Average Risk
        Standard treatment options
        Treatment options under clinical evaluation
High Risk
        Standard treatment options
        Treatment options under clinical evaluation
Children Aged 3 Years and Younger
        Standard treatment options
        Treatment options under clinical evaluation
Current Clinical Trials

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Children with medulloblastoma are stratified into average-risk and poor-risk subsets. Owing to concerns about the long-term neurocognitive sequelae of whole-brain radiation therapy on the developing brain, radiation therapy for younger children has often been delayed or eliminated. Children younger than 3 years and sometimes as old as 5 years have not received the same treatment as older patients.

In all subgroups of patients, surgery is the initial means of therapy, and maximal tumor resection is the goal of treatment. Postsurgical treatment has diverged, to some degree, on the basis of stratification and age of the patient.

The traditional postsurgical treatment for patients with average-risk medulloblastoma has been 54 Gy to 55 Gy of radiation therapy to the posterior fossa and 36 Gy to the entire neuroaxis (i.e., the whole brain and spine).[1-3] With radiation therapy alone, 5-year event-free survival (EFS) ranges between 50% and 65% in those with nondisseminated disease.[1-3] While the standard boost in medulloblastoma is the entire posterior fossa, patterns of failure data suggest that radiation therapy to the tumor bed instead of the entire posterior fossa would be equally effective and possibly associated with reduced toxicity.[4,5] The minimal dose of craniospinal radiation needed for disease control is unknown. Attempts to lower the dose of craniospinal radiation therapy to 23.4 Gy without chemotherapy have resulted in an increased incidence of isolated leptomeningeal relapse.[6] Radiation therapy and chemotherapy given during and after radiation therapy has demonstrated 5-year EFS rates of 70% to 85%.[1-3] Chemotherapy is now a standard component of the treatment of children with average-risk medulloblastoma; a variety of chemotherapeutic regimens has been successfully used, including the combination of cisplatin, lomustine, and vincristine.[1,2,7,8] A lower radiation dose of 23.4 Gy to the neuroaxis when coupled with chemotherapy has been shown to result in disease control in up to 80% of patients and may decrease the severity of long-term neurocognitive sequelae.[8-10]

Long-term survivors who were prepubertal at the time of diagnosis are at high risk for growth failure due to radiation-related hypothalamic failure as well as effects of radiation on spinal growth. Lower doses of craniospinal radiation therapy may decrease the incidence of hypothalamic dysfunction, but this has not yet been proven. Growth hormone replacement therapy has not been shown to increase the likelihood of disease relapse.[11]

The Children’s Oncology Group (COG) phase III trial, COG-ACNS0331, is randomly assigning children between the ages of 3 years and 8 years to receive either 18 Gy or 24 Gy of craniospinal radiation; and randomly assigning children between the ages of 3 years and 21 years to receive either conformal tumor site radiation therapy or posterior fossa radiation therapy. Patients with anaplastic medulloblastoma are not eligible. In this study, children received weekly vincristine during radiation therapy and lomustine, vincristine, cisplatinum, etoposide, and cyclophosphamide after radiation therapy. Information about ongoing clinical trials is available from the NCI Web site.

In high-risk patients, the addition of chemotherapy has improved the duration of disease control and overall disease-free survival.[1,12] Studies show that approximately 50% to 60% of patients with high-risk diseases will experience long-term disease control.[1,12] The drugs that have been found to be useful in children with average-risk disease are the same drugs that have been used extensively in children with poor-risk disease, including cisplatin, lomustine, cyclophosphamide, etoposide, and vincristine.

The COG phase III trial for children older than 3 years, COG-ACNS0332, is evaluating the efficacy of adding carboplatin to radiation therapy with vincristine, followed by maintenance chemotherapy with isotretinoin. Information about ongoing clinical trials is available from the NCI Web site.

A subgroup of patients aged 3 years and younger with newly diagnosed medulloblastoma will respond, at least partially, to chemotherapy.[13-16] Between 15% and 35% of children, primarily those without dissemination and minimal residual postoperative disease, may have a long-lasting response to chemotherapy without the use of radiation therapy.[13,15,16] Children treated with chemotherapy without craniospinal radiation therapy are likely to have better neurocognitive outcomes than those treated initially with radiation therapy with or without chemotherapy.[17] For this reason, strong consideration should be given to entering patients aged 3 years and younger in studies that use chemotherapy to delay, modify, or possibly obviate the need for radiation therapy.

Treatment options that have been or are being used in children aged 3 years and younger with medulloblastoma include combination chemotherapy, systemic and oral chemotherapy plus intrathecal chemotherapy; higher-dose chemotherapy supported by autologous bone marrow rescue or peripheral stem cell rescue,[18][Level of evidence: 2A] and chemotherapy followed by radiation therapy to the primary tumor site. The most commonly used approach is to begin treatment with some form of combination chemotherapy. There is no consensus on the need for, or optimal timing, dose, or volume of, radiation therapy after chemotherapy.[14,15,19] One study has suggested that intrathecal methotrexate given both intraventricularly and intralumbar may improve outcomes for children with medulloblastoma and obviate the need for radiation therapy.[20] Although chemotherapy is being used to prevent neurologic damage caused by radiation therapy in very young children, neurologic deficits may be present in children before the initiation of therapy, and progressive neurologic compromise has been noted during therapy.[21,22]

The COG trial, COG-ACNS0334, is open for children aged 3 years or younger at diagnosis with high-risk disease, which is defined as those with disseminated and/or partially resected tumors. This study is evaluating chemotherapy as given in the completed COG study COG-99703, which used multiagent chemotherapy followed by thiotepa-based higher-dose chemotherapy and peripheral stem cell rescue, and is randomizing patients to treatment with or without intravenous high-dose methotrexate. Patients with cortical primitive neuroectodermal tumors or pineoblastomas are also eligible. Information about ongoing clinical trials is available from the NCI Web site.

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with childhood medulloblastoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References

1. Packer RJ, Sutton LN, Elterman R, et al.: Outcome for children with medulloblastoma treated with radiation and cisplatin, CCNU, and vincristine chemotherapy. J Neurosurg 81 (5): 690-8, 1994.  [PUBMED Abstract]
   
   
2. 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 25 (3): 166-78, 1995.  [PUBMED Abstract]
   
   
3. Kortmann RD, Kühl J, Timmermann B, et al.: Postoperative neoadjuvant chemotherapy before radiotherapy as compared to immediate radiotherapy followed by maintenance chemotherapy in the treatment of medulloblastoma in childhood: results of the German prospective randomized trial HIT '91. Int J Radiat Oncol Biol Phys 46 (2): 269-79, 2000.  [PUBMED Abstract]
   
   
4. Fukunaga-Johnson N, Sandler HM, Marsh R, et al.: The use of 3D conformal radiotherapy (3D CRT) to spare the cochlea in patients with medulloblastoma. Int J Radiat Oncol Biol Phys 41 (1): 77-82, 1998.  [PUBMED Abstract]
   
   
5. Huang E, Teh BS, Strother DR, et al.: Intensity-modulated radiation therapy for pediatric medulloblastoma: early report on the reduction of ototoxicity. Int J Radiat Oncol Biol Phys 52 (3): 599-605, 2002.  [PUBMED Abstract]
   
   
6. Thomas PR, Deutsch M, Kepner JL, et al.: Low-stage medulloblastoma: final analysis of trial comparing standard-dose with reduced-dose neuraxis irradiation. J Clin Oncol 18 (16): 3004-11, 2000.  [PUBMED Abstract]
   
   
7. Jenkin D: Long-term survival of children with brain tumors. Oncology (Huntingt) 10 (5): 715-9; discussion 720, 722, 728, 1996.  [PUBMED Abstract]
   
   
8. Packer RJ, Goldwein J, Nicholson HS, et al.: Treatment of children with medulloblastomas with reduced-dose craniospinal radiation therapy and adjuvant chemotherapy: A Children's Cancer Group Study. J Clin Oncol 17 (7): 2127-36, 1999.  [PUBMED Abstract]
   
   
9. Oyharcabal-Bourden V, Kalifa C, Gentet JC, et al.: Standard-risk medulloblastoma treated by adjuvant chemotherapy followed by reduced-dose craniospinal radiation therapy: a French Society of Pediatric Oncology Study. J Clin Oncol 23 (21): 4726-34, 2005.  [PUBMED Abstract]
   
   
10. Merchant TE, Kun LE, Krasin MJ, et al.: Multi-institution prospective trial of reduced-dose craniospinal irradiation (23.4 Gy) followed by conformal posterior fossa (36 Gy) and primary site irradiation (55.8 Gy) and dose-intensive chemotherapy for average-risk medulloblastoma. Int J Radiat Oncol Biol Phys 70 (3): 782-7, 2008.  [PUBMED Abstract]
    
    
11. Packer RJ, Boyett JM, Janss AJ, et al.: Growth hormone replacement therapy in children with medulloblastoma: use and effect on tumor control. J Clin Oncol 19 (2): 480-7, 2001.  [PUBMED Abstract]
    
    
12. Evans AE, Jenkin RD, Sposto R, et al.: The treatment of medulloblastoma. Results of a prospective randomized trial of radiation therapy with and without CCNU, vincristine, and prednisone. J Neurosurg 72 (4): 572-82, 1990.  [PUBMED Abstract]
    
    
13. Geyer JR, Sposto R, Jennings M, et al.: Multiagent chemotherapy and deferred radiotherapy in infants with malignant brain tumors: a report from the Children's Cancer Group. J Clin Oncol 23 (30): 7621-31, 2005.  [PUBMED Abstract]
    
    
14. Duffner PK, Horowitz ME, Krischer JP, et al.: Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors. N Engl J Med 328 (24): 1725-31, 1993.  [PUBMED Abstract]
    
    
15. 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 32 (3): 243-52, 1997.  [PUBMED Abstract]
    
    
16. Grill J, Sainte-Rose C, Jouvet A, et al.: Treatment of medulloblastoma with postoperative chemotherapy alone: an SFOP prospective trial in young children. Lancet Oncol 6 (8): 573-80, 2005.  [PUBMED Abstract]
    
    
17. Mulhern RK, Palmer SL, Merchant TE, et al.: Neurocognitive consequences of risk-adapted therapy for childhood medulloblastoma. J Clin Oncol 23 (24): 5511-9, 2005.  [PUBMED Abstract]
    
    
18. Sung KW, Yoo KH, Cho EJ, et al.: High-dose chemotherapy and autologous stem cell rescue in children with newly diagnosed high-risk or relapsed medulloblastoma or supratentorial primitive neuroectodermal tumor. Pediatr Blood Cancer 48 (4): 408-15, 2007.  [PUBMED Abstract]
    
    
19. Chi SN, Gardner SL, Levy AS, et al.: Feasibility and response to induction chemotherapy intensified with high-dose methotrexate for young children with newly diagnosed high-risk disseminated medulloblastoma. J Clin Oncol 22 (24): 4881-7, 2004.  [PUBMED Abstract]
    
    
20. Rutkowski S, Bode U, Deinlein F, et al.: Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. N Engl J Med 352 (10): 978-86, 2005.  [PUBMED Abstract]
    
    
21. Copeland DR, deMoor C, Moore BD 3rd, et al.: Neurocognitive development of children after a cerebellar tumor in infancy: A longitudinal study. J Clin Oncol 17 (11): 3476-86, 1999.  [PUBMED Abstract]
    
    
22. Mulhern RK, Horowitz ME, Kovnar EH, et al.: Neurodevelopmental status of infants and young children treated for brain tumors with preirradiation chemotherapy. J Clin Oncol 7 (11): 1660-6, 1989.  [PUBMED Abstract]
    
    

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