Risk stratification of childhood medulloblastoma in the molecular era: the current consensus
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Risk stratification of childhood medulloblastoma in the molecular era: the current consensus. / Ramaswamy, Vijay; Remke, Marc; Bouffet, Eric; Bailey, Simon; Clifford, Steven C; Doz, Francois; Kool, Marcel; Dufour, Christelle; Vassal, Gilles; Milde, Till; Witt, Olaf; von Hoff, Katja; Pietsch, Torsten; Northcott, Paul A; Gajjar, Amar; Robinson, Giles W; Padovani, Laetitia; André, Nicolas; Massimino, Maura; Pizer, Barry; Packer, Roger; Rutkowski, Stefan; Pfister, Stefan M; Taylor, Michael D; Pomeroy, Scott L.
In: ACTA NEUROPATHOL, Vol. 131, No. 6, 04.04.2016, p. 821-31.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Risk stratification of childhood medulloblastoma in the molecular era: the current consensus
AU - Ramaswamy, Vijay
AU - Remke, Marc
AU - Bouffet, Eric
AU - Bailey, Simon
AU - Clifford, Steven C
AU - Doz, Francois
AU - Kool, Marcel
AU - Dufour, Christelle
AU - Vassal, Gilles
AU - Milde, Till
AU - Witt, Olaf
AU - von Hoff, Katja
AU - Pietsch, Torsten
AU - Northcott, Paul A
AU - Gajjar, Amar
AU - Robinson, Giles W
AU - Padovani, Laetitia
AU - André, Nicolas
AU - Massimino, Maura
AU - Pizer, Barry
AU - Packer, Roger
AU - Rutkowski, Stefan
AU - Pfister, Stefan M
AU - Taylor, Michael D
AU - Pomeroy, Scott L
PY - 2016/4/4
Y1 - 2016/4/4
N2 - Historical risk stratification criteria for medulloblastoma rely primarily on clinicopathological variables pertaining to age, presence of metastases, extent of resection, histological subtypes and in some instances individual genetic aberrations such as MYC and MYCN amplification. In 2010, an international panel of experts established consensus defining four main subgroups of medulloblastoma (WNT, SHH, Group 3 and Group 4) delineated by transcriptional profiling. This has led to the current generation of biomarker-driven clinical trials assigning WNT tumors to a favorable prognosis group in addition to clinicopathological criteria including MYC and MYCN gene amplifications. However, outcome prediction of non-WNT subgroups is a challenge due to inconsistent survival reports. In 2015, a consensus conference was convened in Heidelberg with the objective to further refine the risk stratification in the context of subgroups and agree on a definition of risk groups of non-infant, childhood medulloblastoma (ages 3-17). Published and unpublished data over the past 5 years were reviewed, and a consensus was reached regarding the level of evidence for currently available biomarkers. The following risk groups were defined based on current survival rates: low risk (>90 % survival), average (standard) risk (75-90 % survival), high risk (50-75 % survival) and very high risk (<50 % survival) disease. The WNT subgroup and non-metastatic Group 4 tumors with whole chromosome 11 loss or whole chromosome 17 gain were recognized as low-risk tumors that may qualify for reduced therapy. High-risk strata were defined as patients with metastatic SHH or Group 4 tumors, or MYCN-amplified SHH medulloblastomas. Very high-risk patients are Group 3 with metastases or SHH with TP53 mutation. In addition, a number of consensus points were reached that should be standardized across future clinical trials. Although we anticipate new data will emerge from currently ongoing and recently completed clinical trials, this consensus can serve as an outline for prioritization of certain molecular subsets of tumors to define and validate risk groups as a basis for future clinical trials.
AB - Historical risk stratification criteria for medulloblastoma rely primarily on clinicopathological variables pertaining to age, presence of metastases, extent of resection, histological subtypes and in some instances individual genetic aberrations such as MYC and MYCN amplification. In 2010, an international panel of experts established consensus defining four main subgroups of medulloblastoma (WNT, SHH, Group 3 and Group 4) delineated by transcriptional profiling. This has led to the current generation of biomarker-driven clinical trials assigning WNT tumors to a favorable prognosis group in addition to clinicopathological criteria including MYC and MYCN gene amplifications. However, outcome prediction of non-WNT subgroups is a challenge due to inconsistent survival reports. In 2015, a consensus conference was convened in Heidelberg with the objective to further refine the risk stratification in the context of subgroups and agree on a definition of risk groups of non-infant, childhood medulloblastoma (ages 3-17). Published and unpublished data over the past 5 years were reviewed, and a consensus was reached regarding the level of evidence for currently available biomarkers. The following risk groups were defined based on current survival rates: low risk (>90 % survival), average (standard) risk (75-90 % survival), high risk (50-75 % survival) and very high risk (<50 % survival) disease. The WNT subgroup and non-metastatic Group 4 tumors with whole chromosome 11 loss or whole chromosome 17 gain were recognized as low-risk tumors that may qualify for reduced therapy. High-risk strata were defined as patients with metastatic SHH or Group 4 tumors, or MYCN-amplified SHH medulloblastomas. Very high-risk patients are Group 3 with metastases or SHH with TP53 mutation. In addition, a number of consensus points were reached that should be standardized across future clinical trials. Although we anticipate new data will emerge from currently ongoing and recently completed clinical trials, this consensus can serve as an outline for prioritization of certain molecular subsets of tumors to define and validate risk groups as a basis for future clinical trials.
U2 - 10.1007/s00401-016-1569-6
DO - 10.1007/s00401-016-1569-6
M3 - SCORING: Journal article
C2 - 27040285
VL - 131
SP - 821
EP - 831
JO - ACTA NEUROPATHOL
JF - ACTA NEUROPATHOL
SN - 0001-6322
IS - 6
ER -