Neuro-oncology practice最新文献

Background: Chimeric antigen receptor (CAR) T cell therapy is a promising treatment for central nervous system (CNS) tumors like diffuse intrinsic pontine glioma (DIPG) and diffuse midline glioma (DMG). Unlike systemic administration, locoregional CAR T therapy may result in tumor inflammation-associated neurotoxicity (TIAN), which was recently defined. This study retrospectively applies TIAN criteria to patients with DIPG/pontine DMG treated with intraventricular B7-H3 CAR T cells in the BrainChild-03 (BC-03) trial (NCT04185038).

Methods: A retrospective analysis of DIPG/pontine DMG patients treated with locoregional B7-H3 CAR T cells in BC-03 was conducted. Neurological symptoms, headache, fever, hydrocephalus, and inflammatory markers were extracted from case reports and medical records. TIAN was classified as type 1 (mechanical damage) or type 2 (electrophysiologic dysfunction), and symptom patterns, resolution, imaging findings, and management were analyzed.

Results: Among 21 patients (ages 2-22) receiving ≥1 infusion, 16 (76%) met TIAN criteria at least once. TIAN occurred in 49 of 152 infusions (32%), mostly grade 1 (n = 34) or grade 2 (n = 14), with one grade 3 event. Common symptoms included headache with fever (51%) and neurologic changes with headache (31%). In most patients, Type 1 vs Type 2 TIAN could not be defined; however, 1 patient required CSF diversion (type 1 TIAN), and 13 had worsening preexisting deficits (type 2). Median symptom resolution was <24 h (range: 0-33).

Conclusions: TIAN was common within this cohort but mostly low-grade and transient. Refining its classification and understanding its clinical impact will aid safety assessments and trial comparisons for CNS-directed CAR T therapies.

Background: Knowledge about glioma patients' physical functioning and physical fitness throughout the disease trajectory is limited. We analyzed self-reported functioning and fitness in a large sample of glioma patients preoperatively and after primary treatment.

Methods: We used the physical functioning subscale of the 36-Item Short Form Health Survey (SF36) and three questions about physical fitness from the Checklist of Individual Strength (CIS20). Scores were compared to age-, sex-, and education-matched population controls, preoperatively and after treatment. In patients with repeated assessments, changes over time were analyzed. Correlations between patient, disease, and treatment characteristics and functioning and fitness at both time points, and with change over time, were explored. Analyses were performed separately for World Health Organization grade II, III, and IV glioma.

Results: Grade III patients had significantly lower functioning than controls, both preoperatively and after treatment, and declined over time. No significant differences with controls were found for grade II and IV patients, or for fitness. Grade II patients reported better functioning than grade III and IV preoperatively and better than grade III after treatment. Lower Karnofsky Performance Status was generally related to lower functioning and fitness, while older age, female sex, and lower education appeared in subgroup analyses. Age, neurological disabilities and tumor histology were associated with changes over time.

Conclusions: Grade III glioma patients showed poorer functioning than population controls, which declined over time. Grade II patients reported better outcomes than the other subgroups, although individual variability was high. These findings highlight the need for personalized approaches addressing functioning and fitness in glioma.

Background: Awake craniotomy is essential for glioma resection in functionally integrated brain regions, allowing real-time monitoring to reduce cognitive and emotional deficits. Although widely used, its long-term neuropsychological effects remain debated. This systematic review aims to investigate cognitive and emotional outcomes after awake brain surgery and the factors that influence recovery, including extent of resection, follow-up timing, and neural plasticity.

Methods: This systematic review analyzes 34 studies on pre- and postoperative functional outcomes in glioma patients undergoing awake surgery. Following PRISMA guidelines, studies were selected with adult glioma patients (WHO grade I-IV) who had neuropsychological assessments before and after surgery. Data on preoperative cognitive profiles, recovery trajectories, and follow-up durations were examined, focusing on methodological consistency and assessment tools.

Results: The findings demonstrated substantial variability in functional outcomes, with many patients recovering within 3 to 6 months post-surgery, while others experienced persistent deficits. Functional recovery was influenced not only by the extent of tumor resection but also by network-level reorganization. Methodological inconsistencies in neuropsychological assessments highlighted the need for standardized, personalized evaluation protocols, emphasizing the importance of comprehensive functional assessments.

Conclusions: This review emphasizes the shift from a localized cortical approach to a dynamic, network-based view of cognitive and emotional recovery. It calls for standardized, personalized neuropsychological assessments to optimize rehabilitation, along with extended follow-ups, and multidisciplinary care for long-term quality of life. Future research should refine assessment methods and strategies to better understand neuroplasticity and improve clinical outcomes in neuro-oncology.

Background: We developed CARING to support neuro-oncology caregivers. CARING includes eSNAP, a web-based tool to identify social support resources, and 8 weeks of individual phone-based non-clinical navigation focused on support identification and coping skills. This study aimed to evaluate the efficacy of CARING on caregiver and patient psychosocial outcomes.

Methods: We compared CARING to a waitlist control (WLC) in an RCT. Neuro-oncology patients and their caregivers were recruited from a National Cancer Institute (NCI)-designated comprehensive cancer center in Florida from February 2020 to June 2024. Eighty-one caregivers were assigned to CARING and 35 to WLC. All participants completed baseline measures, including demographics and health data. Primary outcomes collected at 8 weeks were caregiver support and self-efficacy. Secondary outcomes were caregiver burden, personal gain, and caregiver and patient anxiety and depressive symptoms. General Linear Mixed Models examined changes in outcomes from baseline to 8 weeks by condition.

Results: No significant demographic differences existed between conditions. CARING caregivers reported significantly lower ratings of stress/frustration compared to feeling in control/hope (F(1,92) = 6.19, P = .015) at 8 weeks compared to WLC. There was a significant increase in personal gain (M = 0.7, SD = 2.5, t(63) = 2.13, P = .037) and a marginally-significant increase in self-efficacy (M = 1.6, SD = 6.6, t(61) = 1.88, P = .065) for CARING caregivers at 8 weeks. Although the intervention is targeted only at caregivers, patients of CARING caregivers reported marginally significantly fewer depressive symptoms (F(1,51) = 2.89, P = .096) at 8 weeks compared to WLC.

Conclusion: CARING decreases the ratio of negative to positive emotions and perceptions of personal gain in caregivers at 8 weeks, compared to WLC.

Background: Cognitive impairments are common in lower-grade gliomas (grades 1-3), but treatment options are limited. Tele-cognitive rehabilitation offers a potential solution. We conducted an interim pilot study to assess the feasibility, satisfaction, and early efficacy of tele-cognitive rehabilitation.

Methods: We enrolled adults with stable LrGG (≥6 months posttreatment) who had subjective and objective cognitive impairments (>1 SD below-average in ≥2 domains). Participants received 3 months of individual Goal Management Training (GMT), app-based ReMind, or texting. Cognition and patient-reported outcomes were assessed at baseline (T1), postintervention (T2), and 9 months postbaseline (T3). We assessed enrollment, adherence, and satisfaction. Adherence was defined as ≥80% of participants completing ≥80% of the protocol; satisfaction as ≥6/7 for GMT and texting, and ≥4/5 for ReMind on a self-report Likert question. We used ANOVA, reliable change indices, and qualitative analytics.

Results: Thirty-nine participants were eligible and 33 prospectively enrolled for the study; an 85% enrollment (17-GMT, 8-ReMind, 8-texting; 46.8 median age, 64.8 months from diagnosis, 55% had astrocytoma, and 76% had prior radiotherapy). Eighty-two percent of GMT (adequate), 100% of texting (adequate), and for ReMind 33% of retraining and 50% of compensation (inadequate) completed ≥80% of the protocol. GMT (mean: 6.75/7) and ReMind (mean: 4.5/5) satisfaction were adequate, and texting (mean: 4.5/7) was inadequate. Working memory improved from T1-to-T2 (P = .02, η² = 0.32) in 26% of the GMT group.

Conclusions: GMT demonstrates adequate feasibility, satisfaction, and may yield improvements in working memory, while texting and ReMind had challenges in acceptability or feasibility. Individual (tele) GMT warrants further investigation in LrGG.

Background: BRAF alterations are common in pediatric low-grade gliomas (LGG) and a subset of high-grade gliomas (HGG) in adults and children. BRAF-targeted therapy can be effective at preventing tumor growth, though resistance commonly emerges in HGG. Recently, tovorafenib was FDA approved for recurrent or refractory LGG with BRAFV600 alterations or BRAF rearrangements. While the trial showed it is effective for children with LGG previously treated with BRAF or MEK inhibitors, the safety in adults and efficacy in HGG is unknown.

Methods: A cohort of appropriate patients was identified through routine clinical care. This research was conducted in accordance with IRB regulations with a waiver of written consent.

Results: Seven adults (5 HGG, 2 LGG) who received tovorafenib were identified. All patients had received prior BRAF-targeted therapy, and all patients with HGG had received prior radiation and temozolomide as well. Three individuals (2 HGG, 1 LGG) experienced stable disease or better for 4 or more months. Median duration of treatment was 8 weeks (range 3 weeks to 10 months). Two individuals experienced CTCAE grade 4 intratumoral hemorrhage (1 HGG, 1 LGG). Two patients remain on therapy at 4 and 10 months of treatment (1 HGG, 1 LGG).

Conclusion: Our experience with tovorafenib indicates some limited efficacy in HGG in combination with other standard treatments. These observations demonstrate the need for further clinical trials in patients with HGG to understand potential clinical utility, either earlier in the disease course or in combination with other therapies.

Background: Adult patients with brain tumors experience cognitive, physical, and emotional sequelae from the disease and treatment. Cognitive changes, in particular, are a common source of distress and can be treated using varied approaches. Establishing the relationship between sources of distress and understanding patient preferences for treatment of cognitive change is necessary for future integrative neurocognitive programmatic development.

Methods: Neuro-oncology patients (primary and metastatic) reported their distress related to common neuro-oncology disease symptoms, treatment preferences for cognitive change (e.g., cognitive rehabilitation, mindfulness training, psychotherapy, medication), and a measure of subjective cognition. Demographics and tumor characteristics were self-reported. Descriptive statistics, correlations, and t-tests were conducted.

Results: One hundred thirty-seven patients (M _age = 49.6 ± 15.8, 58.1% female, 84.8% White) participated. Cognitive change was the most frequently endorsed source of distress (74.1%), followed by fatigue (68.4%) and mood changes (58.5%). Distress due to cognitive changes was rated significantly higher than all other symptoms (Ps < .05) except for fatigue and did not vary based on demographics or disease characteristics (Ps > .05). To address cognitive concerns, patients were most interested in cognitive rehabilitation (63.6%), mindfulness (61.6%), and psychotherapy (56.6%). They were least interested in medication (40.4%).

Conclusions: Neuro-oncology patients reported distress due to cognitive changes more frequently than distress due to other disease sequelae (e.g., mood changes, physical symptoms), and this was robust across patient demographics and disease characteristics. Patients reported high interest in cognitive rehabilitation, mindfulness training, and psychotherapy for management of cognitive concerns, suggesting the need for non-pharmacological multi-modal interventions.

Background: Evidence assessing the impact of neighborhood-level disadvantage and population density on outcomes of individuals with cancer is growing but has not been evaluated among the primary brain tumor (PBT) population. We evaluated associations of neighborhood-level disadvantage and population density with symptoms and health-related quality of life (HRQOL) among adults with a PBT.

Methods: Neighborhood-level disadvantage, measured using the Area Deprivation Index (ADI), and population density were evaluated against symptoms (MDASI-BT and PROMIS Anxiety/Depression Short Forms v1.0 8a) using linear regression models and against HRQOL (EQ-5D-3L) using logistic regression models. Models were adjusted for age, sex, race/ethnicity, tumor grade, functional status, and tumor recurrence. Results were further stratified by tumor grade.

Results: Of 643 participants, 24% lived in more disadvantaged neighborhoods, while 39% resided in non-urbanized areas. Patients in more disadvantaged neighborhoods reported greater symptom severity (β = 1.10, 95%CI [1.00, 1.20], P = .041) and activity-related interference (β = 1.11, 95%CI [1.01, 1.22], P = .03) than those in less disadvantaged neighborhoods. Among patients with low-grade tumors, living in more disadvantaged neighborhoods was associated with worse symptom interference (β=1.24, 95%CI [1.04, 1.50], P = .020), anxiety (β=1.03, 95%CI [1.01, 1.06], P = .023), and difficulties with mobility (OR = 3.30, 95%CI [1.09, 10.01], P = .035) and self-care (OR = 4.68, 95%CI [1.46, 14.96], P = .009). Patients in non-urbanized areas were more likely to experience difficulties with self-care (OR = 2.07, 95%CI [1.23, 3.48], P = .006) than those in urbanized areas.

Conclusion: Future studies should consider evaluating PBT symptoms with data on regional resources other than individual income as the next step to inform interventional work with under-represented and under-resourced populations.Trial Registration Number NCT#: NCT02851706.

Background: Individuals diagnosed with a primary brain tumor often depend on practical assistance and emotional support from family and social network. Supportive care interventions are therefore of importance to informal caregivers. The aim of this review was to identify and explore available evidence of outcomes of supportive group interventions for caregivers to patients diagnosed with a primary brain tumor.

Methods: A systematic review was conducted following the PRISMA guidelines. Six databases: PubMed, Embase, Web of Science, Emcare, Cochrane Library, and PsycINFO were searched for peer-reviewed publications. Quality of included publications was assessed by the Mixed-Methods Appraisal Tool and data synthesis followed Guidance on the Conduct of Narrative Synthesis in Systematic Reviews.

Results: Five eligible publications were identified, published between 2007 and 2021, originating from Australia, Austria, Canada, Denmark, and Germany. Supportive group interventions for caregivers to patients diagnosed with a primary brain tumor were considered feasible, with outcomes evaluated positively in 5 publications. The group interaction within a supportive intervention created a trusted environment for caregivers to share their experiences. Group interactions represented an essential source of support and information to manage the caregiver role. Shared acknowledgment of their new role boosted caregivers' confidence in their abilities to deliver care.

Conclusion: Interventions seeking to facilitate interaction between caregivers may provide an extra supportive resource for the caregivers. Nevertheless, further research is necessary to ascertain the optimal setting, content, and timing for providing caregivers a supportive group intervention.

Background: The incorporation of molecular parameters into WHO CNS5 has led to reclassification of gliomas. We describe presenting clinical and radiographic features of diffuse adult gliomas according to CNS5 category.

Methods: We reviewed pathology reports, clinical and MRI data at presentation of 972 adult patients with glioma between January 2010 and February 2022. Continuous variables were presented as median; categorical variables as numbers and percentages. Comparison was performed using Fisher's exact test.

Results: Seven hundred and thirty-six patients had sufficient data for CNS5 reclassification: Grade 2 IDH mutant (IDHmut) astrocytoma (A2) n = 69, grade 3 IDHmut astrocytoma (A3) n = 37, grade 4 IDHmut astrocytoma (A4), n = 32, grade 2 oligodendroglioma (O2) n = 60, grade 3 oligodendroglioma (O3) n = 23, and IDH-wildtype glioblastoma (GBM) n = 515. Age at presentation differed between grades 2 and 3 gliomas and grade 4 (mean age: 39 vs 61.7; P < .001); A4 were younger than GBM (39.8 vs 63.1). Seizure was more common in IDHmut gliomas than GBM (58.4% vs 31.8%; P < .001); cognitive impairment was more common in GBM than in IDHmut gliomas (64.4% vs 34.4%; P < .001) and A4 (64% vs 40.6%; P = 0.013). Focal deficits were more frequent in GBM than IDHmut gliomas (74.2% vs 30.5%; P < .001). Contrast enhancement was more frequent in GBM than IDHmut gliomas (93% vs 48%; P < .001), similar with A4 (93% vs 96%; P = 1.00). Minimum apparent diffusion coefficient was higher in IDHmut glioma than GBM (P < .001). Calcification was more common in oligodendroglioma than astrocytoma and GBM (P < .001).

Conclusion: Significant differences in the clinical and radiographic features exist among CNS5 glioma subtypes, informing potential diagnosis, management and prognosis at initial presentation.