An international working group consensus report for the prioritization of molecular biomarkers for Ewing sarcoma.
An international working group consensus report for the prioritization of molecular biomarkers for Ewing sarcoma.
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DOI：
10.1038/s41698-022-00307-2
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发表时间：
2022-09-17
影响因子：
7.9
通讯作者：
Grohar, Patrick J.
中科院分区：
文献类型：
--
作者：
Shulman, David S.;Whittle, Sarah B.;Surdez, Didier;Bailey, Kelly M.;de Alava, Enrique;Yustein, Jason T.;Shlien, Adam;Hayashi, Masanori;Bishop, Alexander J. R.;Crompton, Brian D.;DuBois, Steven G.;Shukla, Neerav;Leavey, Patrick J.;Lessnick, Stephen L.;Kovar, Heinrich;Delattre, Olivier;Gruenewald, Thomas G. P.;Antonescu, Cristina R.;Roberts, Ryan D.;Toretsky, Jeffrey A.;Tirode, Franck;Gorlick, Richard;Janeway, Katherine A.;Reed, Damon;Lawlor, Elizabeth R.;Grohar, Patrick J.
剂量强化间隔压缩治疗的出现使局限性尤文肉瘤（EwS）患者的5年无事件生存率提高到78%。然而，近四分之一的局部肿瘤患者和60-80%的转移性肿瘤患者会复发并死于疾病。此外，那些幸存下来的人往往会留下令人衰弱的晚期效应。事实证明，除分期外的临床特征不足以对患者进行有意义的分类以进行风险分层治疗。因此，迫切需要开发基于分子特征对EwS患者进行风险分层的方法。在过去的十年中，新技术使EwS中多种分子生物标志物的研究成为可能。需要验证的初步证据支持拷贝数变化和肿瘤抑制基因的功能缺失突变作为EwS结局的生物标志物。循环肿瘤DNA的初步研究表明，诱导期间的诊断性ctDNA负荷和ctDNA清除也与结果相关。此外，融合伴侣应该是EwS临床试验入组的先决条件，融合类型和结构需要进一步研究以确定预后影响。这些新出现的生物标志物代表了我们对疾病风险理解的新视野，并将使未来的努力能够开发适应风险的治疗方法。
The advent of dose intensified interval compressed therapy has improved event-free survival for patients with localized Ewing sarcoma (EwS) to 78% at 5 years. However, nearly a quarter of patients with localized tumors and 60–80% of patients with metastatic tumors suffer relapse and die of disease. In addition, those who survive are often left with debilitating late effects. Clinical features aside from stage have proven inadequate to meaningfully classify patients for risk-stratified therapy. Therefore, there is a critical need to develop approaches to risk stratify patients with EwS based on molecular features. Over the past decade, new technology has enabled the study of multiple molecular biomarkers in EwS. Preliminary evidence requiring validation supports copy number changes, and loss of function mutations in tumor suppressor genes as biomarkers of outcome in EwS. Initial studies of circulating tumor DNA demonstrated that diagnostic ctDNA burden and ctDNA clearance during induction are also associated with outcome. In addition, fusion partner should be a pre-requisite for enrollment on EwS clinical trials, and the fusion type and structure require further study to determine prognostic impact. These emerging biomarkers represent a new horizon in our understanding of disease risk and will enable future efforts to develop risk-adapted treatment.
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DOI：
10.1097/pas.0000000000001183
发表时间：
2019-03
期刊：
The American journal of surgical pathology
影响因子：
--
作者：
Chougule A;Taylor MS;Nardi V;Chebib I;Cote GM;Choy E;Nielsen GP;Deshpande V
通讯作者：
Deshpande V
影响因子：
5.6
作者：
Choi, Eun-Young Karen;Thomas, Dafydd G.;Lucas, David R.
通讯作者：
Lucas, David R.
影响因子：
19.7
作者：
Aghighi, Maryam;Boe, Justin;Daldrup-Link, Heike E.
通讯作者：
Daldrup-Link, Heike E.
影响因子：
8.8
作者：
Brohl, Andrew S.;Patidar, Rajesh;Khan, Javed
通讯作者：
Khan, Javed
影响因子：
3.3
作者：
Cohen, Jarish N.;Sabnis, Amit J.;Davis, Jessica L.
通讯作者：
Davis, Jessica L.