Pediatric Medulloblastoma Follow-up
- Author: Tobey J MacDonald, MD; Chief Editor: Max J Coppes, MD, PhD, MBA more...
Further Outpatient Care
Daily outpatient radiotherapy (usual dose fractions of 180 cGy/d) is performed for approximately 6 weeks.
Physical and neurologic examination
Careful monitoring of response and treatment-associated side effects is performed weekly during radiotherapy and at least every 2 weeks during chemotherapy.
Reevaluation immediately before each cycle of chemotherapy is necessary to document resolution of previous treatment-related toxicities.
Following the completion of therapy, assessments are conducted every 3 months for the first 12-18 months, every 6 months for the next 2 years, and then annually, provided no complications have occurred.
To have an objective measurement of tumor response to therapy, MRI with contrast of the head is performed at the completion of radiotherapy, after every 2 cycles of chemotherapy, and at the end of therapy.
Unless clinically indicated, follow-up MRI scans after the completion of therapy are performed in conjuncture with the physical and neurologic examination schedule.
MRI with contrast of the spine is performed only at the completion of therapy and annually thereafter unless metastatic spinal disease was observed, in which case more frequent evaluation may be necessary.
Carefully monitor toxicities associated with therapy. Weekly CBC counts are necessary during radiotherapy and chemotherapy, as well as liver function studies, electrolytes, renal function, and a hearing test before each cycle of chemotherapy and again at the end of treatment.
Baseline studies should be performed before the initiation of any therapy. These tests may need to be performed annually for the first 3-5 years after therapy.
A baseline endocrinologic and neuropsychologic evaluation should be performed at the completion of therapy and annually thereafter.
Additional tests for the purposes of monitoring specific investigational protocol treatment-related toxicity (eg, echocardiogram, pulmonary function tests, other studies) may be required according to protocol guidelines.
Further Inpatient Care
Admit patients with medulloblastoma for specific chemotherapy and for complications (eg, fever, neutropenia, infection) as a result of therapy.
Inpatient & Outpatient Medications
Inpatient medications are dictated by the most current chemotherapeutic protocols available for the treatment of medulloblastoma. The most commonly used chemotherapeutic agents are DNA alkylators.
Most regimens require the concomitant use of an antiemetic.
Because of the immunosuppressive effects of chemotherapy, trimethoprim sulfamethoxazole and nystatin are commonly prescribed for prophylaxis against Pneumocystis carinii pneumonia and mucocutaneous candidiasis, respectively, for the duration of treatment.
Granulocyte colony stimulating factor (GCSF) following chemotherapy may be used in treatment regimens expected to cause marked neutropenia.
Transfer to centers that can provide appropriate MRI imaging studies, neurosurgical intervention, radiotherapy, and chemotherapy may be necessary.
Avoid exposure to ill contacts during therapy.
Complications include the following:
- Holland et al conducted a study to identify factors associated with academic difficulties in survivors of pediatric medulloblastoma. The study focused on school competence and fluent academic performance. Thirty-six patients (aged 7-18 years) were recruited for the study. Participants completed a neuropsychological screening battery that included selected Woodcock-Johnson III Tests of Achievement subtests. Parents completed the Child Behavior Checklist. Basic academic skill development was found to be broadly average, in contrast to fluent academic performance, which was significantly worse than average. The investigators concluded that school competence may have utility in estimating levels of educational success in survivors of pediatric medulloblastoma and that academic difficulties in these patients may be better assessed through measures of deficits in fluent academic performance rather than academic skills.
Pain secondary to metastasis
- Thrombocytopenia and increased risk for bleeding
- Neutropenia and increased risk for life-threatening bacterial, viral, and fungal opportunistic infections
- Nephrotoxicity, ototoxicity, hepatotoxicity, and neurotoxicity
- Neurocognitive and endocrinologic dysfunction
- Mineralizing microangiopathy with ischemia or infarct
- Secondary CNS and thyroid malignancies
The clinical criteria used to assign prognostic risk groups is continuing to evolve but is currently based on the following 3 features: age, metastasis at presentation, and extent of postoperative residual disease.
Metastasis stage (M stage) is derived from the Chang classification staging system. The M stage classification is as follows:
M0 - No gross subarachnoid or hematogenous metastasis
M1 - Microscopic tumor cells found in CSF
M2 - Gross nodular seeding in cerebellum, cerebral subarachnoid space, or in the third or fourth ventricles
M3 - Gross nodular seeding in spinal subarachnoid space
M4 - Extraneuraxial metastasis.
The CCG-921 study confirmed prospectively the unequivocal impact of metastasis at diagnosis on early tumor progression or relapse. Although the M1 stage lacked statistical power in this study, the lower M stage correlated with improved progression-free survival rates (M0 > M1 > M2+) in children older than 3 years.
The current risk groups are specifically defined, as follows:
Average-risk disease is defined as patients older than 3 years who are at stage M0 with less than 1.5 cm 2 of residual tumor postoperatively. The 5-year survival rate for this group is currently 78%.
Poor-risk disease is defined as patients older than 3 years who are at stage M1-M4 and/or with more than 1.5 cm 2 of residual tumor postoperatively. The 5-year survival rate for this group is currently 30-55%. Those with anaplastic tumors are also considered poor-risk.
All patients with nonposterior fossa tumors that are morphologically similar to medulloblastoma (primitive neural ectodermal tumors [PNETs]) have a poor prognosis similar to patients with poor-risk medulloblastoma, regardless of dissemination.
Infants are defined as patients younger than 3 years. This group has the worst prognosis, regardless of M stage and extent of postoperative residual disease. The 5-year survival rate is approximately 30%; however, patients with metastatic disease do considerably worse.
Biologic tumor markers will likely supplement stratification in the future.
Patients and family members should be instructed about the care of the central venous catheter.
Patients should be instructed about protection against infection and what to do should infection be suspected during therapy.
Grammel D, Warmuth-Metz M, von Bueren AO, Kool M, Pietsch T, Kretzschmar HA, et al. Sonic hedgehog-associated medulloblastoma arising from the cochlear nuclei of the brainstem. Acta Neuropathol. 2012 Feb 21. [Medline].
Kieffer-Renaux V, Bulteau C, Grill J, et al. Patterns of neuropsychological deficits in children with medulloblastoma according to craniospatial irradiation doses. Dev Med Child Neurol. 2000 Nov. 42(11):741-5. [Medline].
Deorah S, Lynch CF, Sibenaller ZA, Ryken TC. Trends in brain cancer incidence and survival in the United States: Surveillance, Epidemiology, and End Results Program, 1973 to 2001. Neurosurg Focus. 2006 Apr 15. 20(4):E1. [Medline].
Massimino M, Cefalo G, Riva D, Biassoni V, Spreafico F, Pecori E, et al. Long-term results of combined preradiation chemotherapy and age-tailored radiotherapy doses for childhood medulloblastoma. J Neurooncol. 2012 Feb 16. [Medline].
Tait DM, Thornton-Jones H, Bloom HJ, et al. Adjuvant chemotherapy for medulloblastoma: the first multi-centre control trial of the International Society of Paediatric Oncology (SIOP I). Eur J Cancer. 1990 Apr. 26(4):464-9. [Medline].
Robertson PL, Muraszko KM, Holmes EJ, Sposto R, Packer RJ, Gajjar A, et al. Incidence and severity of postoperative cerebellar mutism syndrome in children with medulloblastoma: a prospective study by the Children's Oncology Group. J Neurosurg. 2006 Dec. 105(6 Suppl):444-51. [Medline].
Verma J, Mazloom A, Teh BS, South M, Butler EB, Paulino AC. Comparison of supine and prone craniospinal irradiation in children with medulloblastoma. Pract Radiat Oncol. 2014 Oct 2. [Medline].
Min C, Paganetti H, Winey BA, Adams J, MacDonald SM, Tarbell NJ, et al. Evaluation of permanent alopecia in pediatric medulloblastoma patients treated with proton radiation. Radiat Oncol. 2014 Nov 18. 9(1):220. [Medline].
Brown HG, Kepner JL, Perlman EJ, et al. "Large cell/anaplastic" medulloblastomas: a Pediatric Oncology Group Study. J Neuropathol Exp Neurol. 2000 Oct. 59(10):857-65. [Medline].
Holland AA, Hughes CW, Stavinoha PL. School Competence and Fluent Academic Performance: Informing Assessment of Educational Outcomes in Survivors of Pediatric Medulloblastoma. Appl Neuropsychol Child. 2014 Nov 14. 1-8. [Medline].
Dufour C, Beaugrand A, Pizer B, Micheli J, Aubelle MS, Fourcade A, et al. Metastatic Medulloblastoma in Childhood: Chang's Classification Revisited. Int J Surg Oncol. 2012. 2012:245385. [Medline]. [Full Text].
Cohen BH, Zeltzer PM, Boyett JM, et al. Prognostic factors and treatment results for supratentorial primitive neuroectodermal tumors in children using radiation and chemotherapy: a Childrens Cancer Group randomized trial. J Clin Oncol. 1995 Jul. 13(7):1687-96. [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. 1996 Feb. 38(2):265-71. [Medline].
Boon K, Eberhart CG, Riggins GJ. Genomic amplification of orthodenticle homologue 2 in medulloblastomas. Cancer Res. 2005 Feb 1. 65(3):703-7. [Medline].
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 [see comments]. N Engl J Med. 1993 Jun 17. 328(24):1725-31. [Medline].
Dunkel IJ, Finlay JL. High dose chemotherapy with autologous stem cell rescue for patients with medulloblastoma. J Neurooncol. 1996 Jul. 29(1):69-74. [Medline].
Dupuis-Girod S, Hartmann O, Benhamou E, et al. Will high dose chemotherapy followed by autologous bone marrow transplantation supplant cranio-spinal irradiation in young children treated for medulloblastoma?. J Neurooncol. 1996 Jan. 27(1):87-98. [Medline].
Eberhart CG, Burger PC. Anaplasia and grading in medulloblastomas. Brain Pathol. 2003 Jul. 13(3):376-85. [Medline].
Gajjar A, Chintagumpala M, Ashley D, et al. Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial. Lancet Oncol. 2006 Oct. 7(10):813-20. [Medline].
Gajjar A, Fouladi M, Walter AW, et al. Comparison of lumbar and shunt cerebrospinal fluid specimens for cytologic detection of leptomeningeal disease in pediatric patients with brain tumors. J Clin Oncol. 1999 Jun. 17(6):1825-8. [Medline].
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. 2005 Oct 20. 23(30):7621-31. [Medline].
Grotzer MA, Hogarty MD, Janss AJ, et al. MYC messenger RNA expression predicts survival outcome in childhood primitive neuroectodermal tumor/medulloblastoma. Clin Cancer Res. 2001 Aug. 7(8):2425-33. [Medline]. [Full Text].
Grotzer MA, Janss AJ, Fung K, et al. TrkC expression predicts good clinical outcome in primitive neuroectodermal brain tumors. J Clin Oncol. 2000 Mar. 18(5):1027-35. [Medline].
Hallahan AR, Pritchard JI, Hansen S, et al. The SmoA1 mouse model reveals that notch signaling is critical for the growth and survival of sonic hedgehog-induced medulloblastomas. Cancer Res. 2004 Nov 1. 64(21):7794-800. [Medline]. [Full Text].
Hernan R, Fasheh R, Calabrese C, et al. ERBB2 up-regulates S100A4 and several other prometastatic genes in medulloblastoma. Cancer Res. 2003 Jan 1. 63(1):140-8. [Medline].
Jenkin D. The radiation treatment of medulloblastoma. J Neurooncol. 1996 Jul. 29(1):45-54. [Medline].
Kortmann RD, Kuhl 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. 2000 Jan 15. 46(2):269-79. [Medline].
MacDonald TJ, Brown KM, LaFleur B, et al. Expression profiling of medulloblastoma: PDGFRA and the RAS/MAPK pathway as therapeutic targets for metastatic disease. Nat Genet. 2001 Oct. 29(2):143-52. [Medline].
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. 2008 Mar 1. 70(3):782-7. [Medline].
Oliver TG, Grasfeder LL, Carroll AL, et al. Transcriptional profiling of the Sonic hedgehog response: a critical role for N-myc in proliferation of neuronal precursors. Proc Natl Acad Sci U S A. 2003 Jun 10. 100(12):7331-6. [Medline]. [Full Text].
Packer RJ. Brain tumors in children. Arch Neurol. 1999 Apr. 56(4):421-5. [Medline].
Packer RJ, Finlay JL. Medulloblastoma: presentation, diagnosis and management. Oncology (Huntingt). 1988 Sep. 2(9):35-45, 48-9. [Medline].
Packer RJ, Gajjar A, Vezina G, et al. Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma. J Clin Oncol. 2006 Sep 1. 24(25):4202-8. [Medline].
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. 1999 Jul. 17(7):2127-36. [Medline].
Packer RJ, Sutton LN, Elterman R, et al. Outcome for children with medulloblastoma treated with radiation and cisplatin, CCNU, and vincristine chemotherapy. J Neurosurg. 1994 Nov. 81(5):690-8. [Medline].
Pizzo PA, Poplack DG. Tumors of the central nervous system. Principles and Practice of Pediatric Oncology. 3rd ed. 633-97.
Pomeroy SL, Tamayo P, Gaasenbeek M, et al. Prediction of central nervous system embryonal tumour outcome based on gene expression. Nature. 2002. 415(6870):436-42.
Reddy AT, Packer RJ. Pediatric central nervous system tumors. Curr Opin Oncol. 1998 May. 10(3):186-93. [Medline].
Romer JT, Kimura H, Magdaleno S, et al. Suppression of the Shh pathway using a small molecule inhibitor eliminates medulloblastoma in Ptc1(+/-)p53(-/-) mice. Cancer Cell. 2004 Sep. 6(3):229-40. [Medline].
Rutkowski S, Bode U, Deinlein F, et al. Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. N Engl J Med. 2005 Mar 10. 352(10):978-86. [Medline].
Stearns D, Chaudhry A, Abel TW, et al. c-myc overexpression causes anaplasia in medulloblastoma. Cancer Res. 2006 Jan 15. 66(2):673-81. [Medline].
Strother D, Ashley D, Kellie SJ, et al. Feasibility of four consecutive high-dose chemotherapy cycles with stem-cell rescue for patients with newly diagnosed medulloblastoma or supratentorial primitive neuroectodermal tumor after craniospinal radiotherapy: results of a collaborative study. J Clin Oncol. 2001 May 15. 19(10):2696-704. [Medline].
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. 2000 Aug. 18(16):3004-11. [Medline].
Thorarinsdottir HK, Rood B, Kamani N, et al. Outcome for children 111111111111111111Pediatr Blood Cancer</i>. 2007 Mar. 48(3):278-84. [Medline].
Thorarinsdottir HK, Rood B, Kamani N, et al. Outcome for children 111111111111111111Pediatr Blood Cancer</i>. 2006 Feb 2. [Medline].
Yachnis AT. Neuropathology of pediatric brain tumors. Semin Pediatr Neurol. 1997 Dec. 4(4):282-91. [Medline].
Zeltzer PM, Boyett JM, Finlay JL, 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. 1999 Mar. 17(3):832-45. [Medline].
Zerbini C, Gelber RD, Weinberg D, et al. Prognostic factors in medulloblastoma, including DNA ploidy. J Clin Oncol. 1993 Apr. 11(4):616-22. [Medline].