Adult medulloblastoma: an overview on current and future strategies of treatment

References

• McKean-Cowdin R, Razavi P, Barrington-Trimis J, et al. Trends in childhood brain tumor incidence, 1973–2009. J Neurooncol. 2013;115(2):153–160.
   PubMed Web of Science ®Google Scholar
• Kline CN, Packer RJ, Hwang EI. Case-based review: pediatric medulloblastoma. Neuro-Oncol Pract. 2017;4(3):138–150.
   PubMed Web of Science ®Google Scholar
• Smoll NR, Drummond KJ. The incidence of medulloblastomas and primitive neurectodermal tumours in adults and children. J Clin Neurosci. 2012;19:1541–1544.
   PubMed Web of Science ®Google Scholar
• Ostrom QT, Gittleman H, Fulop J, et al. CBTRUS statistical report: primary brain and central nervous system tumors diagnosedin the United States in 2008–2012. Neuro Oncol. 2015 Oct;17(Suppl 4):1–62.
   PubMedGoogle Scholar
• Mariya K, Suprun A, Ghaffar E, et al. Adult medulloblastoma: occurrence of a rare event. Cureus. 2018;10(7):e3000.
   PubMed Web of Science ®Google Scholar
• Neumann JE, Swartling FJ, Schuller U. Medulloblastoma: exprerimental models and reality. Acta Neuropathol. 2017;134:679–689.
   PubMed Web of Science ®Google Scholar
• Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization Classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016.
   Web of Science ®Google Scholar
• Remke M, Hielscher T, Northcott PA, et al. Adult medulloblastoma comprises three major molecular variants. J Clin Oncol. 2011;29(19):2717–2723. Epub 2011 May 31.
   PubMed Web of Science ®Google Scholar
• Zhao F, Ohgaki H, Xu L, et al. Molecular subgroups of adult medulloblastoma: a long-term single-institution study. Neuro Oncol. 2016;18(7):982–990.
   PubMed Web of Science ®Google Scholar
• Al Rayahi J, Zapotocky M, Ramaswamy V, et al. pediatric brain tumor genetics: what radiologists need to know. RadioGraphics. 2018;38:2102–2122.
   PubMed Web of Science ®Google Scholar
• Kool M, Korshunov A, Remke M, et al. Molecular subgroups of medulloblastoma: an international meta-analysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, group 3, and group 4 medulloblastomas. Acta Neuropathol (Berl). 2012;123(4):473–484.
   PubMed Web of Science ®Google Scholar
• Northcott PA, Hielscher T, Dubuc A, et al. Pediatric and adult sonic hedgehog medulloblastomas are clinically and molecularly distinct. Acta Neuropathol. 2011;122(2):231–240. . Epub 2011 Jun 17.
   PubMed Web of Science ®Google Scholar
• Frappaz D, Faure Conter C, Bonneville Levarda A, et al. Medulloblastomas in adolescents and adults – can the pediatric experience be extrapolated? Neurochirurgie. 2018;13. pii: S0028–3770(18)30361-8. DOI:10.1016/j.neuchi.2018.10.007.
   Google Scholar
• Smith MJ, Beetz C, Williams SG, et al. Germline mutations in SUFU cause Gorlin syndrome-associated childhood medulloblastoma and redefine the risk associated with PTCH1 mutations. J Clin Oncol. 2014;32:4155–4161.
   PubMed Web of Science ®Google Scholar
• Shih DJH, Northcott PA, Remke M, et al. Cytogenetic prognostication within medulloblastoma subgroups. J Clin Oncol. 2014;32:886–896.
   PubMed Web of Science ®Google Scholar
• Ellison DW, Dalton J, Kocak M, et al. Medulloblastoma: clinicopathological correlates of SHH, WNT, and non-SHH/WNT molecular subgroups. Acta Neuropathol. 2011;121:381–396.
   PubMed Web of Science ®Google Scholar
• Hamilton SR, Liu B, Parsons RE, et al. The molecular basis of Turcot’s syndrome. N Engl J Med. 1995;332:839–884.
   PubMed Web of Science ®Google Scholar
• Gupta T, Dasgupta A, Epari S, et al. Extraneuraxial metastases from medulloblastoma: single-institution outcome analyses. Intern J Neuro-Oncology. 2018;1(1):46–52.
   Google Scholar
• Mazloom A, Zangeneh AH, Paulino AC. Prognostic factors after extraneural metastasis of medulloblastoma. Int J Radiat Oncol Biol Phys. 2010;78(1):72–78. Epub 2010 Feb 3.
   PubMed Web of Science ®Google Scholar
• Faried A, Pribadi MA, Sumargo S, et al. Adult Medulloblastoma: A rare case report and literature review. Surg Neurol Int. 2016;7(Suppl 17):S481–4.
   PubMedGoogle Scholar
• Remke M, Schubert S, Bouffet E, et al. MRI surrogates for molecular subgroups of medulloblastoma. AJNR Am J Neuroradiol. 2014;35:1263–1269.
   PubMed Web of Science ®Google Scholar
• Keil VC, Warmuth-Metz M, Reh C, et al. Imaging biomarkers for adult medulloblastomas: genetic entities may be identified by their MRImaging radiophenotype. AJNR Am J Neuroradiol. 2017 10;38:1892–1898. Epub 2017 Aug 10.
   PubMed Web of Science ®Google Scholar
• Beier D, Proescholdt M, Reinert C. Multicenter pilot study of radiochemotherapy as first-line treatment for adults with medulloblastoma (NOA-07). Neuro Oncol. 2018;20(3):400–410. Published online 2017 Aug 21.
   PubMed Web of Science ®Google Scholar
• Lai R. Survival of patients with adult medulloblastoma: a population-based study. Cancer. 2008;112(7):1568–1574.
   PubMed Web of Science ®Google Scholar
• Martin AM1, Raabe E, Eberhart C, et al. Management of pediatric and adult patients with medulloblastoma. Curr Treat Options Oncol. 2014;15(4):581–594.
   PubMed Web of Science ®Google Scholar
• Albright AL, Sposto R, Holmes E, et al. Correlation of neurosurgical subspecialization with outcomes in children with malignant brain tumors. Neurosurgery. 2000;47:879–885.
   PubMed Web of Science ®Google Scholar
• Sherman JH, Sheehan JP, Elias WJ, et al. Cerebellar mutism in adults after posterior fossa surgery: a report of 2 cases. Surg Neurol. 2005;63:476–479.
   PubMedGoogle Scholar
• Doxey D, Bruce D, Sklar F, et al. Posterior fossa syndrome: identifiable risk factors and irreversible complications. Pediatr Neurosurg. 1999;31:131–136.
   PubMed Web of Science ®Google Scholar
• 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. 2005;23:4726–4734.
   PubMed Web of Science ®Google Scholar
• Carrie C, Hoffstetter S, Gomez F, et al. Impact of targeting deviations on outcome in medulloblastoma: study of the French society of pediatric oncology (SFOP). Int J Radiat Oncol Biol Phys. 1999;45:435–439.
   PubMed Web of Science ®Google Scholar
• Carrie C, Muracciole X, Gomez F, et al. Conformal radiotherapy, reduced boost volume, hyperfractionated radiotherapy, and online quality control in standard-risk medulloblastoma without chemotherapy: results of the French M-SFOP 98 protocol. Int J Radiat Oncol. 2005;63:711–716.
   PubMed Web of Science ®Google Scholar
• Thomas PR, Deutsch M, Kepner JL, et al. Low-stage medulloblastoma: final analysis of trial comparing standard-dose withreduced-dose neuraxis irradiation. J Clin Oncol. 2000;18:3004–3011.
   PubMed Web of Science ®Google Scholar
• Evans AE, Jenkin RDT, Sposto R, et al. The treatment of medulloblastoma. J Neurosurg. 1990;72:572–582.
   PubMed Web of Science ®Google Scholar
• 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;26:464–469.
   PubMed Web of Science ®Google Scholar
• 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 GroupStudy. J Clin Oncol. 1999;17:2127–2136.
   PubMed Web of Science ®Google Scholar
• Lannering B, Rutkowski S, Doz F, et al. Hyper-fractionated versus conventional radiotherapy followed by chemotherapyin standard-risk medulloblastoma: results from the randomized multicenter HIT-SIOP PNET 4 trial. J Clin Oncol. 2012;30:3187–3193.
   PubMed Web of Science ®Google Scholar
• 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 Group921 randomized phase III study. J Clin Oncol. 1999;17:832–845.
   PubMed Web of Science ®Google Scholar
• von Hoff K, Hinkes B, Gerber NU, et al. Long-term outcome and clinical prognostic factors in children with medulloblastoma treated in the prospective randomised multicentre trial HIT’91. Eur J Cancer. 2009;45:1209–1217.
   PubMed Web of Science ®Google Scholar
• 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 prospec-tive randomized trial HIT’91. Int J Radiat Oncol Biol Phys. 2000;46:269–279.
   PubMed Web of Science ®Google Scholar
• Packer RJ, Gajjar A, Vezina G, et al. Phase III study of craniospinal radiation therapy followed by adju-vant chemotherapy for newly diagnosed average-risk medulloblastoma. J Clin Oncol. 2006;24:4202–4208.
   PubMed Web of Science ®Google Scholar
• Packer RJ, Zhou T, Holmes E, et al. Survival and secondary tumors in children with medulloblastoma receiving radiotherapy and adju-vant chemotherapy: results of Children’s Oncology Group trial A9961. Neuro-Oncol. 2013;15:97–103.
   PubMed Web of Science ®Google Scholar
• Kennedy C, Bull K, Chevignard M, et al. Quality of survival and growth in children and young adults in the PNET4 European controlled trial of hyperfractionated versus conventional radia-tion therapy for standard-risk medulloblastoma. Int J Radiat Oncol. 2013;88:292–300.
   PubMed Web of Science ®Google Scholar
• Merchant TE, Kun LE, Krasin MJ, et al. Multi-institution prospective trial of reduced-dose craniospinal irradi-ation (23.4 Gy) followed by conformal Posterior Fossa (36 Gy) and primarysite irradiation (55.8 Gy) and dose-intensive chemotherapy for average-riskmedulloblastoma. Int J Radiat Oncol. 2008;70:782–787.
   PubMed Web of Science ®Google Scholar
• Taylor RE, Bailey CC, Robinson KJ, et al. Outcome for patients with metastatic (M2-3) medulloblastoma treated with SIOP/UKCCSG PNET-3 chemotherapy. Eur J Cancer. 2005;41:727–734.
   PubMed Web of Science ®Google Scholar
• Gandola L, Massimino M, Cefalo G, et al. Hyper-fractionated accelerated radiotherapy in the Milan strategy for metastatic medulloblastoma. J Clin Oncol. 2008;27:566–571.
   PubMed Web of Science ®Google Scholar
• Dufour C, Kieffer V, Varlet P, et al. Tandem high-dose chemotherapy and autologous stem cell rescue in children with newly diagnosed high-risk medulloblastoma or supratentorial primitive neuroectodermic tumors. Pediatr Blood Cancer. 2014;61:1398–1402.
   PubMed Web of Science ®Google Scholar
• Gajjar A, Chintagumpala M, Ashley D, et al. Risk-adapted craniospinal radiotherapy followed by high-dose chemother-apy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multi-centre trial. Lancet Oncol. 2006;7:813–820.
   PubMed Web of Science ®Google Scholar
• Tabori U, Sung L, Hukin J, et al. Medulloblastoma in the second decade of life: a specific group with respect to toxicity and management: a Canadian pediatric brain tumor consortium study. Cancer. 2005;103:1874–1880.
   PubMed Web of Science ®Google Scholar
• Pomeroy S Treatment and prognosis of medulloblastoma [ updated 2019 May 16;cited 2019 Aug 10]. Available from:https://www.uptodate.com/contents/treatment-and-prognosis-of-medulloblastoma
   Google Scholar
• Cosman R, Brown CSB, DeBraganca KC, et al. Patterns of care in adult medulloblastoma: results of an international online survey. J Neurooncol. 2014;120:125–129.
   PubMed Web of Science ®Google Scholar
• Frappaz D, Sunyach M-P, Le Rhun E, et al. Adolescent and Young Adults (AYAS) brain tumor national Webconference. On behalf of ANOCEF, GO-AJA and SFCE societies. Bull Cancer. 2016;103:1050–1056.
   PubMed Web of Science ®Google Scholar
• Brandes AA, Franceschi E, Tosoni A, et al. Long-term results of a prospective study on the treatment of medulloblastoma in adults. Cancer. 2007;110:2035–2041.
   PubMed Web of Science ®Google Scholar
• Franceschi E, Bartolotti M, Paccapelo A, et al. Adjuvant chemotherapy in adult medulloblastoma: is it an option for average-risk patients? J Neurooncol. 2016;128:235–240.
   PubMed Web of Science ®Google Scholar
• Kann BH, Lester-Coll NH, Park HS, et al. Adjuvant chemotherapy and overall survival in adult medulloblastoma. NeuroOncol. 2016;19:150.
   Google Scholar
• Atalar B, Ozsahin M, Call J, et al. Treatment outcome and prognostic factors for adult patients with medulloblastoma: the Rare Cancer Network (RCN) experience. DOI:10.1016/j.radonc.2017.12.028
   Google Scholar
• Kocakaya S, Beier CP, Beier D. Chemotherapy increases long-term survival in patients with adult medulloblastoma-a literature-based meta-analysis. Neuro Oncol. 2016;18:408–416.
   PubMed Web of Science ®Google Scholar
• Alberta Health Services. 2010. Clinical practice guidelines, cancer care: medulloblastoma. Effective Date: March, 2014 [cited 2019 May 8. Available from:https://www.albertahealthservices.ca/assets/info/hp/cancer/if-hp-cancer-guide-cns008-medulloblastoma.pdf
   Google Scholar
• Sabel M, Fleischhack G, Tippelt S, et al. Relapse patterns and outcome after relapse in standard riskmedulloblastoma: a report from the HIT-SIOP-PNET4 study. J Neurooncol. 2016;129:515–524.
   PubMed Web of Science ®Google Scholar
• Mokhtech M, Morris CG, Indelicato DJ, et al. Patterns of failure in patients with adult medulloblastoma presenting without extraneural metastasis. Am J Clin Oncol. 2018;41(10):1015–1018.
   PubMed Web of Science ®Google Scholar
• Dasgupta A, Gupta T, Sridhar E, et al. Pediatric patients with SHH medulloblastoma fail differently as compared with adults: possible implications for treatment modifications. J Pediatr Hematol Oncol. 2019;1. DOI:10.1097/MPH.0000000000001484.
   PubMedGoogle Scholar
• Kostaras X, Easaw JC. Management of recurrent medulloblastoma in adult patients: a systematic review and recommendations. J Neurooncol. 2013;115:1–8.
   PubMed Web of Science ®Google Scholar
• Ashley DM, Meier L, Kerby T, et al. Response of recurrent medulloblastoma to low-dose oral etoposide. J Clin Oncol. 1996;14:1922–1927.
   PubMed Web of Science ®Google Scholar
• Chamberlain MC, Kormanik PA. Chronic oral VP-16 for recurrent medulloblastoma. Pediatr Neurol. 1997;17:230–234.
   PubMed Web of Science ®Google Scholar
• Davidson A, Gowing R, Lowis S, et al. Phase II study of 21 day schedule oral etoposide in children. New Agents Group of the United Kingdom Children’s Cancer Study Group (UKCCSG). Eur J Cancer. 1997;33:1816–1822.
   PubMed Web of Science ®Google Scholar
• Durando X, Thivat E, Gilliot O, et al. Temozolomide treatment of an adult with a relapsing medulloblastoma. Cancer Invest. 2007;25:470–475.
   PubMed Web of Science ®Google Scholar
• Nicholson HS, Kretschmar CS, Krailo M, et al. Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors. Cancer. 2007;110:1542–1550.
   PubMed Web of Science ®Google Scholar
• Cefalo G, Massimino M, Ruggiero A, et al. Temozolomide is an active agent in children with recurrent medulloblastoma/primitive neuroectodermal tumor: an Italian multi-institutional phase II trial. Neuro Oncol. 2014;16(5):748–753. Published online 2014 Jan 30.
   PubMed Web of Science ®Google Scholar
• Ruggiero A, Rizzo D, Attinà G, et al. Phase I study of temozolomide combined with oral etoposide in children with recurrent or progressive medulloblastoma. Eur J Cancer. 2010;46:2943–2949.
   PubMed Web of Science ®Google Scholar
• Massimino M, Casanova M, Polastri D, et al. Relapse in medulloblastoma: what can be done after abandoning high-dose chemotherapy? A mono-institutional experience. Childs Nerv Syst. 2013;29:1107–1112.
   PubMed Web of Science ®Google Scholar
• Buglione M, Triggiani L, Grisanti S, et al. Retreatment of recurrent adult medulloblastoma with radiotherapy: a case report and review of the literature. J Med Case Rep. 2013;7:64.
   PubMedGoogle Scholar
• Gupta T, Maitre M, Sastri GJ, et al. Outcomes of salvage re-irradiation in recurrent medulloblastoma correlate with age at initial diagnosis, primary risk-stratification, and molecular subgrouping. J Neurooncol. 2019;144:283–291.
   PubMedGoogle Scholar
• Morrissy AS, Garzia L, Shih DJH, et al. Divergent clonal selection dominates medulloblastoma at recurrence. Nature-. 2016;529:351–357.
   PubMed Web of Science ®Google Scholar
• Bonney PA, Santucci JA, Maurer AJ, et al. Dramatic response to temozolomide, irinotecan, and bevacizumab for recurrent medulloblastoma with widespread osseous metastases. J Clin Neurosci. 2016;26:161–163.
   PubMed Web of Science ®Google Scholar
• Murata D, Mineharu Y, Arakawa Y, et al. High programmed cell death 1 ligand-1 expression: association with CD8+ T-cell infiltration and poor prognosis in human medulloblastoma. J Neurosurg. 2018;128:710-716.
   PubMed Web of Science ®Google Scholar
• Allen J, Donahue B, Mehta M, et al. A Phase II study of preradio therapy chemotherapy followed by hyperfractionated radiotherapy for newly diagnosed high-risk medulloblastoma/primitive neuroectodermal tumor: a report from the Children’s Oncology Group (CCG9931). Int J Radiat Oncol. 2009;74:1006–1011.
   PubMed Web of Science ®Google Scholar
• Morrissy AS, Cavalli FMG, Remke M, et al. Spatial heterogeneity in medulloblastoma. Nat Genet. 2017;49:780–788. . Epub 2017 Apr 10.
   PubMed Web of Science ®Google Scholar
• Rudin CM, Hann CL, Laterra J, et al. Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449. Eng J Med. 2009;361(12):1173–1178.
   PubMed Web of Science ®Google Scholar
• Gajjar A, Stewart CF, Ellison DW, et al. Phase I study of vismodegib in children with recurrent or refractory medulloblastoma: a pediatric brain tumor consortium study. Clin Cancer Res. 2013;19(22):6305–6312.
   PubMed Web of Science ®Google Scholar
• Robinson GW, Orr BA, Wu GA. Vismodegib exerts targeted efficacy against recurrent Sonic Hedgehog-subgroupmedulloblastoma: results from Phase II pediatric brain tumor Consortiumstudies PBTC-025B and PBTC-032. J Clin Oncol. 2015;33:2646–2654.
   PubMed Web of Science ®Google Scholar
• Dijkgraaf GJP, Alicke B, Weinmann L, et al. Small molecule inhibition of GDC-0449 refractory smoothened mutants and down-stream mechanisms of drug resistance. Cancer Res. 2011;71:435–444.
   PubMed Web of Science ®Google Scholar
• Kool M, Jones DT, Jager N, et al. Genome sequencing of SHH medulloblastoma predicts genotype-related response to smooth-ened inhibition. Cancer Cell. 2014;25:393–405.
   PubMed Web of Science ®Google Scholar
• Lou E, Schomaker M, Wilson JD, et al. Completeand sustained response of adult medulloblastoma to first-line sonic hedgehoginhibition with vismodegib. Cancer Biol Ther. 2016;17:1010–1016.
   PubMed Web of Science ®Google Scholar
• Majd N, Penas-Prado M. Updates on management of adult medulloblastoma. Curr Treat Options Oncol. 2019 Jun 24;20(8):64. .
   PubMed Web of Science ®Google Scholar
• Samkari A, White J, Packer R. HH inhibitors for the treatment of medulloblastoma. Expert Rev Neurother. 2015;15:763-770
   PubMedGoogle Scholar
• Kim J, Aftab BT, Tang JY, et al. Itraconazole and arsenic trioxide inhibit hedgehog pathway activation and tumor growth associated with acquired resistance to smoothened antagonists. Cancer Cell. 2013;23:23–34.
   PubMed Web of Science ®Google Scholar
• Bandopadhayay P, Bergthold G, Nguyen B, et al. BET bromodomain inhibition of MYC-amplified medulloblastoma. Clin Cancer Res. 2014;20:912–925.
   PubMed Web of Science ®Google Scholar
• Diaz RJ, Golbourn B, Faria C, et al. Mechanism of action and therapeutic efficacy of Aurora kinase B inhibition in MYC overexpressing medulloblastoma. Oncotarget. 2015;6(5):3359–3374.
   PubMedGoogle Scholar
• Pei Y, Liu KW, Wang J, et al. HDAC and PI3K antagonists cooperate to inhibit growth of MYC-driven medulloblastoma. Cancer Cell. 2016;29:311–323.
   PubMed Web of Science ®Google Scholar
• Frappaz D, Chinot OL, Meyronet D, et al. MEVITEM: A European, randomized, open-label Phase I/II of vismodegib in combination with temozolomide versus temozolomide alone in adult patients with recurrent/refractory medulloblastoma presenting an activation of the Sonic Hedgehog pathway. Neuro Oncol. 2016;18(Suppl 4):iv80. Published online 2016 Sep 21.
   Google Scholar