Neuro-oncology advances最新文献

Background: The optimal regimen, normal tissue tolerances, and appropriate indications for reirradiation for recurrent high-grade glioma (HGG) are uncertain. The aim of this study was to determine whether higher reirradiation dose was associated with toxicity or survival.

Methods: Patients with HGG treated with fractionated reirradiation at a single institution from 2007 to 2022 were retrospectively reviewed. Metrics evaluated included overall survival (OS), prognostic factors for survival, and treatment-related toxicity.

Results: Two hundred and thirty patients with recurrent HGG were reviewed. Median follow-up was 8.8 months. Median reirradiation dose was 41.4 Gy with 80.4% receiving concurrent systemic therapy. Median cumulative maximum doses to brainstem and optic structures were 77.9 Gy (range: 4.6-146.0 Gy) and 55.1 Gy (3.3-106.3 Gy), respectively. No injuries to these structures were identified. Radiation necrosis (RN) was identified in 9.4%. There were no significant associations between RN and target size, systemic therapy use, or reirradiation dose. Median OS was 10.2 months from reirradiation start. On multivariate analysis, improved OS was associated with better KPS, longer interval between radiotherapy sessions, reirradiation at first recurrence, and reirradiation dose ≥ 41.4 Gy. Median OS for those with IDH wildtype glioblastoma was 8.7 months. On multivariate analysis of an IDH wildtype disease subanalysis, improved OS was associated with longer interval between radiotherapy sessions and higher reirradiation dose.

Conclusions: These data support the safety and efficacy of fractionated reirradiation for recurrent HGG. They suggest higher reirradiation dose may be feasible, including for large treatment volumes and for tumors near the brainstem or optic structures.

Background: Adult onset medulloblastoma (aMB) is a rare tumor with limited available evidence. We present a large multi-institutional retrospective cohort of aMB patients treated in the modern era, with an emphasis on understanding the role of chemotherapy at initial diagnosis.

Methods: We included 267 consecutive patients with aMB treated at 7 different institutions from 2000-present, controlling for chemotherapy regimen and cycles received.

Results: Treatment factors were highly intercorrelated with one another and with treating institution. Concurrent chemotherapy was not associated with overall survival (OS). Adjuvant chemotherapy was associated with OS on univariable analyses (HR = 0.55, P = .029) and on multivariable analysis when adjusting for risk status (HR 0.55, P = .026) but not when also adjusting for treating institution. Proton craniospinal irradiation was associated with improved survival on univariable (HR = 0.50, P = .019) and multivariable analysis adjusting for risk status (HR = 0.51, P = .024) but not when treating institution was also considered. On subgroup analysis, adjuvant chemotherapy was associated with improved survival in M0 (HR = 0.55, P = .043) but not M1 disease, in patients with subtotal resection (HR = 0.43, P = .048) but not those with GTR. Similarly, progression-free survival was improved with chemotherapy in patients with M0 (HR = 0.57, P = .032) but not M1 disease, and in patients with subtotal (HR = 0.50, P = .054) but not gross total resection.

Conclusions: There was no benefit of concurrent chemotherapy. Adjuvant chemotherapy was associated with improved overall survival and this effect was driven by select subgroups, specifically those with M0 disease and those with residual tumor. We could not confirm that these associations are independent of the treating institution.

Background: This study aimed to develop an automated algorithm to noninvasively distinguish gliomas from other intracranial pathologies, preventing misdiagnosis and ensuring accurate analysis before further glioma assessment.

Methods: A cohort of 1280 patients with a variety of intracranial pathologies was included. It comprised 218 gliomas (mean age 54.76 ± 13.74 years; 136 males, 82 females), 514 patients with brain metastases (mean age 59.28 ± 12.36 years; 228 males, 286 females), 366 patients with inflammatory lesions (mean age 41.94 ± 14.57 years; 142 males, 224 females), 99 intracerebral hemorrhages (mean age 62.68 ± 16.64 years; 56 males, 43 females), and 83 meningiomas (mean age 63.99 ± 13.31 years; 25 males, 58 females). Radiomic features were extracted from fluid-attenuated inversion recovery (FLAIR), contrast-enhanced, and noncontrast T1-weighted MR sequences. Subcohorts, with 80% for training and 20% for testing, were established for model validation. Machine learning models, primarily XGBoost, were trained to distinguish gliomas from other pathologies.

Results: The study demonstrated promising results in distinguishing gliomas from various intracranial pathologies. The best-performing model consistently achieved high area-under-the-curve (AUC) values, indicating strong discriminatory power across multiple distinctions, including gliomas versus metastases (AUC = 0.96), gliomas versus inflammatory lesions (AUC = 1.0), gliomas versus intracerebral hemorrhages (AUC = 0.99), gliomas versus meningiomas (AUC = 0.98). Additionally, across all these entities, gliomas had an AUC of 0.94.

Conclusions: The study presents an automated approach that effectively distinguishes gliomas from common intracranial pathologies. This can serve as a quality control upstream to further artificial-intelligence-based genetic analysis of cerebral gliomas.

Background: Radiotherapy (RT) and stereotactic radiosurgery (SRS) are important treatment options for central nervous system (CNS) lesions. This review explores the current evidence on the use of radiotherapy and SRS for CNS lesions across Africa.

Methods: A systematic review of the literature was completed according to the PRISMA guidelines. The results were synthesized to provide an overview of the current landscape of RT and SRS, highlighting treatment gaps and areas for further research and collaboration.

Results: Nine studies, involving a total of 397 patients, were included. South Africa contributed the most studies with 4 (44.4%), followed by Nigeria with 3 studies (33.3%). Brain tumors were the most common lesion type, found in 88.8% of cases (95% CI: 66.9-100.0) with metastatic tumors being prevalent in 37.5% of cases (95% CI: 1.6-73.4). The breast was the most frequent origin of metastases seen in 93.67% (95% CI: 80-100). Whole brain radiation therapy was used in 33.3% of patients (95% CI: 0.7-66.0), stereotactic proton beam therapy in 33.3% (95% CI: 0.7-66.1), and gamma knife radiosurgery in 22.3% (95% CI: 0-51.1).

Conclusion: RT and SRS are being implemented for CNS lesions in settings across Africa. Improving access and efficiency of these treatments will require both local and international collaboration to address challenges related to resource management and distribution.

Background: The reported survival data for glioblastoma patients vary strongly between different studies. In our study, we therefore examined which data are applicable in a real-world population in a German center and how these real-world data perform in comparison to survival data presented in randomized controlled trials (RCTs).

Methods: Data of all patients treated with newly diagnosed glioblastoma in a single German center between 2010 and 2019 were analyzed and treatment patterns plus survival rates were matched to existing real-world data and results of RCTs.

Results: Two hundred thirty-three patients were analyzed. Median age was 63 years, f/m ratio was 1:162, and 73% of patients underwent surgery, while 27% had biopsy only. The extent of resection had a significant impact on overall survival (OS; P <.001), as well as age (P <.001), methylguanine methyltransferase methylation status (P <.001), and eastern cooperative oncology group performance status (P <.001). The median OS of our whole study population was 10.55 months. While a fictitious Stupp study cohort (built by using eligibility criteria of the EORTC-22981-26981 trial) with an OS of 14.3 months nearly achieved the survival results of the presented data from the EORTC-22981-26981 trial, the OS of the patients who did not fulfill the eligibility criteria was only 6.9 months.

Conclusion: Survival of patients with unfavorable prognostic factors is still poor and these patients are not represented in recent RCTs. Outcome data of RCTs can be transferred to real world cohorts, if in- and exclusion criteria are fulfilled, while outcome is significantly inferior in cohorts that do not fulfill these criteria.

Background: Novel treatments are needed for oligodendroglioma that has recurred following radiotherapy (RT) and chemotherapy. The cyclin D1-CDK4 axis is frequently dysregulated in oligodendroglioma. Abemaciclib is a selective CDK4/6 inhibitor that achieves pharmacologically relevant concentrations in brain tumor tissue.

Methods: We conducted a single-arm, phase 2 trial evaluating the efficacy of abemaciclib in patients with recurrent oligodendroglioma, isocitrate dehydrogenase (IDH)-mutant and 1p/19q-codeleted, WHO grade 3, following prior RT and ≥1 line of alkylating chemotherapy. Patients received abemaciclib 200 mg twice daily. The primary endpoint was progression-free survival at 6 months (PFS-6).

Results: Ten patients were enrolled. The most common treatment-related adverse event was grade 1-2 diarrhea, occurring in all patients. Five patients (50%) were alive and progression-free at 6 months, below the minimum required (80%) to meet the primary endpoint. In patients with enhancing tumor (n = 9), best response was partial response in 2 patients (objective radiographic response = 22.2%; duration of response [DOR] 13.1 and 7.7 months), stable disease (SD) in 3 patients (33.3%; duration of SD 17.0, 6.7, and 2.5 months), progressive disease in 3 patients (33.3%), and nonevaluable in 1 patient (11.1%). The patient with nonenhancing tumor showed SD lasting 10.2 months. Median PFS was 7.7 months (95% CI, 1.7-13.1 months); median overall survival was not reached (median follow-up 17 months).

Conclusions: The efficacy of abemaciclib in recurrent grade 3 oligodendroglioma was inadequate to warrant further evaluation as monotherapy in unselected patients. However, given the objective responses and durable disease control observed in a subset of patients, further studies are warranted to identify subgroups that may benefit.

Background: Cognitive dysfunction is common among patients with malignant glioma, yet the underlying mechanisms of this dysfunction remain unclear. Protein markers of neurodegeneration, inflammation, and vascular damage have been associated with central nervous system pathology and with cognitive changes in neurological diseases, but their clinical utility in gliomas is unknown. This study examined the relationships between cognitive dysfunction, tumor isocitrate dehydrogenase (IDH) mutation status in gliomas, and a panel of blood-based protein biomarkers.

Methods: This retrospective cohort study included 73 glioma patients with either IDH-mutant (n = 45) or IDH-wildtype tumors (n = 28) enrolled in a natural history study. Cognitive function was assessed using the Montreal Cognitive Assessment (scores <26 indicated cognitive dysfunction). Serum levels of 17 proteins were measured using ultrasensitive assays.

Results: Cognitive dysfunction was present in 53% of participants (n = 39), and more frequently in the IDH-wildtype group (75%) than in the IDH-mutant group (40%). Patients with wildtype tumors had higher levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1, interleukin-6 (IL-6), and tumor necrosis factor-α than patients with IDH-mutant tumors, which remained in multivariate analysis. ICAM-1 and IL-10 were higher in patients with cognitive dysfunction compared to those with normal cognition, even after adjusting for tumor IDH-mutation status, age, tumor grade, and surgery history.

Conclusions: Cognitive dysfunction was associated with protein markers linked to vascular damage and inflammation regardless of tumor IDH status. Our findings suggest an association of cognitive dysfunction with heightened systemic inflammatory status that requires further interrogation for its role in pathophysiologic mechanisms.

The blood-brain barrier (BBB) remains an obstacle for delivery of chemotherapeutic agents to gliomas. High grade and recurrent gliomas continue to portend a poor prognosis. Multiple methods of bypassing or manipulating the BBB have been explored, including hyperosmolar therapy, convection-enhanced delivery (CED), laser-guided interstitial thermal therapy (LITT), and Magnetic Resonance Guided Focused Ultrasound (MRgFUS) to enhance delivery of chemotherapeutic agents to glial neoplasms. Here, we review these techniques, currently ongoing clinical trials to disrupt or bypass the BBB in gliomas, and the results of completed trials.

Background: Effective follow-up of brain metastasis (BM) patients post-treatment is crucial for adapting therapies and detecting new lesions. Current guidelines (Response Assessment in Neuro-Oncology-BM) have limitations, such as patient-level assessments and arbitrary lesion selection, which may not reflect outcomes in high tumor burden cases. Accurate, reproducible, and automated response assessments can improve follow-up decisions, including (1) optimizing re-treatment timing to avoid treating responding lesions or delaying treatment of progressive ones, and (2) enhancing precision in evaluating responses during clinical trials.

Methods: We compared manual and automatic (deep learning-based) lesion contouring using unidimensional and volumetric criteria. Analysis focused on (1) agreement in size and RANO-BM categories, (2) stability of measurements under scanner rotations and over time, and (3) predictability of 1-year outcomes. The study included 49 BM patients, with 184 MRI studies and 448 lesions, retrospectively assessed by radiologists.

Results: Automatic contouring and volumetric criteria demonstrated superior stability (P < .001 for rotation; P < .05 over time) and better outcome predictability compared to manual methods. These approaches reduced observer variability, offering reliable and efficient response assessments. The best outcome predictability, defined as 1-year response, was achieved using automatic contours and volumetric measurements. These findings highlight the potential of automated tools to streamline clinical workflows and provide consistency across evaluators, regardless of expertise.

Conclusion: Automatic BM contouring and volumetric measurements provide promising tools to improve follow-up and treatment decisions in BM management. By enhancing precision and reproducibility, these methods can streamline clinical workflows and improve the evaluation of response in trials and practice.

Background: Polychemotherapy based on high-dose methotrexate (HD-MTX) is the standard therapy for newly diagnosed younger patients (<65 years) with primary CNS lymphoma (PCNSL). In the modified Bonn protocol, consolidation therapy consists of intraventricular chemotherapy that is added to the continuation of HD-MTX-based chemotherapy. This study investigates the efficacy and toxicity of the modified Bonn protocol in first-line therapy of young patients with PCNSL.

Methods: All consecutive immunocompetent patients aged <65 years who were newly diagnosed with PCNSL from 2012 to 2021 and started first-line therapy with the modified Bonn protocol at the Neurooncology Center Bonn were included in this retrospective analysis. Treatment comprised 3 courses of rituximab/HD-MTX/IFO followed by consolidation therapy with 2 courses of HD-AraC and 2 courses of HD-MTX/IFO, including intrathecal MTX and intrathecal AraC. Progression-free and overall survival were evaluated.

Results: Forty-three patients were included. Thirty-seven patients (86%) reached intrathecal consolidation therapy. Grade 3/4 toxicity was observed in 58.1%. The median PFS was 102.8 months; 5-year OS rate was 76% (median not reached). Eighteen patients developing refractory/relapsed PCNSL received second-line therapy using the modified Freiburg protocol (AraC/TT +/- HD-MTX/rituximab followed by BCNU/TT-based HD-ASCT). A second relapse was observed in 11/18 patients (median follow-up of 17 months (IQR 5-43.7 months)).

Conclusions: First-line treatment of PCNSL with the modified Bonn protocol is highly effective. The outcome compares well with other seemingly more toxic PCNSL protocols for younger patients. In patients with disease recurrence, second-line therapy according to the modified Freiburg protocol appears to be effective.