The aim of the Research Topic “Navigating the Landscape of IDH-Mutant Gliomas: Advances in Diagnosis, Therapeutic Management, and Long-Term Monitoring” is to provide a comprehensive overview of the current state of IDH-mutant glioma research, spanning diagnostic challenges, emerging treatment strategies, and long-term patient care. In this editorial, we will present the report from five manuscripts included in this Research Topic (four original research articles, and one perspective).
Integrated diagnosis, incorporating both molecular markers and histology (), has reshaped the classification and prognostic stratification of lower-grade gliomas (). The 2021 WHO Classification has identified three biologically and clinically distinct entities based on the isocitrate dehydrogenase (IDH) status and the chromosome 1p/19q codeletion: IDH-mutant 1p/19q codeleted (oligodendrogliomas), IDH-mutant 1p/19q intact (astrocytomas), and IDH-wildtype gliomas (, ).
As early drivers of gliomagenesis (), IDH1/2 mutations are associated with improved survival (, ) and a better response to alkylating agents (). Therefore, their presence significantly influences patient management. The recent advent of IDH inhibitors () has further emphasized the clinical relevance of IDH1/2 mutations, and the need for non-invasive methods of assessment. Liquid biopsies of cerebrospinal fluid () or plasma (), magnetic resonance spectroscopy (, ), and radiomics () are currently under investigation as non-invasive approaches for the determination of the IDH status. However, resources, time, and expertise limit the widespread implementation of those methods into routine clinical practice. Relying on minimal human input and supervision, deep learning frameworks are emerging and accessible tools for extracting molecular information from neuroimaging. Xie et al. reported a weakly supervised deep learning method able to predict the IDH status from preoperative magnetic resonance imaging with good accuracy, reduced annotation time, and limited manual effort, thus warranting further investigation in molecularly annotated prospective cohorts.
Despite the prognostic relevance of molecular markers, their integration with historical criteria into a unified consensus remains incomplete. Developed in the early 2000s based on clinical trials started over a decade earlier, the prognostic criteria of the European Organization for Research and Treatment of Cancer (EORTC) () and the Radiation Therapy Oncology Group (RTOG) () do not include molecular markers (e.g., CDKN2A/B homozygous deletion) nor account for the recent evidence generated in the molecular era, which has attenuated or even challenged () the prognostic value of some traditional factors (Figure 1).
Figure 1
In a large study on 253 adults with lower-grade gliomas, Carstam et al. showed that histological grade (WHO grade 2 vs. 3) did not significantly impact prognosis in IDH-mutant CDKN2A/B-intact tumors, either when analyzed collectively or when astrocytomas and oligodendrogliomas were considered separately. Similarly, age did not significantly impact survival in multivariable analysis, despite the historical prognostic cut-off of 40 years in low-grade gliomas (). Conversely, residual tumor volume—particularly in astrocytomas ()—was correlated with a worse outcome, as well as the presence of CDKN2A/B homozygous deletions. Similar findings were reported by Aprile et al., who analyzed a cohort of 61 patients with IDH-mutant grade 2 gliomas who underwent active observation after surgery: residual tumor diameters and midline crossing, but not age, were predictive of a shorter progression-free survival.
These observations are consistent with other reports () underscoring the need to reassess traditional prognostic indicators that have lost robustness in the molecular era, to incorporate novel genetic markers, and to establish standardized criteria for measuring residual tumor volume, which has recently been confirmed as a key prognostic factor in IDH-mutant gliomas (). Updated and refined prognostic criteria are crucial to tailor treatment decisions, which may range from watch-and-wait or IDH inhibition in “low-risk” patients to sequential radio-chemotherapy in “high-risk” patients (–).
Given the relatively prolonged disease course of IDH-mutant gliomas, their management is highly challenging and requires to carefully balance the achievement of long-lasting tumor control and preservation of neurological function. This balance begins with surgical resection itself: achieving maximal safe resection while preserving neurological function is difficult, and knowledge of white matter connectivity is key to this goal. In a study of 51 glioma patients, Salvati et al. showed that preoperative tractography (DTI-MRI) can help identify involvement of the frontal aslant tract (FAT), reducing the risk of verbal fluency disorders from its intraoperative damage. Preserving neurological function matters beyond surgery as well: uncontrolled seizures or complex antiseizure polytherapy may negatively affect neurological function status and impair the ability to drive or maintain independence in daily life activities. Additionally, neurocognitive deficits related to radiotherapy can heavily impact work ability, family, and social life, often supporting radiation deferral. To achieve an optimal balance between tumor control and quality of life, a multidisciplinary management is generally recommended. Aucoin et al. reported a multidisciplinary care model that includes neurosurgeons, neuro-oncologists, and epileptologists, who jointly evaluate patients after a collective review of imaging and clinical data. A neuropsychologist, a social worker, and a nurse coordinator are available on demand to address relevant practical and psychological needs in selected cases. Although quantitative evidence supporting the benefits of a multidisciplinary model are still limited, patients with IDH-mutant gliomas are likely to derive benefit from this approach, given the complexity of their disease ().
In conclusion, the landscape of IDH-mutant gliomas is rapidly evolving, driven by advances in molecular biology, imaging, and therapeutic innovation. These progresses highlight critical gaps in prognostic modeling and clinical integration that require coordinated efforts. The definition of risk stratification, as well as the validation of emerging technologies, and the implementation of multidisciplinary care will be crucial to fully translate scientific advances into meaningful improvements in patient outcomes.
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AP: Writing – review & editing, Writing – original draft. GB: Writing – original draft, Writing – review & editing. FB: Writing – original draft, Supervision, Writing – review & editing.
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The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Summary
Keywords
IDH mutation, lower-grade gliomas, multidisciplinary management, noninvasive diagnosis, prognostic prediction, therapeutic targeting, treatment decisions
Citation
Pellerino A, Berzero G and Bruno F (2026) Editorial: Navigating the landscape of IDH-mutant gliomas: advances in diagnosis, therapeutic management, and long-term monitoring. Front. Oncol. 16:1926822. doi: 10.3389/fonc.2026.1926822
Received
02 July 2026
Revised
12 July 2026
Accepted
13 July 2026
Published
21 July 2026
Volume
16 - 2026
Edited and reviewed by
David D. Eisenstat, Royal Children’s Hospital, Australia
Updates
Copyright
© 2026 Pellerino, Berzero and Bruno.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Francesco Bruno, f.bruno@unito.it
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.