Canadian Consensus for Treatment of BRAF V600E Mutated Pediatric and AYA Gliomas.

Background: The treatment of BRAF V600E gliomas with BRAF inhibitors (BRAFis) and MEK inhibitors (MEKis) has been increasingly integrated into clinical practice for pediatric low-grade gliomas (PLGGs) and pediatric high-grade gliomas (HGGs). However, some questions remain unanswered, such as the best time to start targeted therapy, duration of treatment, and discontinuation of therapy. Given that no clinical trial has been able to address these critical questions, we developed a Canadian Consensus statement for the treatment of BRAF V600E mutated pediatric as well as adolescent and young adult (AYA) gliomas. Methods: Canadian neuro-oncologists were invited to participate in the development of this consensus. The consensus was discussed during monthly web-based national meetings, and the algorithms were revised until a consensus was achieved. Results: A total of 26 participants were involved in the development of the algorithms. Two treatment algorithms are proposed, one for the initiation of treatment and one for the discontinuation of treatment. We suggest that most patients with BRAF V600E gliomas should be treated with BRAFis ± MEKis upfront. Discontinuation of treatment can be considered in certain circumstances, and we suggest a slow wean. Conclusions: Based on expert consensus in Canada, we developed algorithms for treatment initiation of children and AYA with BRAF V600E gliomas as well as a discontinuation algorithm.

Molecular testing for adolescent and young adult central nervous system tumors: A Canadian guideline.

The 2021 World Health Organization (WHO) classification of CNS tumors incorporates molecular signatures with histology and has highlighted differences across pediatric vs adult-type CNS tumors. However, adolescent and young adults (AYA; aged 15-39), can suffer from tumors across this spectrum and is a recognized orphan population that requires multidisciplinary, specialized care, and often through a transition phase. To advocate for a uniform testing strategy in AYAs, pediatric and adult specialists from neuro-oncology, radiation oncology, neuropathology, and neurosurgery helped develop this review and testing framework through the Canadian AYA Neuro-Oncology Consortium. We propose a comprehensive approach to molecular testing in this unique population, based on the recent tumor classification and within the clinical framework of the provincial health care systems in Canada. Contributions to the field: While there are guidelines for testing in adult and pediatric CNS tumor populations, there is no consensus testing for AYA patients whose care occur in both pediatric and adult hospitals. Our review of the literature and guideline adopts a resource-effective and clinically-oriented approach to improve diagnosis and prognostication of brain tumors in the AYA population, as part of a nation-wide initiative to improve care for AYA patients.

Outcomes of presumed malignant glioma treated without pathological confirmation: a retrospective, single-center analysis.

BACKGROUND: Tissue diagnosis is essential in the usual management of high-grade glioma. In rare circumstances, due to patient preference, performance status, comorbidities, or tumor location, biopsy is not feasible. Sometimes a biopsy is nondiagnostic. Many neuro-oncology clinics have patients like this, but these patients' outcomes and responses to treatment are not known. METHODS: We retrospectively reviewed records from adult patients diagnosed with presumed high-grade glioma of the brain without definitive pathology, diagnosed between 2004 and 2016. We recorded several clinical variables including date of first diagnostic imaging and date of death. RESULTS: We identified 61 patients and subclassified them to brainstem glioma (n = 32), supratentorial presumed glioblastoma (n = 24), presumed thalamic diffuse midline glioma (n = 2), gliomatosis cerebri (n = 2), and cerebellar glioma (n = 1). Most brainstem glioma patients had no biopsy because of tumor location. Supratentorial presumed glioblastoma patients had no biopsy predominantly because of comorbidities. Median survival, from first diagnostic imaging, was 3.2 months (95% CI: 2.9 to 6.3 months) in the supratentorial glioblastoma group and 18.5 months (95% CI: 13.0 to 44.1 months) in the brainstem group. Treatment with radiation or chemotherapy did not alter the median survival of the supratentorial glioblastoma group (hazard ratio 1.41, uncorrected P = .5). CONCLUSIONS: Patients with imaging diagnoses of high-grade glioma have similar, if not worse, survival than those with pathological confirmation. Based on these uncontrolled data, it is unclear how effective radiation or chemotherapy is in this population.

Generalized epilepsy in Baraitser-Winter cerebrofrontofacial syndrome.

•Baraitser-Winter cerebrofrontofacial syndrome (BWMS) is caused by actin gene mutations.•Key features of BWMS are ptosis, hypertelorism, iris colobomata, and mental retardation.•Generalized epilepsy is seen in half of those with BWMS.•Seizures in BWMS can be absence, myoclonic, tonic, or tonic-clonic.