Glioma+(Child)


 * Epidemiology: || More common in men than in women. 7 ||
 * Etiology: || "Although no familial tendency is prominent overall, an increased incidence of brainstem glioma has been observed consistently in patients with neurofibromatosis up to 14% in some reports." "Thus far, no genetic or molecular markers have been recognized for brainstem gliomas." 6 ||
 * Signs & Symptoms: || Common presenting symptoms include double vision, weakness, unsteady gait, difficulty in swallowing, dysarthria, headache, drowsiness, nausea, and vomiting. Rarely, behavioral changes or seizures may be seen in children. Older children may have deterioration of handwriting and speech. Tectal lesions typically present with headache, nausea, and vomiting. 6 ||
 * Diagnostic Procedures: || CT, MRI, and PET scan, complete blood count, cerebral spinal fluid chemistry tests, cytology and microbiology studies. Neurologic exam includes mental condition, coordination, sensation, reflexes and motor tests. 1 ||
 * Histology: || Low grade gliomas consist of astrocytomas, oligodendrogriomas, mixed gliomas, and mixed neuroepithelial histologic types. Of malignant gliomas, 50% to 60% are anaplastic astrocytomas, 30% to 40% are gliomlastomas, and 10% to 20% are anaplastic oligodendrogliomas and malignant mixed gliomas. 1 

Brainstem gliomas arise in the midbrain (or mesencephalon, including the tegmentum and tectal plate), pons, or medulla. 1 || Gliomas will seed in the CNS and CSF pathways. 9 || Grade 1: is the juvenile pilocytic astrocytoma Grade 2: is the diffuse astrocytoma Grade 3: is the anaplastic astrocytoma Grade 4: is the glioblastoma multiforme. The grading is based on the presence of nuclear atypia, vascular proliferation, mitoses and necrosis. Typically, the necrosis is seen in Grade 4. 6 ||
 * Lymph Node Drainage: || According to the AJCC the reason that the N in the TNM staging doesn’t work for brain and spinal cord cancers is because the brain and spinal cord do not have lymph nodes . 8 ||
 * Metastatic Spread: || “An M classification is not pertinent to the majority of neoplasms that affect the central nervous system, because most patients with tumors of the central nervous system do not live long enough to develop metastatic disease (except for some pediatric tumors that tend to “seed” through the cerebrospinal fluid spaces).” This phenomenon of “seeding” is rarely seen adults and is a hallmark for some childhood tumors. The M category of the TNM staging should help “differentiate between extraneural metastasis and metastasis within CNS and CSF pathways.” 8
 * Grading: || <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">World Health Organization (WHO) Grade 1 to 4:
 * Staging: || <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">There is no generally applied staging system for childhood gliomas. It is uncommon for these tumors to have spread outside the brain itself at the time of diagnosis. <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif; font-size: 80%; vertical-align: super;">5 ||
 * Radiation Side Effects: || <span style="color: #008000; font-family: Arial,Helvetica,sans-serif;">The following side effects are possible with irradiation to the brain in children. The presence of these side effects varies due to tumor location, tumor size, and treatment technique/total dose. Late radiation side effects tend to be worse the younger a child is during treatment. <span style="color: #008000; font-family: Arial,Helvetica,sans-serif; font-size: 80%; line-height: 15px; vertical-align: super;">2

<span style="color: #008000; font-family: Arial,Helvetica,sans-serif;"> -Fatigue, skin irritation (on scalp) and neurologic deterioration can all occur during and shortly after the course of radiation treatment. <span style="color: #008000; font-family: Arial,Helvetica,sans-serif; font-size: 80%; vertical-align: super;">2 <span style="color: #008000; font-family: Arial,Helvetica,sans-serif;"> -Hormone deficiency (growth hormone, thyroid-stimulating hormone, adrenocorticotropic hormone, and gonadotropins) can occur when the pituitary and hypothalamus receive a dose of 20 Gy or more. <span style="color: #008000; font-family: Arial,Helvetica,sans-serif; font-size: 80%; vertical-align: super;">1,2 <span style="color: #008000; font-family: Arial,Helvetica,sans-serif;"> -Hair loss (temporary or permanent) can occur with doses of 20-40 Gy and doses greater than 40 Gy, respectively. <span style="color: #008000; font-family: Arial,Helvetica,sans-serif; font-size: 80%; vertical-align: super;">2 <span style="color: #008000; font-family: Arial,Helvetica,sans-serif;"> -Optic neuropathy and brain necrosis can occur with doses over 60 Gy. <span style="color: #008000; font-family: Arial,Helvetica,sans-serif; font-size: 80%; vertical-align: super;">1 <span style="color: #008000; font-family: Arial,Helvetica,sans-serif;"> -Secondary malignancies in the bone, soft tissue or bone marrow can occur later in life. <span style="color: #008000; font-family: Arial,Helvetica,sans-serif; font-size: 80%; vertical-align: super;">1,2 <span style="color: #008000; font-family: Arial,Helvetica,sans-serif;"> -Late effects from high dose hyperfractionated regimens include: neurocognitive deficits, hearing loss, leukoencephalopathy, diffuse microhemorrhages, and dystrophic calcifications. <span style="color: #008000; font-family: Arial,Helvetica,sans-serif; font-size: 80%; vertical-align: super;">1 || -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%. <span style="color: #008000; font-family: Arial,Helvetica,sans-serif; font-size: 80%; vertical-align: super;">4 || General Management: **<span style="color: #800000; font-family: Arial,Helvetica,sans-serif;"> * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">Treatment is indicated for significant visual or neurologic deficits or for objective evidence of progression based on serial imaging or visual testing. * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">Local treatment volumes are used for optic pathway and hypothalamic tumors.
 * Prognosis: || <span style="color: #008000; font-family: Arial,Helvetica,sans-serif;">-Optic nerve glioma have a very good survival rate at 100% survival for 6 years.
 * Treatments: || **<span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">Low-Grade Gliomas
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">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.
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">Surgical interventin for thalamic glioma has been controversial. Radiation therapy acheives disease control in approximately 50% of cases.
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">There are chemotherapy trials due to radiation induced toxicity in young patients with optic chiasm/hypothalamic gliomas.
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">Most hemispheric gliomas (usually astrocytomas) are surgically resected.
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">There is no indication for adjuvant irradiation in completely resected low-grade astrocytomas. Similar recommendations are suggested for oligoastrocytoma and oligodendroglioma.
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">For incompletely resected tumors, long-term disease control has been well documented after irradiation.
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">Radiation Therapy **<span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">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.
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">Optic pathway tumors that involve the optic nerves or optic tracts require opposed lateral high-energy fields.
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">Dose levels of 50 Gy are recommended for children older than 3 years, but are reduced to 45 Gy for infants.
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">Thalamic gliomas usually require local treatment volumes; evidence of extention (into the midbrain or across the corpus callosum) requires wider margins.
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">A dose of 54 Gy is recommended for low-grade thalamic gliomas.
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">The recommended dose for low-grade astrocytomas is 54-55 Gy; controlled studies of doses of 60 Gy with stereotactic techniques are ongoing.

General Management **<span style="color: #800000; font-family: Arial,Helvetica,sans-serif;"> * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">Outcome is clearly superior after aggressive surgical resection for cerebral hemispheric malignant gliomas.
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">Malignant Gliomas
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">It is rare to achieve more than biopsy or limited resection in thalamic tumors
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">Radiation therapy is indicated post-operatively, except in children younger than 3 to 5 years of age who enter initial chemotherapy studies.
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">The use of chemotherapy in childhood malignant gliomas has been supported by a CCG study testing postoperative irradiation versus combined irradiation and chemotherapy.
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">Radiation Therapy **
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">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.
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">Margins typically are defined at 2 cm beyond the hpodense area on CT or T1-weighted MRI.
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">There has been limited use of CSI in malignant gliomas.
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">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%.
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">Dose recommendations parallel those in adults (54 to 60 Gy with conventional fractionation).
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">Limited data fail to indicate an advantage with "preventative" or therapeutic neuraxis irradiation.

General Management **<span style="color: #800000; font-family: Arial,Helvetica,sans-serif;"> * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">The morbidity of biopsy within the pons and the lack of histology-specific therapeutic options make surgery not a viable option for pontine gliomas. * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">Infiltrating tumors of the pons require 2 to 3 cm margins in defining the target volume.
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">Brainstem Gliomas
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">Dorsally exophytic brainstem gliomas require judicious surgical resection; a significant percentage will need ventriculoperitoneal shunt placement.
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">Biopsy is generally indicated for midbrain tumors.
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">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.
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">Chemotherapy has little efficacy in pontine gliomas.
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">Radiation Therapy **<span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">Opposed lateral high-energy beam fields are used most often.
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">The potential advantage of hyperfractionated irradiation in brainstem gliomas was reported using 72 Gy at 1 Gy twice daily.
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">When disease control and toxicity data are combined a "best" hyperfractionation regimen is suggested at 70.2 or 70.0 Gy using 1.17 or 1.0 Gy fractions, respectively.
 * <span style="color: #800000; font-family: Arial,Helvetica,sans-serif;">It is unclear whether hyperfractionated schedules offer any improvement compared with conventionally fractionated regimens. 1 ||
 * TD5/5: || <span style="color: #008000; font-family: Arial,Helvetica,sans-serif;">The following organs have the potential of being in the treatment field depending on tumor size and location.

Brain: 45Gy (whole), 50Gy (2/3), 60Gy (1/3) Brainstem (large tumors): 50Gy (whole), 53Gy (2/3), 60Gy (1/3) Ear (acute serous otitis): 30Gy Ear (chronic serous otitis): 55Gy Lens: 10 Gy Optic Chiasm: 50 Gy Optic Nerve: 50 Gy Retina: 45 Gy Spinal Cord: 44 Gy (20cm), 50 Gy (10cm), 50 Gy (5cm ) <span style="color: #008000; font-family: Arial,Helvetica,sans-serif; font-size: 80%; vertical-align: super;">3 || || <span style="font-family: Arial,Helvetica,sans-serif;">**References** 1. Chao KS, Perez CA, Brady LW. //<span style="font-family: Arial,Helvetica,sans-serif;">Radiation Oncology - Management Decisions. // <span style="font-family: Arial,Helvetica,sans-serif;"> 2nd ed. Philadelphia: Lippincott, Williams & Wilkins, 2002: 623-639. 2. Washington CM, Leaver D. //<span style="font-family: Arial,Helvetica,sans-serif;">Principles and Practice of Radiation Therapy // <span style="font-family: Arial,Helvetica,sans-serif;">. 2nd ed. Philadelphia, PA: Mosby, Inc; 2004:736-7, 880-1. 3. Radiation Oncology/Toxicity/Emami. [].Accessed February 10, 2010. 4. Cancer Research UK. //<span style="font-family: Arial,Helvetica,sans-serif;">Statistics and outlooks for brian tumors. // <span style="font-family: Arial,Helvetica,sans-serif;">[]. Accessed February 10, 2010. 5. National Cancer Institute. Childhood Brain Stem Glioma Treatment (PDQ) Health Professional Version. []. Accessed February 4, 2010. 6. eMedicine. Brainstem Gliomas. []. Accessed February 4, 2010. 7. Gunderson and Tepper. Clinical Radiation Oncology. 2nd Edition. Philadelphia, PA: Churchill Livingstone. 2007. 8. Greene et al. Cancer Staging Handbook. 6th Edition. Chicago, Illinois: Eli Lilly and Company. 2001. 9. Khan. Treatment Planning in Radiation Oncology. 2nd Edition. Philadelphia, PA: Lippincott Williams and Wilkins. 2007. 10. Fuss M., et al. Proton Radiation Therapy for Pediatric Optic Pathway Gliomas: Comparison with 3D Planned Conventional Photons and a Standard Photon Technique. //<span style="font-family: Arial,Helvetica,sans-serif;">Int. J. Radiation Oncol. // <span style="font-family: Arial,Helvetica,sans-serif;"> 1999; 45(5): 1117-1126. <span style="font-family: Arial,Helvetica,sans-serif; font-size: 10pt;"> Ginnie is <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif; font-size: 10pt;">bright blue <span style="font-family: Arial,Helvetica,sans-serif; font-size: 10pt;">. Bridget is <span style="color: #008000; font-family: Arial,Helvetica,sans-serif; font-size: 10pt;">dark green <span style="font-family: Arial,Helvetica,sans-serif; font-size: 10pt;">. Sheri is <span style="color: #800000; font-family: Arial,Helvetica,sans-serif; font-size: 10pt;">brown <span style="font-family: Arial,Helvetica,sans-serif; font-size: 10pt;">. Zack is <span style="color: #ff00ff; font-family: Arial,Helvetica,sans-serif; font-size: 10pt;">purple <span style="font-family: Arial,Helvetica,sans-serif; font-size: 10pt;">. Matthias is <span style="color: #ff0000; font-family: Arial,Helvetica,sans-serif; font-size: 10pt;">red <span style="font-family: Arial,Helvetica,sans-serif; font-size: 10pt;">.
 * Planning Photos || <span style="color: #ff0000; font-family: Arial,Helvetica,sans-serif;">Dose distributions of a proton plan, 3D photon plan and standard photon plan for a pediatric optic glioma. 10