Medulloblastoma Down Under 2013: a report from the third annual meeting of the International Medulloblastoma Working Group

Abstract

Medulloblastoma is curable in approximately 70 % of patients. Over the past decade, progress in improving survival using conventional therapies has stalled, resulting in reduced quality of life due to treatment-related side effects, which are a major concern in survivors. The vast amount of genomic and molecular data generated over the last 5–10 years encourages optimism that improved risk stratification and new molecular targets will improve outcomes. It is now clear that medulloblastoma is not a single-disease entity, but instead consists of at least four distinct molecular subgroups: WNT/Wingless, Sonic Hedgehog, Group 3, and Group 4. The Medulloblastoma Down Under 2013 meeting, which convened at Bunker Bay, Australia, brought together 50 leading clinicians and scientists. The 2-day agenda included focused sessions on pathology and molecular stratification, genomics and mouse models, high-throughput drug screening, and clinical trial design. The meeting established a global action plan to translate novel biologic insights and drug targeting into treatment regimens to improve outcomes. A consensus was reached in several key areas, with the most important being that a novel classification scheme for medulloblastoma based on the four molecular subgroups, as well as histopathologic features, should be presented for consideration in the upcoming fifth edition of the World Health Organization’s classification of tumours of the central nervous system. Three other notable areas of agreement were as follows: (1) to establish a central repository of annotated mouse models that are readily accessible and freely available to the international research community; (2) to institute common eligibility criteria between the Children’s Oncology Group and the International Society of Paediatric Oncology Europe and initiate joint or parallel clinical trials; (3) to share preliminary high-throughput screening data across discovery labs to hasten the development of novel therapeutics. Medulloblastoma Down Under 2013 was an effective forum for meaningful discussion, which resulted in enhancing international collaborative clinical and translational research of this rare disease. This template could be applied to other fields to devise global action plans addressing all aspects of a disease, from improved disease classification, treatment stratification, and drug targeting to superior treatment regimens to be assessed in cooperative international clinical trials.

Identification of a novel inherited ALK variant M1199L in the WNT type of medulloblastoma

“…WNT tumours by presence of at least two features as recommended by the International Medulloblastoma Working Group [12]: CTNNB1 mutation, immunohistochemical positive nuclear reaction against β-catenin (BD #610154, San Jose, USA, dilution 1 : 800) and presence of chromosome 6 monosomy detected either by interface fluorescence in situ hybridisation (FISH) or by multiplex ligation-dependent probe amplification (MLPA). 2.…”

Évolution de la prise en charge des médulloblastomes de l’enfant et de l’adulte

“…Il comportera une chimiothérapie systémique avec ou sans du méthotrexate intraventriculaire. Pour les médul-loblastomes non desmoplasiques, une étude pilote franç aise est en développement, comportant une chimiothérapie d'induction, une chimiothérapie de haute dose et une radiothérapie adaptée au risque [62].…”

“…Le prochain protocole PNET 5-MB intégrera une stratification selon la présence ou non de caractéristiques de la voie Wnt (définies par la positivité nucléaire de la ß-caténine en immuno-histochimie et/ou la mutation de la ß-caténine) [62]. Les médulloblastomes de bas risque (ceux présentant des caractéristiques de la voie Wnt) seront traités après la chirurgie une irradiation craniospinale de 23,4 Gy, avec un complément jusqu'à 55,4 Gy dans le lit tumoral, suivie d'une chimiothérapie de maintenance réduite.…”

“…Pour les 620 patients consécutifs traités par les protocoles du COG depuis 1989, 19 % de rechutes ont été observés dans le groupe des médulloblastomes de risque standard et 45 % dans le groupe des patients atteints d'un médulloblastome de haut risque. Seuls 7,2 % des patients étaient en vie à 5 ans après une récidive [62].…”

Differences in the prognostic value of tumor extent of resection among the molecular subgroups of medulloblastoma:A single centre study of 113 cases

“…Medulloblastoma is a kind of malignant brain tumor with poor prognosis [1][2][3][4][5] . Recent progress in the genomic characterization of medulloblastoma has shown that medulloblastoma is a heterogeneous disease comprised of 4 molecular subgroups: sonic hedgehog (SHH), wingless (WNT), Group 3, and Group 4 [4][5][6][7][8][9] .…”