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.