Neuro-oncology practice最新文献

Background: BRAF V600E mutations occur in many pediatric malignancies, including ~5% to 10% of pediatric high-grade gliomas (HGGs). Despite efforts over the decades, the prognosis of pediatric HGG remains dismal, with low survival rates. Dabrafenib has shown efficacy in pediatric patients with BRAF V600 mutation-positive malignancies in a phase 1/2a study. This report combines data from all pediatric patients with HGG in both dose escalation (part 1) and tumor-specific dose expansion (part 2) parts of the study, including patients with HGG for the first time in phase 2a.

Methods: Patients aged 1 to < 18 years with BRAF V600 mutation-positive HGG who had refractory or progressive disease after standard therapy received oral dabrafenib 3.0 to 5.25 mg/kg/day (part 1) or the recommended dose (part 2) of 5.25 mg/kg/day (age < 12 years) or 4.5 mg/kg/day (age ≥ 12 years) as 2 equal doses twice daily. The primary objectives were safety and tolerability of dabrafenib (part 1; previously published) and clinical activity (part 2), defined as ORRs reported by investigator assessment and independent review using RANO 2010 criteria.

Results: Overall, 35 pediatric patients with HGG were treated. Histologic diagnosis included pleomorphic xanthoastrocytoma (n = 8), glioblastoma (n = 7), anaplastic astrocytoma (n = 6), anaplastic ganglioglioma (n = 4), and other gliomas (n = 10). The ORRs were 29% (95% CI, 14.6, 46.3) and 46% (28.8, 63.4) by investigator assessment and independent review, respectively. The 24-month PFS rates were 30% and 40%, respectively. The most common treatment-related adverse events were dry skin (31%), fatigue (29%), and pyrexia (26%). No treatment-related deaths were reported.

Conclusions: In pediatric patients with relapsed orrefractory BRAF V600-mutated HGG, dabrafenib exhibited sustained objective tumor responses and a manageable safety profile.

[This corrects the article DOI: 10.1093/nop/npaf018.].

Background: Reproductive health considerations are critical to patients with IDH-mutant (IDHm) glioma as they are mainly diagnosed during their reproductive years. Given the recent introduction of IDH inhibitors (IDHi) for the treatment of IDHm glioma, we sought to review the current understanding of reproductive implications of IDHi therapy, and report how frequently documented reproductive health conversations take place in the clinic when considering IDHi initiation.

Methods: We searched the literature for studies evaluating the effects of IDHi therapy on reproductive health. We additionally retrospectively collected clinical data from reproductive-age patients with IDHm glioma treated at the Dana-Farber Cancer Institute and Mass General Brigham who received or were considered for IDHi therapy between 2018 and 2024. Medical records were reviewed for documentation of fertility and contraception discussions at the time of IDHi consideration.

Results: Other than limited preclinical studies described on Food and Drug Administration labels, no other data on the effects of IDHi on reproductive health were found. Of 119 patients considered for IDHi therapy, 54 (45%) had no documented fertility conversation in relation to IDHi, and 92 (77%) had no documented contraception conversation. On univariable analysis, factors significantly associated with not having fertility conversations were older age (OR: 0.94, CI: 0.88-1.0), male sex (OR: 0.50, CI: 0.23-1.07), and prior fertility conversation (OR: 0.41, CI: 0.18-0.88).

Conclusions: According to our institutional data, conversations regarding IDHi reproductive risks are not generally documented, contrary to guideline recommendations. Future studies are required to better understand the impact of IDHi therapy on fertility and fetal development.

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: 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.