Sheikh Shehryar R, Recinos Violette M R, Thompson Eric M, Mangum Ross, Wright-Nadkarni Mariah, Gampel Bradley, Patel Neha J
Department of Neurosurgery, Cleveland Clinic, Cleveland, OH, United States.
Department of Molecular Medicine, Case Western Reserve University, Cleveland, OH, United States.
Front Oncol. 2024 Dec 23;14:1504440. doi: 10.3389/fonc.2024.1504440. eCollection 2024.
Pediatric diffuse midline glioma (DMG), including diffuse intrinsic pontine glioma (DIPG), are aggressive brainstem tumors with a dire prognosis, traditionally diagnosed based on MRI characteristics. The recognition that molecular characteristics may determine prognosis and response to therapy has led to a reevaluation of biopsy necessity. This comprehensive review addresses the evolving role of brainstem biopsies in diagnosing and managing these tumors - both within the context of a clinical trial and in routine clinical care. We examine practice variability around brainstem biopsies for DMG/DIPG, revealing a global inconsistency in biopsy application and perceptions amongst providers. We show that safety profiles from contemporary studies demonstrate a high diagnostic success rate with minimal permanent morbidity, supporting the feasibility of biopsies in expert centers. Beyond the safety angle, we discuss the utility of biopsies in enabling personalized medicine, highlighting how molecular profiling has been used in multiple centers to guide targeted therapies. We present initial evidence from case studies and registry reports to address whether these molecularly targeted approaches are 1) clinically feasible, and 2) likely to extend survival. Furthermore, we present evidence to support the notion that biopsies facilitate the design of more refined clinical trials, shifting from a one-size-fits-all model to molecularly stratified studies. We discuss how this new paradigm for trial design is likely necessary in the context of DMG/DIPG given the lack of progress in this disease for the last several decades. Future directions discussed in the review include liquid biopsy techniques to complement or replace tissue sampling, aiming to enhance diagnostic precision and treatment monitoring.
小儿弥漫性中线胶质瘤（DMG），包括弥漫性脑桥内生胶质瘤（DIPG），是具有预后不良的侵袭性脑干肿瘤，传统上基于磁共振成像（MRI）特征进行诊断。分子特征可能决定预后和对治疗的反应这一认识，引发了对活检必要性的重新评估。这篇综述探讨了脑干活检在诊断和管理这些肿瘤中不断演变的作用——包括在临床试验背景下以及常规临床护理中。我们研究了DMG/DIPG脑干活检的实践差异，发现不同医疗人员在活检应用和认知方面存在全球范围内的不一致。我们表明，当代研究的安全性数据显示，诊断成功率高，永久性并发症最少，这支持了在专家中心进行活检的可行性。除了安全性方面，我们还讨论了活检在实现个性化医疗中的作用，强调了分子谱分析如何在多个中心用于指导靶向治疗。我们展示了来自病例研究和登记报告的初步证据，以探讨这些分子靶向方法是否1）在临床上可行，以及2）可能延长生存期。此外，我们提供证据支持活检有助于设计更精细的临床试验这一观点，即从一刀切模式转向分子分层研究。鉴于过去几十年这种疾病缺乏进展，我们讨论了在DMG/DIPG背景下这种新的试验设计范式可能是必要的。综述中讨论的未来方向包括液体活检技术，以补充或取代组织采样，旨在提高诊断精度和治疗监测。
