Glioma+(child)

Gliomas present most often as supratentorial tumors. 3 These tumors may give rise to many different signs and symptoms depending on size and location of the tumor. Some common symptoms include: 3 The diagnostic procedures for gliomas are the same as many other Central Nervous System (CNS) abnormailites. These tests include: 3 Childhood brain stem gliomas are tumors that arise from glial cells and are classified according to histology, radiographic appearance and the location within the brain stem. 4 Gliomas can occur in several places in the brain including pons, midbrain, tectum, dorsum of the medulla at the cervicomedullary junction or a combination of areas. 4 Diffuse fibrillary astrocytomas in the pons (diffuse intrinsic pontine gliomas [DIPG]) are the most common types of gliomas in children and have a poor prognosis. 4 This type of glioma occurs from an amino acid mutation that isn’t seen in adult gliomoas or other gliomas in children. Other types of glioma occurring in children are focal pilocytic astrocytomas, ganglioglioma, pilcytic, astrocytoma, diffuse astrocytoma, anaplastic astrocytoma, and glioblastoma muliforme. 4 While MRI is used to further delineate the type of tumor, the treatment modality between DIPG and other childhood gliomas is still the same and histologic classification isn’t always necessary and in the best interest of the patient. The image below is an example of a diffuse brainstem glioma.4 The tumor typically stems from the brainstem and is clearly obstructing the spinal cord.
 * **Epidemiolgy:** || Rachel
 * Almost 40% of pediatric brain tumors are low-grade gliomas (astrocytomas, oligodendrogliomas, mixed gliomas, and mixed neuroepithelial tumors). 1
 * Astrocytomas present most often as supratentorial tumors; 60% occur in the diencephalon and 40% in the cerebral hemispheres.
 * Infratentorial astrocytomas involve the cerebellum or brainstem.
 * Oligodendroglioma is less common in children.
 * Malignant gliomas represent 7% to 10% of pediatric CNS tumors and approximately 15% of astrocytomas and common glial neoplasms.
 * Histologically, 50% to 60% are anaplastic astrocytomas, 30% to 40% are glioblastomas, and 10% to 20% are anaplastic oligodendrogliomas and malignant mixed gliomas. ||
 * **Etiology:** || Rachel
 * The cause of most childhood brain tumors is unknown. 2 ||
 * **Signs & Symptoms:** || Brandon
 * Headaches (especially upon wakening)
 * Lethargy
 * Seizures
 * Compression of surrounding brain tissues may results in
 * behavioral changes
 * weakness and motor dysfunction
 * hormone abnormalities ||
 * **Diagnostic Procedures:** || Brandon
 * Magnetic Resonance Imaging (MRI) scan
 * Magnetic Resonance Spectroscopy (MRS) scan- this scan is done along side of a MRI scan to help determine if the tissue involved is normal or tumor. Also, is some cases may help determine type of tumor
 * Computed Tomography (CT) scan
 * Biopsy- if a tumor is located to determine type and grade
 * Lumbar puncture (spinal tap)- this is useful in determining if any tumor cells have spread distally to the cerebrospinal fluid (CSF). ||
 * **Histology:** || Ashley

|| Because the brain doesn't contain lymph node channels, metastasis do not occur through lymphatics. 6 || Gliomas rarely spread outside the central nervous system. However, the two possible metastasis sites are lung and liver. 7 || World health organization's (WHO) classification for staging ependymal tumors is as follows: 8  || // There is no formal staging system for childhood brain stem glioma. A tumor may be classified as either diffuse or focal. // 9 -Diffuse brain stem glioma. Tumor spreads freely throughout the pons and often spreads to the midbrain, the medulla, or nearby parts of the brain. These tend to be high-grade tumors; they are very aggressive and contain abnormal-looking cells. -Focal brain stem glioma. About 20% of brain stem tumors are focal, meaning they occur in one area or are contained within a small portion of the brain stem. They usually occur in the midbrain or medulla, rather than the pons. These are usually benign or low-grade tumors; they are less aggressive and the tumor cells look fairly normal. || -Growth disturbances are common; growth hormone deficiency in most long term survivors 10 -adverse effects may be directly related to the biologically effective dose -Gradual onset of endocrine deficits (ex: growth hormone, thyroid-stimulating hormone, adrenocorticotropic hormone) -Late optic neuropathy or brain necrosis in < 10% of cases of patients treated to doses > 60Gy -Secondary malignant neoplasms -Hyperfractionated treatments are associated with moderate acute epithelial toxicity such as otitis and radioepidermitis -Late toxicities with high dose hyperfractionated treatments: neurocognitive deficits, hearing loss, leukoencephalopathy, diffuse microhemorrhages, dystrophic calcifications on MRI || Low-Grade GliomasGeneral Management:* Treatment is indicated for significant visual or neurologic deficits or for objective evidence of progression based on serial imaging or visual testing. Radiation Therapy* Local treatment volumes are used for optic pathway and hypothalamic tumors. Malignant GliomasGeneral Management*Outcome is clearly superior after aggressive surgical resection for cerebral hemispheric malignant gliomas. Radiation Therapy Brainstem GliomasGeneral Management* The morbidity of biopsy within the pons and the lack of histology-specific therapeutic options make surgery not a viable option for pontine gliomas. Radiation Therapy*Infiltrating tumors of the pons require 2 to 3 cm margins in defining the target volume.
 * **Lymph node drainage:** || Ashley
 * **Metastatic spread:** || Amanuel
 * **Grading:** || Amanuel
 * **Staging:** || Lindsey
 * **Radiation side effects:** || Lindsey
 * **Prognosis:** || Kevin
 * Optic nerve glioma have a very good survival rate at 100% survival for 6 years.
 * Low-grade gliomas have a 5 year survival rate of 96% if the tumor is completely resected.
 * Childhood gliomas with a "diffuse pattern" (aka: brainstem gliomas) have a survival rate of 48% in 5 years after treatment.
 * High-grade gliomas (grade 2 & 3) have a 5 year survival rate of 73% while glioblastomas (grade 4) have a 5 year survival rate of just 20%. 11 ||
 * **Treatments:** || Kevin
 * Optic nerve glioma is managed by observation or resection, with the latter restricted to patients with disease anterior to the chasm and little or no vision.
 * Surgical interventin for thalamic glioma has been controversial. Radiation therapy acheives disease control in approximately 50% of cases.
 * There are chemotherapy trials due to radiation induced toxicity in young patients with optic chiasm/hypothalamic gliomas.
 * Most hemispheric gliomas (usually astrocytomas) are surgically resected.
 * There is no indication for adjuvant irradiation in completely resected low-grade astrocytomas. Similar recommendations are suggested for oligoastrocytoma and oligodendroglioma.
 * For incompletely resected tumors, long-term disease control has been well documented after irradiation.
 * Lesions confined to the chasm and/or hypothalamus can be treated with conventional arcs or multiple coplanar configurations; early experience suggests excellent coverage with fractionated stereotactic irradiation or 3-D conformal techniques.
 * Optic pathway tumors that involve the optic nerves or optic tracts require opposed lateral high-energy fields.
 * Dose levels of 50 Gy are recommended for children older than 3 years, but are reduced to 45 Gy for infants.
 * Thalamic gliomas usually require local treatment volumes; evidence of extention (into the midbrain or across the corpus callosum) requires wider margins.
 * A dose of 54 Gy is recommended for low-grade thalamic gliomas.
 * The recommended dose for low-grade astrocytomas is 54-55 Gy; controlled studies of doses of 60 Gy with stereotactic techniques are ongoing.
 * It is rare to achieve more than biopsy or limited resection in thalamic tumors
 * Radiation therapy is indicated post-operatively, except in children younger than 3 to 5 years of age who enter initial chemotherapy studies.
 * The use of chemotherapy in childhood malignant gliomas has been supported by a CCG study testing postoperative irradiation versus combined irradiation and chemotherapy.
 * As in adults, current recommendations include wide local volumes for both thalamic and cerebral hemispheric tumors, based on preoperative tumor extent and reconfiguration of the brain after resection.
 * Margins typically are defined at 2 cm beyond the hpodense area on CT or T1-weighted MRI.
 * There has been limited use of CSI in malignant gliomas.
 * Although disseminated disease has been documented in up to 30% to 40% of children with supratentorial lesions, the incidence of islolated neuraxis failure remains at or blow 10%.
 * Dose recommendations parallel those in adults (54 to 60 Gy with conventional fractionation).
 * Limited data fail to indicate an advantage with "preventative" or therapeutic neuraxis irradiation.
 * Dorsally exophytic brainstem gliomas require judicious surgical resection; a significant percentage will need ventriculoperitoneal shunt placement.
 * Biopsy is generally indicated for midbrain tumors.
 * Radiation therapy is the primary treatment for brainstem gliomas arising in the pons. The radiation response and yet poor outcome have encouraged trials of hyperfractionated irradiation.
 * Chemotherapy has little efficacy in pontine gliomas.
 * Opposed lateral high-energy beam fields are used most often.
 * The potential advantage of hyperfractionated irradiation in brainstem gliomas was reported using 72 Gy at 1 Gy twice daily.
 * When disease control and toxicity data are combined a "best" hyperfractionation regimen is suggested at 70.2 or 70.0Gy using 1.17 or 1.0 Gy fractions, respectively.
 * It is unclear whether hyperfractionated schedules offer any improvement compared with conventionally fractionated regimens . 12

Dose distributions of a proton plan, 3D photon plan and standard photon plan for a pediatric optic glioma. 13

||
 * **TD 5/5:** || Jenn
 * Tissue dose associated with 5% injury rate within 5 years ** . **(TD 5/5)** 14


 * Ear (Middle): Serous otitis 5000cGy
 * Ear (Vestibular): Meniere’s syndrome 6000cGy
 * Retina: Blindness 5500cGy
 * Cornea: Blindness 5000cGy
 * Lens: Blindness 500cGy
 * Salivary Glands: Xerostomia 5000cGy
 * Oral cavity and pharynx: Ulceration 6000cGy
 * Pituitary: Reduced hormone production 4500cGy ||
 * **References:** || # Chao KS, Perez CA, Brady LW. Radiation Oncology Management Decisions. 3rd ed. Philadelphia, PA: Lippincott, Williams, and Wilkins; 2011.726-728.
 * 1) Childhood Brain Stem Glioma Treatment. National Cancer Institute. []. Accessed July 5, 2013.
 * 2) Glioblastoma Multiforme and Anaplastic Astrocytoma. Boston Children's Hospital. []. Accessed July 3.2013.
 * 3) Childhood Brain Stem Glioma Treatment. National Cancer Institute Web site. []. Updated January 23, 2013. Accessed June 26, 2013.
 * 4) Rabou A, Gaillard F, et al. Diffuse Brainstem Glioma. Radiopaedia Web site. []. Accessed June 26, 2013.
 * 5) Chao KS, Perez CA, Brady LW. //Radiation Oncology Management Decisions//. 3rd ed. Philadelphia, PA: Lippincott, Williams, and Wilkins; 2011.
 * 6) Rare phenomenon of extracranial metastasis of glioblastoma. []. Accessed July, 2013.
 * 7) A Review of Glioblastoma Multiforme. US Pharmacist. []. Accessed July, 2013.
 * 8) Brain Stem Glioma-Childhood. http://www.cancer.net/cancer-types/brain-stem-glioma-childhood/stages-and-grades. Accessed July 3, 2013.
 * 9) Chao KS, Perez CA, Brady LW. //Radiation Oncology Management Decisions//. 3rd ed. Philadelphia, PA: Lippincott, Williams, and Wilkins; 2011: 733.
 * 10) Cancer Research UK. Statistics and outlooks for brian tumors. [|http://www.cancerhelp.org.uk/type/brain-tumour/treatment/statistics-and-outlook-for-brain-tumours#child]. Accessed July 1, 2013.
 * 11) Chao KS, Perez CA, Brady LW. Radiation Oncology - Management Decisions. 3rd ed. Philadelphia: Lippincott, Williams & Wilkins, 2011: 725-730.
 * 12) Fuss M., et al. Proton Radiation Therapy for Pediatric Optic Pathway Gliomas: Comparison with 3D Planned Conventional Photons and a Standard Photon Technique. Int. J. Radiation Oncol. 1999; 45(5): 1117-1126.
 * 13) Washington C, Leaver D. Principles and Practice of Radiation Oncology. 3rd ed. St. Louis, MO. Mosby Elsevier; 2010: 80-82. ||

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