Neuro-oncology practice最新文献

Background: Incorporating Clinical Outcome Assessments (COAs) in oncology trials is essential for evaluating therapeutic benefits and balancing survival with quality of life and symptom management. Understanding COA adoption trends and gaps is especially critical in neuro-oncology due to the complex symptom profiles of neuro-oncology patients.

Methods: We reviewed neuro-oncology trials in ClinicalTrials.gov, identifying COA instruments using the PROQOLID database. We analyzed trends in COA usage, associations with trial characteristics, and the impact of key regulatory and advocacy efforts using correlation and regression analyses.

Results: Of 1,874 adult interventional neuro-oncology trials with sufficient data, 85% were early-phase, 91% treatment-focused, primarily studying glioblastomas (61%), and unspecified gliomas (42%); 16% used COAs, with 127 distinct instruments reported; of these trials, 71% used Patient Reported Outcomes, 46% used Clinician-Reported Outcomes, with other categories of COAs used by fewer than 12% of the trials. COA use was more likely in later-phase trials (OR = 1.38, P <.00001), supportive care trials (OR > 1, P <.01), studies on novel versus FDA-approved interventions (OR = 1.72, P <.00001), single- versus multi-arm trials (OR = 1.62, P =.027), and randomized versus nonrandomized trials (OR = 3.28, P <.00001). COA incorporation increased over time (R = 0.77, P <.00001), especially in treatment-focused trials (R = 0.88, P <.00001) and across all COA types except composite measures.

Conclusions: Our computational assessment highlights low but increasing COA adoption in neuro-oncology trials, mirroring broader oncology trends and reflecting a cumulative impact of regulatory and advocacy efforts. Priority areas for improvement include early-phase trials, FDA-approved interventions, and treatment-focused studies. Our findings emphasize the need for COA-specific reporting improvements and greater standardization in neuro-oncology research.

Background: The COVID-19 pandemic caused unprecedented strains on healthcare. With resources appropriately diverted toward managing the pandemic, less prevalent pathology was uniquely susceptible to the negative impacts of resource constraints. IDH-wildtype glioblastoma (WT-GBM) is one such example, as it yields a poor prognosis even in the most optimal resource setting.

Methods: The Surveillance, Epidemiology, and End Results (SEER) database was employed to isolate cases of WT-GBM with a minimum 24-month follow-up. Cases were grouped into pre-pandemic (2019) and pandemic-era (2020) cohorts. Kaplan-Meier log rank and multivariate cox regression survival analyses as well as univariate comparison analyses were performed.

Results: Pre-pandemic (n = 2562) compared to pandemic-era (n = 2690) survival in Kaplan-Meier analysis (10 ± 9.4 vs 10 ± 6.4 months, respectively, P = .47) as well as mortality risk in multivariate analysis (HR = 1.0, 95% CI [0.94-1.07], P = .90) were similar. Additionally, the rates of surgery performed (P = .66), rates of adjuvant systemic therapy (P = .58), and tumor size at diagnosis (P = .82) between pre-pandemic and pandemic-era cohorts did not differ. Surgery not performed (surgery not performed/contraindicated vs surgery performed: HR = 1.4, 95% CI [1.29-1.58], P < .001) and no adjuvant systemic therapy (no systemic therapy vs adjuvant systemic therapy: HR = 3.3, 95% CI [3.03-3.56], P < .001) were associated with increased risk of mortality.

Conclusions: These real-world data suggest that the COVID-19 pandemic did not affect WT-GBM all-cause survival nor did it significantly impact the care of these patients. Further study with long-term follow-up is necessary to better understand the impacts of the COVID-19 pandemic on rare pathologies, such as neuro-oncological diseases.

The application of objective radiological data in glioma research remains an underexplored opportunity in neuro-oncology. Despite multiple efforts to incorporate radiomic features in glioma analysis, the lack of a unified imaging reporting system in gliomas prevents large-scale, multi-center scientific collaborations from integrating comparable imaging variables to their work. VASARI lexicon, a set of 30 semantic radiomic features using controlled vocabulary and visual guides, was created to become a shared language for neuroscientists evaluating gliomas. It has been proven, that VASARI features are not only reliably correlated with various genetic aberrations but are also increasingly included in numerous statistical and machine learning models for predicting overall survival, tumor recurrence, glioma grade, and tumor molecular characteristics. In this review, we present an overview of VASARI application in prediction modeling, including the best-performing models and relevance of VASARI features depending on the predicted outcomes. We delve into the opportunities related to the inclusion of VASARI along with clinical, computational radiomic, and multi-omic features to construct combined neuro-oncological prediction models. Lastly, we discuss the challenges and limitations of currently performed models as well as the methods to overcome them using automatic feature extraction solutions.

Background: Informed, value-based healthcare decisions depend on individuals' decisional needs and preferences. Adequately addressing them may improve decision experience and quality. This scoping review aims to assess study findings on decisional needs and preferences of patients with a brain tumor (PwBT) (glioma, meningioma, brain metastases) throughout the disease trajectory, including findings on decision aids and interventions.

Method: The methodological framework by Arksey & O-Malley for scoping reviews was used. A systematic search was performed in PubMed.

Results: We identified 20 studies on decisional needs and preferences of PwBT and 6 studies on decision aids. Most patients prefer a collaborative or active role in decision-making, and they value quality of life (QoL), functional independence, and survival as treatment outcomes. Patients require tailored amounts and types of information and need support maintaining hope, establishing trust, and with diminished medical decision-making abilities. Decision aids focused on information provision or shared decision-making (SDM), with mixed results on patient participation and satisfaction.

Discussion: SDM could help address PwBT's needs and preferences. QoL and functional independence are crucial yet underexplored factors in decision-making. Further research is needed to better integrate individual patient outcome preferences into SDM and to evaluate tools that support informed and value-based decisions.

Cancer-related movement disorders (CRMDs) comprise a diverse group of neurological complications of cancer. They result from varied etiologies and can be associated with compromised quality of life and poor prognosis. CRMDs can be divided into two broad categories: movement disorders resulting from cancer-related processes, such as direct tumor infiltration and paraneoplastic disease, and those that are a consequence of cancer-directed treatments, including classic therapies, such as chemotherapy and radiation therapy, novel treatments (eg immunotherapies and CAR T-Cell therapies), and various supportive treatments. A clear understanding of the breadth of CRMDs is vital, as effective management relies upon accurately identifying their underlying etiology. In this scoping review, we provide a comprehensive categorization of CRMDs based on their underlying etiology and phenomenology. Additionally, we propose a structured framework to guide the diagnostic evaluation and management of CRMDs, with the goal of facilitating timely diagnosis and, ultimately, improved patient outcomes.

Background: Subpopulation underrepresentation in clinical trials contributes to biases in clinical data and systemic healthcare inequities. We aim to evaluate reporting and representation, as well as the effect of geography and socioeconomic trends, in spinal oncology trials.

Methods: Data were collected from completed spinal oncology trials registered on ClinicalTrials.gov from 2000 to 2023. A total of 42 trials with 5679 participants were included. The demographics of participants were compared with national spinal tumor incidence data and demographic data from patients undergoing spinal oncology surgery at a quaternary care center.

Results: Only 50% of clinical trials reported race and 28.6% reported the ethnicity of participants, with privately funded trials less likely to report ethnicity (25% vs. 66.7%, P = .02574). When compared with their respective national incidences, Black (4.6% vs. 11.3%, P < .00001), American Indian or Alaska Native (0.2% vs. 0.6%, P = .00084), and Hispanic (4.7% vs 11.4%, P < .00001) patients were significantly underrepresented in trials. Black (4.6% vs. 18.9%, P < .00001) and female (44.5% vs. 48.9%, P = .00438) patients were also underrepresented when compared with the population of patients undergoing spinal oncology surgery. Trials post-2020 had increases in representation of several minority groups compared to pre-2020 trials. Trial sites were mostly located in metropolitan areas, with gaps in the Mountain region and parts of the Southern U.S.

Conclusions: There has been progress in diversifying spinal oncology trials, but there are still large racial, ethnic, and geographic disparities in the composition of clinical trial patients. Major reporting lapses hinder understanding the gaps in equitable enrollment.

Background: Mebendazole (MBZ) is an anti-helminthic that has shown antitumor activity in mice with gliomas and subsequently in medulloblastoma models. Safety and tolerability have been demonstrated in adults with brain tumors but not explored in children as a monotherapy. We characterized the safety and maximum tolerated dose of oral MBZ in pediatric patients with refractory or progressive brain tumors and assessed progression-free survival (PFS) as a secondary objective.

Methods: Patients up to 21 years of age with refractory or progressive brain tumors were enrolled at 2 centers in a 3 + 3 design with 3 doses of MBZ (1250, 1875, or 2500 mg/m²/day). MBZ was taken orally 3 times per day and continued until there were signs of toxicity or clinical/radiographic progression. Safety and tolerability were analyzed with descriptive statistics.

Results: There were 17 patients enrolled between 2017 and 2022 with diffuse intrinsic pontine gliomas, high-grade astrocytomas, diffuse midline gliomas, glioblastoma multiform, ependymoma, and nonspecific gliomas. At all 3 dose levels, MBZ was well-tolerated with no dose-limiting toxicities. 121 adverse events (AE) including 69 AEs possibly/probably related to MBZ occurred-the most common being decreased lymphocyte count (n = 6). Six grade 3 (anorexia, dehydration, hypokalemia, increased GGT, blood bilirubin increased, and aspartate aminotransferase increased) and 1 grade 4 (vomiting) were reported. The mean PFS was 7.6 weeks (range of 2 to 24 weeks).

Conclusions: MBZ is safe and tolerable in treating refractory or progressive pediatric brain tumors, with doses up to 2500 mg/m²/day. There was limited evidence of single-agent efficacy.

Cerebral radiation necrosis (CRN) is a serious complication of high-dose radiotherapy in patients with high-grade glioma (HGG) and brain metastases (BM). Approximately half of the patients with radiological CRN develop debilitating neurological symptoms that significantly affect their neurocognitive functioning, performance status, and health-related quality of life (HRQoL), requiring treatment. While corticosteroids are the standard first-line treatment for symptomatic CRN (sCRN), they have considerable drawbacks, including limited efficacy, severe side effects affecting various organ systems, and interference with concurrent therapies, such as immunotherapy. Prolonged corticosteroid use can lead to adrenal insufficiency and dependence on hormone replacement. Bevacizumab has been shown to reduce the contrast-enhancing CRN lesion on MRI and surrounding edema, improving clinical outcomes in most patients. However, most evidence comes from smaller, single-center, retrospective studies focusing on short-term radiological and clinical outcomes, typically in patients already treated with corticosteroids. Information on the optimal timing of bevacizumab administration and its long-term effects and impact on patient-reported outcomes, including HRQoL, is lacking. These limitations prevented the adoption of first-line bevacizumab treatment for sCRN in international guidelines and insurance coverage policies. A well-powered prospective clinical trial comparing the clinical and cost-effectiveness of first-line bevacizumab versus corticosteroids in HGG and BM patients is essential.

Background: The aim of this manuscript was to describe the frequency and types of nurse-identified needs, recommendations, and referrals delivered to intervention-arm carers of patients with high-grade glioma (HGG) during monthly nurse-led telephone assessments in the Care-IS randomized controlled trial.

Methods: Primary carers of patients diagnosed with HGG (≤2 months prior) and undergoing active treatment were randomized to: a 12-month Care-IS intervention; or, a control group. Carers randomized to the intervention were included in this sub-analysis. Nurses recorded carers' needs and made recommendations and referrals. Data analysis descriptively explored categories of needs, recommendations, or referrals.

Results: An initial Nurse Telephone Assessment (NTA) was conducted with carers (N = 92) with drop-out related to time constraints, patient deterioration or death, or study withdrawal (N = 10 at month 10). Nurses identified ≥1 need, recommendation, or referral during the majority (≥90%) of NTAs. Up to 6 months, the most common needs were: dealing with treatment and side effects (74%-85%), understanding physical symptoms and side effects (60%-76%), mental and behavioral changes (53%-67%), and caring for yourself (51%-68%). The top recommendations were: tailored resources from the Care-IS resource manual (81%-96%), community-based support (47%-65%), medical specialist and clinical care (39%-56%), and additional information provision (30%-38%). The top referrals were for medical specialists and clinical care (27%-48%). Palliative care was the main recommendation (29%) and referral (19%) at months 9-10.

Conclusions: NTAs identified a high frequency of carer unmet needs. Carer needs were highly variable, patient-focused, and changed over time. Nurses must accommodate a broad range of recommendations from providing additional information to making health/community referrals.

Background: Incidence, survival, and optimal choice of therapy for central nervous system (CNS) metastasis are well characterized in human epidermal growth factor receptor 2 positive (HER2+) breast cancer (BC), yet remain poorly defined in other HER2+ solid tumors (STs).

Methods: A retrospective cohort analysis was performed to characterize the incidence of CNS metastasis and clinical outcomes in patients with HER2+ breast cancer and ST treated at the University of Virginia Emily Couric Cancer Center between January 2010 and January 2022.

Results: In the cohort, 50 patients had HER2+ ST and 383 had HER2+ BC. Of the ST group, 48.0% received CNS imaging at diagnosis as compared to 2.9% of breast cancer patients (P < .001). Cumulative incidence of CNS metastasis at diagnosis was 4% in the ST vs 1% in the breast cancer cohort (P < .001). Cumulative incidence of CNS metastasis was 20% in ST vs 6.8% in breast cancer cohorts (P < .001). In ST patients with CNS metastasis, 50% received CNS surgery/radiotherapy plus HER2-targeted therapy and 30% received CNS surgery/radiotherapy alone. Overall survival (OS) was significantly poorer in ST (median 1.7 years) vs breast cancer (median 18.5 years) cohorts overall (P < .001), as well as among Stage IV patients (1 year for ST vs 6.3 years for breast cancer).

Conclusions: Patients with non-breast cancer HER2+ STs had higher risk of CNS metastasis and poorer OS compared to HER2+ breast cancer patients, with lower utilization of HER2-directed therapy.