Risk stratification of childhood medulloblastoma in the molecular era: the current consensus.
Risk stratification of childhood medulloblastoma in the molecular era: the current consensus.
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DOI：
10.1007/s00401-016-1569-6
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发表时间：
2016-06
影响因子：
12.7
通讯作者：
Pomeroy SL
中科院分区：
文献类型：
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作者：
Ramaswamy V;Remke M;Bouffet E;Bailey S;Clifford SC;Doz F;Kool M;Dufour C;Vassal G;Milde T;Witt O;von Hoff K;Pietsch T;Northcott PA;Gajjar A;Robinson GW;Padovani L;André N;Massimino M;Pizer B;Packer R;Rutkowski S;Pfister SM;Taylor MD;Pomeroy SL
髓母细胞瘤的历史风险分层标准主要依赖于与年龄、转移的存在、切除程度、组织学亚型以及在某些情况下个体遗传畸变如MYC和MYCN扩增有关的临床病理学变量。2010年，一个国际专家小组达成共识，通过转录谱确定了髓母细胞瘤的四个主要亚组（WNT，SHH，第3组和第4组）。这导致了当前一代生物标志物驱动的临床试验，除了包括MYC和MYCN基因扩增的临床病理学标准外，还将WNT肿瘤分配到有利的预后组。然而，非WNT亚组的预后预测是一个挑战，由于不一致的生存报告。2015年，在海德堡召开了一次共识会议，目的是进一步完善亚组背景下的风险分层，并就非婴儿儿童髓母细胞瘤（3-17岁）风险组的定义达成一致。回顾了过去五年中发表和未发表的数据，并就目前可用的生物标志物的证据水平达成了共识。根据目前的生存率定义了以下风险组：低风险（>90%生存率），平均（标准）风险（75-90%生存率），高风险（50-75%生存率）和非常高风险（<50%生存率）疾病。WNT亚组和非转移性第4组肿瘤伴完整11号染色体缺失或完整17号染色体获得被认为是低风险肿瘤，可能有资格减少治疗。高风险分层定义为转移性SHH或第4组肿瘤或MYCN扩增的SHH髓母细胞瘤患者。极高风险患者是具有转移的第3组或具有TP 53突变的SHH。此外，还达成了一些共识，这些共识应该在未来的临床试验中标准化。虽然我们预计新的数据将出现在目前正在进行的和最近完成的临床试验中，但这一共识可以作为优先考虑某些肿瘤分子子集的大纲，以定义和验证风险组作为未来临床试验的基础。
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 Published and unpublished data over the past five years were reviewed, and a consensus was reached regarding the level of evidence for currently available biomarkers.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.