Medulloblastoma+(Child)

The tumor usually arises in the midline of the cerebellum, can invade the fourth ventricle and brainstem, and has a high propensity to spread throughout the CSF. 5 || -Headaches as a result of coughing or physical activity -Vomitting shorly after waking in the morning. -Papilledema--swollen optic nerve -Seizures -Clumsiness/unsteadiness 1 || CBC count, electrolytes, liver, and renal function tests. It is also recommended to get a baseline thyroid function study and viral titers.
 * Epidemiology: || Medulloblastoma is the prototype posterior fossa malignancy and constitutes about 25% of all childhood brain tumors. It usually occurs in children 2 to 12 years old, with a peak at 5 years. It rarely occurs in adults. 5 ||
 * Etiology: || Medulloblastoma is an undifferentiated tumor believed to arise from the primitive multipotential medulloblast, embryologically located in the external granular layer of the cerebellum. It is classically identified as a primitive neuroectodermal tumor presenting in the posterior fossa. 4
 * Signs & Symptoms: || -Headaches that start in the morning and get progressively better throughout the day.
 * Diagnostic Procedures: || __Lab Studies__:

__Imaging Studies__: --CT scans of the head with and without contrast. "On CT scans, prominent hydrocephalus and a solid, homogeneous, isodense to hyperdense, contrast-enhancing, midline cerebellar mass are characteristic of (although not diagnostic of) medulloblastoma. --MRI scans of the head and spinal canal with and without gadolinium should be performed on anyone suspected of having a medulloblastoma. Other midline posterior fossa tumors can have a similar appearance to medulloblastoma on CT. Examples of these are cerebellar astrocytoma and ependymoma. MRI's can be more useful in demonstrating the extent and anatomic origin of the tumor. "Preoperative and postoperative MRI is required for detection and measurement of residual disease following surgical resection. Postoperative MRI evaluation should be performed within 72 hours of surgery to delineated residual tumor from the postsurgical inflammatory changes that are visualized on MRI at this time." The reason for the spinal MRI is because it is the most sensitive modality for detecting spinal cord metastasis. --Bone Scans may be useful in symptomatic patients because medulloblastoma can metastasize outside the CNS, especially to bone.

__Miscellaneous tests:__ As a result of the potential toxicity from radiation and chemo, a baseline hearing test is recommended. Other protocols might require other tests such as echocardiography, pulmonary function tests, etc. to help monitor treatment-related toxicity.

Procedures: --Lumbar puncture--"CSF cytologic examination is useful for the detection of microscopic leptomeningeal tumor dissemination. However, neither clinical symptoms nor negative CSF cytologic findings can be relied upon to indicated the presence of nodular spinal cord disease. As many as 50% of patients with positive spine MRI studies are asymptomatic and have negative cytologic results." Fuduscopic examination through a CT or MRI has to be performed before the lumbar puncture to rule out the presence of hydrocephaly. --Bone Marrow aspirate and biopsy--medulloblastoma rarely metastasizes to the bone marrow so these tests are usually only performed on those "patients who demonstrate abnormal peripheral blood findings that have no clear etiology." 2 || __**Grade**__
 * Histology: || "Medulloblastomas are undifferentiated embryonal neuroepithelial tumors of the cerebellum. They are highly cellular, soft, and friable tumors composed of cells with deeply basophilic nuclei of variable size and shape, little discernible cytoplasm, and often abundant mitoses. These characteristics give the microscopic appearance of a small, round, blue cell tumor. Morphologically identical tumors arising in the pineal region are termed pineoblastomas, and those arising in other CNS locations are called primitive neuroectodermal tumors (PNETs)." 2 ||
 * Lymphatic drainage: || There are no lymphatic channels in the brain. 5 ||
 * Metastatic spread: || It is common for Medulloblastoma to spread through the cerebral spinal fluid (CSF) to the subarachnoid space. Approximately 10-15% of patients have CSF dissemination at diagnosis. It is rare, but systemic metastatic spread can occur ( 5%of patients) to the lymph nodes and bone. 4 ||
 * Grading: || The grade of the tumor and its location in determining the treatment for each patient. The grade of the tumor is based on the microscopic appearance of the tumor cells. 3 Grade 1 tumors being the least aggressive and grade 4 the most aggressive.
 * G1-** Well differentiated ( low grade)
 * G2-** Moderately differentiated (intermediate grade)
 * G3 -** Poorly differentiated ( high grade)
 * G4-** Undifferentiated ( high grade) ||
 * Staging: || Langston Modification of Chang Staging for Medulloblastoma

T1= Tumor less than 3 cm in diameter T2= Tumor greater than or equal to 3 cm in diameter T3a= Tumor greater than 3 cm with extension into aqueduct of Sylvius or foramen of Luschka (or both) T3b= Tumor greater than 3 cm with extension into brainstem T4= Tumor greater than 3 cm with extension past aqueduct of Sylvius or foramen magnum

M0= No gross subarachnoid or hematogenous metastasis M1= Microscopic tumor cells in cerebrospinal fluid M2= Gross nodular seeding beyond primary site in the cerebellar or cerebral subarachnoid space M3= Gross noldular spinal seeding M4= Metastases outside the cerebrospinal axis 10 || -Inital approach, a gross total resection. Complete and near total resections are associated with improved disease control. -Medulloblastoma is sensitive to chemotherapy. -High response rates have been seen with alkylating agents (especially cyclophosphamide) and platinum compunds. -Pre- Craniospinal axis (CSI) radiation has a risk of neuroaxis progression is associated with an increased length of chemotherapy treatments. -Often curative, central in the management of Medulloblastoma - Full neuroaxis irradiation is mandatory. -Coverage of the subfrontal cribiform plate is particularly important (area is common for recurrances) -Patient can be treated either prone or supine. -Lateral Cranial fields are used with a posterior spine field ( two posterior spine fields may be needed for larger children) -The juction of the lateral cranial fields and spinal field is critical, achieved by using collimaor angles to correct spinal field divergence and couch angles on the lateral fields. -An "exact" junction is prefered without a gap but still requires junction shifts (moving junction) to minimize inhomogeneity at the match line. 4
 * Radiation Side Effects: || * Acute and late radiation side effects are related to the specific site treated.
 * Growth disturbances are common in children. Most long-term survivors that had radiation for brain tumors have developed a growth hormone deficiancy, and the adverse effects may be directly related to the biologically effective dose.
 * Another radiation-related toxicity is the gradual onset of endocrine deficits, earliest and most commonly in growth hormone; subsequent treatment-related deficits, in thyroid-stimulating hormone, adrenocorticotropic hormone, and gonadotropins are noted.
 * Serious neurotoxicites are recorded in less than 10% of cases, but are identifiable as a late optic neuropathy or brain necrosis; the incidence is related to doses greater than 60 Gy.
 * Secondary malignant neoplasms have been reported after radiation.
 * Hyperfractionated regimens are associated with moderate acute epithelial toxicity and dose-related subacute toxicity.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Late toxicities with high-dose hyperfractionation, including neurocognitive deficits and hearing loss clinically and leukoencephalopathy, diffuse microhemorrhages, and dystrophic calcification or MRI, limit enthusiasm for routine use of hyperfractionated therapy for pontine gliomas or brainstem tumors.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Decreased morbidity has been described in preliminary reports in children treated with proton beams. <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 88%; vertical-align: super;">4 ||
 * Prognosis: || Treatment begins with maximal resection of the tumor. The addition of //radiation// to the entire neuraxis and chemotherapy may increase the disease-free survival. This combination may permit a 5 year survival in more than 80% of cases. The presence of desmoplastic features such as connective tissue formation offers a better prognosis. Prognosis is worse if the child is less than 3 years old, there is an inadequate degree of resection, or if there is any CSF, spinal, supratentorial or systemic spread. 6 ||
 * Treatments: || <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif;">**__Surgery__**
 * __Chemotherapy__**
 * __Radiation Therapy__**

<span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif;">Figure 1: Lateral cranial fields matched with posterior spinal field. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; vertical-align: super;">7 <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif;"> -"The posterior orbit is not included for CNS tumors requiring CSI." <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; vertical-align: super;"> 4 <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif;">-"The spinal subarachnoid space extends caudally to S2 or beyond." <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; vertical-align: super;">4 <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif;">-The lateral margins should include (dosimetrically) the width of the vertebral bodies beyond the neural foramina (younger children with a thoracic spinal component can be blocked to help spare the heart and lungs. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif;">Figure 2: Isodose lines for CSI irradiation. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; vertical-align: super;">8 <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif;">Figure 3: Field arrangement with two spinal fields. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; vertical-align: super;">9 <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif;">Figure 4: Field arrangement with skin rendering. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; vertical-align: super;"> 7 <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif;">Figure 5: Formulas for CSI fields. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; vertical-align: super;">7 <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif;"> -A posterior fossa boost is given and includes the entire infratentorial compartment. -Medulloblastoma is a radiosensitive tumor. "Local tumor control exceeds 80% control with posterior fossa doses of 54 to 55 Gy (with a field reduction after 45 Gy) in 1.6 to 1.8 Gy fractions." <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; vertical-align: super;">4 || <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif;">Table provided by Wikibooks. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; vertical-align: super;"> 11 || References: <span style="color: #008000; font-family: 'Times New Roman',Times,serif; font-size: 110%;">1. The University of Texas M.D. Anderson Cancer Center. //Childhood Medulloblastoma.// Available at: http://www.mdanderson.org/patient-and-cancer-information/cancer-information/cancer-types/childhood-medulloblastoma/index.html Accessed February 8, 2010. 2. Medscape. //Medulloblastoma: Differential Diagnoses & Workup.// Available at: http://emedicine.medscape.com/article/987886-diagnosis Accessed February 8, 2010. <span style="color: #0000ff; font-family: 'Times New Roman',Times,serif; font-size: 110%;">3. The U.S. National Cancer Institute of Health Cancer fact sheet. Available at http;//www.Cancer.gov/cancertopics/factsheet/Detection/tumor-grade. Accessed Feb. 10, 2010. 4. Chao CK, Perez CA, Brady LW.// Radiation Oncology Management Decisions//. Second Edition. Philadelphia, PA: Lippincott Williams & Wilkins. 2002; 149, 878, //<span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">637 //.// <span style="color: #000080; font-family: 'Times New Roman',Times,serif;">//5. Washington CM, Leaver D. Principles// and Practice of Radiation Therapy. Second Edition. St. Louis, Missouri: Mosby Inc. 2004;727-728, 878. 6. Wikipedia. Medulloblastoma. Available at: []. Accessed February 11, 2010. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif;">7. Levitt, SH, Purdy, JA, Perez, CA, & Vijayakumar, S. Technical Basis of Radiation Therapy. Fourth revised edition. Germany: Springer Science and Business Media. 2006:103,446. 8. R Prabhakar R, Haresh KP, Munshi K, Sridhar PS, Subramani V, Julka PK, Rath GK.(2009) A simple technique for cranio-spinal irradiation in pediatric patients. Journal of Cancer Research and Therapeutics. Vol 5, Issue 2: 113-115. Retrieved from <span style="font-family: 'Times New Roman',Times,serif;">[]. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif;">9. Khan, FM. Treatment Planning in Radiation Oncology. Second edition. Philadelphia, PA: Lippincott, Williams & Wilkins. 2007: 425. <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">10. Lenhard RE, Osteen RT, Gansler T. The American Cancer Society's Clinical Oncology. 1st edition. Atlanta, GA: The American Cancer Society, Inc. 2001: 599. 11. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 90%;"><span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 121%;">Radiation Oncology/Toxicity/Emami. Wikibooks. Available at: <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 110%;">[]. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 121%;">Accessed: February 13, 2010.
 * TD5/5: || [[image:Cranio_and_Meningio2.jpg]]