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.

Background: Preventing Type I leptomeningeal metastasis (LM) is critical when treating brain metastases (BMs). The aim of this study was to extract risk factors for Type I LM and to clarify the optimal treatment for BMs from the perspective of Type I LM prevention.

Methods: The clinical course of consecutive cases of BMs derived from non-small cell lung cancer (NSCLC) treated at our hospital was retrospectively evaluated. The relationship between clinicopathological factors, including molecular background, and Type I LM development was verified. In addition, the difference in the time to Type I LM because of treatment for BMs was evaluated to clarify the effectiveness of each treatment in preventing Type I LM.

Results: Of 784 patients with BMs, 44 exhibited Type I LM at the onset of BMs. Poor performance status (P < .0001) and mutated epidermal growth factor receptor (EGFR) gene (P = .004) were significant risk factors for Type I LM. Among the 740 patients without LMC at diagnosis, 85 developed Type I LM. Younger age (P = .011) and mutated EGFR (P < .0001) were risk factors for developing LMC after BMs. Osimertinib reduced the incidence of Type I LM (hazard ratio [HR]: 0.48; 95% confidence interval [CI]: 0.24-0.97) in EGFR-mutated cases. Immune checkpoint inhibitors (ICIs) showed a tendency to prolong the time to Type I LM (HR: 0.15; 95% CI: 0.02-1.11) in EGFR-wild-type cases.

Conclusions: Patients with EGFR-mutated NSCLC are prone to developing Type I LM. Osimertinib for EGFR-mutated cases and ICIs are expected to prevent Type I LM after the diagnosis of BMs.

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.

Background: Meningiomas frequently recur after surgery. Existing guidelines for postoperative surveillance are based on customary practices or limited data. This may result in excessive or inadequate surveillance.

Methods: We compared 8 studies involving 1519 resected meningiomas with postoperative follow-up ranging from 7 to 23 years. Meningiomas were stratified using the World Health Organization and Simpson grading systems, and progression-free survival data were compared. Recurrence patterns were validated using 2 additional studies involving 2463 meningiomas.

Results: Incompletely resected meningiomas of all grades displayed recurrences throughout the observation period. The 5-year and 10-year cumulative incidence of recurrence for completely resected Grade 1 meningiomas was 10% and 20%, with no recurrences beyond 11 years. For completely resected Grade 2 meningiomas, the 5-year and 10-year cumulative incidence of recurrence was 24% and 50%, with ongoing recurrences throughout the observation period. Elevated recurrence rates for Grade 1/2 meningiomas persisted beyond 5 years. For completely resected Grade 3 meningiomas, the 5-year cumulative incidence of recurrence was 63%, and all recurred before 10 years.

Conclusions: Postoperative magnetic resonance imaging (MRI) at 48 h to determine the extent of resection and at 4 months to detect rapid regrowth is recommended. For completely resected Grade 1 meningiomas, annual MRI followed by discontinuation of surveillance if there is no recurrence after 11 years is reasonable. For completely resected Grade 2 meningiomas, annual MRI indefinitely is recommended. For Grade 3 meningiomas, MRI every 3-4 months for 2 years, followed by every 6 months indefinitely, is recommended. Incompletely resected meningiomas should be followed indefinitely.

Background: Embryonal tumor with multilayered rosettes (ETMR) is a rare and deadly pediatric central nervous system tumor often seen before the age of 3. ETMR consists of embryonal tumors with abundant neuropil and true rosettes, ependymoblastoma, and medulloepithelioma. The 5-year survival rate has been reported to be between 0% and 30%. Treatment of ETMR is very unstandardized and typically consists of surgical resection, chemotherapy, and radiotherapy. A systematic review was performed to better understand treatment-related outcome trends.

Methods: The authors performed a PRISMA guidelines-based systematic review of the literature. Survival curve analysis using Kaplan-Meier curves and Cox proportional hazards models were used to estimate survival rates between 2 groups and multiple risk factors, respectively.

Results: The average survival time was 31.1 months in patients treated with radiotherapy compared to 11.2 months in patients who did not. Radiotherapy was a significant covariate on overall survival (P < .001) with an 82% lower risk of death compared to patients who did not receive radiotherapy. The average survival time for patients with focal radiotherapy was 35.8 months compared to 29.8 months in patients with CSI radiotherapy, but there was a great number of patients with pretreatment metastasis in the CSI group. In patients without pretreatment metastasis, focal radiotherapy had non-inferior outcomes for survival rates and times.

Conclusions: Patients treated with radiotherapy in addition to chemotherapy demonstrated a significantly higher survival time. For patients with no metastasis prior to treatment, focal radiotherapy should be strongly considered.

Background: This analysis aims to provide insight into differences in symptom burden and general health status between young adults (YA; 18-39 years old) and older adults (OA; ≥40 years old) with primary central nervous system tumors.

Methods: Data were retrospectively analyzed from the National Cancer Institute Neuro-Oncology Branch's Natural History Study (NCT02851706 PI: T.S. Armstrong) to determine differences in patient-reported outcomes (general health status [EQ-5D-3L], symptom burden [MDASI-BT and MDASI-SP], anxiety/depression [Patient-Reported Outcomes Measurement Information System], and perceived cognition [Neuro-QOL]) and demographic and clinical data using chi-square, one-way ANOVA, and Student's t-tests. Linear regression with backward elimination determined which characteristics impacted perceived symptom burden and general health status.

Results: The sample included 271 YA (82% with a primary brain tumor (PBT); median age 31 [range, 18-39]) and 516 OA (88% with a PBT; median age 54 [range, 40-85]). YA were more likely to be single (P < .001), employed (P < .001), and make < $50 000 per year (P = .014). More YA reported pain (P = .008), nausea (P < .001), drowsiness (P = .043), and vomiting (P = .001) than OA. Among demographic and clinical characteristics, when controlling for age, Karnofsky Performance Scale score (P < .001) and employment status (P < .001) were predictors of symptom interference, activity- and mood-related interference in patients with PBTs. Compared to OA with spinal tumors, YA reported more moderate-severe anxiety (P = .050) and moderate-severe perceived cognitive deficits (P = .023).

Conclusions: Significant differences in characteristics and symptom burden exist between YA and OA. Developmentally tailored survivorship programs providing additional psychosocial support and resources to address symptom presentation in YA are needed.

Background: Effective therapy for medulloblastoma at the time of relapse is limited. The objective of this study is to review outcomes from the Seattle Children's Hospital (SCH) institutional standard therapy for relapsed medulloblastoma, modified from the published ACNS0821 regimen.

Methods: Retrospective review of patients treated for relapsed medulloblastoma from 2012-2024 treated with modified ACNS0821 therapy, including combination bevacizumab, irinotecan, and temozolomide, referred to as "TIB." Each TIB cycle includes oral temozolomide (200 mg/m²/day) for the first 5 days, intravenous (IV) bevacizumab (10 mg/kg/dose), and IV irinotecan (125 mg/m²/dose or 340 mg/m²) on days 1 and 15 of each cycle. Patient medical history, prior treatment, therapy toxicity, response, and outcome were collected. The analysis included Kaplan-Meier estimates of 3-year overall survival (OS) and 3-year progression-free survival.

Results: Fifteen patients were treated with TIB for relapsed medulloblastoma at SCH (median age 5.81 (0.21-23.6) years, 60% male). Twelve patients completed planned therapy. Therapy was discontinued for toxicity (n = 1) and family preference (n = 1). The most common toxicities were thrombocytopenia (n = 7), neutropenia (n = 4), nausea (n = 5), vomiting (n = 5), and diarrhea (n = 3). Five patients required dose modification of one agent for toxicity. Median follow-up from TIB therapy start was 1.61 (0.47-7.66) years. Three-year OS was 48% (95% CI: 18%-74%) and 3-year event-free survival was 16% (95% CI: 1%-49%).

Conclusions: TIB was well-tolerated in pediatric patients with relapsed medulloblastoma, and outcomes were similar to those published in clinical trials. TIB therapy should be considered for patients with relapsed medulloblastoma, especially patients with limited access to care due to travel barriers.

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.

Background: Malignant brain tumors often lead to death. While improving future treatments is essential, end-of-life care must also be addressed. To ensure equitable palliative care, understanding the place of death is crucial, as disparities may lead to inequity of care. This study aims to identify the place of death in adults with malignant brain tumors in Sweden, and the potential associations with official palliative care status by the ICD-10 code Z51.5, sociodemographic factors, health service characteristics, and healthcare service utilization.

Methods: A population-level registry study examined the place of death among adults who died of malignant brain tumors in Sweden from 2013 to 2019. Descriptive statistics, univariable, and multivariable binary logistic regression analyses were performed.

Results: We identified 3,888 adults who died from malignant brain tumors. Of these, 64.4% did not receive an official palliative care status. Specialized palliative care was not utilized in 57.2% at the place of death and in 80% of nursing home deaths. In the last month of life, 53.5% of hospital deaths involved 1 transfer, while 41.8% had 2 or more transfers. The odds ratio (OR) of dying in hospital versus at home was higher, with 2 or more transfers (OR 0.63 [0.40, 0.99]). The OR of dying in a hospital versus at home showed significant regional differences.

Conclusions: Despite the severity of their diagnosis, only a minority of patients utilized specialized palliative services at death, and this varied by the place of death. Significant regional disparities were found between hospital and home deaths, indicating unequal end-of-life palliative care in this patient group.