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Medulloblastoma Treatment & Management

  • Author: George I Jallo, MD; Chief Editor: Amy Kao, MD  more...
 
Updated: Oct 16, 2014
 

Medical Care

Approach Considerations

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.[4, 5]

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.

In addition to alterations in the Hedgehog and Wnt pathways,inactivating mutations of the histone-lysine N-methyltransferase genes MLL2 or MLL3 were identified in 16% of MB patients

G-protein coupled receptor expression patterns delineate medulloblastoma subgroups which act as imaging and therapeutic targets.

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.

Rieken et al found that craniospinal irradiation following complete resection of medulloblastoma yielded overall survival and local and distant progression-free survival rates of 73%, 62%, and 77% at 60 months in children and adults.[6] The authors delivered a median craniospinal dose of 35.5 Gy and administered additional boosts to the posterior fossa up to 54.0 Gy. Initiating treatment within 28 days, macroscopic complete tumor resection, and desmoplastic histology were associated with improved outcome.

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).

A small study by Gupta et al reported a good overall survival rate for standard-risk children treated with hyperfractionated therapy (two daily fractions) with a total tumor bed dose of 68 Gy for 6-7 weeks. This treatment approach may be reasonable in centers without access to chemotherapy, but caution must be undertaken as the median follow-up was only 33 months. The authors found preserved cognitive function at 2 years posttreatment but long-term results were not available. In addition, secondary malignancies were not reported.[7]

White matter necrosis, which can enlarge and produce significant mass effect and vascular disorders,[8] 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.

In children with metastatic MB, tandem HDCT (high dose chemotherapy) with ASCT (autologous stem cell therapy) followed by conventional craniospinal RT proved its feasibility without jeopardizing survival.

Other data suggest that oncolytic measles viruses encoding anti-angiogenic proteins may have therapeutic benefit against medulloblastoma and support ongoing efforts to target angiogenesis in medulloblastoma.

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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.[9, 10]

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.
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Consultations

See the list below:

  • Oncologist
  • Neurosurgeon
  • Radiation oncologist
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Diet

No special diet is beneficial.

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Activity

No activity restrictions are necessary.

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Contributor Information and Disclosures
Author

George I Jallo, MD Professor of Neurosurgery, Pediatrics, and Oncology, Director, Clinical Pediatric Neurosurgery, Department of Neurosurgery, Johns Hopkins University School of Medicine

George I Jallo, MD is a member of the following medical societies: American Association of Neurological Surgeons, American Medical Association, American Society of Pediatric Neurosurgeons

Disclosure: Received grant/research funds from Codman (Johnson & Johnson) for consulting; Received grant/research funds from Medtronic for consulting.

Coauthor(s)

David A Chesler, MD, PhD Clinical and Research Fellow, Division of Pediatric Neurosurgery, Johns Hopkins University School of Medicine

David A Chesler, MD, PhD is a member of the following medical societies: American Association of Neurological Surgeons, American Medical Association, Congress of Neurological Surgeons

Disclosure: Nothing to disclose.

Faisal A Almayman, MBBS Post Doctorate Research Fellow, Department of Neurosurgery, Johns Hopkins University School of Medicine

Faisal A Almayman, MBBS is a member of the following medical societies: American Association of Neurological Surgeons, Saudi Stroke Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Kenneth J Mack, MD, PhD Senior Associate Consultant, Department of Child and Adolescent Neurology, Mayo Clinic

Kenneth J Mack, MD, PhD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, Phi Beta Kappa, Society for Neuroscience

Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD Attending Neurologist, Children's National Medical Center

Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, Child Neurology Society

Disclosure: Have stock from Cellectar Biosciences; have stock from Varian medical systems; have stock from Express Scripts.

Additional Contributors

Raj D Sheth, MD Chief, Division of Pediatric Neurology, Nemours Children's Clinic; Professor of Neurology, Mayo College of Medicine; Professor of Pediatrics, University of Florida College of Medicine

Raj D Sheth, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, American Neurological Association, Child Neurology Society

Disclosure: Nothing to disclose.

Acknowledgements

Alvin Marcovici, MD Consulting Staff, Southcoast Neurosurgery

Alvin Marcovici, MD is a member of the following medical societies: American Association of Neurological Surgeons, Congress of Neurological Surgeons, and Phi Beta Kappa

Disclosure: Nothing to disclose.

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CT scan demonstrates a hyperdense lesion within the posterior fossa of an 8-year-old boy who presented with nausea and vomiting.
T1-weighted sagittal MRI of an 8-year-old boy who presented with nausea and vomiting reveals an enhancing tumor within the fourth ventricle. The child underwent a suboccipital craniotomy and resection of his medulloblastoma.
T1-weighted sagittal MRI of 4-year-old boy who presented with gait ataxia and precocious puberty. MRI shows a heterogenous enhancing tumor located within the fourth ventricle with marked hydrocephalus.
T1-weighted axial MRI shows heterogeneous enhancement of the medulloblastoma in a 4-year-old boy who presented with gait ataxia and precocious puberty.
Coronal MRI confirms the presence of the tumor within the fourth ventricle of a 4-year-old boy who presented with gait ataxia and precocious puberty.
High-power magnification hematoxylin and eosin (H&E) section of a typical medulloblastoma
 
 
 
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