Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
Current Treatment Options in Oncology
Erschienen in: Current Treatment Options in Oncology 8/2019

01.08.2019 | Neuro-oncology (GJ Lesser, Section Editor)

Updates on Management of Adult Medulloblastoma

verfasst von: Nazanin Majd, MD, PhD, Marta Penas-Prado, MD

Erschienen in: Current Treatment Options in Oncology | Ausgabe 8/2019

Einloggen, um Zugang zu erhalten

Opinion statement

Medulloblastoma (MB) is a malignant embryonal tumor of the posterior fossa and is the most common type of brain cancer in pediatric patients. In contrast, adult MB is very rare with an incidence of 0.6 per million per year and mostly affects young adults below the age of 40. Recent molecular analyses of pediatric and adult MB have classified these tumors into at least four individual molecular subgroups (SHH, WNT, group 3, and group 4) with distinct demographics, histology, and prognosis. The discrete biological composition of these tumors likely explains the marked heterogeneity in responses seen to conventional therapies such as radiation and cytotoxic chemotherapies. Given the low incidence of adult MB, prospective studies are challenging and scarce, and management guidelines are largely derived from the pediatric MB patient population and retrospective data. However, adult MB is clinically and molecularly distinct from pediatric MB and a comprehensive review of published literature on adult MB highlighting their differences is warranted. Here, we review the management of adult MB focusing on recent studies exploring the effectiveness of upfront chemotherapy, clinical trials in the context of molecular subgroup-specific therapies, and the potential role of immunotherapy in treating this disease.
Literatur
1.
Farwell JR, Dohrmann GJ, Flannery JT. Medulloblastoma in childhood: an epidemiological study. J Neurosurg. 1984;61:657–64.PubMed
2.
Merchant TE, Pollack IF, Loeffler JS. Brain tumors across the age spectrum: biology, therapy, and late effects. Semin Radiat Oncol. 2010;20:58–66.PubMedPubMedCentral
3.
Ostrom QT, Gittleman H, Truitt G, Boscia A, Kruchko C, Barnholtz-Sloan JS. CBTRUS Statistical Report: primary brain and other central nervous system tumors diagnosed in the United States in 2011-2015. Neuro-Oncology. 2018;20:iv1–iv86.PubMedPubMedCentral
4.
•• Kann BH, Lester-Coll NH, Park HS, Yeboa DN, Kelly JR, Baehring JM, et al. Adjuvant chemotherapy and overall survival in adult medulloblastoma. Neuro-Oncology. 2017;19:259–69 National database analysis regarding the role of adjuvant chemotherapy in adult MB. Kann et al. showed that survival was superior in patients who received chemotherapy and radiation vs. radiation alone in adult MB patients. Importantly, they demonstrated a similar survival benefit in the subgroup of patients in whom chemotherapy is likely to be eliminated in common clinical practice including those with M0 and those who received high-dose craniospinal radiation.
5.
Mastall M, Majd N, Fuller G, Gule-Monroe MT, Huse J, Khatua S, et al. Rare-13. Characterization of adult medulloblastoma patients at recurrence: retrospective review of the MD Anderson Cancer Center experience. Neuro-Oncology. 2018;20:vi239.PubMedCentral
6.
•• Kocakaya S, Beier CP, Beier D. Chemotherapy increases long-term survival in patients with adult medulloblastoma--a literature-based meta-analysis. Neuro-Oncology. 2016;18:408–16 Meta-analysis of the role of chemotherapy in adult MB. Kocakaya et al. demonstrated that adjuvant chemotherapy significantly improved survival of adult MB patients. In this study, 20% of patients showed signs of metastasis at diagnosis (higher than prior literature in adult MB) which was not prognostic for OS.
7.
del Charco JO, Bolek TW, McCollough WM, Maria BL, Kedar A, Braylan RC, et al. Medulloblastoma: time-dose relationship based on a 30-year review. Int J Radiat Oncol Biol Phys. 1998;42:147–54.
8.
Brandes AA, Franceschi E, Tosoni A, Frezza G, Agati R, Maestri A, et al. Efficacy of tailored treatment for high- and low-risk medulloblastoma in adults: a large prospective phase II trial. J Clin Oncol. 2010;28:2003.
9.
von Bueren AO, Friedrich C, von Hoff K, Kwiecien R, Muller K, Pietsch T, et al. Metastatic medulloblastoma in adults: outcome of patients treated according to the HIT2000 protocol. Eur J Cancer. 2015;51:2434–43.
10.
Frost PJ, Laperriere NJ, Wong CS, Milosevic MF, Simpson WJ, Pintilie M. Medulloblastoma in adults. Int J Radiat Oncol Biol Phys. 1995;32:951–7.PubMed
11.
Carrie C, Lasset C, Alapetite C, Haie-Meder C, Hoffstetter S, Demaille MC, et al. Multivariate analysis of prognostic factors in adult patients with medulloblastoma. Retrospective study of 156 patients. Cancer. 1994;74:2352–60.PubMed
12.
Remke M, Hielscher T, Northcott PA, Witt H, Ryzhova M, Wittmann A, et al. Adult medulloblastoma comprises three major molecular variants. J Clin Oncol. 2011;29:2717–23.PubMed
13.
DeSouza RM, Jones BR, Lowis SP, Kurian KM. Pediatric medulloblastoma - update on molecular classification driving targeted therapies. Front Oncol. 2014;4:176.PubMedPubMedCentral
14.
Brandes AA, Ermani M, Amista P, Basso U, Vastola F, Gardiman M, et al. The treatment of adults with medulloblastoma: a prospective study. Int J Radiat Oncol Biol Phys. 2003;57:755–61.
15.
Brandes AA, Franceschi E, Tosoni A, Blatt V, Ermani M. Long-term results of a prospective study on the treatment of medulloblastoma in adults. Cancer. 2007;110:2035–41.PubMed
16.
•• Beier D, Proescholdt M, Reinert C, Pietsch T, Jones DTW, Pfister SM, et al. Multicenter pilot study of radiochemotherapy as first-line treatment for adults with medulloblastoma (NOA-07). Neuro-Oncology. 2018;20:400–10 Phase II study of radio-chemotherapy as first-line treatment for adult MB. This study marks the most current prospective study in adult MB which treated 30 patients older than age 21 with photon craniospinal radiation and concurrent vincristine followed by cisplatin, lomustine, and vincristine. Seventy percent of patients received more than 4 cycles of this regimen, but all needed dose reduction. This recent prospective trial serves as benchmark for future prospective studies in adult MB.
17.
Brandes AA, Franceschi E, Tosoni A, Reni M, Gatta G, Vecht C, et al. Adult neuroectodermal tumors of posterior fossa (medulloblastoma) and of supratentorial sites (stPNET). Crit Rev Oncol Hematol. 2009;71:165–79.PubMed
18.
Coluccia D, Figuereido C, Isik S, Smith C, Rutka JT. Medulloblastoma: tumor biology and relevance to treatment and prognosis paradigm. Curr Neurol Neurosci Rep. 2016;16:43.PubMed
19.
Aboian MS, Kline CN, Li Y, Solomon DA, Felton E, Banerjee A, et al. Early detection of recurrent medulloblastoma: the critical role of diffusion-weighted imaging. Neurooncol Pract. 2018;5:234–40.PubMedPubMedCentral
20.
Beier D, Kocakaya S, Hau P, Beier CP. The neuroradiological spectra of adult and pediatric medulloblastoma differ: results from a literature-based meta-analysis. Clin Neuroradiol. 2018;28:99–107.PubMed
21.
Perreault S, Ramaswamy V, Achrol AS, Chao K, Liu TT, Shih D, et al. MRI surrogates for molecular subgroups of medulloblastoma. AJNR Am J Neuroradiol. 2014;35:1263–9.PubMedPubMedCentral
22.
Keil VC, Warmuth-Metz M, Reh C, Enkirch SJ, Reinert C, Beier D, et al. Imaging biomarkers for adult medulloblastomas: genetic entities may be identified by their MR imaging radiophenotype. AJNR Am J Neuroradiol. 2017;38:1892–8.PubMedPubMedCentral
23.
Warren KE, Vezina G, Poussaint TY, Warmuth-Metz M, Chamberlain MC, Packer RJ, et al. Response assessment in medulloblastoma and leptomeningeal seeding tumors: recommendations from the Response Assessment in Pediatric Neuro-Oncology Committee. Neuro-Oncology. 2018;20:13–23.PubMedPubMedCentral
24.
Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016;131:803–20.PubMed
25.
Brandes AA, Bartolotti M, Marucci G, Ghimenton C, Agati R, Fioravanti A, et al. New perspectives in the treatment of adult medulloblastoma in the era of molecular oncology. Crit Rev Oncol Hematol. 2015;94:348–59.PubMed
26.
Eberhart CG, Kepner JL, Goldthwaite PT, Kun LE, Duffner PK, Friedman HS, et al. Histopathologic grading of medulloblastomas: a Pediatric Oncology Group study. Cancer. 2002;94:552–60.
27.
Rutkowski S, Bode U, Deinlein F, Ottensmeier H, Warmuth-Metz M, Soerensen N, et al. Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. N Engl J Med. 2005;352:978–86.
28.
Kool M, Korshunov A, Remke M, Jones DT, Schlanstein M, Northcott PA, 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. 2012;123:473–84.PubMedPubMedCentral
29.
Zhukova N, Ramaswamy V, Remke M, Pfaff E, Shih DJ, Martin DC, et al. Subgroup-specific prognostic implications of TP53 mutation in medulloblastoma. J Clin Oncol. 2013;31:2927–35.
30.
Kool M, Jones DT, Jager N, Northcott PA, Pugh TJ, Hovestadt V, et al. Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition. Cancer Cell. 2014;25:393–405.
31.
Northcott PA, Korshunov A, Pfister SM, Taylor MD. The clinical implications of medulloblastoma subgroups. Nat Rev Neurol. 2012;8:340–51.PubMed
32.
Shih DJ, Northcott PA, Remke M, Korshunov A, Ramaswamy V, Kool M, et al. Cytogenetic prognostication within medulloblastoma subgroups. J Clin Oncol. 2014;32:886–96.
33.
Korshunov A, Remke M, Werft W, Benner A, Ryzhova M, Witt H, et al. Adult and pediatric medulloblastomas are genetically distinct and require different algorithms for molecular risk stratification. J Clin Oncol. 2010;28:3054–60.PubMed
34.
Zhao F, Ohgaki H, Xu L, Giangaspero F, Li C, Li P, et al. Molecular subgroups of adult medulloblastoma: a long-term single-institution study. Neuro-Oncology. 2016;18:982–90.PubMedPubMedCentral
35.
Schwalbe EC, Lindsey JC, Nakjang S, Crosier S, Smith AJ, Hicks D, et al. Novel molecular subgroups for clinical classification and outcome prediction in childhood medulloblastoma: a cohort study. Lancet Oncol. 2017;18:958–71.PubMedPubMedCentral
36.
• Cavalli FMG, Remke M, Rampasek L, Peacock J, Shih DJH, Luu B, et al. Intertumoral heterogeneity within medulloblastoma subgroups. Cancer Cell. 2017;31:737–754 e736 Network fusion applied to genome-wide DNA methylation and gene expression data across 763 MB samples. The main four subgroups of MB were further divided into 12 subtypes based on distinct somatic copy-number aberrations, activated pathways, and clinical outcomes which describe the unexplained variations that were seen in clinical behavior and response to therapy in the four subgroups.
37.
Chang CH, Housepian EM, Herbert C Jr. An operative staging system and a megavoltage radiotherapeutic technic for cerebellar medulloblastomas. Radiology. 1969;93:1351–9.PubMed
38.
Packer RJ, Cogen P, Vezina G, Rorke LB. Medulloblastoma: clinical and biologic aspects. Neuro-Oncology. 1999;1:232–50.PubMedPubMedCentral
39.
Packer RJ, Goldwein J, Nicholson HS, Vezina LG, Allen JC, Ris MD, 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;17:2127–36.PubMed
40.
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;38:265–71.PubMed
41.
Thompson EM, Hielscher T, Bouffet E, Remke M, Luu B, Gururangan S, et al. Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis. Lancet Oncol. 2016;17:484–95.
42.
Padovani L, Sunyach MP, Perol D, Mercier C, Alapetite C, Haie-Meder C, et al. Common strategy for adult and pediatric medulloblastoma: a multicenter series of 253 adults. Int J Radiat Oncol Biol Phys. 2007;68:433–40.
43.
Lai R. Survival of patients with adult medulloblastoma: a population-based study. Cancer. 2008;112:1568–74.PubMed
44.
Friedrich C, von Bueren AO, von Hoff K, Kwiecien R, Pietsch T, Warmuth-Metz M, et al. Treatment of adult nonmetastatic medulloblastoma patients according to the paediatric HIT 2000 protocol: a prospective observational multicentre study. Eur J Cancer. 2013;49:893–903.PubMed
45.
Silvani A, Gaviani P, Lamperti E, Botturi A, Dimeco F, Franzini A, et al. Adult medulloblastoma: multiagent chemotherapy with cisplatinum and etoposide: a single institutional experience. J Neuro-Oncol. 2012;106:595–600.PubMed
46.
Hubbard JL, Scheithauer BW, Kispert DB, Carpenter SM, Wick MR, Laws ER Jr. Adult cerebellar medulloblastomas: the pathological, radiographic, and clinical disease spectrum. J Neurosurg. 1989;70:536–44.PubMed
47.
Packer RJ, Sutton LN, Atkins TE, Radcliffe J, Bunin GR, D'Angio G, et al. A prospective study of cognitive function in children receiving whole-brain radiotherapy and chemotherapy: 2-year results. J Neurosurg. 1989;70:707–13.PubMed
48.
Harrison RA, Kesler SR, Johnson JM, Penas-Prado M, Sullaway CM, Wefel JS. Neurocognitive dysfunction in adult cerebellar medulloblastoma. Psychooncology. 2019;28:131–8.PubMed
49.
Thomas PR, Deutsch M, Kepner JL, Boyett JM, Krischer J, Aronin P, et al. Low-stage medulloblastoma: final analysis of trial comparing standard-dose with reduced-dose neuraxis irradiation. J Clin Oncol. 2000;18:3004–11.PubMed
50.
Packer RJ, Gajjar A, Vezina G, Rorke-Adams L, Burger PC, Robertson PL, et al. Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma. J Clin Oncol. 2006;24:4202–8.PubMed
51.
Gajjar A, Chintagumpala M, Ashley D, Kellie S, Kun LE, Merchant TE, 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;7:813–20.PubMed
52.
Brown AP, Barney CL, Grosshans DR, McAleer MF, de Groot JF, Puduvalli VK, et al. Proton beam craniospinal irradiation reduces acute toxicity for adults with medulloblastoma. Int J Radiat Oncol Biol Phys. 2013;86:277–84.
53.
Fukunaga-Johnson N, Lee JH, Sandler HM, Robertson P, McNeil E, Goldwein JW. Patterns of failure following treatment for medulloblastoma: is it necessary to treat the entire posterior fossa? Int J Radiat Oncol Biol Phys. 1998;42:143–6.PubMed
54.
Wolden SL, Dunkel IJ, Souweidane MM, Happersett L, Khakoo Y, Schupak K, et al. Patterns of failure using a conformal radiation therapy tumor bed boost for medulloblastoma. J Clin Oncol. 2003;21:3079–83.PubMed
55.
Abacioglu U, Uzel O, Sengoz M, Turkan S, Ober A. Medulloblastoma in adults: treatment results and prognostic factors. Int J Radiat Oncol Biol Phys. 2002;54:855–60.PubMed
56.
Taylor RE, Bailey CC, Robinson K, Weston CL, Ellison D, Ironside J, et al. Results of a randomized study of preradiation chemotherapy versus radiotherapy alone for nonmetastatic medulloblastoma: The International Society of Paediatric Oncology/United Kingdom Children’s Cancer Study Group PNET-3 Study. J Clin Oncol. 2003;21:1581–91.PubMed
57.
Lee CT, Bilton SD, Famiglietti RM, Riley BA, Mahajan A, Chang EL, et al. Treatment planning with protons for pediatric retinoblastoma, medulloblastoma, and pelvic sarcoma: how do protons compare with other conformal techniques? Int J Radiat Oncol Biol Phys. 2005;63:362–72.
58.
St Clair WH, Adams JA, Bues M, Fullerton BC, La Shell S, Kooy HM, et al. Advantage of protons compared to conventional X-ray or IMRT in the treatment of a pediatric patient with medulloblastoma. Int J Radiat Oncol Biol Phys. 2004;58:727–34.
59.
Moeller BJ, Chintagumpala M, Philip JJ, Grosshans DR, McAleer MF, Woo SY, et al. Low early ototoxicity rates for pediatric medulloblastoma patients treated with proton radiotherapy. Radiat Oncol. 2011;6:58.PubMedPubMedCentral
60.
Kortmann RD, Kuhl J, Timmermann B, Mittler U, Urban C, Budach V, 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;46:269–79.
61.
• Moots PL, O'Neill A, Londer H, Mehta M, Blumenthal DT, Barger GR, et al. Preradiation chemotherapy for adult high-risk medulloblastoma: a trial of the ECOG-ACRIN Cancer Research Group (E4397). Am J Clin Oncol. 2018;41:588–94 Prospective study of neoadjuant chemotherapy followed by craniospinal radiation in adults. This study closed early due to poor accrual. The outcome of this study was worse than expected, questioning the benefit from neoadjuvant chemotherapy in adult MB.PubMedPubMedCentral
62.
Fouladi M, Gururangan S, Moghrabi A, Phillips P, Gronewold L, Wallace D, et al. Carboplatin-based primary chemotherapy for infants and young children with CNS tumors. Cancer. 2009;115:3243–53.PubMed
63.
DJ N, Anna E, TJ C, Jana P, AL S, Branko Z, et al. Feasibility of an attenuated maintenance chemotherapy regimen directed at adolescents and young adults with newly diagnosed localized medulloblastoma and other central nervous system embryonal tumors. J Adolesc Young Adult Oncol. 2014;3:106–11.
64.
Herrlinger U, Steinbrecher A, Rieger J, Hau P, Kortmann RD, Meyermann R, et al. Adult medulloblastoma: prognostic factors and response to therapy at diagnosis and at relapse. J Neurol. 2005;252:291–9.PubMed
65.
Ramaswamy V, Remke M, Bouffet E, Faria CC, Perreault S, Cho YJ, et al. Recurrence patterns across medulloblastoma subgroups: an integrated clinical and molecular analysis. Lancet Oncol. 2013;14:1200–7.
66.
Morrissy AS, Garzia L, Shih DJ, Zuyderduyn S, Huang X, Skowron P, et al. Divergent clonal selection dominates medulloblastoma at recurrence. Nature. 2016;529:351–7.
67.
Phi JH, Park AK, Lee S, Choi SA, Baek IP, Kim P, et al. Genomic analysis reveals secondary glioblastoma after radiotherapy in a subset of recurrent medulloblastomas. Acta Neuropathol. 2018;135:939–53.PubMed
68.
Packer RJ, Zhou T, Holmes E, Vezina G, Gajjar A. Survival and secondary tumors in children with medulloblastoma receiving radiotherapy and adjuvant chemotherapy: results of Children’s Oncology Group trial A9961. Neuro-Oncology. 2013;15:97–103.PubMed
69.
Goldstein AM, Yuen J, Tucker MA. Second cancers after medulloblastoma: population-based results from the United States and Sweden. Cancer Causes Control. 1997;8:865–71.PubMed
70.
Balter-Seri J, Mor C, Shuper A, Zaizov R, Cohen IJ. Cure of recurrent medulloblastoma: the contribution of surgical resection at relapse. Cancer. 1997;79:1241–7.PubMed
71.
Wetmore C, Herington D, Lin T, Onar-Thomas A, Gajjar A, Merchant TE. Reirradiation of recurrent medulloblastoma: does clinical benefit outweigh risk for toxicity? Cancer. 2014;120:3731–7.PubMed
72.
Dunkel IJ, Gardner SL, Garvin JH Jr, Goldman S, Shi W, Finlay JL. High-dose carboplatin, thiotepa, and etoposide with autologous stem cell rescue for patients with previously irradiated recurrent medulloblastoma. Neuro-Oncology. 2010;12:297–303.PubMedPubMedCentral
73.
Bakst RL, Dunkel IJ, Gilheeney S, Khakoo Y, Becher O, Souweidane MM, et al. Reirradiation for recurrent medulloblastoma. Cancer. 2011;117:4977–82.PubMed
74.
Cefalo G, Massimino M, Ruggiero A, Barone G, Ridola V, Spreafico F, et al. Temozolomide is an active agent in children with recurrent medulloblastoma/primitive neuroectodermal tumor: an Italian multi-institutional phase II trial. Neuro-Oncology. 2014;16:748–53.PubMedPubMedCentral
75.
Durando X, Thivat E, Gilliot O, Irthum B, Verrelle P, Vincent C, et al. Temozolomide treatment of an adult with a relapsing medulloblastoma. Cancer Investig. 2007;25:470–5.PubMed
76.
Privitera G, Acquaviva G, Ettorre GC, Spatola C. Antiangiogenic therapy in the treatment of recurrent medulloblastoma in the adult: case report and review of the literature. J Oncol. 2009;2009:247873.PubMedPubMedCentral
77.
Levy A, Williams-Hughes C, Villaluna D, Krailo M, Bancroft M, Chi S, et al. PDCT-09. Temozolomide with irinotecan versus temozolomide, irinotecan plus bevacizumab for recurrent medulloblastoma/cns pnet of childhood: report of a Cog Randomized Phase II Screening Trial. Neuro-Oncology. 2017;19:vi186.PubMedCentral
78.
Kalifa C, Hartmann O, Demeocq F, Vassal G, Couanet D, Terrier-Lacombe MJ, et al. High-dose busulfan and thiotepa with autologous bone marrow transplantation in childhood malignant brain tumors: a phase II study. Bone Marrow Transplant. 1992;9:227–33.
79.
Graham ML, Herndon JE 2nd, Casey JR, Chaffee S, Ciocci GH, Krischer JP, et al. High-dose chemotherapy with autologous stem-cell rescue in patients with recurrent and high-risk pediatric brain tumors. J Clin Oncol. 1997;15:1814–23.PubMed
80.
Dunkel IJ, Boyett JM, Yates A, Rosenblum M, Garvin JH Jr, Bostrom BC, et al. High-dose carboplatin, thiotepa, and etoposide with autologous stem-cell rescue for patients with recurrent medulloblastoma. Children’s Cancer Group. J Clin Oncol. 1998;16:222–8.PubMed
81.
Zia MI, Forsyth P, Chaudhry A, Russell J, Stewart DA. Possible benefits of high-dose chemotherapy and autologous stem cell transplantation for adults with recurrent medulloblastoma. Bone Marrow Transplant. 2002;30:565–9.PubMed
82.
Gill P, Litzow M, Buckner J, Arndt C, Moynihan T, Christianson T, et al. High-dose chemotherapy with autologous stem cell transplantation in adults with recurrent embryonal tumors of the central nervous system. Cancer. 2008;112:1805–11.PubMed
83.
Gajjar A, Stewart CF, Ellison DW, Kaste S, Kun LE, Packer RJ, et al. Phase I study of vismodegib in children with recurrent or refractory medulloblastoma: a pediatric brain tumor consortium study. Clin Cancer Res. 2013;19:6305–12.PubMed
84.
Robinson GW, Orr BA, Wu G, Gururangan S, Lin T, Qaddoumi I, et al. Vismodegib exerts targeted efficacy against recurrent Sonic Hedgehog–subgroup medulloblastoma: results from Phase II Pediatric Brain Tumor Consortium Studies PBTC-025B and PBTC-032. J Clin Oncol. 2015;33:2646–54. https://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​27682250
85.
86.
87.
Yauch RL, Dijkgraaf GJ, Alicke B, Januario T, Ahn CP, Holcomb T, et al. Smoothened mutation confers resistance to a Hedgehog pathway inhibitor in medulloblastoma. Science. 2009;326:572–4.PubMedPubMedCentral
88.
Buonamici S, Williams J, Morrissey M, Wang A, Guo R, Vattay A, et al. Interfering with resistance to smoothened antagonists by inhibition of the PI3K pathway in medulloblastoma. Sci Transl Med. 2010;2:51ra70.PubMedPubMedCentral
89.
Tang Y, Gholamin S, Schubert S, Willardson MI, Lee A, Bandopadhayay P, et al. Epigenetic targeting of Hedgehog pathway transcriptional output through BET bromodomain inhibition. Nat Med. 2014;20:732–40.PubMedPubMedCentral
90.
91.
Cimmino F, Scoppettuolo MN, Carotenuto M, De Antonellis P, Dato VD, De Vita G, et al. Norcantharidin impairs medulloblastoma growth by inhibition of Wnt/beta-catenin signaling. J Neuro-Oncol. 2012;106:59–70.
92.
Zinke J, Schneider FT, Harter PN, Thom S, Ziegler N, Toftgard R, et al. beta-Catenin-Gli1 interaction regulates proliferation and tumor growth in medulloblastoma. Mol Cancer. 2015;14:17.
93.
Northcott PA, Jones DT, Kool M, Robinson GW, Gilbertson RJ, Cho YJ, et al. Medulloblastomics: the end of the beginning. Nat Rev Cancer. 2012;12:818–34.PubMedPubMedCentral
94.
95.
Morfouace M, Shelat A, Jacus M, Freeman BB 3rd, Turner D, Robinson S, et al. Pemetrexed and gemcitabine as combination therapy for the treatment of group3 medulloblastoma. Cancer Cell. 2014;25:516–29.PubMedPubMedCentral
96.
Clifford SC, Lannering B, Schwalbe EC, Hicks D, O'Toole K, Nicholson SL, et al. Biomarker-driven stratification of disease-risk in non-metastatic medulloblastoma: results from the multi-center HIT-SIOP-PNET4 clinical trial. Oncotarget. 2015;6:38827–39.
97.
Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372:2521–32.
98.
Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016;375:1823–33.
99.
Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373:1803–13.
100.
101.
Sampson JH, Vlahovic G, Sahebjam S, Omuro AMP, Baehring JM, Hafler DA, et al. Preliminary safety and activity of nivolumab and its combination with ipilimumab in recurrent glioblastoma (GBM): CHECKMATE-143. J Clin Oncol. 2015;33:3010.
102.
Reardon DA, Nayak L, Peters KB, Clarke JL, Jordan JT, Groot JFD, et al. Phase II study of pembrolizumab or pembrolizumab plus bevacizumab for recurrent glioblastoma (rGBM) patients. J Clin Oncol. 2018;36:2006.
103.
Groot JFD, Penas-Prado M, Mandel JJ, O'Brien BJ, Weathers S-PS, Zhou S, et al. Window-of-opportunity clinical trial of a PD-1 inhibitor in patients with recurrent glioblastoma. J Clin Oncol. 2018;36:2008.
104.
Vermeulen JF, Van Hecke W, Adriaansen EJM, Jansen MK, Bouma RG, Villacorta Hidalgo J, et al. Prognostic relevance of tumor-infiltrating lymphocytes and immune checkpoints in pediatric medulloblastoma. Oncoimmunology. 2018;7:e1398877.PubMedPubMedCentral
105.
Nellan A, Rota C, Majzner R, Lester-McCully CM, Griesinger AM, Mulcahy Levy JM, et al. Durable regression of medulloblastoma after regional and intravenous delivery of anti-HER2 chimeric antigen receptor T cells. J Immunother Cancer. 2018;6:30.
106.
Nair SK, Driscoll T, Boczkowski D, Schmittling R, Reynolds R, Johnson LA, et al. Ex vivo generation of dendritic cells from cryopreserved, post-induction chemotherapy, mobilized leukapheresis from pediatric patients with medulloblastoma. J Neuro-Oncol. 2015;125:65–74.PubMedPubMedCentral
107.
Vivier E, Raulet DH, Moretta A, Caligiuri MA, Zitvogel L, Lanier LL, et al. Innate or adaptive immunity? The example of natural killer cells. Science. 2011;331:44–9.PubMedPubMedCentral
108.
Castriconi R, Dondero A, Negri F, Bellora F, Nozza P, Carnemolla B, et al. Both CD133+ and CD133- medulloblastoma cell lines express ligands for triggering NK receptors and are susceptible to NK-mediated cytotoxicity. Eur J Immunol. 2007;37:3190–6.PubMed
109.
110.
Bockmayr M, Mohme M, Klauschen F, Winkler B, Budczies J, Rutkowski S, et al. Subgroup-specific immune and stromal microenvironment in medulloblastoma. Oncoimmunology. 2018;7:e1462430.PubMedPubMedCentral
111.
Pham CD, Flores C, Yang C, Pinheiro EM, Yearley JH, Sayour EJ, et al. Differential immune microenvironments and response to immune checkpoint blockade among molecular subtypes of murine medulloblastoma. Clin Cancer Res. 2016;22:582–95.PubMedPubMedCentral
Metadaten
Titel
Updates on Management of Adult Medulloblastoma
verfasst von
Nazanin Majd, MD, PhD
Marta Penas-Prado, MD
Publikationsdatum
01.08.2019
Verlag
Springer US
Erschienen in
Current Treatment Options in Oncology / Ausgabe 8/2019
Print ISSN: 1527-2729
Elektronische ISSN: 1534-6277
DOI
https://doi.org/10.1007/s11864-019-0663-0

Weitere Artikel der Ausgabe 8/2019

Current Treatment Options in Oncology 8/2019 Zur Ausgabe

Genitourinary Cancers (S Gupta, Section Editor)

Role of Targeted Therapies in Management of Metastatic Urothelial Cancer in the Era of Immunotherapy

Head and Neck Cancer (CP Rodriguez, Section Editor)

Approach to the Patient with Recurrent/Metastatic Disease

Skin Cancer (T Ito, Section Editor)

Adjuvant Therapy for Melanoma

Cardio-oncology (MG Fradley, Section Editor)

Cardiac Tumors: Clinical Presentation, Diagnosis, and Management

Breast Cancer (EA Comen, Section Editor)

Emerging Role of Genomics and Cell-Free DNA in Breast Cancer

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

23.04.2024 Medikamente in Schwangerschaft und Stillzeit Nachrichten

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen
Bildnachweise