Resection Of Glioblastoma Research Articles

Optimal Timing of Radiotherapy Following Gross Total or Subtotal Resection of Glioblastoma: A Real-World Assessment using the National Cancer Database

Treatment for glioblastoma (GBM) includes surgical resection and adjuvant radiotherapy (RT) and chemotherapy. The optimal time interval between surgery and RT remains unclear. The National Cancer Database (NCDB) was queried for patients with GBM. Overall survival (OS) was estimated using Kaplan-Meier and log-rank tests. Univariate (UVA) and multivariable Cox regression (MVA) modeling was used to determine predictors of OS. A total of 45,942 patients were included. On MVA: younger age, female gender, black ethnicity, higher KPS, obtaining a gross total resection (GTR), MGMT promoter-methylated gene status, unifocal disease, higher RT dose, and RT delay of 4–8 weeks had improved OS. Patients who underwent a subtotal resection (STR) had worsened survival with RT delay ≤4 weeks and patients with GTR had worsened survival when RT was delayed >8 weeks. This analysis suggests that an interval of 4–8 weeks between resection and RT results in better survival. Delays >8 weeks in patients with a GTR and delays <4 weeks in patients with a STR/biopsy resulted in worse survival. This impact of time delay from surgery to RT, in conjunction with extent of resection, should be considered in the clinical management of patients and future designs of clinical trials.

High Interobserver Agreement in the Subjective Classification of 5-Aminolevulinic Acid Fluorescence Levels in Newly Diagnosed Glioblastomas.

Background and ObjectivesFluorescence‐guided resection of glioblastomas (GBM) using 5‐aminolevulinic acid (5‐ALA) improves intraoperative tumor visualization and is thus widely used nowadays. During resection, different fluorescence levels can usually be distinguished within the same tumor. Recently, we demonstrated that strong, vague, and no fluorescence correspond to distinct histopathological characteristics in newly diagnosed GBM. However, the qualitative fluorescence classification by the neurosurgeon is subjective and currently no comprehensive data on interobserver variability is available. The aim of this study was thus to investigate the interobserver variability in the classification of 5‐ALA fluorescence levels in newly diagnosed GBM.Study Design/Materials and MethodsA questionnaire investigating the interobserver variability in 5‐ALA fluorescence quantification was performed at a nation‐wide neurosurgical oncology meeting. The participants involved in the neurosurgical/neurooncological field were asked to categorize 30 cases of 5‐ALA fluorescence images derived from GBM resection on a lecture hall screen according to the widely used three‐tier fluorescence classification scheme (negative, vague, or strong fluorescence). Additionally, participants were asked for information on their medical background such as specialty, level of training, and experience with 5‐ALA fluorescence‐guided procedures. Interobserver agreement was defined as the calculated mean κ values for each observer.ResultsA total of 36 questionnaires were included in the final analysis. The mean average κ value in fluorescence classification within the entire cohort was 0.71 ± 0.12 and 29 (81%) participants had a substantial or almost perfect interobserver agreement (κ values 0.6–1.0). Interobserver agreement was significantly higher in neurosurgeons (mean κ: 0.83) as compared with non‐neurosurgeons involved in the neurooncological field (mean κ: 0.52; P < 0.001). Furthermore, interobserver agreement was significantly higher in participants who had experience with at least 25 5‐ALA fluorescence‐guided surgeries (mean κ: 0.87) compared with less experienced colleagues (mean κ: 0.82; P = 0.039).ConclusionOur study found a high interobserver agreement in the qualitative classification of different 5‐ALA fluorescence levels in newly diagnosed GBM. Interobserver agreement increases significantly in more experienced participants and therefore a high level of experience is crucial for reliable intraoperative fluorescence classification. Lasers Surg. Med. © 2020 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals, Inc.

The SHORT Score for Preoperative Assessment of the Risk for Short-Term Survival in Glioblastoma

Despite recent improvements in treatment of glioblastoma (GBM), some patients still have a short survival. We sought to develop a new risk score for preoperative assessment of short-term survival (STS) (<6 months) in patients with GBM. All adult patients who underwent surgical resection of GBM between 2004 and 2014 were included (N= 379). Demographic and clinical parameters, which were available at admission, were assessed. Variables were evaluated in univariate and multivariate analyses. The score was validated in a separate cohort of patients with GBM who underwent surgical resection between 2015 and2018. The following independent predictors of STS were integrated into a new score: body height (<169 cm, 1 point), arterial hypertension (1 point), age (≤54 years, 0 points; 55-74 years, 1 points; ≥75 years, 2 points), and poor clinical status (Karnofsky performance scale [KPS] score: ≤60%, 2 points; 70%-80%, 1 point; ≥90%, 0 points). The new risk score, SHORT (Small body height, Hypertension, Older age, Reduced KPS score, short-Term survival), ranged from 0 to 6 points and showed good accuracy of risk estimation for STS in GBM (area under the curve: 0.715). STS rates were 9.7%, 23.1%, and 70% in patients with GBM scoring <2 points, 2-4 points, and >4 points (P < 0.0001). The score was successfully validated (area under the curve: 0.770). This study presents the SHORT score for preoperative assessment of STS risk in patients with GBM. This risk score needs external validation in larger patient cohorts from other institutions. Our score might be a tool to facilitate treatment decisions in patients with GBM before surgery.

Demeclocycline Reduces the Growth of Human Brain Tumor-Initiating Cells: Direct Activity and Through Monocytes.

Myeloid cells that infiltrate into brain tumors are deactivated or exploited by the tumor cells. We previously demonstrated that compromised microglia, monocytes, and macrophages in malignant gliomas could be reactivated by amphotericin-B to contain the growth of brain tumorinitiating cells (BTICs). We identified meclocycline as another activator of microglia, so we sought to test whether its better-tolerated derivative, demeclocycline, also stimulates monocytes to restrict BTIC growth. Monocytes were selected for study as they would be exposed to demeclocycline in the circulation prior to entry into brain tumors to become macrophages. We found that demeclocycline increased the activity of monocytes in culture, as determined by tumor necrosis factor-α production and chemotactic capacity. The conditioned medium of demeclocycline-stimulated monocytes attenuated the growth of BTICs generated from human glioblastoma resections, as evaluated using neurosphere and alamarBlue assays, and cell counts. Demeclocycline also had direct effects in reducing BTIC growth. A global gene expression screen identified several genes, such as DNA damage inducible transcript 4, frizzled class receptor 5 and reactive oxygen species modulator 1, as potential regulators of demeclocycline-mediated BTIC growth reduction. Amongst several tetracycline derivatives, only demeclocycline directly reduced BTIC growth. In summary, we have identified demeclocycline as a novel inhibitor of the growth of BTICs, through direct effect and through indirect stimulation of monocytes. Demeclocycline is a candidate to reactivate compromised immune cells to improve the prognosis of patients with gliomas.

Developing Implantable Scaffolds to Enhance Neural Stem Cell Therapy for Post-Operative Glioblastoma.

Pre-clinical and clinical studies have shown that engineered tumoricidal neural stem cells (tNSCs) are a promising treatment strategy for the aggressive brain cancer glioblastoma (GBM). Yet, stabilizing human tNSCs within the surgical cavity following GBM resection is a significant challenge. As a critical step toward advancing engineered human NSC therapy for GBM, we used a preclinical variant of the clinically utilized NSC line HB1.F3.CD and mouse models of human GBM resection/recurrence to identify a polymeric scaffold capable of maximizing the transplant, persistence, and tumor kill of NSC therapy for post-surgical GBM. Using kinetic bioluminescence imaging, we found that tNSCs delivered into the mouse surgical cavity wall by direct injection persisted only 3days. We found that delivery of tNSCs into the cavity on nanofibrous electrospun poly-l-lactic acid scaffolds extended tNSC persistence to 8days. Modifications to fiber surface coating, diameter, and morphology of the scaffold failed to significantly extend tNSC persistence in the cavity. In contrast, tNSCs delivered into the post-operative cavity on gelatin matrices (GEMs) persisted 8-fold longer as compared to direct injection. GEMs remained permissive to tumor-tropic homing, as tNSCs migrated off the scaffolds and into invasive tumor foci both invitro and invivo. To mirror envisioned human brain tumor trials, we engineered tNSCs to express the prodrug/enzyme thymidine kinase (tNSCstk) and transplanted the therapeutic cells in the post-operative cavity of mice bearing resected orthotopic patient-derived GBM xenografts. Following administration of the prodrug ganciclovir, residual tumor volumes in mice receiving GEM/tNSCs were reduced by 10-fold at day 35, and median survival was extended from 31 to 46days. Taken together, these data begin to define design parameters for effective scaffold/tNSC composites and suggest a new approach to maximizing the efficacy of tNSC therapy in human patient trials.

Sodium fluorescein shows high surgeon-reported usability in glioblastoma surgery

IntroductionGlioblastoma has a high mortality rate. Current treatment includes largest possible surgical resection of the tumour using neuronavigation and fluorescence to better identify tumour tissue. In recent years, sodium fluorescein has been reintroduced in neurosurgery as a fluorescence to increase the resection rate. In this study we aimed to measure the surgeons experience of using sodium fluorescein to locate and remove tumour tissue. Furthermore we describe a case of sodium fluorescein tissue distribution. Material and methods13 patients with glioblastoma and seven patients with cerebral metastases undergoing surgical resection were included. Surgery was performed using microscope alternating between white light and the YELLOW 560 filter, which visualized sodium fluorescein. Surgeons graded its usability in terms of location and removal on a scale from one to four. The resection rate was determined by neuroradiologists. Tissue samples obtained during surgery were analysed in relation to fluorescence and dysmorphic cells. ResultsSurgeons reported high usability in terms of location and removal of tumours using sodium fluorescein with medians of four in all groups, except for sub-total resections which had a median of three. Surgical complications were minimal and both resection rate and survival rate was within international standards. Histological analysis showed a visual correlation between tumorous tissue and intensity of fluorescence. ConclusionSodium fluorescence is an effective and useful tool for surgeons during fluorescence-guided surgery for the resection of glioblastoma and cerebral metastases.

A Common Rule for Resection of Glioblastoma in the Molecular Era

A Common Rule for Resection of Glioblastoma in the Molecular Era

Combination of ALA-induced fluorescence-guided resection and intraoperative open photodynamic therapy for recurrent glioblastoma: case series on a promising dual strategy for local tumor control.

High-grade glioma (HGG) prognosis remains dismal, with inevitable, mostly local recurrence. Regimens for improving local tumor control are therefore needed. Photodynamic therapy (PDT) using porfimer sodium has been investigated but was abandoned due to side effects and lack of survival benefits. Intracellular porphyrins induced by 5-aminolevulinic acid (5-ALA) are approved for fluorescence-guided resections (FGRs), but are also photosensitizers. Activated by light, they generate reactive oxygen species with resultant cytotoxicity. The authors present a combined approach of 5-ALA FGR and PDT. After 5-ALA FGR in recurrent HGG, laser diffusors were strategically positioned inside the resection cavity. PDT was applied for 60 minutes (635 nm, 200 mW/cm diffusor, for 1 hour) under continuous irrigation for maintaining optical clarity and ventilation with 100% oxygen. MRI was performed at 24 hours, 14 days, and every 3 months after surgery, including diffusion tensor imaging and apparent diffusion coefficient maps. Twenty patients were treated. One surgical site infection after treatment was noted at 6 months as the only adverse event. MRI revealed cytotoxic edema along resection margins in 16 (80%) of 20 cases, mostly annular around the cavity, corresponding to prior laser diffusor locations (mean volume 3.3 cm3). Edema appeared selective for infiltrated tissue or nonresected enhancing tumor. At the 14-day follow-up, enhancement developed in former regions of edema, in some cases vanishing after 4-5 months. Median progression-free survival (PFS) was 6 months (95% CI 4.8-7.2 months). Combined 5-ALA FGR and PDT provides an innovative and safe method of local tumor control resulting in promising PFS. Further prospective studies are warranted to evaluate long-term therapeutic effects.

Photodynamic Therapy for the Treatment of Glioblastoma.

Glioblastoma is the most common form of adult brain cancer and remains one of the deadliest of human cancers. The current standard-of-care involves maximal tumor resection followed by treatment with concurrent radiation therapy and the chemotherapy temozolomide. Recurrence after this therapy is nearly universal within 2 years of diagnosis. Notably, >80% of recurrence is found in the region adjacent to the resection cavity. The need for improved local control in this region, thus remains unmet. The FDA approval of 5-aminolevulinic acid (5-ALA) for fluorescence guided glioblastoma resection renewed interests in leveraging this agent as a means to administer photodynamic therapy (PDT). Here we review the general principles of PDT as well as the available literature on PDT as a glioblastoma therapeutic platform.

Efficacy of sequential radiation and chemotherapy in treating glioblastoma with poor performance status.

While the current standard of care after maximal safe resection for glioblastoma (GBM) is concomitant radiation and chemotherapy, the ideal therapy for patients with poor performance status remains in question due to concerns about treatment tolerance. We sought to evaluate an alternative regimen, sequential radiation and chemotherapy, to assess its efficacy as a treatment option for poorly performing patients. We performed a retrospective analysis using the 2015 National Cancer Database in which the survival of patients with a KPS ≤ 70 who received sequential radiation and chemotherapy were compared to those who received radiation therapy alone. Survival outcomes were compared using Kaplan-Meier curves with log rank testing and Cox proportional hazard regression. There were 84 patients analyzed in this study, all of whom had a KPS between 10 and 70. Of those analyzed, 73.8% received radiation therapy alone, and 26.2% received sequential radiation and chemotherapy. There was no difference in survival between the two treatment groups (p = 0.84). Patient age of 70years or older (n = 31) was associated with decreased survival (HR 1.06 per year, p < 0.0001), regardless of KPS and a KPS of < 70 correlated with a near-significant trend toward worse survival (HR 1.63, p = 0.06). Treatment with sequential radiation and chemotherapy in poorly performing patients is not associated with an advantage in survival outcome when compared to radiation alone in GBM patients with poor performance status.

Self-assembling and self-formulating prodrug hydrogelator extends survival in a glioblastoma resection and recurrence model

Glioblastoma multiforme (GBM) is the most common and devastating type of primary brain cancer. Despite surgery and chemo/radiation therapy, recurrence often takes place and leads to patient death. We report here on the development of a camptothecin (CPT)-based self-assembling prodrug (SAPD) hydrogel that can be used as an adjunct therapy for local treatment of GBM following maximal tumor resection. When dispersed in aqueous solution, the designed CPT prodrug spontaneously assembles into supramolecular filaments with a 100% CPT loading. In both in vitro and ex vivo assays, we show that the designed CPT prodrug can be steadily released from its supramolecular filament hydrogel, effectively killing primary GBM cells derived from patients. We also found that the solution containing self-assembling CPT filaments can be directly applied to the tumor cavity after surgical removal, and forms a gel immediately upon contact with the brain tissue. Our in vivo studies with a resection and recurrence mouse model suggest that this prodrug hydrogel can release cancer therapeutics into brain parenchyma over a long period of time, suppressing tumor recurrence and leading to prolonged survival. We believe that the simplicity in prodrug design and the high efficacy in suppressing GBM growth enable the unique potential of this SAPD hydrogels for clinical translation as an adjunct therapy for GBM treatment.

Awake craniotomy for resection of supratentorial glioblastoma: a systematic review and meta-analysis

BackgroundThe goal of glioblastoma (GBM) surgery is to maximize the extent of resection (EOR) while minimizing postoperative neurological complications. Awake craniotomy (AC) has been demonstrated to achieve this goal for low-grade gliomas in or near eloquent areas. However, the efficacy of AC for GBM resection has not been established. Therefore, we aimed to investigate the outcomes of AC for surgical resection of GBM using a systematic review and meta-analysis of published studies.MethodsSystematic searches of Ovid MEDLINE, Embase, Cochrane Controlled Register of Controlled Trials, and PubMed were performed from database inception to September 14, 2019 for published studies reporting outcomes of AC for GBM resection. Outcome measures analyzed included EOR and the event rate of postoperative neurological deficits.ResultsA total of 1928 unique studies were identified. Fourteen studies reporting 278 patients were included in our meta-analysis. Mean age of patients was 46.9 years (95% confidence interval [CI]: 43.9–49.9). Early and late postoperative neurological deficits occurred in 34.5% (95% CI: 21.9–48.2) and 1.9% (95% CI: 0.0–9.2) of patients, respectively. Pooled percentage of gross total resection (GTR) was 74.7% (95% CI: 66.7–82.1), while the pooled percentage reduction in tumor volume was 95.3% (95% CI: 92.2–98.4).ConclusionsLimited current evidence suggests that the use of AC for resection of supratentorial GBM is associated with a low rate of persistent neurological deficits while achieving an acceptable rate of GTR. Our findings demonstrate the potential viability of AC in GBM resection and highlight the need for further research on this topic.

Resection of recurrent glioblastoma multiforme in elderly patients: a pseudo-randomized analysis revealed clinical benefit.

Elderly patients constitute an expanding part of our society. Due to a continuously increasing life expectancy, an optimal quality of life is expected even into advanced age. Glioblastoma (GBM) is more common in older patients, but they are still often withheld from efficient treatment due to worry of worse tolerance and have a significantly worse prognosis compared to younger patients. Our retrospective observational study aimed to investigate the therapeutic benefit from a second resection in recurrent glioblastoma of elderly patients. We included a cohort of 39 elderly patients (> 65years) with a second resection as treatment option in the case of a tumor recurrence. A causal inference model was built by multiple non- and semiparametric models, which was used to identify matched patients from our elderly GBM database which comprises 538 patients. The matched cohorts were analyzed by a Cox-regression model adjusted by time-dependent covariates. The Cox-regression analysis showed a significant survival benefit (Hazard Ratio: 0.6, 95% CI 0.36-0.9, p-value = 0.0427) for the re-resected group (18.0months, 95% CI 13.97-23.2months) compared to the group without re-resection (10.1months, 95% CI 8.09-20.9months). No differences in the co-morbidities or hemato-oncological side effects during chemotherapy could be detected. Anesthetic- and surgical complications were rare and comparable to the complication rate of patients undergoing the first-line resection. Taken together, in elderly patients, re-resection is an acceptable treatment option in the recurrent state of a glioblastoma. The individual evaluation of the patients' medical status as well as the chances of withstanding general anesthesia needs to be done in close interdisciplinary consultation. If these requirements are met, elderly patients benefit from a re-resection.

Temporospatial genomic profiling in glioblastoma identifies commonly altered core pathways underlying tumor progression.

BackgroundTumor heterogeneity underlies resistance and disease progression in glioblastoma (GBM), and tumors most commonly recur adjacent to the surgical resection margins in contrast non-enhancing (NE) regions. To date, no targeted therapies have meaningfully altered overall patient survival in the up-front setting. The aim of this study was to characterize intratumoral heterogeneity in recurrent GBM using bulk samples from primary resection and recurrent samples taken from contrast-enhancing (EN) and contrast NE regions.MethodsWhole exome and RNA sequencing were performed on matched bulk primary and multiple recurrent EN and NE tumor samples from 16 GBM patients who received standard of care treatment alone or in combination with investigational clinical trial regimens.ResultsPrivate mutations emerge across multi-region sampling in recurrent tumors. Genomic clonal analysis revealed increased enrichment in gene alterations regulating the G2M checkpoint, Kras signaling, Wnt signaling, and DNA repair in recurrent disease. Subsequent functional studies identified augmented PI3K/AKT transcriptional and protein activity throughout progression, validated by phospho-protein levels. Moreover, a mesenchymal transcriptional signature was observed in recurrent EN regions, which differed from the proneural signature in recurrent NE regions.ConclusionsSubclonal populations observed within bulk resected primary GBMs transcriptionally evolve across tumor recurrence (EN and NE regions) and exhibit aberrant gene expression of common signaling pathways that persist despite standard or targeted therapy. Our findings provide evidence that there are both adaptive and clonally mediated dependencies of GBM on key pathways, such as the PI3K/AKT axis, for survival across recurrences.

Role of Resection of Glioblastoma

Correspondence: Raymond Sawaya, MD, Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 442, PO Box 301402, Houston, TX 77230-1402, USA. Email: [email protected] Accepted May 24, 2020 Received May 13, 2020 Online date: November 16, 2020 This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Evidence-Based Medicine Through Development of Home-Grown Databases

Evidence-Based Medicine Through Development of Home-Grown Databases

Perilesional Resection of Glioblastoma Is Independently Associated With Improved Outcomes.

Resection is a critical component in the initial treatment of glioblastoma (GBM). Often GBMs are resected using an intralesional method. Circumferential perilesional resection of GBMs has been described, but with limited data. To conduct an observational retrospective analysis to test whether perilesional resection produced a greater extent of resection. We identified all patients with newly diagnosed GBM who underwent resection at our institution from June 1, 1993 to December 31, 2015. Demographics, presenting symptoms, intraoperative data, method of resection (perilesional or intralesional), volumetric imaging data, and postoperative outcomes were obtained. Complete resection (CR) was defined as 100% resection of all contrast-enhancing disease. Univariate analyses employed analysis of variance (ANOVA) and Fisher's exact test. Multivariate analyses used propensity score-weighted multivariate logistic regression. Newly diagnosed GBMs were resected in 1204 patients, 436 tumors (36%) perilesionally and 766 (64%) intralesionally. Radiographic CR was achieved in 69% of cases. Multivariate analysis demonstrated that perilesional tumor resection was associated with a significantly higher rate of CR than intralesional resection (81% vs 62%, multivariate odds ratio=2.5, 95% confidence interval: 1.8-3.4, P<.001). Among tumors in eloquent cortex, multivariate analysis showed that patients who underwent perilesional resection had a higher rate of CR (79% vs 58%, respectively, P<.001) and a lower rate of neurological complications (11% vs 20%, respectively, P=.018) than those who underwent intralesional resection. Circumferential perilesional resection of GBM is associated with significantly higher rates of CR and lower rates of neurological complications than intralesional resection, even for tumors arising in eloquent locations. Perilesional resection, when feasible, should be considered as a preferred option.

Endoscopic Fluorescence-Guided Resection Increases Radicality in Glioblastoma Surgery.

Several studies have proven the benefit of a greater extent of resection on progression-free survival and overall survival in glioblastoma (GBM). Possible reasons for incomplete tumor resection might be wrong interpretation of fading fluorescence or overseen fluorescent tumor tissue by a lacking line of sight between tumor tissue and the microscope. To evaluate if an endoscope being capable of inducing fluorescence might overcome some limitations of microscopic fluorescence-guided (FG) resection. 5-Aminolevulinic acid (20 mg/kg) was given 4 h before surgery. Microsurgical resection of all fluorescent tissue was performed. Then, the resection cavity was scanned with the endoscope. Fluorescent tissue, not being visualized by the microscope, was additionally removed and histopathologically examined separately. Neuronavigation was used for defining the sites of additional tumor resection. All patients underwent magnetic resonance imaging within 48 h after surgery. Twenty patients with GBM were operated using microscopic and endoscopic FG resection. In all patients, additional fluorescent tissue was detected with the endoscope. This tissue was completely resected in 19 patients (95%). Eloquent localization precluded complete resection in the remaining patient. In 19 patients (95%), histopathological examination confirmed tumor in the additionally resected tissue. In 19 patients (95%), complete resection was confirmed. In all patients, endoscopic FG resection reached beyond the borders of contrast-enhancing tumor. Endoscopic FG resection of GBM allows increasing the complete resection rate substantially and therefore is a useful adjunct to microscopic FG resection.

T2 Fluid-Attenuated Inversion Recovery Resection for Glioblastoma Involving Eloquent Brain Areas Facilitated Through Awake Craniotomy and Clinical Outcome

Despite evidence that a greater extent of resection (EOR) improves survival, the role of extended resection based on magnetic resonance imaging (MRI) fluid-attenuated inversion recovery (FLAIR) in the prognosis of glioblastoma (GBM) remains controversial. This study aims to investigate the role of additional resection of FLAIR-detected abnormalities and its influence on clinical outcomes of patients with GBM. Forty-six patients with newly diagnosed GBM involving eloquent brain areas were included. Surgeries were performed using awake craniotomy (AC) or AC combined with sodium fluorescein (SF) guidance. Following total removal of the contrast-enhancing tumor area, the EOR of FLAIR abnormalities was dichotomized to identify the best separation threshold for progression-free survival (PFS), overall survival (OS), and 30-day postoperative neurologic function of patients with GBM. The threshold for removal of FLAIR abnormalities affecting survival was determined to be 25%. The median OS and PFS were shorter in the group with FLAIR resection <25% compared with the group with FLAIR resection ≥25% (12 months vs. 26 months; P= 0.001 and 6months vs. 15 months; P= 0.016, respectively). Univariate and multivariate analyses identified tumor location within or near the eloquent brain areas and the 25%threshold for FLAIR EOR as independent factors affecting OS and PFS. Identifying a feasible threshold for the resection of FLAIR abnormalities is valuable in improving the survival of patients with GBM. Extended resection of GBM involving eloquent brain areas was safe when using a combination of AC and SF-guided surgery.

In Reply to the Letter to the Editor Regarding “A Novel Wavelength-Specific Blue Light-Emitting Headlamp for 5-Aminolevulinic Acid Fluorescence-Guided Resection of Glioblastoma.”

In Reply to the Letter to the Editor Regarding “A Novel Wavelength-Specific Blue Light-Emitting Headlamp for 5-Aminolevulinic Acid Fluorescence-Guided Resection of Glioblastoma.”