Short-term outcomes associated with temozolomide or PCV chemotherapy for 1p/19q-codeleted WHO grade 3 oligodendrogliomas: a national evaluation

Background The optimal chemotherapy regimen between temozolomide and procarbazine, lomustine, and vincristine (PCV) remains uncertain for W.H.O. grade 3 oligodendroglioma (Olig3) patients. We therefore investigated this question using national data. Methods Patients diagnosed with radiotherapy-treated 1p/19q-codeleted Olig3 between 2010-2018 were identified from the National Cancer Database. The OS associated with first-line single-agent temozolomide vs. multi-agent PCV was estimated by Kaplan-Meier techniques and evaluated by multivariable Cox regression. Results 1,596 radiotherapy-treated 1p/19q-codeleted Olig3 patients were identified: 88.6% (n=1,414) treated with temozolomide and 11.4% (n=182) with PCV (from 5.4% in 2010 to 12.0% in 2018) in the first-line setting. The median follow-up was 35.5 months (interquartile range [IQR] 20.7-60.6 months) with 63.3% of patients alive at time of analysis. There was a significant difference in unadjusted OS between temozolomide (5yr-OS 58.9%, 95%CI: 55.6-62.0) and PCV (5yr-OS 65.1%, 95%CI: 54.8-73.5; p=0.04). However, a significant OS difference between temozolomide and PCV was not observed in the Cox regression analysis adjusted by age and extent of resection (PCV vs. temozolomide HR 0.81, 95%CI: 0.59-1.11, p=0.18). PCV was more frequently used for younger Olig3s, but otherwise was not associated with patient’s insurance status or care setting. Conclusions In a national analysis of Olig3s, first-line PCV chemotherapy was associated with a slightly improved unadjusted short-term OS compared to temozolomide; but not following adjustment by patient age and extent of resection. There has been an increase in PCV utilization since 2010. These findings provide preliminary data while we await the definitive results from the CODEL trial.

Case Series of Applications of Resting State Functional MRI in Brain Tumor Surgery: A Novel Technique

Background The extent of resection for brain tumors is a critical factor in determining the oncologic outcome for a patient. However, a balance between preservation of neurological function and maximal resection is essential for true benefit.Functional magnetic resonance imaging (fMRI) is one of the approaches that augments the neurosurgeon's ability to attain maximal safe resection by providing preoperative mapping. It may not be possible to perform awake craniotomy with intraoperative localization by direct cortical stimulation in all patients, such as children and those with neurocognitive impairment. Task-based fMRI may have limited value in these cases due to low patient cooperability. Methods In this article we present in a case-based format, the various clinical scenarios where resting state fMRI (rs-fMRI) can be helpful in guiding neurosurgical resection. rs-fMRI of the patients has been acquired on Philips 1.5 T system. Seed voxel method has been used for processing and analysis. Conclusion rs-fMRI does not require active patient cooperation to generate useful information and thus can be a promising tool in patients unable to cooperate for task-based studies.

Multivariate Analysis of Associations between Clinical Sequencing and Outcome in Glioblastoma

Background Many factors impact survival in patients with glioblastoma, including age, Karnofsky Performance Status, post-operative chemoradiation, IDH1/2 mutation status, MGMT promoter methylation status, and extent of resection. High-throughput next generation sequencing is a widely available diagnostic tool, but the independent impact of tumors harboring specific mutant genes on survival and the efficacy of extent of resection are not clear. Methods We utilized a widely available diagnostic platform (FoundationOne CDx) to perform high-throughput next generation sequencing on 185 patients with newly diagnosed glioblastoma in our tertiary care center. We performed multivariate analysis to control for clinical parameters with known impact on survival to elucidate the independent prognostic value of prevalent mutant genes and the independent impact of gross total resection. Results When controlling for factors with known prognostic significance including IDH1/2 mutation and after multiple comparisons analysis, CDKN2B and EGFR mutations were associated with reduced overall survival while PTEN mutation was associated with improved overall survival. Gross total resection, compared to other extent of resection, was associated with improved overall survival in patients with tumors harboring mutations in CDKN2A, CDKN2B, EGFR, PTEN, TERT promoter, and TP53. All patients possessed at least one of these six mutant genes. Conclusions This study verifies the independent prognostic value of several mutant genes in glioblastoma. Six commonly found mutant genes were associated with improved survival when gross total resection was achieved. Thus, even when accounting for known predictors of survival and multiple mutant gene comparisons, extent of resection continues to be strongly associated with survival.

Surgery vs. Biopsy in the Treatment of Butterfly Glioblastoma: A Systematic Review and Meta-Analysis

Butterfly glioblastomas (bGBM) are grade IV gliomas that spread to bilateral hemispheres by infiltrating the corpus callosum. Data on the effect of surgery are limited to small case series. The aim of this meta-analysis was to compare resection vs. biopsy in terms of survival outcomes and postoperative complications. A systematic review of the literature was conducted using PubMed, EMBASE, and Cochrane databases through March 2021 in accordance with the PRISMA checklist. Pooled hazard ratios were calculated and meta-analyzed in a random-effects model including assessment of heterogeneity. Out of 3367 articles, seven studies were included with 293 patients. Surgical resection was significantly associated with longer overall survival (HR 0.39, 95%CI 0.2–0.55) than biopsy. Low heterogeneity was observed (I2: 0%). In further analysis, the effect persisted in extent of resection subgroups of both ≥80% and <80%. No statistically significant difference between surgery and biopsy was detected in terms of postoperative complications, although these were numerically larger for surgery. In patients with bGBM, surgical resection was associated with longer survival prospects compared with biopsy.

Nanomedicine in Clinical Photodynamic Therapy for the Treatment of Brain Tumors

The current treatment for malignant brain tumors includes surgical resection, radiotherapy, and chemotherapy. Nevertheless, the survival rate for patients with glioblastoma multiforme (GBM) with a high grade of malignancy is less than one year. From a clinical point of view, effective treatment of GBM is limited by several challenges. First, the anatomical complexity of the brain influences the extent of resection because a fine balance must be struck between maximal removal of malignant tissue and minimal surgical risk. Second, the central nervous system has a distinct microenvironment that is protected by the blood–brain barrier, restricting systemically delivered drugs from accessing the brain. Additionally, GBM is characterized by high intra-tumor and inter-tumor heterogeneity at cellular and histological levels. This peculiarity of GBM-constituent tissues induces different responses to therapeutic agents, leading to failure of targeted therapies. Unlike surgical resection and radiotherapy, photodynamic therapy (PDT) can treat micro-invasive areas while protecting sensitive brain regions. PDT involves photoactivation of photosensitizers (PSs) that are selectively incorporated into tumor cells. Photo-irradiation activates the PS by transfer of energy, resulting in production of reactive oxygen species to induce cell death. Clinical outcomes of PDT-treated GBM can be advanced in terms of nanomedicine. This review discusses clinical PDT applications of nanomedicine for the treatment of GBM.

Critical Appraisal of Minimally Invasive Keyhole Surgery for Intracranial Meningioma

Purpose Minimally invasive meningioma removal through transcranial and endoscopic endonasal keyhole routes remain controversial. Herein we detail results of keyhole meningioma removal defined as use of a minimally invasive “retractorless” approach for which a traditional larger approach is often used instead. Methods Retrospective analysis from 2008-2021 of consecutive patients undergoing keyhole meningioma removal through one of six approaches: extent of resection, complications, endoscopy use, MRI FLAIR/T2 changes. Surgical goal was maximal safe removal including conservative(subtotal) removal for some invasive locations. Results Of 329 patients, keyhole approaches were utilized in 193(59%) patients (mean age 59±13; 30(15.5%) prior surgery) who underwent 213 operations; 205(96%) were skull base location. Approaches included: endoscopic endonasal(n=74,35%), supraorbital(n=73,34%), retromastoid(n=38,18%), mini-pterional(n=20,9%), suboccipital(n=4,2%), and contralateral transfalcine(n=4,2%). Primary outcomes: Gross total/near total(>90%) resection: 125(59%); (5% for petroclival, cavernous sinus/Meckel’s cave, spheno-cavernous locations vs 77% other locations). Complications included: permanent neurological worsening12(6%); CSF leak 2(1%); meningitis 2(1%); no patients sustained DVT, PE, MI, or 30-day mortality. Median LOS was 3 days with 94% discharged home and 96% with favorable 90-day KPS. Secondary outcomes: Small persistent FLAIR/T2 changes: 11(5.2%) patients. Endoscopy use: 87/139(63%) of craniotomies, facilitating additional tumor removal in 55%. Tumor progression was observed in 26(13%) patients(mean follow-up 42±36 months). Conclusion This analysis suggests keyhole meningioma removal can be associated with reasonable resection rates, low complication rates, short hospitalizations and high 90-day performance scores. Subtotal removal may be appropriate for invasive/adherent meningiomas to avoid complications. With careful patient selection and requisite experience, these approaches may be considered alternatives to traditional approaches.

Contralateral interhemispheric transfalcine approach to precuneal glioblastoma: fluorescein guided microsurgical resection and endoscopic microinspection tool

Maximum safe resection remains a primary goal in the treatment of glioblastoma, with gross-total resection conveying additional survival benefit. Multiple intraoperative visualization techniques have been developed to improve the extent of resection. Herein, the authors describe the use of fluorescein and endoscopic assistance with a novel microinspection device in achieving a gross-total resection of a deep seated precuneal glioblastoma. An interhemispheric transfalcine approach was utilized and microsurgical resection was completed with fluorescein guidance. A 45° endoscope was then used to inspect the resection bed, and remaining areas of concern were then resected under endoscopic visualization. The video can be found here: https://stream.cadmore.media/r10.3171/2021.10.FOCVID21195

Circumferential sulcus-guided resection technique for improved outcomes of low-grade gliomas

OBJECTIVE Many neurosurgeons resect nonenhancing low-grade gliomas (LGGs) by using an inside-out piecemeal resection (PMR) technique. At the authors’ institution they have increasingly used a circumferential, perilesional, sulcus-guided resection (SGR) technique. This technique has not been well described and there are limited data on its effectiveness. The authors describe the SGR technique and assess the extent to which SGR correlates with extent of resection and neurological outcome. METHODS The authors identified all patients with newly diagnosed LGGs who underwent resection at their institution over a 22-year period. Demographics, presenting symptoms, intraoperative data, method of resection (SGR or PMR), volumetric imaging data, and postoperative outcomes were obtained. Univariate analyses used ANOVA and Fisher’s exact test. Multivariate analyses were performed using multivariate logistic regression. RESULTS Newly diagnosed LGGs were resected in 519 patients, 208 (40%) using an SGR technique and 311 (60%) using a PMR technique. The median extent of resection in the SGR group was 84%, compared with 77% in the PMR group (p = 0.019). In multivariate analysis, SGR was independently associated with a higher rate of complete (100%) resection (27% vs 18%) (OR 1.7, 95% CI 1.1–2.6; p = 0.03). SGR was also associated with a statistical trend toward lower rates of postoperative neurological complications (11% vs 16%, p = 0.09). A subset analysis of tumors located specifically in eloquent brain demonstrated SGR to be as safe as PMR. CONCLUSIONS The authors describe the SGR technique used to resect LGGs and show that SGR is independently associated with statistically significantly higher rates of complete resection, without an increase in neurological complications, than with PMR. SGR technique should be considered when resecting LGGs.