Medulloblastoma Treatment & Management

Updated: Jan 10, 2018
  • Author: George I Jallo, MD; Chief Editor: Amy Kao, MD  more...
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Approach Considerations

For the patient with few neurological signs and no 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 flow) to the hospital in a monitored setting. [31]

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 (Monroe-Kellie Doctrine). 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 hypertonic saline and emergent neurosurgical consultation for placement of an external ventricular drain.


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 [32] 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. For years, since 1999 when a consensus regarding risk stratification was published, neurosurgeons have used a risk management tool looking at residual tumor (more or les than 1.5 cm2, metastases, etc.). Extent of resection is still identified as a high-risk marker. Specifically, most protocols identify a residual tumor of 1.5 cm2 as being high risk warranting intensification of craniospinal irradiation to 36 Gy. [33] However, this is predominantly based on the CCG-921 trial, which was conducted in the pre-MRI era, and was based on the limit of detection by CT scanning. [34] Moreover, the question of near-total resections (0–1.5 cm2) has not been discussed for the past 25 years. Thompson and colleagues showed in 2016 that near-total resection poses no additional survival risk to gross total resection, and that the prognostic benefit of a subtotal resection is attenuated after accounting for molecular subgroup affiliation.


Medical Care


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 [35, 36]  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. [35]  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, which has been shown in one study to have the same efficacy with potential decrease in adverse effects of radiation. [37]

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. [38]

White matter necrosis, which can enlarge and produce significant mass effect and vascular disorders, [39]  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 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, especially infants. 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 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. Another important advance in adjuvant therapy is the use of vismodegib (SMO inhibitor) against some SHH subtype medulloblastomas, which showed very promising results in adults as well as the pediatric population. [40]  Yet, research is still ongoing in that perspective.


Surgical Care

Surgery is still the mainstay initial therapy for medulloblastoma, as both a tool for diagnosis and as a risk-stratification factor. The recommendation is still to go for the safest resection possible, and if a second surgery is needed it is better to do it before starting the adjuvant treatment. This strategy might change in the near future, with better understanding of the specific subgroups biology and with the advance in new treatment agents. As for today, 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. [41, 42]

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. Several important points in regard to 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 with or without brainstem invasion precluding gross total resection.
  • The purpose of postoperative MRI within 48 hours after surgery is twofold. 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 brainstem, 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 might be placed at the time of surgery.
  • Postoperative drainage is maintained for a variable duration depending on the appearance of the CSF, amount of output and intracranial pressure (ICP) readings. When deemed appropriate by the surgeon, the drain is clamped and the ICP is monitored. If the patient tolerates 24 hours of having the drain clamped, the ventriculostomy is removed.
  • Decrease in mental status, sustained elevated ICP, or uncontrolled headache are indications for opening the ventriculostomy and continuing drainage. Continued drainage will allow blood and postoperative cellular debris to clear; clamping can be reattempted after CSF clears.
  • 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. 

Molecular and Genetic Alteration

WNT activation

Patients with WNT-activated medulloblastoma are ideal candidates for therapy reduction to minimize the long-term effects of current therapy (reduce not only their cranio-spinal radiation dose but also their chemotherapy). These patients tend to have the most favorable outcomes (the tumor tends to be very vascular so even drugs that usually will not cross the blood-brain barrier will have good effect in this subgroup [15] ); hence, current treatment protocols for this subgroup tumors are designed to minimize radiation and standard chemotherapy and seek new treatments that target oncogenic mechanisms.  

SHH pathway

This subgroup is much more complex for treatment than the WNT group, especially since tumors are much less vascular making it harder to get to a desirable level of drug activity when treating these patients with chemotherapy. There are 2 main components to identify these patients: age and the presence of TP53.

Infants and toddlers (0–4 years old) tend to have a more unfavorable gene mutation that will lead to poorer outcome. In older patients, there is a higher likelihood of PTCH1 and SMO mutations that in some cases can be treated with SMO inhibitors that can lead to better prognosis.

As a group, TP53 must be checked, with advisable genetic family consult when positive. [33] These mutations are highly enriched in children aged 3–17 years. When this mutation is present in SHH, prognosis is very poor regardless of age. Patients with SHH medulloblastoma and positive TP53 should be selected for more intensive therapies. For these patients, protocols include removing DNA alkylating chemotherapy and minimizing radiation therapy and relying instead on antimetabolite, microtubule-disrupting, or other types of chemotherapy. Agents like, PI3K, mTOR, arsenic trioxide, and AKT inhibitors are potentially valuable in controlling specific targets in the SHH pathway and its interaction and links with the PI3K, mTOR, and AKT pathways. [16, 43] In this subgroup (SHH with TP53 positive), the real treatment for residual tumor or recurrent disease is surgery. The overall outcome is intermediate depending on the age group. [33]  Young children have a more favorable outcome, while patients with TP53-mutated SHH medulloblastoma do poorly. [44, 20] Compared to the other subgroups, SHH tumors more frequently recur locally in the original resection cavity. [33]

Non-WNT/non-SHH: Group 3

Patients within this group have a poor prognosis. Their classic fingerprint is the MYC amplification. More than 50% of cases are metastatic at the time of diagnosis, which serves as a poor prognostic factor. Older children in group 3 have a 50% survival in 5 years if they have risk-adapted therapy. These tumors are more common in males and infants (which tend to have poorer prognosis). 17q is a predictor of poor outcome in group 3 medulloblastomas.  There are few gene mutations already known that are with potential therapy implication: MYC over-expression, GABRA5 overexpression, transforming growth factor beta (TGF-β) signaling pathway mutations. Cytotoxic drugs, like pemetrexed and gemcitabine or MYC-inhibitors as well as others are under trials that are open across the United States. For example, The SJMB12 study (for all medulloblastoma subgroups, mentioned in the previous section) is also prospectively evaluating the use of pemetrexed, gemcitabine, vincristine, cisplatin, and cyclophosphamide in the high-risk medulloblastoma cases, and this study is currently open. [16]  Unless under research protocol, the real treatment for residual tumor or recurrent disease is surgery. Group 3 patients recur most frequently with metastatic dissemination and a tumor bed devoid of disease.

Non-WNT/non-SHH: Group 4

This group is also known as the glutamatergic subgroup, and it is the most common molecular subgroup and much more common among males. The average-risk patients in this subgroup have excellent survival with the current standard-of-care treatment options. Presence of metastatic disease at diagnosis or chromosome 11 loss and chromosome 17 gain appear to dictate the prognosis in this subgroup of medulloblastoma patients. As mentioned, this group tends to have more vascular tumors, which might explain their good response to regular treatment. Yet, approximately 30% are metastatic at diagnosis, [27] which makes surgery less effective as a treatment tool. Irradiated Group 4 patients recur most frequently with metastatic dissemination and a tumor bed typically devoid of disease. [42, 16]  



Consultations with an oncologist, neurosurgeon and/or a radiation oncologist may prove helpful.



No special diet is beneficial.



No activity restrictions are necessary.