Pizer Barry L, Clifford Steven C
Department of Paediatric Oncology, Alder Hey Children's Hospital, Liverpool, UK.
Br J Neurosurg. 2009 Aug;23(4):364-75. doi: 10.1080/02688690903121807.
Medulloblastoma is the most common malignant brain tumour of childhood and accounts for around 10% of all childhood cancer deaths. Despite recent improvements in survival rates, the delivery of individualised therapies based on disease-risk remains a major goal; intensified treatment for poor-risk disease, whilst reducing therapy for favourable-risk cases, with the overall aim of maximising survival whilst minimising late effects. Current clinical indices for the prediction of disease course are imprecise, however a series of molecular and histopathological biomarkers have been identified recently, which may allow a more accurate prediction of disease outcome (e.g., beta-catenin status as a favourable-risk marker, MYC gene amplification and large-cell histology as high-risk markers). Pan-European clinical trials being planned for medulloblastoma by the SIOP Brain tumour group will assess the stratification of patients using molecular and histological biomarkers, alongside clinical indices, to select favourable, standard and high-risk treatment groups. This selection will underpin two concurrent trials; PNET 5, which will test whether treatment can be reduced for a favourable-risk disease sub-group, with the aim of maintaining survival rates while reducing late-effects, and PNET 6, which will aim to improve survival rates in the standard-risk group. The implementation of these trials presents important new logistical challenges within routine practice, involving (i) the development of quality-controlled sample collection and handling systems across multiple treatment centres, including the mandatory ascertainment of fresh-frozen tumour material, and (ii) the delivery of standardised central biomarker analysis and histopathological review, within the approximately 30-day post-surgical window, prior to the selection and commencement of adjuvant therapy. Feasibility studies to establish these systems are underway across SIOP Europe national groups. Their success will require a coordinated approach by the entire multidisciplinary team, including neurosurgeons, oncologists and neuropathologists, with the common aim of facilitating targeted delivery of individualised risk-adapted therapies for children with medulloblastoma.
髓母细胞瘤是儿童期最常见的恶性脑肿瘤，约占儿童癌症死亡总数的10%。尽管近期生存率有所提高，但基于疾病风险提供个体化治疗仍是一个主要目标；对高危疾病加强治疗，同时减少对低危病例的治疗，总体目标是在将晚期效应降至最低的同时使生存率最大化。然而，目前用于预测疾病进程的临床指标并不精确，不过最近已鉴定出一系列分子和组织病理学生物标志物，这可能使疾病预后的预测更加准确（例如，β-连环蛋白状态作为低危标志物，MYC基因扩增和大细胞组织学作为高危标志物）。由国际小儿肿瘤学会（SIOP）脑肿瘤组计划开展的针对髓母细胞瘤的泛欧洲临床试验，将评估使用分子和组织学生物标志物以及临床指标对患者进行分层，以选择低危、标准和高危治疗组。这种选择将为两项并行试验提供依据；PNET 5试验将测试是否可以减少对低危疾病亚组的治疗，目的是在降低晚期效应的同时维持生存率，而PNET 6试验旨在提高标准风险组的生存率。这些试验的实施在常规实践中带来了重要的新后勤挑战，包括（i）在多个治疗中心开发质量控制的样本采集和处理系统，包括强制获取新鲜冷冻的肿瘤材料，以及（ii）在辅助治疗选择和开始前，在术后约30天的窗口期内提供标准化的中央生物标志物分析和组织病理学审查。欧洲SIOP各国家小组正在开展建立这些系统的可行性研究。其成功将需要整个多学科团队采取协调一致的方法，包括神经外科医生、肿瘤学家和神经病理学家，共同目标是为髓母细胞瘤患儿促进个体化风险适应性治疗的靶向实施。
