The latest medical research on Neuro Oncology

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Prognostic impact of obesity in newly-diagnosed glioblastoma: a secondary analysis of CeTeG/NOA-09 and GLARIUS.

Journal of Neuro-Oncology

The role of obesity in glioblastoma remains unclear, as previous analyses have reported contradicting results. Here, we evaluate the prognostic impact of obesity in two trial populations; CeTeG/NOA-09 (n = 129) for MGMT methylated glioblastoma patients comparing temozolomide (TMZ) to lomustine/TMZ, and GLARIUS (n = 170) for MGMT unmethylated glioblastoma patients comparing TMZ to bevacizumab/irinotecan, both in addition to surgery and radiotherapy.

The impact of obesity (BMI ≥ 30 kg/m2) on overall survival (OS) and progression-free survival (PFS) was investigated with Kaplan-Meier analysis and log-rank tests. A multivariable Cox regression analysis was performed including known prognostic factors as covariables.

Overall, 22.6% of patients (67 of 297) were obese. Obesity was associated with shorter survival in patients with MGMT methylated glioblastoma (median OS 22.9 (95% CI 17.7-30.8) vs. 43.2 (32.5-54.4) months for obese and non-obese patients respectively, p = 0.001), but not in MGMT unmethylated glioblastoma (median OS 17.1 (15.8-18.9) vs 17.6 (14.7-20.8) months, p = 0.26). The prognostic impact of obesity in MGMT methylated glioblastoma was confirmed in a multivariable Cox regression (adjusted odds ratio: 2.57 (95% CI 1.53-4.31), p < 0.001) adjusted for age, sex, extent of resection, baseline steroids, Karnofsky performance score, and treatment arm.

Obesity was associated with shorter survival in MGMT methylated, but not in MGMT unmethylated glioblastoma patients.

Modern surgical management of incidental gliomas.

Journal of Neuro-Oncology

Gliomas are the most common primary tumors of the central nervous system and are categorized by the World Health Organization into either low-grade (grades 1 and 2) or high-grade (grades 3 and 4) gliomas. A subset of patients with glioma may experience no tumor-related symptoms and be incidentally diagnosed. These incidental low-grade gliomas (iLGG) maintain controversial treatment course despite scientific advancements. Here we highlight the recent advancements in classification, neuroimaging, and surgical management of these tumors.

A review of the literature was performed. The authors created five subtopics of focus: histological criteria, diagnostic imaging, surgical advancements, correlation of surgical resection and survival outcomes, and clinical implications.

Alternating studies suggest that these tumors may experience higher mutational rates than their counterparts. Significant progress in management of gliomas, regardless of the grade, has been made through modern neurosurgical treatment modalities, diagnostic neuroimaging, and a better understanding of the genetic composition of these tumors. An optimal treatment approach for patients with newly diagnosed iLGG remains ill-defined despite multiple studies arguing in favor of safe maximal resection. Our review emphasizes the not so benign nature of incidental low grade glioma and further supports the need for future studies to evaluate survival outcomes following surgical resection.

Diversity within the Neurosurgical Oncology Workforce in the United States: A Cross-Sectional Study with Proposed Strategies to Pave the Path Forward.

Neuro-Oncology

Improving and fostering diversity within the neurosurgical workforce has become a high priority. This cross-sectional study aims to provide data on the diversity of neurosurgical oncology faculty (NSOF) in the US.

All 115 neurosurgery (NS) ACGME accredited programs were included in this study. The academic rank, academic and clinical title(s), gender, race, and hiring date of neurosurgical faculty with a primary focus on neurosurgical oncology (NSOF) were recorded. Geographical distribution and "top 10" programs were tabulated according to published data. Underrepresented minorities in medicine (URiM) faculty were identified according to the AAMC definition.

The NSOF workforce constitute 21% of the total NS faculty. Of these, 10.1% are women and 9.9% are URiM (p<0.001). Currently, 58% of neurosurgery programs (NSP) do not have URiM and/or women NSOF. The top 10 ranked NSP, according to Blue Ridge Institute for Medical Research, had a significantly less URiM NSOF (p= 0.019) than non-top 10 ranked programs. There was a decreasing trend in the proportion of URiM at higher academic ranks (p= 0.019). All of the URiM department chairs (3/113)- all men- and 1/3 women department chairs nationwide subspecialized in neurosurgical oncology.

Neurosurgical oncology is a sought-after subspecialty attracting a fifth of neurosurgeons practicing in ACGME-accredited training programs. Changing demographics and the benefits of workforce diversity represent a great opportunity for our field to continue leading inclusion efforts and attracting the best and brightest.

The early infiltrative phase of GBM hypothesis: are molecular glioblastomas histological glioblastomas in the making? A preliminary multicenter study.

Journal of Neuro-Oncology

The presence of necrosis or microvascular proliferation was previously the hallmark for glioblastoma (GBM) diagnosis. The 2021 WHO classification now considers IDH-wildtype diffuse astrocytic tumors without the histological features of glioblastoma (that would have otherwise been classified as grade 2 or 3) as molecular GBM (molGBM) if they harbor any of the following molecular abnormalities: TERT promoter mutation, EGFR amplification, or chromosomal + 7/-10 copy changes. We hypothesize that these tumors are early histological GBM and will eventually develop the classic histological features.

Medical records from 65 consecutive patients diagnosed with molGBM at three tertiary-care centers from our institution were retrospectively reviewed from November 2017-October 2021. Only patients who underwent reoperation for tumor recurrence and whose tissue at initial diagnosis and recurrence was available were included in this study. The detailed clinical, histopathological, and radiographic scenarios are presented.

Five patients were included in our final cohort. Three (60%) patients underwent reoperation for recurrence in the primary site and 2 (40%) underwent reoperation for distal recurrence. Microvascular proliferation and pseudopalisading necrosis were absent at initial diagnosis but present at recurrence in 4 (80%) patients. Radiographically, all tumors showed contrast enhancement, however none of them showed the classic radiographic features of GBM at initial diagnosis.

In this manuscript we present preliminary data for a hypothesis that molGBMs are early histological GBMs diagnosed early in their natural history of disease and will eventually develop necrosis and microvascular proliferation. Further correlative studies are needed in support of this hypothesis.

The role of cesium-131 brachytherapy in brain tumors: a scoping review of the literature and ongoing clinical trials.

Journal of Neuro-Oncology

Cesium-131 radioactive isotope has favored the resurgence of intracavitary brachytherapy in neuro-oncology, minimizing radiation-induced complications and maximizing logistical and clinical outcomes. We reviewed the literature on cesium-131 brachytherapy for brain tumors.

PubMed, Web-of-Science, Scopus, Clinicaltrial.gov, and Cochrane were searched following the PRISMA extension for scoping reviews to include published studies and ongoing trials reporting cesium-131 brachytherapy for brain tumors.

We included 27 published studies comprising 279 patients with 293 lesions, and 3 ongoing trials. Most patients had brain metastases (63.1%), followed by high-grade gliomas (23.3%), of WHO Grade III (15.2%) and Grade IV (84.8%), and meningiomas (13.6%), mostly of WHO Grade II (62.8%) and Grade III (27.9%). Most brain metastases were newly diagnosed (72.3%), while most gliomas and meningiomas were recurrent (95.4% and 88.4%). Patients underwent gross-total (91.1%) or subtotal (8.9%) resection, with median postoperative cavity size of 3.5 cm (range 1-5.8 cm). A median of 20, 28, and 16 seeds were implanted in gliomas, meningiomas, and brain metastases, with median seed activity of 3.8 mCi (range 2.4-5 mCi). Median follow-up was 16.2 months (range 0.6-72 months). 1-year freedom from progression rates were local 94% (range 57-100%), regional 85.1% (range 55.6-93.8%), and distant 53.5% (range 26.3-67.4%). Post-treatment radiation necrosis, seizure, and surgical wound infection occurred in 3.4%, 4.7%, and 4.3% patients.

Initial data suggest that cesium-131 brachytherapy is safe and effective in primary or metastatic malignant brain tumors. Ongoing trials are evaluating long-term locoregional tumor control and future studies should analyze its role in multimodal systemic tumor management.

Investigational PET tracers in neuro-oncology-What's on the horizon? A report of the PET/RANO group.

Neuro-Oncology

Many studies in patients with brain tumors evaluating innovative PET tracers have been published in recent years, and the initial results are promi...

Time interval between the diagnosis of breast cancer and brain metastases impacts prognosis after metastasis surgery.

Journal of Neuro-Oncology

Breast cancer (BC) is the most frequently diagnosed tumor entity in women. Occurring at different time intervals (TI) after BC diagnosis, brain metastases (BM) are associated with poor prognosis. We aimed to identify the risk factors related to and the clinical impact of timing on overall survival (OS) after BM surgery.

We included 93 female patients who underwent BC BM surgery in our institution (2008-2019). Various clinical, radiographic, and histopathologic markers were analyzed with respect to TI and OS.

The median TI was 45.0 months (range: 9-334.0 months). Fifteen individuals (16.1%) showed late occurrence of BM (TI ≥ 10 years), which was independently related to invasive lobular BC [adjusted odds ratio (aOR) 9.49, 95% confidence interval (CI) 1.47-61.39, p = 0.018] and adjuvant breast radiation (aOR 0.12, 95% CI 0.02-0.67, p = 0.016). Shorter TI (< 5 years, aOR 4.28, 95% CI 1.46-12.53, p = 0.008) was independently associated with postoperative survival and independently associated with the Union for International Cancer Control stage (UICC) III-IV of BC (aOR 4.82, 95% CI 1.10-21.17, p = 0.037), midline brain shift in preoperative imaging (aOR10.35, 95% CI 1.09-98.33, p = 0.042) and identic estrogen receptor status in BM (aOR 4.56, 95% CI 1.35-15.40, p = 0.015).

Several factors seem to influence the period between BC and BM. Occurrence of BM within five years is independently associated with poorer prognosis after BM surgery. Patients with invasive lobular BC and without adjuvant breast radiation are more likely to develop BM after a long progression-free survival necessitating more prolonged cancer aftercare of these individuals.

Spectroscopic imaging of D-2-hydroxyglutarate and other metabolites in pre-surgical patients with IDH-mutant lower-grade gliomas.

Journal of Neuro-Oncology

Prognostically favorable IDH-mutant gliomas are known to produce oncometabolite D-2-hydroxyglutarate (2HG). In this study, we investigated metabolite-based features of patients with grade 2 and 3 glioma using 2HG-specific in vivo MR spectroscopy, to determine their relationship with image-guided tissue pathology and predictive role in progression-free survival (PFS).

Forty-five patients received pre-operative MRIs that included 3-D spectroscopy optimized for 2HG detection. Spectral data were reconstructed and quantified to compare metabolite levels according to molecular pathology (IDH1R132H, 1p/19q, and p53); glioma grade; histological subtype; and T2 lesion versus normal-appearing white matter (NAWM) ROIs. Levels of 2HG were correlated with other metabolites and pathological parameters (cellularity, MIB-1) from image-guided tissue samples using Pearson's correlation test. Metabolites predictive of PFS were evaluated with Cox proportional hazards models.

Quantifiable levels of 2HG in 39/42 (93%) IDH+ and 1/3 (33%) IDH- patients indicated a 91.1% apparent detection accuracy. Myo-inositol/total choline (tCho) showed reduced values in astrocytic (1p/19q-wildtype), p53-mutant, and grade 3 (vs. 2) IDH-mutant gliomas (p < 0.05), all of which exhibited higher proportions of astrocytomas. Compared to NAWM, T2 lesions displayed elevated 2HG+ γ-aminobutyric acid (GABA)/total creatine (tCr) (p < 0.001); reduced glutamate/tCr (p < 0.001); increased myo-inositol/tCr (p < 0.001); and higher tCho/tCr (p < 0.001). Levels of 2HG at sampled tissue locations were significantly associated with tCho (R = 0.62; p = 0.002), total NAA (R = - 0.61; p = 0.002) and cellularity (R = 0.37; p = 0.04) but not MIB-1. Increasing levels of 2HG/tCr (p = 0.0007, HR 5.594) and thresholding (≥ 0.905, median value; p = 0.02) predicted adverse PFS.

In vivo 2HG detection can reasonably be achieved on clinical scanners and increased levels may signal adverse PFS.

Long-term outcomes and late toxicity of adult medulloblastoma treated with combined modality therapy: a contemporary single-institution experience.

Neuro-Oncology

Medulloblastoma (MB) is a rare central nervous system malignancy of adults, with limited contemporary studies to define treatment guidelines and expected late toxicity.

A single-center, retrospective study was conducted of patients age ≥18-years from 1997-2019 with MB and who were treated with postoperative radiotherapy. Late toxicity was defined as a minimum of 18-months from diagnosis. Overall survival (OS) and progression-free survival (PFS) were characterized using Kaplan-Meier and Cox regression analyses.

Fifty-nine patients met criteria, with median age of 25-years (range 18-62y) and median follow-up of 6.5-years (range 0.7-23.1y). At diagnosis, 68% were standard-risk, 88% Chang M0, and 22% with anaplastic histology. Gross total resection was achieved in 75%; median craniospinal irradiation dose was 30.6Gy(relative biological effectiveness [RBE]), median total dose was 54.0Gy(RBE), 80% received proton radiotherapy; 81% received chemotherapy. 5-year PFS and OS were 86.5% and 95.8%, respectively; 10-year PFS and OS were 83.9% and 90.7%, respectively. Anaplastic histology was associated with worse PFS (p=0.04). Among eight recurrences, 25% presented after 5-years. Most common grade ≥2 late toxicities were anxiety/depressive symptoms (30%), motor dysfunction (25%), and ototoxicity (22%). Higher posterior fossa radiation dose was associated with increased risk of late toxicity, including worse cognitive dysfunction (p = 0.05).

Adults with MB have favorable survival outcomes, but late failures and toxicity are not uncommon. Better understanding of prognostic factors, possibly from molecular subtyping, may help to define more personalized treatments for patients with high risk of recurrence and long-term treatment sequelae.

Prognostic utility of lncRNAs (LINC00565 and LINC00641) as molecular markers in glioblastoma multiforme (GBM).

Journal of Neuro-Oncology

Glioblastoma multiforme (GBM) is primary brain tumor grade IV characterized by fast cell proliferation, high mortality and morbidity and most lethal gliomas. Molecular approaches underlying its pathogenesis and progression with diagnostic and prognostic value have been an area of interest. Long-non coding RNAs (lncRNAs) aberrantly expressed in GBM have been recently studied. The aim is to investigate the clinical role of lncRNA565 and lncRNA641 in GBM patients.

Blood samples were withdrawn from 35 newly diagnosed GBM cases with 15 healthy individuals, then lncRNA565 and lncRNA641 expression were evaluated using real time-PCR. Their diagnostic efficacy was detected using receiver operating characteristic curve. Progression free survival (PFS) and overall survival (OS) were studied using Kaplan-Meier curves.

lncRNAs expressions were increased significantly among GBM as compared to control group. Their expressions were correlated with clinico-pathological data and survival pattern for the studied GBM patients. Higher levels of both lncRNAs were correlated to worse performance status. Expression of lncRNA565 was increased with large tumor size (≥ 5 cm). Survival analysis showed that both investigated lncRNA were increased with worse PFS and OS.

Expression of lncRNA565 and lncRNA641 in a liquid biopsy sample can be used as prognostic biomarker for GBM patients.

Low-Risk Meningioma: Initial Outcomes from NRG Oncology/RTOG 0539.

Neuro-Oncology

Three- and five-year progression-free survival (PFS) for low-risk meningioma managed with surgery and observation exceeds 90%. Herewith we summarize outcomes for low-risk meningioma patients enrolled on NRG/RTOG 0539.

This phase II trial allocated patients to 1 of 3 groups per WHO grade, recurrence status, and resection extent. Low-risk patients had either gross total (GTR) or subtotal resection (STR) for a newly diagnosed grade 1 meningioma and were observed after surgery. The primary endpoint was 3-year PFS. Adverse events (AEs) were scored using CTCAE version 3.

Among 60 evaluable patients, median follow-up was 9.1 years. The 3, 5, and 10 year rates were 91.4% (95% CI:84.2-98.6), 89.4% (95% CI:81.3-97.5), 85.0% (95% CI:75.3-94.7) for PFS and 98.3% (95% CI:94.9-100), 98.3%, (95% CI:94.9-100), 93.8% (95% CI:87.0-100) for overall survival (OS), respectively. With centrally confirmed GTR, 3/5/10y PFS and OS rates were 94.3/94.3/87.6% and 97.1/97.1/90.4%. With STR, 3/5/10y PFS rates were 83.1/72.7/72.7% and 10y OS 100%. Five patients reported 1 grade 3, 4 grade 2, and 5 grade 1 adverse events. There were no grade 4 or 5 adverse events.

These results prospectively validate high PFS and OS for low-risk meningioma managed surgically but raise questions regarding optimal management following STR, a subcohort that could potentially benefit from adjuvant therapy.

Management of Neurofibromatosis Type 1-Associated Plexiform Neurofibromas.

Neuro-Oncology

Plexiform Neurofibromas (PN) are a common manifestation of the genetic disorder neurofibromatosis type 1 (NF1). These benign nerve sheath tumors of...