Neuro-oncology advances最新文献

Background: Despite improvements in our understanding of glioblastoma pathophysiology, there have been no major improvements in treatment in recent years. Animal models are a vital tool for investigating cancer biology and its treatment, but have known limitations. There have been advances in glioblastoma modeling techniques in this century although it is unclear to what extent they have been adopted.

Methods: We searched Pubmed and EMBASE using terms designed to identify all publications reporting an animal glioma experiment, using a machine learning algorithm to assist with screening. We reviewed the full text of a sample of 1000 articles and then used the findings to inform a screen of all included abstracts to appraise the modeling applications across the entire dataset.

Results: The search identified 26 201 publications of which 13 783 were included at screening. The automated screening had high sensitivity but limited specificity. We observed a dominance of traditional cell line paradigms and the emergence of advanced tumor model systems eclipsed by a large increase in the volume of cell line experiments. Few studies used more than 1 model in vivo and most publications did not verify critical genetic features.

Conclusions: Advanced models have clear advantages in terms of tumor and disease recapitulation and have largely not replaced traditional cell lines which have a number of critical deficiencies that limit their viability in modern animal research. The judicious use of advanced models or more relevant cell lines might improve the translational relevance of future animal glioblastoma experimentation.

Background: This study aimed to explore the potential of the Advanced Data Analytics (ADA) package of GPT-4 to autonomously develop machine learning models (MLMs) for predicting glioma molecular types using radiomics from MRI.

Methods: Radiomic features were extracted from preoperative MRI of n = 615 newly diagnosed glioma patients to predict glioma molecular types (IDH-wildtype vs IDH-mutant 1p19q-codeleted vs IDH-mutant 1p19q-non-codeleted) with a multiclass ML approach. Specifically, ADA was used to autonomously develop an ML pipeline and benchmark performance against an established handcrafted model using various MRI normalization methods (N4, Zscore, and WhiteStripe). External validation was performed on 2 public glioma datasets D2 (n = 160) and D3 (n = 410).

Results: GPT-4 achieved the highest accuracy of 0.820 (95% CI = 0.819-0.821) on the D3 dataset with N4/WS normalization, significantly outperforming the benchmark model's accuracy of 0.678 (95% CI = 0.677-0.680) (P < .001). Class-wise analysis showed performance variations across different glioma types. In the IDH-wildtype group, GPT-4 had a recall of 0.997 (95% CI = 0.997-0.997), surpassing the benchmark's 0.742 (95% CI = 0.740-0.743). For the IDH-mut 1p/19q-non-codel group, GPT-4's recall was 0.275 (95% CI = 0.272-0.279), lower than the benchmark's 0.426 (95% CI = 0.423-0.430). In the IDH-mut 1p/19q-codel group, GPT-4's recall was 0.199 (95% CI = 0.191-0.206), below the benchmark's 0.730 (95% CI = 0.721-0.738). On the D2 dataset, GPT-4's accuracy was significantly lower (P < .001) than the benchmark's, with N4/WS achieving 0.668 (95% CI = 0.666-0.671) compared with 0.719 (95% CI = 0.717-0.722) (P < .001). Class-wise analysis revealed the same pattern as observed in D3.

Conclusions: GPT-4 can autonomously develop radiomics-based MLMs, achieving performance comparable to handcrafted MLMs. However, its poorer class-wise performance due to unbalanced datasets shows limitations in handling complete end-to-end ML pipelines.

Background: Intrathecal (IT) chemotherapy is essential in treating hematological malignancies, but it can lead to ascending paraplegia, a condition that currently lacks clear management guidelines.

Methods: We conducted a systematic review, analyzing 1219 studies and 116 patients, adhering to PRISMA guidelines for individual patient data. The study, registered under PROSPERO (CRD42022362121), focused on the onset, diagnostic approaches, and therapeutic interventions associated with this complication, and management strategies to tackle the ascending paraplegia.

Results: Paraplegia typically manifests approximately 10 days after chemotherapy, irrespective of injection frequency. In 95% of cases, paralysis stabilizes around the umbilical region, although some patients progress to upper limb involvement and respiratory compromise. Despite various diagnostic methods, consistent inflammatory markers in blood or cerebrospinal fluid are lacking, with approximately 60% of patients showing normal magnetic resonance imaging results at presentation. Misdiagnoses often include transverse myelitis, Guillain-Barré syndrome, and autoimmune radiculitis. Common treatments such as corticosteroids and intravenous immunoglobulins show limited effectiveness.

Conclusion: Our review delineates the clinical entity of ascending paraplegia following IT chemotherapy, aiming to increase clinician awareness and provide prognostic insight. We introduce the term post-IT paraplegia syndrome to facilitate accurate diagnosis and optimize treatment strategies for affected patients.

Background: Laser interstitial thermal therapy (LITT) is a minimally invasive surgical treatment being employed frequently for radiographically progressive brain metastases. Considerable interest exists in combining LITT-mediated in situ vaccination to license immune checkpoint blockade (ICB). No studies have examined the clinical feasibility of this combination in brain metastases.

Methods: All patients receiving LITT for radiographically progressive non-small cell lung carcinoma (NSCLC) brain metastases at a single center from 2015 to 2023 were retrospectively reviewed. Combination therapy was defined as ICB within 6 weeks of LITT. Clinical data, post-LITT freedom from local progression, and overall survival (OS) were collected. Adverse events (AEs) were evaluated according to Common Terminology Criteria.

Results: Eighteen patients received LITT + ICB for a total of 19 lesions. The median time between therapies was 2.29 weeks (range 0.85-5.98). In comparison to NSCLC patients receiving LITT alone or with targeted therapy (LITT only) (n = 25), there was no decrement in procedural outcomes. Patients receiving LITT + ICB discontinued steroids at a median of 11 (4-147) days post-LITT vs. 24 (3-242) days for patients receiving LITT only (P = .62). At study cutoff, the local control rate was 18/19 (94.7%) lesions in the LITT + ICB group and 22/25 (88.0%) in the LITT only group. There were 3 and 5 AEs ≥Grade 3 in the LITT + ICB and LITT-only groups, respectively.

Conclusions: Combination of LITT and ICB does not compromise procedural outcomes or time to steroid discontinuation in NSCLC. Prospective studies are needed to assess biomarkers of immune response.

Background: Few studies have evaluated predictive factors of isolated pituitary stalk thickening (iPST) in children.

Methods: In this retrospective study, radiology, endocrinology, and neuro-oncology databases were interrogated to identify patients with iPST between January 2000 and June 2019. A blinded, longitudinal assessment of MRIs was performed using quantitative, semi-quantitative, and qualitative metrics. Neuroimaging parameters were correlated to clinical parameters.

Results: Forty-seven patients were identified, with 40 meeting the inclusion criteria. Median age at baseline MRI was 9.6 years (range 0.9-17.5) with median follow-up of 5.2 years (range 0.3-18.6). Twenty-five (63%) were female. Thirty-four (85%) had pituitary dysfunction, including 31 with central diabetes insipidus (cDI). cDI was not predictive of proliferative disease (PfD): 69% of those with presumed primary hypophysitis (PPH) versus 93% with PfD (P = .1). Fourteen (35%) patients were diagnosed with PfD (germinoma = 8, Langerhans cell histiocytosis = 5, lymphoma = 1) at median of 1.3 years (range 0.3-4.0) after initial MRI. Progressive thickening of the stalk over time was associated with PfD (86% vs 4% in PPH, P < .0001), as was thickening of the entire stalk (56% in PfD vs 27% in PPH, P < .0001) with different imaging trends over time observed in PfD versus PPH. A "sack of marbles" appearance with heterogeneous enhancement on post-contrast imaging was associated with germinoma.

Conclusions: In this cohort, 35% of children with iPST were diagnosed with PfD. The association of cDI and PfD was not statistically significant. Progressive thickening of the entire stalk was predictive of PfD and a "sack of marbles" pattern was found to be highly suggestive of germinoma.

Background: Postoperative pediatric cerebellar mutism syndrome (ppCMS) poses serious morbidity after posterior fossa tumor surgery. Neuroimaging studies aim to understand its pathophysiology, yet these vary in methodology and outcome measures. Therefore, we systematically reviewed the current literature to evaluate the evidence for differences in neuroimaging features between children with and without ppCMS.

Methods: Following PRISMA guidelines, a systematic review was conducted by searching for original articles on neuroimaging in children undergoing posterior fossa tumor surgery, comparing patients with and without ppCMS. Articles were selected based on predefined eligibility criteria. Data were systematically extracted, and risk of bias was evaluated.

Results: From the 866 articles identified, 50 studies fulfilled the inclusion criteria. Studies were categorized into 3 imaging domains: structural, diffusion, and functional imaging. Risk of bias assessment revealed a medium risk in most articles, predominantly due to unclear ppCMS definition and qualitative image analysis without blinding for ppCMS diagnosis. Preoperative structural imaging showed the association of ppCMS with midline tumor localization and involvement of the brainstem, superior cerebellar peduncle (SCP), or middle cerebellar peduncle. Postoperative structural and diffusion imaging highlighted SCP injury with reduced white matter integrity, while functional imaging demonstrated hypoperfusion in frontal lobes. Late follow-up showed T2-weighted hyperintensities in the inferior olivary nuclei of ppCMS patients.

Conclusion: Neuroimaging features suggest that ppCMS is associated with efferent cerebellar pathway injury and hypoperfusion in frontal lobes, with level 2 a/b evidence. Large-scale prospective longitudinal neuroimaging studies comparing pre- and postoperative imaging are needed to further elucidate the pathophysiological mechanism of ppCMS.

Background: This study is a phase II clinical trial to evaluate the efficacy, safety, and tolerability of the blood-brain barrier (BBB) permeable peptide-paclitaxel conjugate ANG1005 in patients with recurrent high-grade glioma (HGG) (NCT01967810).

Methods: Seventy-three patients were enrolled in 3 separate arms-recurrent glioblastoma (GBM) (Arm 1), bevacizumab refractory GBM (Arm 2), and grade 3 anaplastic gliomas (AGs) (Arm 3). The study was started in October 2013, and the data were locked on September 29, 2017. Safety was evaluated for all three arms (n = 73), and the primary endpoint for Arms 1 and 3 was objective response rate (ORR), and Arm 2 primary endpoint was progression-free survival rate at 3 months (PFS3).

Results: Overall, the safety of ANG1005 was found to be consistent with a taxane toxicity profile. Otherwise, the primary efficacy endpoints of ORR and PFS were not met. The most common adverse events (AEs) were hematologic (32.9%), alopecia (31.5%), and fatigue (30.1%). The median PFS was 1.4 months (95% CI: 1.4, 2.1) and similar across all the treatment arms. The median overall survival was 13.4 months (95% CI: 3.4, 14.6) in Arm 1, 5.8 months (95% CI: 1.9, 9.7) in Arm 2, and 18.2 months (95% CI: 10.7, 35.3) in Arm 3.

Conclusion: A dose of 600 mg/m² was determined to be safe in this study. However, the primary efficacy endpoint was not met in the NCT01967810-ANG1005 trial, and no further studies are planned in the glioma setting with this compound.

Background: Fully automatic skull-stripping and tumor segmentation are crucial for monitoring pediatric brain tumors (PBT). Current methods, however, often lack generalizability, particularly for rare tumors in the sellar/suprasellar regions and when applied to real-world clinical data in limited data scenarios. To address these challenges, we propose AI-driven techniques for skull-stripping and tumor segmentation.

Methods: Multi-institutional, multi-parametric MRI scans from 527 pediatric patients (n = 336 for skull-stripping, n = 489 for tumor segmentation) with various PBT histologies were processed to train separate nnU-Net-based deep learning models for skull-stripping, whole tumor (WT), and enhancing tumor (ET) segmentation. These models utilized single (T2/FLAIR) or multiple (T1-Gd and T2/FLAIR) input imaging sequences. Performance was evaluated using Dice scores, sensitivity, and 95% Hausdorff distances. Statistical comparisons included paired or unpaired 2-sample t-tests and Pearson's correlation coefficient based on Dice scores from different models and PBT histologies.

Results: Dice scores for the skull-stripping models for whole brain and sellar/suprasellar region segmentation were 0.98 ± 0.01 (median 0.98) for both multi- and single-parametric models, with significant Pearson's correlation coefficient between single- and multi-parametric Dice scores (r > 0.80; P < .05 for all). Whole tumor Dice scores for single-input tumor segmentation models were 0.84 ± 0.17 (median = 0.90) for T2 and 0.82 ± 0.19 (median = 0.89) for FLAIR inputs. Enhancing tumor Dice scores were 0.65 ± 0.35 (median = 0.79) for T1-Gd+FLAIR and 0.64 ± 0.36 (median = 0.79) for T1-Gd+T2 inputs.

Conclusion: Our skull-stripping models demonstrate excellent performance and include sellar/suprasellar regions, using single- or multi-parametric inputs. Additionally, our automated tumor segmentation models can reliably delineate whole lesions and ET regions, adapting to MRI sessions with missing sequences in limited data context.

Background: Survival of pediatric and young adults with malignant glioma remains poor despite progress in treatment. This is especially true for diffuse hemispheric glioma (DHG), H3 G34-mutant, which is often present in adolescent and young adult patients. This scoping review consolidates existing knowledge of DHG H3 G34-mutant and identifies future targets and therapeutic options. By streamlining this information, we aim to elucidate knowledge gaps in the field to better inform the community and motivate future research efforts.

Methods: In October 2024, MEDLINE, Embase, Cochrane Library, and Web of Science Core Collection were searched. Two reviewers screened all articles by title and abstract review and 3 independent reviewers extracted all studies meeting inclusion criteria relevant to H3G34R/V tumors (preclinical and clinical studies).

Results: Of the 2203 articles screened, 220 were deemed eligible (79 literature reviews, 7 systematic reviews, 63 preclinical studies, and 71 clinically oriented studies). We found that the United States and Acta Neuropathologica were the top country and journal contributors, respectively.

Conclusion: For this disease, it is critical to the field to conduct further research related to complexities of the tumor microenvironment, translation of preclinical studies to therapeutic early phase trials, and determining the role of targeted central nervous system drug delivery, so as to improve disease prognosis and survival.

Background: The majority of patients diagnosed with glioblastoma are >60 years. Three randomized trials addressed the roles of radiotherapy (RT) and temozolomide (TMZ) for elderly patients. NORDIC and NOA-08 compared RT versus TMZ, while CE.6 randomized between hypofractionated RT and RT + TMZ. All showed significant benefits for the TMZ arms, especially for those patients with O⁶-methylguanine DNA methyltransferase (MGMT) promoter-methylated tumors. This pooled analysis aimed at identifying additional factors that could improve individualized treatment recommendations.

Methods: Analyses were performed separately in the RT and TMZ arms of the pooled NORDIC and NOA-08 data, and in the RT and TMZ/RT arms of CE.6. The prognostic value of baseline clinical factors, comorbidities, and quality of life (QoL) scores were assessed.

Results: NORDIC + NOA-08 (NN) included 715 patients and CE.6 included 562 patients. Median age for NN was 71 and 73 years for CE.6. In NN and CE.6 respectively, 66.2% versus 70.5% underwent resection and 50.9% and 75.3% were on steroids. In NN, 401 patients received RT alone and 281 in CE.6, while 314 were randomized to TMZ alone in NN and 281 to concomitant RT + TMZ in CE.6. Known clinical prognostic factors, such as extent of resection and WHO performance status were confirmed, as was MGMT promoter methylation status for TMZ-treated patients. TMZ-treated patients with 2 or 3 comorbidities; hypertension, diabetes, and/or stroke had worse survival, both in NN (P = .022) and CE.6 (P = .022). Baseline QoL had a minor association with outcome.

Conclusion: Consideration of comorbidities allows improved personalized treatment decisions for elderly glioblastoma patients.