Department of Neurosurgery, Montpellier University Medical Center, Gui-de-Chauliac Hospital, 80, avenue Augustin-Fliche, 34295 Montpellier, France; Team "Plasticity of Central Nervous System, Stem Cells and Glial Tumors", National Institute for Health and Medical Research (Inserm), U1191 Laboratory, Institute of Functional Genomics, University of Montpellier, 34091 Montpellier, France.
Rev Neurol (Paris). 2023 Jun;179(5):437-448. doi: 10.1016/j.neurol.2023.01.724. Epub 2023 Mar 10.
For decades, diffuse glioma (DG) studies mostly focused on oncological considerations, whereas functional outcomes received less attention. Currently, because overall survival has increased in DG, especially in low-grade glioma (overall survival > 15 years), quality of life including neurocognitive and behavioral aspects should be assessed and preserved more systematically, particularly regarding surgery. Indeed, early maximal tumor removal results in greater survival in both high-grade and low-grade gliomas, leading to propose "supra-marginal" resection, with excision of the peritumoral zone in diffuse neoplasms. To minimize functional risks while maximizing the extent of resection, traditional "tumor-mass resection" is replaced by "connectome-guided resection" conducted under awake mapping, taking into account inter-individual brain anatomo-functional variability. A better understanding of the dynamic interplay between DG progression and reactional neuroplastic mechanisms is critical to adapt a personalized multistage therapeutic strategy, with integration of functional neurooncological (re)operation(s) in a multimodal management scheme including repeated medical therapies. Because the therapeutic armamentarium remains limited, the aims of this paradigmatic shift are to predict one/several step(s) ahead glioma behavior, its modifications, and compensatory neural networks reconfiguration over time in order to optimize the onco-functional benefit of each treatment - either in isolation or in combination with others - in human beings bearing a chronic tumoral disease while enjoying an active familial and socio-professional life as close as possible to their expectations. Thus, new ecological endpoints such as return to work should be incorporated into future DG trials. "Preventive neurooncology" might also be envisioned, by proposing a screening policy to discover and treat incidental glioma earlier.
几十年来,弥漫性神经胶质瘤(DG)的研究主要集中在肿瘤学方面,而功能结果则较少受到关注。目前,由于 DG 患者的总体生存率提高,尤其是低级别神经胶质瘤(总体生存率>15 年),因此应该更系统地评估和保留生活质量,包括神经认知和行为方面,尤其是在手术方面。事实上,高等级和低等级神经胶质瘤患者早期最大程度地切除肿瘤都可以显著提高生存率,从而提出“边缘上切除”的理念,即切除弥漫性肿瘤的瘤周区域。为了在最大限度地切除肿瘤的同时最大限度地降低功能风险,传统的“肿瘤切除术”已被“连接组引导切除术”取代,该手术在清醒状态下进行映射,考虑到个体间大脑解剖和功能的变异性。更好地理解 DG 进展与反应性神经可塑性机制之间的动态相互作用,对于制定个性化的多阶段治疗策略至关重要,该策略将功能神经肿瘤学(再)手术整合到多模态管理方案中,包括重复的药物治疗。由于治疗手段仍然有限,因此这种范式转变的目的是预测胶质瘤行为及其随时间的变化,并预测代偿性神经网络的重构,以便优化每种治疗方法的肿瘤-功能获益,无论是单独使用还是与其他治疗方法联合使用,在患有慢性肿瘤疾病的患者中,同时尽可能使其保持积极的家庭和社会职业生活,满足其期望。因此,未来的 DG 试验应纳入新的生态终点,例如重返工作岗位。还可以设想“预防性神经肿瘤学”,通过提出筛查政策来更早地发现和治疗偶发性胶质瘤。