Adult Gliomas: From Molecular Insight to Clinical Horizons.

Gliomas are a heterogeneous group that account for ∼86% of primary brain neoplasms, and include astrocytic and oligodendroglial tumours, as well as a variety of less common histopathological subtypes. Magnetic resonance imaging has become the accepted mode of imaging for the clinical management of these tumours. MRI features bear close resemblance to the histopathology grading and prognosis of these tumours. Currently, conventional MRI is used to aid diagnosis, plan neurosurgical approaches, and monitor response to therapy and disease progression. More recent developments in the field of MRI include MR spectroscopy, perfusion MRI, diffusion-weighted imaging, intraoperative MRI and functional MRI. These newer techniques have been adopted with varying success in the management of adult gliomas. This review focuses on the application of advanced MR imaging in the clinical management of adult gliomas.

This article highlights important aspects of the evaluation, diagnosis, and treatment of adult gliomas, including lower-grade astrocytomas and oligodendrogliomas, glioblastomas, and ependymomas. The appropriate initial evaluation and accurate diagnosis of gliomas require an understanding of the spectrum of clinical and radiographic presentations. Recent advances in the understanding of distinct molecular prognostic subtypes have led to major revisions in the diagnostic classification of gliomas. Integration of these new diagnostic and molecular classifications is an important part of the modern management of gliomas and facilitates better understanding and interpretation of the efficacy of different therapies in specific glioma subtypes. The management of adult gliomas is a multidisciplinary endeavor. However, despite recent molecular and treatment advances, the majority of diffuse gliomas remain incurable, and efforts aimed at the development and testing of new therapies in clinical trials are ongoing.

(1) What is the optimal role of external beam radiotherapy in the management of adult patients with newly diagnosed low-grade glioma (LGG) in terms of improving outcome (i.e., survival, complications, seizure control or other reported outcomes of interest)? (2) Which radiation strategies (dose, timing, fractionation, stereotactic radiation, brachytherapy, chemotherapy) improve outcomes compared to standard external beam radiation therapy in the initial management of low grade gliomas in adults? (3) Do specific factors (e.g., age, volume, extent of resection, genetic subtype) identify subgroups with better outcomes following radiation therapy than the general population of adults with newly diagnosed low-grade gliomas? These recommendations apply to adults with newly diagnosed diffuse LGG. OUTCOMES IN ADULT PATIENTS WITH NEWLY DIAGNOSED LOW GRADE GLIOMA TREATED WITH RADIOTHERAPY: Level I Radiotherapy is recommended in the management of newly diagnosed low-grade glioma in adults to prolong progression free survival, irrespective of extent of resection. Level II Radiotherapy is recommended in the management of newly diagnosed low grade glioma in adults as an equivalent alternative to observation in preserving cognitive function, irrespective of extent of resection. Level III Radiotherapy is recommended in the management of newly diagnosed low grade glioma in adults to improve seizure control in patients with epilepsy and subtotal resection. Level III Radiotherapy is recommended in the management of newly diagnosed low-grade glioma in adults to prolong overall survival in patients with subtotal resection. Level III Consideration of the risk of radiation induced morbidity, including cognitive decline, imaging abnormalities, metabolic dysfunction and malignant transformation, is recommended when the delivery of radiotherapy is selected in the management of newly diagnosed low-grade glioma in adults. STRATEGIES OF RADIOTHERAPY IN ADULT PATIENTS WITH NEWLY DIAGNOSED LOW GRADE GLIOMA: Level I Lower dose radiotherapy is recommended as an equivalent alternative to higher dose immediate postoperative radiotherapy (45-50.4 vs. 59.4-64.8 Gy) in the management of newly diagnosed low-grade glioma in adults with reduced toxicity. Level III Delaying radiotherapy until recurrence or progression is recommended as an equivalent alternative to immediate postoperative radiotherapy in the management of newly diagnosed low-grade glioma in adults but may result in shorter time to progression. Level III The addition of chemotherapy to radiotherapy is not recommended over whole brain radiotherapy alone in the management of low-grade glioma, as it provides no additional survival benefit. Level III Limited-field radiotherapy is recommended over whole brain radiotherapy in the management of low-grade glioma. Level III Either stereotactic radiosurgery or brachytherapy are recommended as acceptable alternatives to external radiotherapy in selected patients. PROGNOSTIC FACTORS IN ADULT PATIENTS WITH NEWLY DIAGNOSED LOW GRADE GLIOMA TREATED WITH RADIOTHERAPY: Level II It is recommended that age greater than 40 years, astrocytic pathology, diameter greater than 6 cm, tumor crossing the midline and preoperative neurological deficit be considered as negative prognostic indicators when predicting overall survival in adult low grade glioma patients treated with radiotherapy. Level II It is recommended that smaller tumor size, extent of surgical resection and higher mini-mental status exam be considered as positive prognostic indicators when predicting overall survival and progression free survival in patients in adult low grade glioma patients treated with radiotherapy. Level III It is recommended that seizures at presentation, presence of oligodendroglial histological component and 1p19q deletion (along with additional relevant factors-see Table 1) be considered as positive prognostic indicators when predicting response to radiotherapy in adults with low grade gliomas. Level III It is recommended that increasing age, decreasing performance status, decreasing cognition, presence of astrocytic histological component (along with additional relevant factors (see Tables 1, 2) be considered as negative prognostic indicators when predicting response to radiotherapy.

e14011 Background: It is known that gliomas represent a wide variety of entities with varying biological features and clinical outcomes (Neuropathol Exp Neurol 2019, 78). Hence, optimal tumor classification that aids in the diagnosis and management of patients and which supports the use of specific treatment modalities is of critical importance in neuro-oncology. Targeted next-generation sequencing (NGS) has proven to be an efficient and reliable tool for identifying prognostic biomarkers for the diagnosis of CNS tumors (Neurooncol Adv 2020, 2). Here, an analysis of the impact of using NGS in addition to traditional molecular tools on tumor classification and therapy selection was analyzed; and the overall concordance was evaluated. Methods: Patients with glial tumors who were seen at our clinic between 2019-2020 and had an NGS analysis in addition to traditional molecular studies were included. All clinical data, histopathological findings and genetic reports were retrieved from the electronic medical record. We retrospectively studied each of the patients’ findings with regards to their clinical diagnosis, grade, anatomic localization; ki67 (%); TP53, IDH and ATRX mutations; as well as microsatellite instability (MSI) and additional mutational studies such as HER2 and BRAF for some patients. The concordance between the genetic and molecular data regarding TP53 and IDH mutations was also analyzed. Results: 9 patients (66.7% male) with grade 3-4 gliomas were identified at our single-center oncology institution. Most patients had a diagnosis of glioblastoma (55.6%), with a median age of 43 years at the time of diagnosis. 22.2% (2/9) had a genetic analysis through FoundationOneCDx. The concordance of the identification of mutations by NGS and immunohistochemistry (IHC) was 77.8% (7/9) for IDH mutations, and 55.6% (5/9) for TP53 mutations. NGS led to the identification of TP53 mutation in 1 patient (11%) which IHC failed to show. NGS also supported the use of targeted therapy [dabrafenib] in 1 patient (11.1%) with BRAF positivity. Conclusions: Traditional molecular diagnostic tools and targeted NGS are not perfectly concordant, but when integrated together can lead to a more comprehensive identification of genetic mutations and potential biomarkers. This can have significant implications on the precise diagnosis and potential use of targeted therapies of adult gliomas in the future.

Management of Adult Glioma in Nursing Practice

Primary brain tumours in adults

The tumor microenvironment (TME) is a critical determinant of tumor progression and therapeutic response in gliomas. While pediatric gliomas have historically been treated using strategies derived from the management of adult gliomas, emerging evidence reveals that pediatric gliomas possess a unique TME. The pediatric TME is distinct, characterized not only by differences in cellular composition but a lower mutational burden, diminished neoantigen presentation, and heightened immunosuppressive activity. The unique immune landscape, developmental trajectories, and immune escape mechanisms in the pediatric TME create barriers to effective therapy. Recent studies show promising results in novel and advanced therapeutic strategies, highlighting the potential for innovative immunotherapeutic approaches. Advances in methodologies for modeling the TME, including computational approaches and animal-based models, provide new insights into pediatric glioma biology. Utilization of computational models may provide opportunities to predict tumor response to specific therapies and tailor immunotherapy regimes to individuals, allowing for personalized care. Leveraging the unique features of the pediatric TME offers an opportunity to overcome current barriers to immunotherapy and develop more effective, age- and tumor-specific treatment strategies.

Référentiel gliomes diffus de l’adulte de grade OMS II, III et IV : anatomie pathologique et biologie

Histone mutant gliomas (HMG) with histone H3 K27 and G34 mutations are recognized as biologically discrete entities with distinct anatomical locations, younger age at presentation (in comparison to the most common high-grade gliomas, IDH wildtype glioblastoma), and poor prognosis. There is a paucity of data regarding the management of adult HMG patients and no consensus on management. This study aims to identify current patterns of Australian and US neuro-oncology clinical practice for this entity. Following institutional approvals, patterns of care questionnaire designed to capture relevant clinical variables was circulated through the Cooperative Trials Group for Neuro-Oncology (COGNO) in Australia and the Caris Precision Oncology Alliance in the United States (US). Between 4/2021 and 10/2021, 43 responses were collected. 33% (n = 14) of responders tested all patients for HMGs routinely; 40.92% (n = 18) tested in select patients 26% (n = 11) did not test for HMGs. The common indications for testing selected patients were midline anatomic location (n = 18) and age (n = 11) (<50 years). 23 used molecular sequencing, 22 used IHC at their centers. Nine participants stated knowledge of histone H3 mutations did not affect their management of these gliomas, 11 said it affected their management at the time of recurrence, 23 stated it affected the management of midline K27M patients, 11 participants stated it affected the management of K27M mutant gliomas in other locations, and 3 felt it affected the management of G34R/V mutant gliomas. Here we present a description of how the discovery of a new molecular subtype of primary glial tumors, histone mutated gliomas in adults, is being introduced into clinical practice.

Objective: To evaluate the effect of stereotactic iodine-125 brachytherapy in the management of adult thalamic high grade gliomas. Methods: Five cases of adult thalamic high grade gliomas (WHO Ⅲ-Ⅳ) were treated with stereotactic iodine-125 brachytherapy and temozolomide chemotherapy at the Second Affiliated Hospital of Zhejiang University School of Medicine between December 2016 and February 2018, assisted with stereotactic plan and radiation therapy planning system. Results: Pathology revealed anaplastic astrocytoma (WHO Ⅲ, 2 cases) and glioblastoma (WHO Ⅳ, 3 cases). The average amount of iodine-125 implanted was 10.6 seeds. After surgery, the Karnofsky Performance Scale (KPS) was the same as preoperative KPS, and there was no severe surgery related neurological deficits. The follow-up time was from 2 months to 16 months, with an average of 7.8 months. One patient (WHO Ⅲ) without chemotherapy presented with tumor progression 6.5 months later. The other four cases showed tumor stable on MRI. Conclusions: Stereotactic iodine-125 brachytherapy in the management of adult thalamic high grade gliomas showed satisfactory recent curative effect. Large case studies and long follow-up are needed for further evaluation.

Updated Management of Colorectal Cancer Liver Metastases: Scientific Advances Driving Modern Therapeutic Innovations

Radiotherapeutic approaches in the treatment of adult gliomas.

Molecular pathology in adult gliomas: diagnostic, prognostic, and predictive markers

Aim:We performed a systematic review of the evidence for effectiveness and acceptability of different ketogenic diets (KDs) in the therapeutic management of gliomas.Methods:The search strategy included searches of seven electronic databases. Data extraction and quality assessment were undertaken independently by two authors.Results:No randomized clinical trials were identified. Six studies (n = 39) met the eligibility criteria for this review – all were case series or reports and therefore at high risk of bias. All studies reported overall or progression-free survival; however the effectiveness of KD interventions could not be established. Dietary acceptability was not reported.Conclusion:The effectiveness and acceptability of KDs in the management of gliomas is unknown and high quality randomized controlled trials are needed.

European Cancer Organisation Essential Requirements for Quality Cancer Care: Adult glioma