Neuro-oncology practice最新文献

Recent interest has been in using mIDH inhibitors in patients with IDH-mutant gliomas. This review paper summarizes the indications, side effects, recommended dosing, and management for patients on ivosidenib and vorasidenib.

The isocitrate dehydrogenase (IDH) inhibitor, vorasidenib, may offer a promising new treatment option for patients with IDH-mutant gliomas. However, the indefinite nature of this targeted therapy raises significant financial concerns. High costs of targeted cancer therapies, often exceeding $150 000 annually, contribute to financial toxicity, characterized by medical debt, income loss, and psychological stress, and place stress on health systems. This review analyzes the drug approval and pricing mechanisms in various countries and their impact on healthcare costs and patient access, focusing specifically on the impacts in neuro-oncology. The United States employs a market-driven approach resulting in higher drug prices, while most countries, such as the United Kingdom, Germany, France, Italy, Japan, South Africa, and Brazil, use negotiated pricing and health technology assessment to manage costs. The financial burden of expensive medications affects patient adherence and quality of life, with many cancer patients facing substantial out-of-pocket expenses and potential treatment abandonment, and many more unable to access these drugs altogether. Vorasidenib's introduction, while potentially improving patient outcomes, may exacerbate financial toxicity unless mitigated by patient access programs and cost-management strategies. As neuro-oncology treatment paradigms evolve, understanding the economic implications of new therapies is essential to ensure equitable access and optimize patient care.

The clinical efficacy of isocitrate dehydrogenase (IDH) inhibitors in the treatment of patients with grade 2 IDH-mutant (mIDH) gliomas is a significant therapeutic advancement in neuro-oncology. It expands treatment options beyond traditional radiation therapy and cytotoxic chemotherapy, which may lead to significant long-term neurotoxic effects while extending patient survival. The INDIGO study demonstrated that vorasidenib, a pan-mIDH inhibitor, improved progression-free survival for patients with grade 2 mIDH gliomas following surgical resection or biopsy compared to placebo and was well tolerated. However, these encouraging results leave a wake of unanswered questions: Will higher-grade mIDH glioma patients benefit? When is the appropriate timing to start and stop treatment? Where does this new treatment option fit in with other treatment modalities? In this study, we review the limited data available to start addressing these questions, provide a framework of how to discuss these gaps with current patients, and highlight what is needed from the neuro-oncology community for more definitive answers.

According to the 2021 World Health Organization classification of CNS tumors, gliomas harboring a mutation in isocitrate dehydrogenase (mIDH) are considered a distinct disease entity, typically presenting in adult patients before the age of 50 years. Given their multiyear survival, patients with mIDH glioma are affected by tumor and treatment-related symptoms that can have a large impact on the daily life of both patients and their caregivers for an extended period of time. Selective oral inhibitors of mIDH enzymes have recently joined existing anticancer treatments, including resection, radiotherapy, and chemotherapy, as an additional targeted treatment modality. With new treatments that improve progression-free and possibly overall survival, preventing and addressing daily symptoms becomes even more clinically relevant. In this review we discuss the management of the most prevalent symptoms, including tumor-related epilepsy, cognitive dysfunction, mood disorders, and fatigue, in patients with mIDH glioma, and issues regarding patient's health-related quality of life and caregiver needs in the era of mIDH inhibitors. We provide recommendations for practicing healthcare professionals caring for patients who are eligible for treatment with mIDH inhibitors.

Background: The optimal diagnosis and management of patients with brain tumors currently uses the 2021 WHO integrated diagnosis of histomorphologic and molecular features. However, neuro-oncology practice in resource-limited settings usually relies solely on histomorphology. This study aimed to classify glioma cases diagnosed in the Department of Anatomic and Molecular Pathology, Lagos University Teaching Hospital, using the 2021 WHO CNS tumor classification.

Methods: Fifty-six brain tumors from 55 patients diagnosed with glioma between 2013 and 2021 were reevaluated for morphologic diagnosis. Molecular features were determined from formalin-fixed paraffin-embedded (FFPE) tissue using immunohistochemistry (IHC) for IDH1-R132H, ATRX, BRAF-V600E, p53, Ki67, and H3-K27M, OncoScan chromosomal microarray for copy number, targeted next generation sequencing for mutation and fusion and methylation array profiling.

Results: Of 55 central nervous system tumors, 3 were excluded from histomorphologic reevaluation for not being of glial or neuroepithelial origin. Of the remaining 52 patients, the median age was 20.5 years (range: 1 to 60 years), 38(73%) were males and 14(27%) were females. Seventy-one percent of the gliomas evaluated provided adequate DNA from archival FFPE tissue blocks. After applying the 2021 WHO diagnostic criteria the initial morphologic diagnosis changed for 35% (18/52) of cases. Diagnoses of 5 (9.6%) gliomas were upgraded, and 7 (14%) were downgraded.

Conclusions: This study shows that the incorporation of molecular testing can considerably improve brain tumor diagnoses in Nigeria. Furthermore, this study highlights the diagnostic challenges in resource-limited settings and what is at stake in the global disparities of brain tumor diagnosis.

Background: Glioblastoma and high-grade glioma (HGG) remain non-curable diseases. Symptoms and Quality-of-life (QoL) in the end-of-life (EoL) phase have not been prospectively studied with validated instruments. Therefore, we prospectively assessed symptom progression, symptom management, and hospice utilization in patients with treatment-refractory progressive HGG.

Methods: Patients failing bevacizumab and presenting with a Karnofsky performance score of ≤60, and their caregivers, were eligible. Symptoms, medication, and clinical management were tracked with serial telephone calls every 2 weeks until death utilizing clinical evaluations and the MD Anderson Symptom Inventory Brain Tumor Module (MDASI-BT). The MDASI-BT rates symptoms on a scale from 0 (no symptoms) to 10 (worst).

Results: Fifty-four patient-caregiver dyads were enrolled in the study. Amongst 50 evaluable patients, the most severe symptoms during the last 2 weeks prior to death were drowsiness (9.09 ± 1.44), difficulty with concentration (8.87 ± 2.29), fatigue (8.63 ± 2.03), difficulty speaking (8.44 ± 2.42), weakness (8.27 ± 3.44), and difficulty with understanding (7.71 ± 2.94). All symptoms, except weakness and memory impairment, which were high at baseline, showed statistically significant progression. Seizures were rare and did not progressively worsen near the end of life (1.38 ± 3.02). The decision-making composite score almost doubled during the EoL phase (8.58 ± 1.53).

Conclusions: This is the first prospective study describing symptoms and QoL issues in patients with HGG. Patients suffer from high morbidity in the EoL phase and should be offered early palliative and hospice care to assure proper symptom management and advance care planning.

Background: Spinal cord tumors (SCTs) comprise 10% of all central nervous system (CNS) tumors. Pediatric SCTs are often excluded and underrepresented in clinical trials though exclusion rates haven't been reported.

Methods: We reviewed all interventional clinical trials recruiting patients <21 years with SCTs on ClinicalTrials.gov between 1989 and 2023.

Results: Five hundred and two CNS tumor trials were identified, of which 255 included SCTs and/or spincal metastases. Among these, 96.5% were open to all CNS tumors (brain or spine); however, only 3.5% were exclusive to spine tumors. One trial was specific to pediatric spine tumors (inclusive of bone, soft tissue, and neural tumors); no trial was specific to primary pediatric SCTs. Most trials were located in North America, with multisite investigations being more common than single-institution designs. Trials frequently evaluated interventions/treatments (89%), supportive care/quality of life measures (7.1%), or diagnostic protocols (3.1%). Among included treatment paradigms, systemic therapies using cytotoxic chemotherapies, targeted therapies, and/or immunotherapies were more common among brain/spine trials, while radiotherapy, surgical adjuncts, and/or local drug delivery more frequently occurred in spinal tumor trials.

Conclusions: Though SCTs comprise 10% of pediatric CNS tumors, they remain underrepresented in clinical trials. This lack of trials specific to advancing pediatric SCTs management highlights an area of clinical and research need.