The latest medical research on Neuro Oncology
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Request AccessReappraisal of prognostic factors in CNS WHO grade 3 oligodendrogliomas IDH-mutant and 1p/19q co-deleted: lessons from the French POLA cohort.
Neuro-OncologyIn POLA cohort, three pathological groups of CNS WHO grade 3 oligodendroglioma IDH-mutant and 1p/19q co-deleted have been described: group 1 (high mitotic count only), group 2 (microvascular proliferation MVP and no necrosis), and group 3 (MVP and necrosis).
494 patients from the POLA cohort, with a median follow up of 96 months were included. To identify the impact of the pathological groups and contrast enhancement in group 1 on overall survival (OS) or progression free survival (PFS), survival curves were obtained (Kaplan-Meier method) and compared (log-rank test). Prognostic value of clinical factors and CDKN2A homozygous deletion HD were also tested. Multivariate analysis was performed.
Survival analysis demonstrated that the pathological groups were associated with both progression-free survival (PFS P=0.01) and overall survival (OS P=0.001). In group 1, patients with contrast enhancement (1CE+) had a poorer prognosis compared to those without (OS P=0.028, PFS P=0.006). Further stratification into group 1CE-, group 1CE+, group 2, and group 3 provided clearer prognostic distinctions (OS P=0.002, PFS P<0.0001). Other prognostic factors included age (OS P<0.0001, PFS P=0.002), extent of surgical resection (OS P=0.001, PFS P=0.003), KPS (OS P<0.0001, PFS P=0.002), postoperative treatment (OS P=0.007, PFS P<0.0001), and CDKN2A HD (OS and PFS P<0.0001). The pathological groups remained of prognostic significance for PFS in multivariate analysis.
Necrosis and CDKN2A HD are adverse prognostic factors of WHO grade 3 oligodendrogliomas, IDH mutant and 1p/19q co-deleted. Besides, in group 1 patients, lack of contrast enhancement is a factor of better prognosis.
A multi-center, clinical analysis of IDH-mutant gliomas, WHO Grade 4: implications for prognosis and clinical trial design.
Journal of Neuro-OncologyMutations in the Isocitrate Dehydrogenase (IDH) genes, IDH1 or IDH2, define a group of adult diffuse gliomas associated with a younger age at diagnosis and better prognosis than IDH wild-type glioblastoma. Within IDH mutant gliomas, a small fraction of astrocytic tumors present with grade 4 histologic features and poor prognosis. In molecular studies, homozygous deletion of CDKN2A/B is independently predictive of poor prognosis and short survival. As a consequence, 2021 WHO classification now also recognizes this molecular feature, CDKN2A/B deletion, as sufficient for classifying an astrocytoma as IDH-mutant, WHO Grade 4, regardless of histological grading. Here, we investigate outcomes of patients with WHO Grade 4 IDH-mutant astrocytoma both with and without CDKN2A/B deletion, to compare these groups and evaluate clinical and radiographic factors that contribute to survival.
We retrospectively identified 79 patients with IDH-mutant astrocytoma with CDKN2A/B deletion detected at initial diagnosis across five international institutions as well as a comparison group of 51 patients with IDH-mutant, astrocytoma, histologically Grade 4 without detectable CDKN2A/B deletion. We assembled clinical and radiographic features for all patients.
We find that CDKN2A/B deletion was associated with significantly worse overall survival (OS; p = 0.0004) and progression-free survival (PFS; p = 0.0026), with median OS of 5.0 years and PFS of 3.0 years, compared to 10.1 and 5.0 years for tumors with a grade 4 designation based only on histologic criteria. Multivariate analysis confirmed CDKN2A/B deletion as a strong negative prognosticator for both OS (HR = 3.51, p < 0.0001) and PFS (HR = 2.35, p = 0.00095). In addition, in tumors with CDKN2A/B deletion, preoperative contrast enhancement is a significant predictor of worse OS (HR 2.19, 95% CI 1.22-3.93, p = 0.0090) and PFS (HR = 1.74, 95% CI = 1.02-2.97, p = 0.0420).
These findings underscore the severe prognostic impact of CDKN2A/B deletion in IDH-mutant astrocytomas and highlight the need for further refinement of tumor prognostic categorization. Our results provide a key benchmark of baseline patient outcomes for therapeutic trials, underscoring the importance of CDKN2A/B status assessment, in addition to histologic grading, in clinical trial design and therapeutic decision-making for IDH-mutant astrocytoma patients.
Quality of life after stereotactic radiosurgery for brain metastasis: an assessment from a prospective national registry.
Journal of Neuro-OncologyStereotactic radiosurgery (SRS) is frequently used in the management of brain metastasis patients. However, there is an urgent need to evaluate post-treatment outcomes and quality of life metrics for patients undergoing SRS for brain metastases.
The NeuroPoint Alliance (NPA) SRS Quality Registry conducted prospective enrollment of patients undergoing SRS from 2017 to 2024. Patients with brain metastases from lung cancer, breast cancer, and melanoma were included in the analysis. Outcomes of interest included quality of life metrics, as captured by the five-dimension Euro-QOL (EQ-5D) at 6-12 months and last record follow-up, overall survival, local progression, out-of-field progression, and overall intracranial progression.
522 patients comprised our analytic cohort, and 315 patients had available EQ-5D data at the time of SRS and final follow-up. 264 (47.8%), 197 (35.7%), and 91 (16.5%) patients had 1, 2-4, and 5-14 lesions pre-SRS, respectively. The median overall survival time from diagnosis was 27.3 months. The median time-to-local progression was not reached. At final follow-up, 107 (34.0%) patients had improvement, 51 (16.2%) patients had stable, and 113 patients (35.9%) had worsening EQ-5D scores when compared to baseline. For 44 (13.9%) patients mixed responses across the EQ-5D indices were reported. Linear regression analysis showed that male sex, smoking status, primary tumor type, time-to-overall progression, cumulative intracranial tumor volume (CITV), and baseline EQ-5D were statistically significantly associated with EQ-5D single index at the final follow-up.
Real-world data from the SRS NPA Registry demonstrated that most patients with brain metastasis had no change or improvement in quality of life after SRS. Baseline EQ-5D was predictive of EQ-5D single index at final follow-up, and, as such, EQ-5D at baseline would be a valuable assessment measure for brain metastasis patients undergoing SRS.
Comparative analysis of hypofractionated short-course versus standard radiation therapy in elderly patients with glioblastoma: analysis of nationwide database.
Journal of Neuro-OncologyHypofractionated short-course radiation therapy (SCRT) is an alternative treatment option for elderly or frail patients with newly diagnosed glioblastoma (GBM) post-surgery. This study compares survival outcomes and treatment costs between patients receiving SCRT and those undergoing standard long-course radiation therapy (LCRT).
This retrospective study utilized health insurance claims and national cancer registry data from Korea to compare overall survival (OS) and treatment costs between patients receiving SCRT and LCRT across all ages and sub-group analysis within the subgroup of cases aged 65 and older from 2016 onwards, a period when intensity-modulated radiotherapy (IMRT) was widely adopted.
A total of 1,598 patients were included. Median OS since the first day of radiation therapy was 10.4 months (95% CI [9.6; 12.8]) for SCRT (n = 197) versus 16.2 months (95% CI [15.5; 16.9]) for LCRT (n = 1401) respectively. Subgroup analysis using stabilized inverse probability of treatment weighting (S-IPTW) showed indicating non-inferiority in elderly patients in median OS for elderly patients (≥ 65) with 10.6 months (95% CI [8.9; 14.0]) for SCRT (n = 147) versus 13.2 months (95% CI [8.9; 14.0]) for LCRT (n = 541). The median treatment cost of SCRT is about 6,000 USD lower, 25% less than LCRT. Compliance with the standard TMZ regimen post-radiation improved OS across all age groups.
Considering comparable OS and shorter treatment duration, SCRT offers a viable, cost-effective option for elderly GBM patients. Adhering to standard TMZ also contributes to OS improvement. Further research reflecting key prognostic factors is essential to refining the role of SCRT.
Is modulation of immune checkpoints on glioblastoma-infiltrating myeloid cells a viable therapeutic strategy?
Neuro-OncologyThe field of immunology has traditionally focused on immune checkpoint modulation of adaptive immune cells. However, many malignancies such as glio...
Early experience with an artificial intelligence-based module for brain metastasis detection and segmentation.
Journal of Neuro-Oncology- Accurate detection, segmentation, and volumetric analysis of brain lesions are essential in neuro-oncology. Artificial intelligence (AI)-based models have improved the efficiency of these processes. This study evaluated an AI-based module for detecting and segmenting brain metastases, comparing it with manual detection and segmentation.
- MRIs from 51 patients treated with Gamma Knife radiosurgery for brain metastases were analyzed. Manual lesion identification and contouring on Leksell Gamma Plan at the time of treatment served as the gold standard. The same MRIs were processed through an AI-based module (Brainlab Smart Brush), and lesion detection and volumes were compared. Discrepancies were analyzed to identify possible sources of error.
- Among 51 patients, 359 brain metastases were identified. The AI module achieved a sensitivity of 79.2% and a positive predictive value of 95.6%, compared to a 93.3% sensitivity for manual detection. However, for lesions > 0.1 cc, the AI's sensitivity rose to 97.5%, surpassing manual detection at 93%. Volumetric agreement between AI and manual segmentations was high (Spearman's ρ = 0.997, p < 0.001). Most lesions missed by the AI (53.8%) were near anatomical structures that complicated detection.
- The AI module demonstrated higher sensitivity than manual detection for metastases larger than 0.1 cc, with robust volumetric accuracy. However, human expertise remains critical for detecting smaller lesions, especially near complex anatomical areas. AI offers significant potential to enhance neuro-oncology practice by improving the efficiency and accuracy of lesion management.
Intrathecal anti-PD-1 treatment in metastatic melanoma patients with leptomeningeal disease (LMD): real-world data and evidence.
Journal of Neuro-OncologyLeptomeningeal disease (LMD) is a severe complication of melanoma with a very poor prognosis. Despite improved treatment strategies and prolonged survival, the incidence of LMD has increased over the past decade. This real-world study aims to evaluate the efficacy and safety of intrathecal anti-PD-1 treatment in melanoma patients with LMD.
Melanoma patients with LMD diagnosed by magnetic resonance imaging (MRI) and/or cerebrospinal fluid (CSF) cytology were treated with intrathecal infusions of nivolumab 20 mg once every 2 weeks (n = 5) or pembrolizumab 20 mg once every 3 weeks (n = 3), alongside systemic therapy. Patients received a median of 5.5 treatment cycles (range 2-9). Efficacy and safety analyses were performed on all treated patients.
From June 2022 to February 2023, eight patients were treated, including four with cutaneous melanoma, two with acral melanoma, and two with primary leptomeningeal melanoma. All patients exhibited linear or small nodular enhancement of the leptomeninges on MRI. Four patients had concurrent parenchymal brain metastases. Tumor cells were identified in six patients by CSF cytology, and two patients underwent leptomeningeal biopsy for pathological diagnosis. According to the RANO-LM criteria, five patients responded to treatment with symptom improvement and reduction or disappearance of linear enhancement on MRI, while three patients developed progressive disease. With a median follow-up of 20.7 weeks (range 8.1-45.3 weeks), the median OS and median intracranial progression-free survival (IPFS) for intrathecal anti-PD-1 treatment were 21.1 and 16.1 weeks, respectively. All treatment-related adverse events were grade 1-2, including headache (grade 1, n = 1; grade 2, n = 2) and low back pain (grade 1, n = 1).
In this real-world study, intrathecal anti-PD-1 treatment demonstrated potential clinical benefits and was well tolerated in metastatic melanoma patients with LMD.
Therapeutic strategies for mobile spine chordoma: en bloc Versus intralesional surgery with adjuvant charged-particle therapy.
Journal of Neuro-OncologyThe aim of this retrospective study is to analyze the impact of en bloc resection with negative margins versus intralesional resection plus adjuvant hadron-therapy (HT) on local control (LC) and overall survival (OS) in patients with mobile spine chordomas. Mechanical complications incidence as well as risk factors, and outcome differences are investigated as secondary endpoints.
33 patients in a period from January 2013 to December 2021 were enrolled for the final analysis. The inclusion criteria were: lesions located in the mobile spine (C1-L5), age ≥ 15 years, minimum follow-up of 2 years, en bloc or intralesional surgical resection, virgin or recurrent chordomas, with only one previous surgical treatment.
No difference was found in terms of LC between the two groups. The presence of pathologic fracture at pre-operative imaging and the presence of macroscopic residual tumor after surgery, independently from its entity, seemed to be associated with an increased risk of LR. No difference was found between planned en bloc and planned intralesional surgery in terms of mechanical complications occurrence. Eight patients (24.24%) had mechanical complications during the follow up period: male sex, presence of pathologic fracture at baseline, a combined surgical approach, the use of carbon fiber-only hardware appeared to be associated with an increased risk of mechanical complications after the primary surgery.
En bloc resection, whenever possible, is always to be preferred for its widely recognized potential in LC and OS improvement. However, technology advances in high-dose conformal charged-particle therapy have allowed improvement of local control rates as an adjuvant therapy of intralesional surgery for mobile spine chordoma, with acceptable acute and chronic toxicity.
Financial toxicity in patients with glioblastoma.
Journal of Neuro-OncologyThere has been mounting interest in understanding the impact of financial toxicity (FT) in various cancer types; however, it remains poorly understood and understudied within neuro-oncology-especially as it relates to neurosurgical components of patient care.
Retrospective, single-center study of patients who underwent craniotomy for resection of glioblastoma from 2020 to 2022. OIBEE™ (Austin, Texas) software was queried to identify the subset of these patients who had a bad debt charged to their account. These patients were deemed to qualify as experiencing FT. Chi Square analysis was conducted between FT and non-FT patient groups. Additionally, survival analyses were performed to determine predictors of progression free and overall survival.
74 patients were included in this sample. 33/74 (44%) met criteria for FT. The average bad debt amount was $7,476.76 and the median debt amount was $2,015.96, with the average time to financial toxicity after surgery being approximately 127 days. FT patients were significantly younger at diagnosis than those who were not FT (64.6 years- non-FT vs. 59.0 years- FT, p = 0.0344). FT patients were more likely to have undergone subtotal resections rather than a gross total resection compared to non-FT patients (FT GTR 27.3%, non-FT GTR 52.4%, p = 0.028). Hospital length of stay was significantly longer for FT patients compared to non-FT patients (LOS FT 9.5 days, non-FT 6.5 days, p = 0.0312).
Glioblastoma patients are at high risk of experiencing FT with our series showing no significant impact on overall survival. Larger studies are needed to understand the impact of FT on patient outcomes.
Intracranial administration of anti-PD-1 and anti-CTLA-4 immune checkpoint-blocking monoclonal antibodies in patients with recurrent high-grade glioma.
Neuro-OncologyRecurrent high-grade glioma (rHGG) lacks effective life-prolonging treatments and the efficacy of systemic PD-1 and CTLA-4 immune checkpoint inhibitors is limited. The multi-cohort Glitipni phase I trial investigates the safety and feasibility of intraoperative intracerebral (iCer) and postoperative intracavitary (iCav) nivolumab (NIVO) ± ipilimumab (IPI) treatment following maximal safe resection (MSR) in rHGG.
Patients received 10 mg IV NIVO within 24 h before surgery, followed by MSR, iCer 5 mg IPI and 10 mg NIVO, and Ommaya catheter placement in the resection cavity. Biweekly postoperative iCav administrations of 1-5-10 mg NIVO (cohort 4) or 10 mg NIVO plus 1-5-10 mg IPI (cohort 7) were combined with 10 mg IV NIVO for 11 cycles.
42 rHGG patients underwent MSR with iCer NIVO + IPI. 16 pts were treated in cohort 4 (postoperative iCav NIVO at escalating doses) while 28 patients were treated in cohort 7 (intra and postoperative iCav NIVO and escalating doses of IPI). The most common TRAE was fatigue; no grade 5 AE occurred. Dose-limiting toxicity was grade 3 neutrophilic pleocytosis (4 pts) receiving iCav NIVO plus 5 or 10 mg IPI. PFS and OS did not significantly differ between cohorts (median OS: 42 [95% CI 26-57] vs. 35 [29-40] weeks; 1-year OS rate: 37% vs. 29%). Baseline B7-H3 expression significantly correlated with worse survival. OS compared favorably to a historical pooled cohort (n = 469) of Belgian rHGG pts treated with anti-VEGF therapies (log-rank P = .015).
Intraoperative iCer IPI + NIVO with postoperative iCav NIVO ± IPI up to biweekly doses of 1 mg IPI + 10 mg NIVO is feasible and safe, showing encouraging OS in rHGG patients. ClinicalTrials.gov registration: NCT03233152.
DTI fiber-tracking parameters adjacent to gliomas: the role of tract irregularity value in operative planning, resection, and outcome.
Journal of Neuro-OncologyThe goal of glioma surgery is maximal tumor resection associated with minimal post-operative morbidity. Diffusion tensor imaging-tractography/fiber tracking (DTI-FT) is a valuable white-matter (WM) visualization tool for diagnosis and surgical planning. Still, it assumes a descriptive role since the main DTI metrics and parameters showed several limitations in clinical use. New applications and quantitative measurements were recently applied to describe WM architecture that surround the tumor area. The brain adjacent tumor area (BAT) is defined as the region adjacent to the gross tumor volume, which contains signal abnormalities on T2-weighted or FLAIR sequences. The DTI-FT analysis of the BAT can be adopted as predictive values and a guide for safe tumor resection.
This is an observational prospective study on an extensive series of glioma patients who performed magnetic resonance imaging (MRI) with pre-operative DTI-FT analyzed on the BAT by two different software. We examined DTI parameters of Fractional anisotropy (FA mean, min-max), Mean diffusivity (MD), and the shape-metric "tract irregularity" (TI) grade, comparing it with the surgical series' clinical, radiological, and outcome data.
The population consisted of 118 patients, with a mean age of 60.6 years. 82 patients suffering from high-grade gliomas (69.5%), and 36 from low-grade gliomas (30.5%). A significant inverse relationship exists between the FA mean value and grading (p = 0.001). The relationship appears directly proportional regarding MD values (p = 0.003) and TI values (p = 0.005). FA mean and MD values are susceptible to significant variations with tumor and edema volume (p = 0.05). TI showed an independent relationship with grading regardless of tumor radiological features and dimensions, with a direct relationship with grading, ki67% (p = 0,05), PFS (p < 0.001), and EOR (p < 0.01).
FA, MD, and TI are useful predictive measures of the clinical behavior of glioma, and TI could be helpful for tumor grading identification and surgical planning.
The Immune Landscape in Brain Metastasis.
Neuro-OncologyThe prognosis for patients with brain metastasis remains dismal despite intensive therapy including surgical resection, radiotherapy, chemo-, targe...
