Risk-stratification for treatment de-intensification in WNT-pathway medulloblastoma: finding the optimal balance between survival and quality of survivorship.

IF 2.9 3区 医学 Q2 ONCOLOGY Expert Review of Anticancer Therapy Pub Date : 2024-07-01 Epub Date: 2024-05-24 DOI:10.1080/14737140.2024.2357807
Tejpal Gupta, Shakthivel Mani, Abhishek Chatterjee, Archya Dasgupta, Sridhar Epari, Girish Chinnaswamy
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Abstract

Introduction: Advances in molecular biology have led to consensus classification of medulloblastoma into four broad molecular subgroups - wingless (WNT), sonic hedgehog (SHH), Group 3, and Group 4, respectively. Traditionally, children >3 years of age, with no/minimal residual tumor (<1.5 cm2) and lack of metastasis were classified as average-risk disease with >80% long-term survival. Younger age (<3 years), large residual disease (≥1.5 cm2), and leptomeningeal metastases either alone or in combination were considered high-risk features yielding much worse 5-year survival (30-60%). This clinico-radiological risk-stratification has been refined by incorporating molecular/genetic information. Contemporary multi-modality management for non-infantile medulloblastoma entails maximal safe resection followed by risk-stratified adjuvant radio(chemo)therapy. Aggressive multi-modality management achieves good survival but is associated with substantial dose-dependent treatment-related toxicity prompting conduct of subgroup-specific prospective clinical trials.

Areas covered: We conducted literature search on PubMed from 1969 till 2023 to identify putative prognostic factors and risk-stratification for medulloblastoma, including molecular subgrouping. Based on previously published data, including our own institutional experience, we discuss molecular risk-stratification focusing on WNT-pathway medulloblastoma to identify candidates suitable for treatment de-intensification to strike the optimal balance between survival and quality of survivorship.

Expert opinion: Prospective clinical trials and emerging biological information should further refine risk-stratification in WNT-pathway medulloblastoma.

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WNT通路髓母细胞瘤去强化治疗的风险分级:在生存期和生存质量之间找到最佳平衡点。
导言:分子生物学的发展已将髓母细胞瘤分为四大分子亚组--无翼(WNT)、声波刺猬(SHH)、第3组和第4组。传统上,年龄大于 3 岁、无/极少残留肿瘤(2)且无转移的儿童被归类为平均风险疾病,长期生存率大于 80%。而年龄较小(2)、单独或合并有脑脊髓转移瘤则被认为是高风险特征,5 年生存率更低(30%-60%)。这种临床放射学风险分级已通过纳入分子/遗传信息而得到完善。非隐匿性髓母细胞瘤的现代多模式治疗包括最大限度的安全切除,然后进行风险分级的放射(化疗)辅助治疗。积极的多模式治疗可获得较好的生存率,但与剂量相关的毒性较大,因此需要开展针对亚组的前瞻性临床试验:我们在PubMed上搜索了1969年至2023年的文献,以确定髓母细胞瘤的潜在预后因素和风险分级,包括分子亚组。根据以前发表的数据,包括我们自己的机构经验,我们讨论了分子风险分级,重点是WNT通路髓母细胞瘤,以确定适合减低治疗强度的候选者,从而在生存期和生存质量之间取得最佳平衡:前瞻性临床试验和新出现的生物学信息应进一步完善WNT通路髓母细胞瘤的风险分级。
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来源期刊
CiteScore
5.10
自引率
3.00%
发文量
100
审稿时长
4-8 weeks
期刊介绍: Expert Review of Anticancer Therapy (ISSN 1473-7140) provides expert appraisal and commentary on the major trends in cancer care and highlights the performance of new therapeutic and diagnostic approaches. Coverage includes tumor management, novel medicines, anticancer agents and chemotherapy, biological therapy, cancer vaccines, therapeutic indications, biomarkers and diagnostics, and treatment guidelines. All articles are subject to rigorous peer-review, and the journal makes an essential contribution to decision-making in cancer care. Comprehensive coverage in each review is complemented by the unique Expert Review format and includes the following sections: Expert Opinion - a personal view of the data presented in the article, a discussion on the developments that are likely to be important in the future, and the avenues of research likely to become exciting as further studies yield more detailed results Article Highlights – an executive summary of the author’s most critical points.
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