Editorial: Recent advances in diagnosis and treatment of brain tumours: From paediatrics to adults

John Bianco¹Dimitrios N. Kanakis²Archya Dasgupta³Majaz Moonis⁴Cesare Zoia^5*

• ¹Image Sciences Institute, University Medical Center Utrecht, Utrecht, Netherlands, Netherlands
• ²School of Medicine, University of Nicosia, Nicosia, Cyprus
• ³Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Mumbai, Maharashtra, India
• ⁴UMass Memorial Medical Center, Worcester, Massachusetts, United States
• ⁵UOC Neurochirurgia, Ospedale Moriggia Pelascini, Gravedona e Uniti, Italy

According to Hu and Zhang, advanced mul parametric MRI (DSC, DWI, DTI, MRS) had the poten al to noninvasively predict Ki-67 labelling index, a marker of tumour prolifera on, in a cohort of 109 glioma pa ent. Their model, combining rCBVmax, rCBFmax, rADCmin, rFAmax, and Cho/Cr ra o, achieved high accuracy (R²=0.80), correla ng with tumour grade. This approach could enhance preopera ve planning by iden fying high-prolifera on gliomas, predic ng prognosis before surgery, though valida on in larger cohorts is needed. In another study by Yang and colleagues, the cost effec ve diagnos c poten al of peripheral blood parameters, including neutrophil-lymphocyte ra o (NLR), systemic immune-inflamma on index (SII), and pan-immuneinflamma on value (PIV), where gliomas could be dis nguished from benign tumours, underscores their role in malignancy assessment. Supplemen ng these two studies, Lange and colleagues iden fied a 7-gene glutamatergic panel differen a ng glioblastomas (GBMs) from brain metastases with 88% accuracy. Although larger valida on is needed, this tool could supplement pathology in ambiguous cases, reducing reliance on invasive biopsies. Guo et al. developed a scoring system predic ng ventriculoperitoneal shunt need postpaediatric tumour resec on. They show that factors such as age (< 3 years), midline loca on, preopera ve hydrocephalus, and total resec on stra fy risk, aiding postopera ve monitoring, providing a prac cal evalua on. Scores ranging from 6 to 14 points indicate high risk, while the model also emphasises blood loss as a novel, objec ve predictor linked to inflamma on and CSF dynamics. The grim prognosis of diffuse intrinsic pon ne gliomas (DIPGs), nowadays referred to as diffuse midline gliomas (DMGs) was reinforced by Boukaka and colleagues, showing that benign brainstem tumours treated surgically display a survival rate of over 90%, compared to 3-year survival of just 2% for diffuse pon ne gliomas. While stereotac c biopsy is not part of the standard of care in DMG of the pons, the heterogeneity of this disease advocated their use in providing cri cal on molecular and gene c characteris cs that can guide treatment decisions, including entry into clinical trials. They advocate for individualised treatments based on molecular profiling to guide emerging therapies, stressing the urgency for targeted drug development, and highligh ng the balance between aggressive resec on (for benign lesions) and quality of life, and more biomolecular and gene c research for DMG. Future efforts must priori se valida ng these tools in diverse cohorts and integra ng molecular data into clinical algorithms, ensuring precision medicine becomes a tangible reality for glioma pa ents.Clinical trials assessing feasibility, efficacy and benefit of therapies in glioblastoma and craniopharyngioma Two clinical trials presented in this research topic explore adjuvant strategies in glioma treatment, addressing dura on of standard therapy and novel drug repurposing. Anvari et al. challenges the u lity of extended temozolomide dosing (12 vs. 6 cycles) in high-grade gliomas. Despite comparable survival rates, the authors demonstrate that extended therapy showed no survival benefit, as well as lower comple on rates, where toxicity, cost, and poten reduced salvage response underscore 6 cycles as standard. However, molecularly defined subgroups may warrant tailored approaches, necessita ng further study. Pace et al. inves drug repurposing, where they evaluated chlorpromazine combined with temozolomide in unmethylated MGMT GBM. In a phase II clinical trial, a median progression free survival of 8 months was achieved (vs. historical 5 months), with an overall survival of 15 months, mee ng primary endpoints. They also found that the safety profile of chlorpromazine was manageable, and its repurposing to disrupt neuron-GBM signalling and therapeu c resistance merits phase III evalua on. What these studies do is to highlight the need of op mising exis ng protocols, and the importance of exploring repurposed drugs to overcome resistance in glioma therapy. Similarly, in their brief research report, Hendrich et al. retrospec document the feasibility of intracys c treatment with peginterferon alfa-2a in five pa ents (4 pa ents <12 years, 1 adult pa ent) with cys c craniopharyngioma, observing cyst reduc on with minimal toxicity, while also reducing hospital visits. Although some challenges such as cyst leakage need to be addressed, this approach aligns with the paradigm of trea ng craniopharyngioma as a chronic condi on, priori sing quality of life over aggressive interven ons.The diagnosis and management of central nervous system tumours presents unique challenges, frequently requiring integra on of advanced molecular profiling and mul disciplinary collabora on. Recent case reports presented in this research topic highlight these complexi es, offering insights into diagnos c pi alls, molecular advancements, and therapeu c strategies. Liu and colleagues present a case of intraventricular Rosai-Dorfman disease (RDD), a rare his ocy c disorder, in a young pa ent with no recurrence at 10-year follow-up following resec on. Six similar cases in the literature were reviewed and showed that, although treatment guidelines for RDD have not been established, individualised surgical interven ons and vigilant postopera ve monitoring offer a favourable prognosis for this rare condi on. The authors highlight the importance of considering RDD, though rare, in the differen al diagnosis of intraventricular masses in paediatric pa ents. Wu et al. present a case of pleomorphic xanthoastrocytoma (PXA, WHO 2) with an NTRK fusion and a CDKN2A dele on in a 2-yearold pa ent with spontaneous intracranial haemorrhage. This case is one of few paediatric PXA reports that offers molecular profiling and illustrates the role of genomic tes ng in iden fying targetable altera ons, while underscoring haemorrhage as a rare presenta on of low-grade gliomas. A case of synchronous IDH-NOS grade II (frontal) and IDH-mutant grade IV (parietal) astrocytomas is presented by Jia, Kang & Wang, which challenges the norms of glioma progression through molecular analysis revela ons of divergent clonal origins, where an EGFR amplifica in the parietal lesion was observed. This case highlights the necessity of comprehensive molecular workup in mul focal gliomas to inform surgical and adjuvant strategies. Edelbach et al. presents a case of glioblastoma in the brainstem, the diagnosis of which relied on molecular profiling a er inconclusive biopsy. Although radiotherapy with concomitant and adjuvant temozolomide improved symptoms, this report stresses the dismal prognosis of infratentorial GBM and highlights the challenges of managing diffuse primary pon ne glioblastoma, s pula ng the need for more effec ve treatment op ons for this rare subtype of GBM. In another study, the Todai OncoPanel was used to analyse recurrent meningioma, revealing NF2 loss, CDKN2A dele on, and subclonal TRAF7 muta ons. Ohara and colleagues highlighted the limita ons of current meningioma therapies by showing that although high-risk markers were iden fied with this panel, no ac onable targets were found. This case study advocates for expanded molecular panels and trials targe ng pathways like PI3K or CDK inhibitors. A case of polymorphous low-grade neuroepithelial tumour of the young (PLNTY), harbouring a FGFR3-TACC3 fusion and a TERT promoter muta on, was presented by Golub et al. showing that this en ty mimics high-grade glioma in histological and molecular features. This case emphasizes the need for a en ve follow-up of low-grade lesions such as PLNTY and the diagnos c value of methyla on profiling to help elucidate the role and ming of adjuvant treatment. Consoli et al. presents two GBM cases which were misdiagnosed as autoimmune encephali s due to atypical MRI features and false-posi ve onconeural an bodies, but later confirmed as GBM following biopsies prompted by unresponsiveness to immunosuppression treatment. This report warns against overreliance on serological markers in atypical presenta ons and advocates early biopsy in ambiguous cases. These case studies highlight that there is a need to priori efforts in valida ng molecular biomarkers in clinical trials, to expand targeted therapies, and to refine guidelines for rare en es. As molecular diagnos cs evolve, so too must therapeu c paradigms, ensuring precision medicine transcends common tumours to address the full spectrum of CNS malignancies. For both paediatric DIPG/DMG and adult GBM, the future hinges on bridging diagnos c accuracy with innova ve treatments, ensuring aggressive interven ons are balanced against quality of life and the promise of tailored therapies.The evolving landscape of neuro-oncology demands innova ve diagnos c and therapeu c strategies, par cularly for rare or complex CNS tumours. This research topic also contains a number of reviews that shed light on cri cal advancements, highligh ng that improved outcomes can be achieved by integra ng technology, molecular insights, and pa ent-centred care. Through a bibliometric analysis of 179 studies from the Web of Science core database, Abudueryimu et al. reveal the pivotal role of MRI surgical planning and recurrence monitoring following spinal schwannoma diagnosis, while highligh ng dispari es in terms of research quality between Eastern and Western ins tu ons. They point out that while China leads in publica on volume, ins tutes in Europe and America dominate in cita on impact. To bridge quan ty and quality, future efforts must priori se standardised imaging protocols and transla onal studies to refine feature analysis, enhancement studies, and quan ta ve assessments. Progress in these domains raises the bar for diagnos c and therapeu c approaches for spinal intradural schwannomas, improving pa ent care and outcomes. Yu and colleagues performed a meta-analysis comparing [¹⁸F]FET and [¹⁸F]FDOPA PET for glioma recurrence diagnosis. They found that while both demonstrate similar specificity, [¹⁸F]FDOPA shows superior sensi vity, a ributed to its dual targe ng of dopamine pathways and amino acid metabolism, although sample sizes were limited. As limited availability and higher costs hinder widespread adop on of [¹⁸F]FDOPA, the authors advocate using hybrid approaches combining PET's molecular sensi vity with MRI's anatomical specificity. A narra ve review by Chen, Ai, and Sun explores the evolving landscape of treatment efficacy of the complex intracranial tumour adaman nomatous craniopharyngioma. The take home message of this review is that alterna ve approaches for sustained disease control, such as subtotal resec on paired with radiotherapy, which achieves comparable tumour control with fewer complica ons, could pose a paradigm shi away from radical resec on, while emerging targeted therapies and cyst-directed treatments offer promise. Namiot et al. inves gated brain tumour diagnosis by exploring the poten al of in situ hybridisa on (ISH) techniques. By cross-referencing 513 records with the OMIM database, a large number of muta ons suitable for ISH were pinpointed, such as amplifica ons in EGFR, MDM2, and MDM4, and dele ons of PTEN, CDKN2/p16, TP53, and DMBT1 that correlate with poor prognosis in glioma pa ents, as well as other chromosomal anomalies across different nonglioma brain tumours. Though highligh ng the poten al of this technique in diagnosing and prognos ca ng various brain tumours, the authors concede that while ISH enhances subclassifica on, its inability to resolve small muta ons limits standalone use, urging integra on with next-genera on sequencing for comprehensive profiling. Many therapeu cs fail in the clinic because of the blood-brain barrier (BBB) disallowing chemo-/immune-therapies to reach the target site. Recent research analysing the applica on of ultrasound for therapeu c purposes has highlighted the role of focused ultrasound (FUS) as a treatment modality for gliomas, as presented by Nwafor et al.. FUS has emerged as a dual tool for thermal abla on and blood-brain barrier disrup on (BBBD), enhancing chemotherapeu c delivery beyond the BBB. While challenges remain and further inves ga on is s ll needed, early clinical trials show promising results in enhanced drug delivery in brain tumours using this non-invasive approach. The reviews outlined above map a path forward where technology and pa ent-centricity converge, urging clinicians and researchers to embrace mul disciplinary collabora on for transforma ve progress in neuro-oncology.Liquid biopsies and ar ficial intelligence for iden fying tumour burden and monitoring progression Technological advancements that promise to refine diagnos cs, enhance treatment efficacy, and support clinical decision-making con nue to evolve, where novel strategies such as liquid biopsies and ar ficial intelligence (AI) integra on underline the field's trajectory toward precision medicine. Barber et al. inves gated techniques for enriching circula ng tumour cells (CTCs) by comparing four CTC enrichment methods to address GBM's diagnos c challenges. The authors found that the ScreenCell® system emerged as the most viable for clinical use due to its simplicity, speed, and biomarker-agnos c approach, achieving CTC isola on via size-based filtra with minimal cell loss, while having compa bility with downstream analysis. Gnanasekaran and colleagues introduce a novel imaging framework that integrates Gray-Level Co-occurrence Matrix (GLCM) and Local Binary Pa ern (LBP) features, augmented by interac on features derived from their outer product. By using this approach in classifying gliomas, meningiomas, and pituitary tumours using a linear SVM classifier, they were able to achieve an accuracy rate of 98.84%. These methods have the poten al to improve the precision of medical image processing significantly, in turn assis ng clinicians to provide more accurate diagnoses and treatments for brain tumours. Along these lines, Mut et al. explored the role of AI in GBM surgery, highligh ng its strengths in tumour segmenta on and resec on extent predic on via radiomics and connectomics. However, the authors go on to report that predic ng postopera ve outcomes was limited due to data variability and less quan fiable pa ent-related factors. As such, they advocate for standardised datasets, mul modal imaging integra on, and ethical AI frameworks, and conclude that while AI can aid in training, it cannot yet replicate the nuanced judgment of experienced neurosurgeons.This research topic combines 23 studies spanning diagnos cs, therapeu cs, and emerging technologies in neuro-oncology, emphasising the mul disciplinary advances in brain tumour diagnosis and therapy and progress towards precision medicine. Key advancements include non-invasive diagnos c tools that can predict glioma prolifera on, differen ate gliomas from benign tumours, and provide molecular profiles that further refine diagnos cs. Therapeu c innova ons also challenge conven onal protocols, ques oning the benefit on overall survival of extended treatment in pa ents with newly diagnosed GBM, advoca ng for molecularly tailored approaches. Repurposing of drugs was also shown to hold promise by demonstra ng improved progression free survival in unmethylated MGMT GBM, warran ng further phase III trials. For rare tumours, adapted treatment protocols, priori sing quality of life over aggressive surgery, has been shown to be effec ve and well tolerated. The complexity of diagnosis, where different en es can give rise to ambigui es, shows the need for advancing genomic tes ng and molecular profiling, where imaging, liquid biopsies and ar ficial intelligence have emerged as poten ally transforma ve tools for tumour classifica on and intraopera ve decision-making. Drug delivery enhancement through FUS mediated BBB-opening could increase efficacy, reduce toxicity, and improve overall quality of life. These studies collec vely promote the shi towards minimally invasive diagnos cs, targeted therapies, and data-driven tools, where molecular insights can be integrated with mul disciplinary care, balancing aggressive interven on with pa ent-centred outcomes. While challenges such as valida on requirements, lack of druggable targets for rare subtypes, as well as cost barriers and availability remain, technological breakthroughs in neuro-oncology as outlined in this research topic can bridge the gap between innova on and impac ul outcomes, delivering innova on and cu ng-edge therapies that bring the field closer to personalised medicine for both common and rare CNS malignancies.