weeks showed superior survival in the first group 12 months vs. Low-grade tumors Treatment options for patients with low-grade gliomas i. Most of the control patients received radiation therapy at the time of progression.

Nervous System Tumors

After a median follow-up of 93 months, median progression-free survival PFS was 5. The investigators did not collect reliable quality-of-life measurements, so it is not clear whether the delay in initial relapse in the radiation therapy arm translated into improved function or quality of life. Radiation therapy consisted of conformal treatment up to Disease progression, subsequent neoplasms, or recurrences There are no randomized trials to delineate the role of repeat radiation after disease progression or the development of radiation-induced cancers.

Localized chemotherapy carmustine wafer The concept of delivering high doses of chemotherapy while avoiding systemic toxicity is attractive because malignant glioma—related deaths are nearly always the result of an inability to control intracranial disease rather than the result of distant metastases. Evidence carmustine wafer : A small trial was closed because of a lack of continued availability of the carmustine wafers after 32 patients with high-grade gliomas had been entered. A multicenter study of patients with primary malignant gliomas, of whom had glioblastoma, was more informative.

Unlike the initial trial, patient characteristics were well balanced between the study arms. Median survival in the two groups was A systematic review combining both studies [ 26 - 28 ] estimated an HR for overall mortality of 0. Active surveillance Active surveillance is appropriate in some circumstances.

Supportive therapy Dexamethasone, mannitol, and furosemide are used to treat the peritumoral edema associated with brain tumors. Expert Rev Anticancer Ther 3 5 : , J Neurosurg 99 3 : , JAMA 5 : , Mayo Clin Proc 76 7 : , N Engl J Med 1 : , JAMA 20 : , Surgery 3 : , Neuro Oncol 7 1 : , Radiother Oncol 64 3 : , Br J Cancer 64 4 : , N Engl J Med 23 : , Stewart LA: Chemotherapy in adult high-grade glioma: a systematic review and meta-analysis of individual patient data from 12 randomised trials.

N Engl J Med 10 : , Lancet Oncol 10 5 : , J Clin Oncol 31 3 : , Neurosurgery 41 1 : ; discussion , Neuro-oncol 5 2 : , Acta Neurochir Wien 3 : ; discussion , Neurosurgery 53 1 : ; discussion , J Neurosurg 4 : , Astrocytic Tumors Treatment Brain stem gliomas treatment Patients with brain stem gliomas have relatively poor prognoses that correlate with histology when biopsies are performed , location, and extent of tumor.

Standard treatment options for brain stem gliomas include the following: Radiation therapy. Pineal astrocytic tumors treatment Depending on the degree of anaplasia, patients with pineal astrocytomas have variable prognoses. Standard treatment options for pineal astrocytic tumors include the following: Surgery plus radiation therapy for pineal astrocytoma. Standard treatment options for pilocytic astrocytomas include the following: Surgery alone if the tumor is totally resectable.

Diffuse astrocytomas treatment This WHO grade II astrocytic tumor is less often curable than is a pilocytic astrocytoma. Standard treatment options for diffuse astrocytomas WHO grade II include the following: Surgery with or without radiation therapy. In the same trial, there was no difference in overall survival OS between patients who had radiation therapy after surgery and those who were treated with radiation therapy at the time of progression.

Notably, the RTOG study enrolled patients with a variety of tumors, including astrocytomas, oligodendrogliomas, and mixed oligoastrocytomas. In a risk-adjusted multivariate analysis, patients treated with PCV and patients with an oligodendroglial histology had better survival outcomes. A subset analysis of histologic type suggested that the addition of PCV mainly benefited patients with oligodendroglial tumors, although this data is yet to be validated. Anaplastic astrocytomas treatment Patients with anaplastic astrocytomas WHO grade III have a low cure rate with standard local treatment.

Standard treatment options for anaplastic astrocytomas include the following: Surgery plus radiation therapy with or without chemotherapy. Postoperative radiation alone has been compared with postoperative chemotherapy alone in patients with anaplastic gliomas i. Of the patients randomly assigned to undergo radiation therapy, were randomly assigned to receive chemotherapy, with a week course of either PCV or single-agent temozolomide randomization. Glioblastomas treatment For patients with glioblastoma WHO grade IV , the cure rate is very low with standard local treatment.

Standard treatment options for patients with newly diagnosed glioblastoma include the following: Surgery plus radiation therapy and chemotherapy. This trial reported a survival benefit with concurrent radiation therapy and temozolomide, compared with radiation therapy alone. OS was statistically significantly better in the combined radiation therapy—temozolomide group HR death , 0. All patients were treated with surgery followed by radiation therapy and concurrent daily temozolomide.

Patients were then randomly assigned to receive either standard adjuvant temozolomide or dose-dense temozolomide. There was no survival advantage for the use of dose-dense temozolomide versus standard-dose temozolomide in newly diagnosed glioblastoma patients, regardless of MGMT status. The efficacy of dose-dense temozolomide for patients who have recurrent glioblastoma, however, is yet to be determined.

RTOG NCT : Patients were randomly assigned to receive standard therapy chemoradiation with temozolomide or standard therapy plus bevacizumab. OS and PFS were coprimary endpoints. AVAglio NCT : Patients were randomly assigned to receive standard therapy chemoradiation with temozolomide or standard therapy plus bevacizumab. The PFS result was statistically significant and associated with clinical benefit because bevacizumab-treated patients remained functionally independent longer 9.

Bevacizumab-treated patients also had delayed initiation of corticosteroids Oligodendroglial Tumors Treatment Oligodendrogliomas treatment Patients who have oligodendrogliomas WHO grade II generally have better prognoses than do patients who have diffuse astrocytomas. Standard treatment options for oligodendrogliomas include the following: Surgery with or without radiation therapy. Anaplastic oligodendrogliomas treatment Patients with anaplastic oligodendrogliomas WHO grade III have a low cure rate with standard local treatment, but their prognoses are generally better than are the prognoses of patients with anaplastic astrocytomas.

Standard treatment options for anaplastic oligodendrogliomas include the following: Surgery plus radiation with or without chemotherapy. In contrast, the RTOG trial RTOG [ NCT ] demonstrated no differences in median survival by treatment arm between an 8-week, intensive PCV chemotherapy regimen followed by immediate involved-field-plus-radiation therapy and radiation therapy alone. For patients with non-codeleted tumors, there was no difference in median survival by treatment arm 2. Postoperative radiation therapy alone has been compared with postoperative chemotherapy alone in patients with anaplastic gliomas including astrocytomas, 91 oligoastrocytomas, and 39 oligodendrogliomas with crossover to the other modality at the time of tumor progression.

TTF or OS did not differ across the treatment arms and were not affected by the order of the modalities. Standard treatment options for mixed gliomas include the following: Surgery plus radiation therapy with or without chemotherapy. Standard treatment options for grades I and II ependymal tumors include the following: Surgery alone if the tumor is totally resectable. Embryonal Cell Tumors Medulloblastomas Treatment Medulloblastoma occurs primarily in children, but may also occur in adults. Standard treatment options for medulloblastomas include the following: Surgery plus craniospinal radiation therapy for good-risk patients.

Treatment options under clinical evaluation for medulloblastomas Treatment options under clinical evaluation include the following: Surgery plus craniospinal radiation therapy and various chemotherapy regimens are being evaluated for poor-risk patients. Standard treatment options for pineal parenchymal tumors include the following: Surgery plus radiation therapy for pineocytoma. Research is being done in this area, but more extensive research is necessary to translate this knowledge into potential therapies.

Symptoms vary depending on the location of the brain tumor, but the following may accompany different types of brain tumors:. Sophisticated imaging techniques can pinpoint brain tumors. Other MRI sequences can help the surgeon plan the resection of the tumor based on the location of the normal nerve pathways of the brain.

Intraoperative MRI also is used during surgery to guide tissue biopsies and tumor removal. Magnetic resonance spectroscopy MRS is used to examine the tumor's chemical profile and determine the nature of the lesions seen on the MRI. Positron emission tomography PET scan can help detect recurring brain tumors.

Central Nervous System Tumors - Brain Tumors

Sometimes the only way to make a definitive diagnosis of a brain tumor is through a biopsy. The neurosurgeon performs the biopsy and the pathologist makes the final diagnosis, determining whether the tumor appears benign or malignant, and grading it accordingly. While it is true that radiation and chemotherapy are used more often for malignant, residual or recurrent tumors, decisions as to what treatment to use are made on a case-by-case basis and depend on a number of factors. There are risks and side effects associated with each type of therapy.

It is generally accepted that complete or nearly complete surgical removal of a brain tumor is beneficial for a patient. The neurosurgeon's challenge is to remove as much tumor as possible, without injuring brain tissue important to the patient's neurological function such as the ability to speak, walk, etc.

Traditionally, neurosurgeons open the skull through a craniotomy to insure they can access the tumor and remove as much of it as possible. A drain EVD may be left in the brain fluid cavities at the time of surgery to drain the normal brain fluid as the brain recovers from the surgery.

Another procedure that is commonly performed, sometimes before a craniotomy, is called a stereotactic biopsy. This smaller operation allows doctors to obtain tissue in order to make an accurate diagnosis. Usually, a frame is attached to the patient's head, a scan is obtained, and then the patient is taken to the operating area, where a small hole is drilled in the skull to allow access to the abnormal area.

Based on the location of the lesion, some hospitals may do this same procedure without the use of a frame. A small sample is obtained for examination under the microscope. In the early s, computerized devices called surgical navigation systems were introduced. These systems assisted the neurosurgeon with guidance, localization and orientation for tumors. This information reduced the risks and improved the extent of tumor removal. In many cases, surgical navigation systems allowed previously inoperable tumors to be excised with acceptable risks.

Some of these systems also can be used for biopsies without having to attach a frame to the skull. One limitation of these systems is that they utilize a scan CT or MRI obtained prior to surgery to guide the neurosurgeon. Thus, they cannot account for movements of the brain that may occur intraoperatively. Investigators are developing techniques using ultrasound and performing surgery in MRI scanners to help update the navigation system data during surgery.

Intraoperative language mapping is considered by some as a critically important technique for patients with tumors affecting language function, such as large, dominant-hemisphere gliomas. This procedure involves operating on a conscious patient and mapping the anatomy of their language function during the operation. The doctor then decides which portions of the tumor are safe to resect. Recent studies have determined that cortical language mapping may be used as a safe and efficient adjunct to optimize glioma resection while preserving essential language sites.

Ventriculoperitoneal shunting may be required for some patients with brain tumors. Everyone has cerebrospinal fluid CSF within the brain and spine that is slowly circulating all the time. If this flow becomes blocked, the sacs that contain the fluid the ventricles can become enlarged, creating increased pressure within the head, resulting in a condition called hydrocephalus. If left untreated, hydrocephalus can cause brain damage and even death.

The neurosurgeon may decide to use a shunt to divert the spinal fluid away from the brain and, therefore, reduce the pressure. The body cavity in which the CSF is diverted usually is the peritoneal cavity the area surrounding the abdominal organs.