Neuro-oncology practice最新文献

Background: Although progress has been made in understanding the effects of adjuvant therapy on health-related quality of life (HR-QoL) in diffuse glioma patients, less is known about the impact of surgical resection. To address this, we conducted a systematic review and pooled quantitative analysis.

Methods: PubMed, MEDLINE, and Embase were searched for studies measuring HR-QoL before and after surgery for WHO grade 2-4 adult-type diffuse gliomas. Inclusion was limited to prospective cohort studies and trials on adults with ≥1 month of postoperative follow-up. Metric outcomes were assessed with pooled odds, competing risk analysis, and meta-regression using a random effects model. Bias was assessed using the Newcastle-Ottawa Scale and Cochrane Risk of Bias 2.0 tool.

Results: Twelve studies comprising 1000 patients were included. The pooled odds of an unfavorable versus favorable HR-QoL change compared to baseline was not significantly different from 1 within 3 months of surgery (0.843, 95% CI, 0.339-2.100), but significantly less than 1 at final follow-up (0.481, 95% CI, 0.260-0.888). The cumulative incidence of favorable HR-QoL change was significantly higher than that of unfavorable change, with the incidence curves separating after 3 months (χ²(1) = 95.0, P < .001). This was attributable to EQ-5D and EORTC QLQ-C30 but not SF-36. Studies with younger patients, more high-grade tumors, and lower gross total resection rates showed worse outcomes.

Conclusion: Surgical resection can maintain or improve HR-QoL, but patients at risk of deterioration should be identified early. Future studies must carefully select and interpret HR-QoL instruments, as preference-based and non-preference-based tools may lack comparability.

Background: We assessed clinical features, treatment, and survival of pediatric patients with neurofibromatosis type 1 (NF1) with high-grade glioma (HGG).

Methods: Patients from this retrospective cohort study were identified through an international collaborative effort by the SIOPE HGG/DIPG working group. NF1 was diagnosed based on clinical presentation and confirmed by either a pathogenic germline NF1 gene alteration or the exclusion of mismatch repair deficiency. A control cohort without genetic cancer predisposition was matched in a 2:1-ratio from the HIT-HGG database.

Results: We identified 29 pediatric patients with NF1-associated HGG. Median age at diagnosis of HGG was 11 years. All but 1 tumor arose outside the optic pathway and included circumscribed and diffuse HGG. Molecular analysis in a subset of tumors identified an enrichment of alterations in CDKN2A, TP53, and ATRX. Event-free and overall survival were as poor as in matched sporadic HGG patients. The prognosis was not superior with upfront radiotherapy compared with delayed radiotherapy.

Conclusions: NF1-associated HGGs behave as aggressively as their sporadic counterparts. The relevance of delaying radiotherapy until the time of progression and adjuvant MEK inhibitor treatment needs further investigation.

Background: Medulloblastoma (MB) is a rare tumor in adults, with treatment strategies derived largely from pediatric data. Prognostic factors have not been uniformly defined in adults to date.

Methods: We retrospectively reviewed the medical records of 89 adult MB patients treated between 1995 and 2019 in our institution. Patient's characteristics, disease features, and treatment modalities were analyzed for prognostic factors using univariate and multivariate analysis.

Results: Of the 89 patients, 66% were male. Most MBs were in the cerebellum (48%), with desmoplastic/nodular histology (43%), Sonic Hedgehog molecular type (79%), and M0 Chang´s stage (72%). Intermediate- and high-risk MBs were identified in ~46% and ~47% of cases, respectively. Complete/near complete tumor resection was achieved in 62% of cases. Surgery followed by chemoradiotherapy (CT/RT) was the most frequent treatment (76%) with carboplatin-based regimens used in 70% of cases. After the first-line treatment, complete response (CR) was achieved in 80% of patients. Median overall survival (mOS) was 124.4 months (95%CI 68.5-180.1) and the median progression free survival (mPFS) was 30.5 months (95%CI 13.5-47.5), the 5-year OS was 67% and the 5-year PFS was 51%. In multivariate analysis, Chang´s stage ≥ M2 metastatic classification (P = .001), RT without CT in first line setting (P = .005), and craniospinal RT < 30 Gy (P = .015) were associated with worse survival outcomes.

Conclusions: Chang's stage ≥ M2, first-line treatment lacking CT, and first-line treatment with craniospinal RT < 30 Gy were significant predictors of poor survival. Chemoradiotherapy with craniospinal RT ≥ 30 Gy improved survival outcomes.

Experts and generalists from numerous clinical disciplines are likely to encounter and be involved in the care of patients with neurogenetic tumor syndromes. Considerations for genetic testing are discussed. Specific conditions including neurofibromatosis type 1, neurofibromatosis type 2-related schwannomatosis, von Hippel-Lindau disease, tuberous sclerosis, Lynch syndrome, Turcot syndrome, Li-Fraumeni syndrome, and others are reviewed. A variety of targeted therapies which have received regulatory approval for these disorders are described and promising future directions for therapeutics are highlighted.

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.