eMedicine Specialties > Neurology > Pediatric Neurology
Medulloblastoma: Treatment & Medication
Updated: Dec 4, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
- For the patient with few neurological signs and little hydrocephalus, the entire presurgical workup can be facilitated on an outpatient basis. Admit patients with significant neurological symptoms (especially those with either change in mental status or imaging evidence of considerable hydrocephalus such as transependymal edema) to the hospital in a monitored setting.
- The cranium initially can accommodate a small increase of CSF volume with little change in intracranial pressure. However, since the skull is a rigid container with a finite volume (threshold), further increases in ventricular size lead to dramatic increases of intracranial pressure. Decreased mental status is an indication that the ventricular volume is approaching that threshold; enlargement of ventricles beyond the threshold is accompanied by potentially disastrous consequences.
- Frequent neurologic assessment by the nursing staff is extremely important. Any further decline in mental status is indication for administration of mannitol and emergent neurosurgical consultation for placement of an external ventricular drain.
- Staging
- Postoperatively, medical care revolves around staging, chemotherapy, and irradiation. Within 48 hours of surgery, a follow-up gadolinium-enhanced MRI is necessary to assess residual tumor size prior to the onset of enhancing reactive gliosis, which may be interpreted as tumor.
- Staging is dependent upon extent of resection, radiographic evidence of tumor spread, and CSF cytology. Recently, a move away from the Chang TNM staging system to a simplified high-risk/low-risk categorization has occurred. Those patients who undergo gross total resection, with no radiographic evidence of spread and no malignant cells on CSF cytology, are considered in a low-risk category; however, presence of any of the 3 would place the patient into the high-risk group.
- Irradiation
- Radiation therapy for medulloblastoma is aimed at destroying cells along the entire neuraxis. Local recurrence has been associated with a lower radiation dose at the primary site. Patients receiving less than 5000 centigray (cGy) have over twice the local recurrence rate as those receiving at least this dose.
- In addition, clinical trials have documented that radiation therapy to only the cranium results in metastasis to the spine (even in the absence of positive cytology or radiographic evidence of spread). Most standard therapy for low-stage disease includes 36 cGy to both the brain and spinal cord with a boost of 18-20 cGy to the primary tumor site. Some institutions use different regimens including higher doses in several fractions. Others recommend proton beam therapy
- Unfortunately, radiation can have a destructive influence on the developing nervous system. Complications of radiotherapy can include lowered intelligence quotient (IQ) score, small stature, endocrine dysfunction, behavioral abnormalities, and secondary neoplasms (experienced by those fortunate to have prolonged survival).
- White matter necrosis, which can enlarge and produce significant mass effect, is another feared long-term complication of radiation. Reduction in IQ and neurobehavioral function is related directly to the age at which radiation is administered. Radiotherapy, however, remains the most effective adjunct for medulloblastoma and is used in children despite its consequences.
- Chemotherapy
- Chemotherapy has evolved from use for advanced recurrent disease to use as a common tool in the modern armamentarium against medulloblastoma. However, despite the common use of chemotherapy today, exact benefits remain unclear.
- To reduce radiation dose or postpone irradiation until it can be better tolerated, chemotherapy utilization is focusing on young children. Among the several regimens now being used, one of the most aggressive is the "8 drugs in 1 day" protocol, which employs vincristine, carmustine, procarbazine, hydroxyurea, cisplatin, cytarabine, prednisone, and cyclophosphamide.
- Children's Cancer Group recently reported better results with a vincristine, lomustine, and prednisone (VCP) protocol. The study reported a 63% 5-year progression-free survival rate for VCP as opposed to 45% in the same group for the "8 in 1 day" regimen.
- Pediatric Oncology Group showed similar survival results in the same age group when chemotherapy was followed by radiation. That study protocol utilized vincristine, cyclophosphamide, etoposide, and cisplatin. Thus far, the greatest benefit from the addition of chemotherapy has been seen in those patients with more advanced disease.
- New studies are looking at sensitizing the tumor to irradiation with the concomitant use of chemotherapy. Also, the use of presurgical chemotherapy to treat patients in extremis prior to surgery has been reported.
- Like radiation, chemotherapy involves toxic effects. Adverse effects include renal toxicity, ototoxicity, hepatotoxicity, pulmonary fibrosis, and gastrointestinal disturbances. Most of these effects are transient and reverse with the withdrawal of the drug. However, when methotrexate is used in combination with irradiation, irreversible necrotizing leukoencephalopathy can occur.
Surgical Care
Aside from histologic confirmation, the fundamental goal of surgery is removal of as much tumor as possible. Patients in whom gross total resection is possible are found to have longer recurrence-free intervals than patients who have residual tumor at the end of surgery.
Surgery also has the added benefit of restoring the natural CSF pathways in the brain. A majority of patients will have resolution of their hydrocephalus after surgery.
- At the time of surgery, the extent of subarachnoid spread of the tumor can be assessed. When involved with tumor, the surrounding subarachnoid space is opaque, with a granular appearance often referred to as "sugar coating." This condition is associated with early subarachnoid seeding along the entire neuraxis and early recurrence.
- In one third of cases, the tumor adheres to the floor of the fourth ventricle, precluding gross total resection.
- The purpose of postoperative MRI within 48 hours after surgery is 2-fold. Aside from staging, the MRI delineates any residual tumor; if the surgeon believes the residual tumor is removable, re-exploration of the patient during the same hospitalization for additional tumor removal is a reasonable possibility. The patient spends the first postoperative night in ICU.
- If the surgery entails significant manipulation or invasion of the brain stem, the patient should remain intubated for the first postoperative night and be extubated carefully once lower cranial nerve function has been assessed. However, if the surgeon believes that involvement of the floor of the fourth ventricle was minimal, the patient may be extubated in the operating room.
- If the patient has not had an external ventricular drain placed preoperatively, one usually is placed at the time of surgery.
- Postoperative drainage is maintained for 3 days, after which the drain is clamped and connected to pressure monitoring. If the patient tolerates 24 hours of having the drain clamped, the ventriculostomy is removed.
- Decrease in mental status is an indication for opening the ventriculostomy and continuing drainage. Continued drainage will allow blood and postoperative cellular debris to clear; clamping can be reattempted after an additional 5 days.
- If repeated drainage fails to relieve symptoms, a ventriculoperitoneal shunt must be placed for long-term control of hydrocephalus; however, this is necessary in only approximately 15% of patients. The alternative to shunting is a third ventriculostomy. This can reestablish CSF flow without the potential for peritoneal seeding of tumor.
Consultations
- Oncologist
- Neurosurgeon
- Radiation oncologist
Diet
No special diet is beneficial.
Activity
No activity restrictions are necessary.
Medication
Medulloblastoma is treated primarily with surgical excision followed by radiation therapy and chemotherapy. Few drugs are of benefit in this disease. Exceptions are glucocorticoids, which can aid in decreasing vasogenic edema. Mannitol is useful in the acute setting when the physician is faced with a herniating patient. Chemotherapy is used as adjuvant therapy in some patients. Administration of toxic compounds that affect multiple organ systems is in the realm of the experienced oncologist.
Glucocorticoids
Reduction of vasogenic edema is the role of glucocorticoids in malignant brain tumors. They can be very effective in medulloblastoma and can even alleviate hydrocephalus by reopening CSF pathways in the posterior fossa. Although any of several glucocorticoids can be used, dexamethasone is used most often. Equivalent doses of various glucocorticoids are 0.75 mg for dexamethasone, 4 mg for methylprednisolone and triamcinolone, 5 mg for prednisolone and prednisone, 20 mg for hydrocortisone, and 25 mg for cortisone.
Dexamethasone (Decadron, Dexasone)
Most commonly used drug to treat vasogenic edema secondary to medulloblastoma. Promotes reduction of edema after craniotomy.
Adult
Initial: 10 mg IV q6h
Pediatric
Administer as in adults
Barbiturates, ephedrine, phenytoin, and rifampin decrease effects; decreases effect of salicylates and vaccines used for immunization
Documented hypersensitivity; active bacterial or fungal infection
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Increases risk of multiple complications, including severe infections; monitor for signs of adrenal insufficiency when tapering drug—abrupt discontinuation may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections are possible complications
Methylprednisolone (Solu-Medrol, Depo-Medrol)
Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.
Adult
2-60 mg/d PO in 1-4 divided doses followed by gradual reduction to lowest level that maintains clinical response
Pediatric
0.5-1.7 mg/kg/d or 5-25 mg/m2/d PO/IV/IM divided q6-12h
May increase digitalis (ie, digoxin) toxicity secondary to hypokalemia; estrogens may increase levels; phenobarbital, phenytoin, and rifampin may decrease levels of methylprednisolone (adjust dose); diuretics may cause hypokalemia—monitor patient
Documented hypersensitivity; viral, fungal, or tubercular skin infections
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications
Prednisolone (AK-Pred, Delta-Cortef, Articulose-50, Econopred)
Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reducing capillary permeability.
Adult
5-60 mg/d PO/IV/IM
Pediatric
0.1-2 mg/kg/d PO/IV/IM qd or divided tid/qid
Decreases effects of salicylates and toxoids (for immunizations); phenytoin, carbamazepine, barbiturates, and rifampin decrease effects
Documented hypersensitivity; viral, fungal, or tubercular skin lesions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hyperthyroidism, osteoporosis, cirrhosis, nonspecific ulcerative colitis, peptic ulcer, diabetes, or myasthenia gravis
Prednisone (Deltasone, Sterapred, Orasone)
May decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear cell activity.
Adult
5-60 mg/d PO qd or divided bid/qid; taper over 2 wk as symptoms resolve
Pediatric
4-5 mg/m2/d PO; alternatively, 0.05-2 mg/kg PO divided bid/qid; taper over 2 wk as symptoms resolve
Estrogens may decrease clearance; may increase digitalis (ie, digoxin) toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism (consider increasing maintenance dose); diuretics increase risk of hypokalemia—monitor patients
Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Abrupt discontinuation may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur
Hydrocortisone (Solu-Cortef, Westcort)
Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.
Adult
100 mg IV bolus, followed by continuous infusion of 100 mg q8h for 24-48 h; once patient's condition is stable, initiate PO hydrocortisone (50 mg q8h for another 48 h; may taper dose to 30-50 mg/d in divided doses)
Pediatric
1-5 mg/kg/d or 75-300 mg/m2/d PO divided q12-24h
Estrogens may decrease clearance; may increase digitalis (ie, digoxin) toxicity secondary to hypokalemia
Documented hypersensitivity; viral, fungal, or tubercular skin infections
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hyperthyroidism, osteoporosis, peptic ulcer, cirrhosis, nonspecific ulcerative colitis, diabetes, or myasthenia gravis
Cortisone acetate (Cortone acetate)
Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.
Adult
25-300 mg/d PO/IM divided q12-24h
Pediatric
0.5-0.75 mg/kg/d PO/IM or 20-25 mg/m2/d divided q8h
Alternative IM administration: 0.25-0.35 mg/kg/d qd or 12.5 mg/m2/d
Estrogen may increase levels; may increase digitalis (ie, digoxin) toxicity secondary to hypokalemia
Documented hypersensitivity; viral, fungal, or tubercular skin lesions
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in patients with hyperthyroidism, cirrhosis, nonspecific ulcerative colitis, osteoporosis, peptic ulcer, diabetes, or myasthenia gravis
Diuretics
These agents are used in the acute setting to prevent further increases of intracranial pressure.
Mannitol (Osmitrol)
May reduce subarachnoid space pressure by creating osmotic gradient between CSF in arachnoid space and plasma. Not for long-term use.
Adult
1.5-2 g/kg IV as 20% solution (7.5-10 mL/kg) or as 15% solution (10-13 mL/kg) over period as short as 30 min
Pediatric
Initial: 0.5-1 g/kg IV
Maintenance: 0.25–0.5 g/kg IV q4-6h
None reported
Documented hypersensitivity; anuria; severe pulmonary congestion; progressive renal damage; severe dehydration; active intracranial bleeding; progressive heart failure
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Carefully evaluate cardiovascular status before rapid administration since sudden increase in extracellular fluid may lead to fulminating CHF
More on Medulloblastoma |
| Overview: Medulloblastoma |
| Differential Diagnoses & Workup: Medulloblastoma |
 Treatment & Medication: Medulloblastoma |
| Follow-up: Medulloblastoma |
| Multimedia: Medulloblastoma |
| References |
| « Previous Page | Next Page » |
References
Bailey P, Cushing H. A common type of midcerebellar glioma of childhood. Arch Neurol Psychiatr. 1925;14:192-224.
Rorke LB. The cerebellar medulloblastoma and its relationship to primitive neuroectodermal tumors. J Neuropathol Exp Neurol. Jan 1983;42(1):1-15. [Medline].
Albright AL, Wisoff JH, Zeltzer PM, Boyett JM, Rorke LB, Stanley P. Effects of medulloblastoma resections on outcome in children: a report from the Children's Cancer Group. Neurosurgery. Feb 1996;38(2):265-71. [Medline].
Allen JC, Epstein F. Medulloblastoma and other primary malignant neuroectodermal tumors of the CNS. The effect of patients' age and extent of disease on prognosis. J Neurosurg. Oct 1982;57(4):446-51. [Medline].
Ater JL, van Eys J, Woo SY, et al. MOPP chemotherapy without irradiation as primary postsurgical therapy for brain tumors in infants and young children. J Neurooncol. May 1997;32(3):243-52. [Medline].
Bailey CC, Gnekow A, Wellek S, et al. Prospective randomised trial of chemotherapy given before radiotherapy in childhood medulloblastoma. International Society of Paediatric Oncology (SIOP) and the (German) Society of Paediatric Oncology (GPO): SIOP II. Med Pediatr Oncol. Sep 1995;25(3):166-78. [Medline].
Balter-Seri J, Mor C, Shuper A, et al. Cure of recurrent medulloblastoma: the contribution of surgical resection at relapse. Cancer. Mar 15 1997;79(6):1241-7. [Medline].
Blaser SI, Harwood-Nash DC. Neuroradiology of pediatric posterior fossa medulloblastoma. J Neurooncol. Jul 1996;29(1):23-34. [Medline].
Carrie C, Muracciole X, Gomez F, et al. Conformal radiotherapy, reduced boost volume, hyperfractionated radiotherapy, and online quality control in standard-risk medulloblastoma without chemotherapy: results of the French M-SFOP 98 protocol. Int J Radiat Oncol Biol Phys. Nov 1 2005;63(3):711-6. [Medline].
Chang CH, Housepian EM, Herbert C. An operative staging system and a megavoltage radiotherapeutic technic for cerebellar medulloblastomas. Radiology. Dec 1969;93(6):1351-9. [Medline].
Cohen BH, Packer RJ. Chemotherapy for medulloblastomas and primitive neuroectodermal tumors. J Neurooncol. Jul 1996;29(1):55-68. [Medline].
Dennis M, Spiegler BJ, Hetherington CR, et al. Neuropsychological sequelae of the treatment of children with medulloblastoma. J Neurooncol. Jul 1996;29(1):91-101. [Medline].
Dunkel IJ, Boyett JM, Yates A, Rosenblum M, Garvin JH Jr, Bostrom BC, et al. High-dose carboplatin, thiotepa, and etoposide with autologous stem-cell rescue for patients with recurrent medulloblastoma. Children's Cancer Group. J Clin Oncol. Jan 1998;16(1):222-8. [Medline].
Friedberg MH, David O, Adelman LS. Recurrence of medulloblastoma: violation of Collins' law after two decades. Surg Neurol. Jun 1997;47(6):571-4. [Medline].
Giordana MT, Cavalla P, Dutto A, et al. Is medulloblastoma the same tumor in children and adults?. J Neurooncol. Nov 1997;35(2):169-76. [Medline].
Giordana MT, Migheli A, Pavanelli E. Isochromosome 17q is a constant finding in medulloblastoma. An interphase cytogenetic study on tissue sections. Neuropathol Appl Neurobiol. Jun 1998;24(3):233-8. [Medline].
Giordana MT, Schiffer P, Schiffer D. Prognostic factors in medulloblastoma. Childs Nerv Syst. Jun 1998;14(6):256-62. [Medline].
Giralt J, Sánchez de Toledo J, Moraga F, et al. Improving survival of medulloblastoma: results in two groups of patients. Oncology. Jan-Feb 1996;53(1):38-42. [Medline].
Jenkin D. The radiation treatment of medulloblastoma. J Neurooncol. Jul 1996;29(1):45-54. [Medline].
Kiltie AE, Lashford LS, Gattamaneni HR. Survival and late effects in medulloblastoma patients treated with craniospinal irradiation under three years old. Med Pediatr Oncol. May 1997;28(5):348-54. [Medline].
Miralbell R, Bieri S, Huguenin P, et al. Prognostic value of cerebrospinal fluid cytology in pediatric medulloblastoma. Swiss Pediatric Oncology Group. Ann Oncol. Feb 1999;10(2):239-41. [Medline].
Pollack IF, Polinko P, Albright AL, et al. Mutism and pseudobulbar symptoms after resection of posterior fossa tumors in children: incidence and pathophysiology. Neurosurgery. Nov 1995;37(5):885-93. [Medline].
Rossi A, Caracciolo V, Russo G, Reiss K, Giordano A. Medulloblastoma: from molecular pathology to therapy. Clin Cancer Res. Feb 15 2008;14(4):971-6. [Medline].
Rutka JT, Hoffman HJ. Medulloblastoma: a historical perspective and overview. J Neurooncol. Jul 1996;29(1):1-7. [Medline].
Saran FH, Driever PH, Thilmann C, et al. Survival of very young children with medulloblastoma (primitive neuroectodermal tumor of the posterior fossa) treated with craniospinal irradiation. Int J Radiat Oncol Biol Phys. Dec 1 1998;42(5):959-67. [Medline].
Schmandt S, Kuhl J. Chemotherapy as prophylaxis and treatment of meningosis in children less than 3 years of age with medulloblastoma. J Neurooncol. Jun-Jul 1998;38(2-3):187-92. [Medline].
Sure U, Berghorn WJ, Bertalanffy H. Collins' law. Prediction of recurrence or cure in childhood medulloblastoma?. Clin Neurol Neurosurg. May 1997;99(2):113-6. [Medline].
Sutton LN, Phillips PC, Molloy PT. Surgical management of medulloblastoma. J Neurooncol. Jul 1996;29(1):9-21. [Medline].
Tomita T. Medulloblastomas. In: Youmans JR, ed. Neurolgical Surgery. Vol 4. 5th ed. Philadelphia: WB Saunders; 1996:2570-92.
Weil MD, Lamborn K, Edwards MS, Wara WM. Influence of a child's sex on medulloblastoma outcome. JAMA. May 13 1998;279(18):1474-6. [Medline].
Weitman DM, Cogen PH. Contemporary management of medulloblastoma. Contemporary Neurosurgery. 1998;20(2):1-8.
Whelan HT, Krouwer HG, Schmidt MH, et al. Current therapy and new perspectives in the treatment of medulloblastoma. Pediatr Neurol. Feb 1998;18(2):103-15. [Medline].
Yang SY, Wang KC, Cho BK, et al. Radiation-induced cerebellar glioblastoma at the site of a treated medulloblastoma: case report. J Neurosurg. May 2005;102(4 Suppl):417-22. [Medline].
Zeltzer PM, Boyett JM, Finlay JL, Albright AL, Rorke LB, Milstein JM, et al. Metastasis stage, adjuvant treatment, and residual tumor are prognostic factors for medulloblastoma in children: conclusions from the Children's Cancer Group 921 randomized phase III study. J Clin Oncol. Mar 1999;17(3):832-45. [Medline].
Further Reading
Keywords
medulloblastoma, tumor, primitive neuroectodermal tumor, PNET, Gorlin syndrome, nevoid basal cell carcinoma syndrome, blue rubber-bleb nevus syndrome, Turcot syndrome, glioma polyposis syndrome, Rubinstein-Taybi syndrome
