Glioblastoma Surgery Research Articles

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.

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.

Interval brain imaging for adults with cerebral glioma.

Clinical practice guidelines suggest that magnetic resonance imaging (MRI) of the brain should be performed at certain time points or intervals distant from diagnosis (interval or surveillance imaging) of cerebral glioma, to monitor or follow up the disease; it is not known, however, whether these imaging strategies lead to better outcomes among patients than triggered imaging in response to new or worsening symptoms. To determine the effect of different imaging strategies (in particular, pre-specified interval or surveillance imaging, and symptomatic or triggered imaging) on health and economic outcomes for adults with glioma (grades 2 to 4) in the brain. The Cochrane Gynaecological, Neuro-oncology and Orphan Cancers (CGNOC) Group Information Specialist searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase up to 18 June 2019 and the NHS Economic Evaluation Database (EED) up to December 2014 (database closure). We included randomised controlled trials, non-randomised controlled trials, and controlled before-after studies with concurrent comparison groups comparing the effect of different imaging strategies on survival and other health outcomes in adults with cerebral glioma; and full economic evaluations (cost-effectiveness analyses, cost-utility analyses and cost-benefit analyses) conducted alongside any study design, and any model-based economic evaluations on pre- and post-treatment imaging in adults with cerebral glioma. We used standard Cochrane review methodology with two authors independently performing study selection and data collection, and resolving disagreements through discussion. We assessed the certainty of the evidence using the GRADE approach. We included one retrospective, single-institution study that compared post-operative imaging within 48 hours (early post-operative imaging) with no early post-operative imaging among 125 people who had surgery for glioblastoma (GBM: World Health Organization (WHO) grade 4 glioma). Most patients in the study underwent maximal surgical resection followed by combined radiotherapy and temozolomide treatment. Although patient characteristics in the study arms were comparable, the study was at high risk of bias overall. Evidence from this study suggested little or no difference between early and no early post-operative imaging with respect to overall survival (deaths) at one year after diagnosis of GBM (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.61 to 1.21; 48% vs 55% died, respectively; very low certainty evidence) and little or no difference in overall survival (deaths) at two years after diagnosis of GBM (RR 1.06, 95% CI 0.91 to 1.25; 86% vs 81% died, respectively; very low certainty evidence). No other review outcomes were reported. We found no evidence on the effectiveness of other imaging schedules. In addition, we identified no relevant economic evaluations assessing the efficiency of the different imaging strategies. The effect of different imaging strategies on survival and other health outcomes remains largely unknown. Existing imaging schedules in glioma seem to be pragmatic rather than evidence-based. The limited evidence suggesting that early post-operative brain imaging among GBM patients who will receive combined chemoradiation treatment may make little or no difference to survival needs to be further researched, particularly as early post-operative imaging also serves as a quality control measure that may lead to early re-operation if residual tumour is identified. Mathematical modelling of a large glioma patient database could help to distinguish the optimal timing of surveillance imaging for different types of glioma, with stratification of patients facilitated by assessment of individual tumour growth rates, molecular biomarkers and other prognostic factors. In addition, paediatric glioma study designs could be used to inform future research of imaging strategies among adults with glioma.

Supramaximal resection: A systematic review of its safety, efficacy and feasibility in glioblastoma

The philosophy of ‘supramaximal resection’ (SMR) beyond the T1-enhanced margin holds some potential in glioblastoma surgery, but the quality of available literature has not been elucidated. A systematic review of published studies of SMR in glioblastoma surgery was performed. Articles were sought in MEDLINE, EMBASE, Scopus and Cochrane Central Register for Clinical Trials. The search items were grouped into three themes; supramaximal resection, glioblastoma and outcomes. Cases were included wherein the initial extent of resection was described as exceeding gross total resection, that is to say, beyond the area of T1-enhancement on MRI. Only newly diagnosed glioblastoma was considered. Articles containing primary patient data, including outcome data, were included; reviews, editorials, descriptive articles and systematic reviews were excluded. Subsequently, 1123 unique articles were initially retrieved. After screening article titles and abstracts for relevance to SMR in glioblastoma, seven articles remained, and were all included post-full text review. No randomized controlled trials were discovered. Almost all studies were of Level 4 quality, according to Oxford Center for Evidence-Based Medicine guidelines. The included articles yielded a total of 2019 surgically treated glioblastoma patients, 13.5% of whom underwent SMR. Preliminary results suggest SMR of glioblastoma positively impacts overall and progression free survival. However, the contemporaneous literature supporting glioblastoma SMR is of low quality, with neither anatomical nor radiographic definitional consensus for what constitutes SMR. Prospective studies of larger pooled populations with standardized technical, radiological and outcome measures in designated centers would help minimize bias and validate SMR in appropriately selected glioblastoma patients.

STMO-03 ROLE OF INTRAOPERATIVE COMPUTED TOMOGRAPHY IN GLIOBLASTOMA RESECTION GUIDED BY 5-ALA

OBJECTIVETo improve resection rate, multiple operative modalities have been essential for glioblastoma (GBM) surgery. Aim of this study is to clarify the impact of intraoperative computed tomography (i-CT) for GBM surgery with 5-aminolevulinic acid photodynamic diagnosis (5-ALA PDD).METHODSConsecutive 24 patients newly diagnosed GBM were analyzed, retrospectively. To exclude 6 patients decided timing for i-CT based on neural monitoring, 18 patients performed i-CT after total resection of 5-ALA positive lesion were included, finally.RESULTSThe median age was 58 years old, and average preoperative tumor volume was 47.78 cm3. Tumor locations were frontal lobe 5 (27%), parietal lobe 3 (17%), temporal lobe 9 (50%), and corpus callosum 1 (6%). Seventeen tumors (78%) harbored in eloquent area. After i-CT performed, 7 (39%) were confirmed residual tumor, and additional resections were needed. Subtotal resection (STR) was 5 and partial resection (PR) was 2 on volumetry in i-CT before additional resection. After additional resection, those cases were judged as 2 gross total resection (GTR), 4 STR and 1 PR in postoperative magnetic resonance imaging (MRI). 11 cases without additional resection were judged as 4 GTR, 3 STR and 4 PR in postoperative MRI. In 18 patients confirmed total resection of 5-ALA positive lesion, i-CT and postoperative MRI revealed 14 (78%) residual tumors. I-CT revealed 7 (50%) in all residual tumor.DISCUSSIONHemorrhage, brain edema, air, invasive lesion, and limitation of resolution of CT might make difficult to detect residual tumor.CONCLUSIONI-CT may be useful to detect residual tumor even with 5-ALA and improve resection rate.

NI-14 EVALUATION OF PREOPERATIVE APPARENT DIFFUSION COEFFICIENT (ADC) OF PERITUMORAL LESION FOR PREDICTING SITE PRONE TO RECURRENCE IN PATIENTS WITH GLIOBLASTOMA

PURPOSEIn the surgery of glioblastoma (GBM), the maximum safe resection is desired in order to prevent recurrence. The purpose of this study is to make it possible to evaluate the site in which the recurrence after resection of the tumor occur, according to the findings in preoperative MRI, and to avoid the recurrence.METHODThe 26 initial cases with GBM treated in our department was investigated. Preoperative MRI, postoperative MRI, and follow-up MRI during the course were analyzed in a retrospective view. In the FLAIR high-signal area around the contrast-enhanced tumor body in preoperative MRI, we investigated the relationship between the site and the ADC value, from the standpoint of whether a recurrence occurred or not.RESULTSFor preoperative MRI of 26 patients, the FLAIR high-signal region was set to a total of 54 ROI, and several values, such as the ADC values, were measured. In the preoperative images, ADC were higher in the site where the no recurrence occurred during the postoperative course and lower in the site where the recurrence occurred.CONCLUSIONIn the FLAIR high-signal area around the tumor in preoperative images, ADC value is useful in evaluating whether it has tendency to develop the recurrence in the future course or not. It was suggested that significant recurrence occurs at part with low-ADC value. It is considered useful for the planning of the extent of resection in the surgery and the irradiation range in radiation treatment.

NIMG-06. OUR THERAPEUTIC STRATEGIES FOR GLIOBLASTOMA: INTRAOPERATIVE SUPPORT SYSTEMS [INTRAOPERATIVE MRI, PET, 5-AMINOLEVULINIC ACID (5-ALA)] AND NEOADJUVANT CHEMOTHERAPY

Abstract OBJECTIVE Neuronavigation systems with magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging (methionine [MET], fluorothymidine [FLT], and fluoromisonidazole [FMISO]) are routinely used in glioblastoma surgery. Residual tumor identified using intraoperative MRI (IoMRI) or 5-aminolevulinic acid (5-ALA) fluorescence is removed. Neoadjuvant bevacizumab therapy is offered to patients with low Karnovsky performance status (KPS) or with tumors in eloquent regions. We evaluated the usefulness of neoadjuvant bevacizumab therapy. METHODS Twelve patients with glioblastoma with low KPS or tumors in eloquent regions on multiple PET and IoMRI evaluations were enrolled between January 2016 and April 2019. Six had received neoadjuvant bevacizumab before surgery; six had not. Postsurgical 5-ALA fluorescence (strong, vague, and none) tumor extraction rate, residual volume on MRI and PET imaging, and prognosis in the patients with and without bevacizumab were compared. RESULTS In patients with bevacizumab adjuvant therapy, the KPS scores immediately prior to surgery were 90 in 3 cases, 80 in 2, and 70 in 1. The scores in patients without bevacizumab were 50 in 2 and 40 in 4. The 5-ALA fluorescence in patients with bevacizumab was vague in one and none in five. Vague fluorescence was noted in all six patients without bevacizumab. Tumor extraction rates in patients with vs. those without bevacizumab were 97.6% vs. 91.5% by T1-Gd, 95.4% vs. 99.9% by MET, 96.2% vs. 90.2% by FLT, and 97% vs. 92% by FMISO. Corresponding residual volumes (ml) were (0.6 vs. 1.7) for T1-Gd, 1.2 vs. 2.9 for MET, 1.0 vs. 2.1 for FLT, and 0.5 vs. 1.1 for. FLT. Median progression free survival (PFS) was 10.1 vs. 4.9 months; median overall survival (OS) was 15.7 vs. 13.3 months. CONCLUSIONS Neoadjuvant bevacizumab therapy improved KPS at the time of surgery, increased extraction rate, reduced residual tumor volume, and improved PFS and OS prognosis.

QOLP-22. DRIVERS OF COST OF SURGERY IN NEWLY-DIAGNOSED GLIOBLASTOMA PATIENTS

Abstract INTRODUCTION Glioblastoma carries a high economic burden for patients and caregivers. We investigated drivers of hospital costs of surgery for newly-diagnosed glioblastoma. METHODS Retrospective review of GBM patients undergoing first resection at UCSF (2010–2015) and corresponding hospital charges. Our cohort was divided into low (LC) and high cost (HC) groups for total surgical cost. Multivariate regression was used to identify factors driving cost of surgery. RESULTS Of 242 patients, 36.7% (n=86) were females (median age=62 years). The mean total hospital cost for surgery among our patient cohort was $40,384. When comparing the LC and HC groups, mean total hospital cost for surgery for HC patients was almost twice as much as LC group ($51,744 vs $29,023, p< 0.001). Kaplan-Meier analysis revealed that having higher cost of surgery worsened patient prognosis, with a 21% longer overall survival in the LC cohort versus the HC cohort (14.7 vs 17.9 months, p=0.02; HR=1.41 [1.05–1.91], p= 0.023). Tumor diameter at diagnosis was largest for HC group (4.7 cm) versus LC patients (3.9 cm, p=0.002). Multivariate analysis revealed longer hospital stay (F-ratio=8.87; p=0.01), longer ICU stay (F-ratio= 12.34, p< 0.001), younger age at surgery (F-ratio=6.71, p=0.02) and multifocal disease (F-ratio=6.26, p=0.02) to be independent predictors of higher cost of surgery, while having PCP at diagnosis (F-ratio=6.92, p=0.02), health insurance coverage (F-ratio= 4.23, p=0.03) and being married (F-ratio=3.71, p=0.04) were independent predictors of lower cost of surgery. CONCLUSIONS Higher costs of surgery correlate with worse survival outcomes in glioblastoma patients. Beyond the anticipated finding that greater disease burden drives some of this inverse correlation between cost and survival, correctable socioeconomic factors such as PCP and insurance status also drive higher hospital charges for GBM surgery. Manipulation of these factors is necessary to minimize the economic burden of disease and adopt cost-effective surgical treatments for GBM patients.

INNV-21. IN NEWLY-DIAGNOSED GLIOBLASTOMA, FRAILTY/SARCOPENIA PREDICTS 30D MORBIDITY & 30D, 90D, AND OVERALL MORTALITY AS ACCURATELY AS CURRENT STANDARDS

Abstract INTRODUCTION Identification of novel prognostic biomarkers for glioblastoma (GBM) could stratify patients between aggressive or palliative treatments. Frailty, as measured by sarcopenia (lack of muscle mass), has been proven to predict survival in cancers. We evaluate whether the frailty/sarcopenia phenotype (FSP) predicts morbidity and mortality in GBM, and compare it to other survival markers. METHODS In 257 patients undergoing initial diagnostic surgery for GBM, FSP was defined by temporalis muscle thickness from preoperative MRI; patients were grouped into tertiles (thirds) based on size, which corresponded to the severity of FSP. Morbidity and mortality hazard ratios were calculated from surgery using multivariate analysis, accounting for age, gender, past medical history, tumor focality / laterality / eloquence / volume, extent of resection, MGMT / IDH status, and initiation of postoperative chemo/radiation. Morbidity was defined as any of these events within 30d: DVT, PE, SSI, UTI, MI, urinary retention, ileus, readmission. RESULTS FSP at diagnostic surgery predicted any morbidity (OR2.98, P= 0.005) at 30d. FSP at diagnostic surgery was the only risk factor associated with 30d mortality (OR10.0, P= 0.030), and was also strongly associated with 90d mortality (OR25.0, P= 0.003). FSP at diagnostic surgery was associated with decreased overall survival (OR0.41, P< 0.001) at a level comparable to other mortality predictors, including temozolomide/EBRT (OR0.27), gross total resection (OR0.54), favorable MGMT (OR0.44) or IDH (OR0.44) mutations. Kaplan-Meier curves display overall survival based on severity of FSP. CONCLUSION FSP is a preoperative, simple, accurate, and non-invasive methodology to predict 30d morbidity & 30-day, 90-day, and overall mortality from diagnosis in GBM. FSP is independent of age (not an age surrogate), demographic, oncologic, genetic, surgical, and therapeutic factors. Mortality prediction is comparable to temozolamid/EBRT, total resection, MGMT, and IDH. It is a low cost, intuitive, and potentially universal methodology to guide treatment decision making.

Prolonged tracheal extubation time after glioma surgery was associated with lack of familiarity between the anesthesia provider and the operating neurosurgeon. A retrospective, observational study

Study objectiveWe consider the effect of the number of previous interactions between the anesthesia provider and a single neurosurgeon during neurosurgical procedures (“familiarity”) and occurrence of an interval ≥15 min from the end of surgery (i.e., dressings applied) to tracheal extubation (“prolonged extubation”) during subsequent glioma procedures by that neurosurgeon. The value of 15min is a threshold at which post-case activity by non-anesthesia personnel in the operating room ends. DesignHistorical observational study. SettingNeurosurgical operating room suite in an academic teaching hospital. Patients294 patients undergoing elective supratentorial glioma surgery between 2012 and 2017 by a single neurosurgeon. Measurements1) Time from end of surgery (“dressings applied”) to extubation; 2) number of previous cases where the anesthesia provider had been present at the end of a neurosurgical procedure performed by the neurosurgeon; 3) case duration. Main resultsAnesthesia providers (nurse anesthetists or anesthesia residents) were considered “unfamiliar” with the neurosurgeon if they had been present at the time of extubation for <5 previous neurosurgical cases (including glioma and non-glioma surgery) performed by the neurosurgeon during the study interval. For approximately half the cases the anesthesia provider was unfamiliar with the neurosurgeon. There was an association between the provider's number of historical cases with the neurosurgeon and prolonged extubation (P = 0.0048); the adjusted odds ratio (by unadjusted logistic regression) for unfamiliarity was 2.10 (95% CI 1.28 to 3.44, P = 0.025). Consistent with previously shown associations between case duration and prolonged extubation, analyses were valid based on a near-linear relationship between the logit (prevalence of prolonged extubation) and the case duration quintile. ConclusionsLack of familiarity between the anesthesia provider and neurosurgeon during previous anesthetics is associated with prolonged tracheal extubation following intracranial glioblastoma surgery.

P14.56 Recurrent Glioblastomas: Should we operate a second and even a third time

Abstract BACKGROUND The aim of this study was i) to analyse the effect of repeat surgeries on the survival of patients with focally recurrent glioblastoma who have benefited from temozolomide treatment and ii) to identify potential prognostic factors for survival. MATERIAL AND METHODS Cases from 2005 to 2014 in the glioblastoma database of our department were retrospectively reviewed. The Kaplan-Meier method was used to estimate overall survival (OS) as a function of time after one, two and three surgical resections. All patients received the standard of care after the first surgery (temozolomide during and after radiotherapy) and adjuvant treatment after repeat surgeries. RESULTS One hundred-thirty-two glioblastoma patients (median age: 57 years) were included in the study. Among them, 68, 53 and 11 patients underwent one, two and three surgical resections, respectively. The median OS was 11, 16 and 18 months, respectively, for patients who underwent one, two and three surgical resections. Patients who underwent two (p&lt;0.001) or three (p&lt;0.01) surgeries survived significantly longer than patients who underwent only one. No significant difference was observed between patients who underwent two versus three surgeries (p=0.76). A second resection performed more than 6 months after the initial resection was the only factor associated with prolonged survival (p=0.008). CONCLUSION Glioblastoma patients who benefited from temozolomide treatment and underwent surgery for recurrent glioblastoma exhibited a significant increase in survival compared with patients who did not undergo a second surgery. By contrast, a third surgery for a second recurrence did not contribute to any significant survival benefit.

P03.10 Analyzing the role of reoperation in high grade gliomas: a retrospective study

Abstract BACKGROUND Primary treatment of high grade glioma consists in a standard therapeutic regimen that involves maximal surgical safe resection followed by chemoradiotherapy. Unfortunately, due to its aggressive behavior, relapse is the rule in all patients. When this situation arises, treatment strategy is less clear and reintervention in selected cases is controversial and still a reason for debate. MATERIAL AND METHODS We retrospectively analysed (n=393) patients affected with high grade glioma in our institution during a period of 14 years (from January 2005 to March 2019). Treatment modality at diagnosis and recurrence, overall and progression-free survival were reviewed. RESULTS There were 320 grade IV and 73 grade III gliomas. Regarding to the modality of treatment, more procedures with radical intention (n=227) than biopsies (n=166) were performed. At progression, glioblastoma patients were treated in (n=118) cases. We decided to reoperate (n=30) cases who also received second-line chemotherapies.The other group (n=88) received only systemic treatment. Median overall survival assessed from initial diagnosis was 23 months(95% CI 17–28.9) versus 17 months (95% CI 15.7–18.2) in patients with surgery at recurrence comparing to those who did not undergo second surgery, (p&lt; 0.05). In addition, clinical condition of most patients did not worsen after the second surgery. CONCLUSION Second surgery for recurrent glioblastoma was associated with a survival advantage. Reoperation should be considered in patients with tumours located in low eloquence areas and good clinical condition.

P12.07 Minimal bimodular G-quadruplex nano-construct as cryptic therapeutic DNA oligonucleotide to suppress glioblastoma cell functioning

Abstract BACKGROUND G-quadruplex folding oligodeoxyribonucleotides (G4 ODNs) are considers to be potential anticancer agents, because G4 interferes with some functions of cell, like survival, proliferation, ets, by interacting with G4 binding regulatory proteins. There are some experimental data on anti-proliferative activities of G4: for telomerase complex, aptamers for STAT3, nucleolin, TOP1, SP1, VEGF, and SHP-2, but there is no molecular mechanism yet. Because ODNs are supposed to block regulatory proteins, like cryptic aptamers do, they could be potentially therapeutics, like monoclonal antibodies. The only current approach to find proper model for G4 plus reference cell line, is to screen sets of G4 for sets of cancer cell lines. To avoid selection from large number of G4 structures, we have initiated anti-proliferative study of minimal DNA nano-construct biHD1, built from two minimal active G4 15-mer, by testing 7 human cancer cell lines, including glioblastoma (GBM): U87 and primary cultures from GBM surgery samples. MATERIAL AND METHODS ODN were from Evrogen (Russia). ODN were folded: heated to 950C, slowly cooled to 250C. biHD1, GGTTGGTGTGGTTGG TGGTTGGTGTGGTTGG, and derivatives with G4 structure variations. CD in saline phosphate, pH 7.5; CHIRASCAN (UK) and MARK-5 (France); melting curves at 294 nm. 7 human cancer cell lines: colon, HCT116; prostate, PC3; lung, RL-67; breast adenocarcinoma, MCF7; melanoma, mS; HeLa; GBM, U87 and primary cultures from surgery samples; and human embryonic fibroblast, hEF, as control. MTT for cell viability by colorimetric measurements of metabolic activity (Tecan plate reader, Switzerland). ODN: 0.10 μM, 1.0 μM, 10 μM for 3 days. RESULTS biHD1 is dose-dependent toxic for several human cancer cell lines, most active for lung cancer RL-67 and GBM U87, survival at 10 μM ODN 35% and 45%, respectively. According to data for biHD1 derivatives with deviations from G4 conformation: length of linker joining modules, light distortions of loops, strong distortions of G4, freezing of G4 conformation, it is G4 fold which is responsible for toxicity for U87 cell line. CONCLUSION Cell survival after treatment with G4 minimal bimodular DNA oligonucleotide biHD1 and its derivatives have been tested for 7 human cancer cell lines, including CNS, U87. biHD1 is toxic for cancer cells, but not for embryonic fibroblast, as control; activity depends on G4 fold. Therefore, it is possible to manipulate with minimal G4 as module, and build G4 nano-construct being toxic for cancer cells, including GBM, U87. Research is supported by RFBR grants 17-00-00157, 18-29-01047

Recurrent glioblastomas: Should we operate a second and even a third time?

ObjectivesThe aim of this study was i) to analyse the effect of repeat surgeries on the survival of patients with focally recurrent glioblastoma who have benefited from temozolomide treatment and ii) to identify potential prognostic factors for survival. Patients and methodsCases from 2005 to 2014 in the glioblastoma database of our department were retrospectively reviewed. The Kaplan-Meier method was used to estimate overall survival (OS) as a function of time after one, two and three surgical resections. All patients received the standard of care after the first surgery (temozolomide during and after radiotherapy) and adjuvant treatment after repeat surgeries. ResultsOne hundred-thirty-two glioblastoma patients (median age: 57 years) were included in the study. Among them, 68, 53 and 11 patients underwent one, two and three surgical resections, respectively. The median OS was 11, 16 and 18 months, respectively, for patients who underwent one, two and three surgical resections. Patients who underwent two (p < 0.001) or three (p < 0.01) surgeries survived significantly longer than patients who underwent only one. No significant difference was observed between patients who underwent two versus three surgeries (p = 0.76). A second resection performed >6 months after the initial resection was the only factor associated with prolonged survival (p = 0.008). ConclusionGlioblastoma patients who benefited from temozolomide treatment and underwent surgery for recurrent glioblastoma exhibited a significant increase in survival compared with patients who did not undergo a second surgery. By contrast, a third surgery for a second recurrence did not contribute to any significant survival benefit.

An Awake Contralateral, Transcallosal Approach for Deep-Seated Gliomas of the Basal Ganglia

The basal ganglia and thalamus are uncommon locations for infiltrating gliomas. Tumors here are usually managed with biopsy and adjuvant therapy, with relatively poor results. Rarely do patients undergo extensive surgical intervention. It seems reasonable to suggest that successful cytoreduction may help these patients. However, this hypothesis has not been studied because of the general view that it is not possible to remove deep-seated brain tumors with acceptable outcomes. Through retrospective data collection, we describe a small case series of patients undergoing awake contralateral, transcallosal surgery for deep-seated brain tumors affecting the basal ganglia. We describe our patient cohort, report on patient outcomes, and describe our surgical technique. Four patients underwent awake contralateral, transcallosal surgery for glioblastoma invading the basal ganglia. All 4 patients demonstrated hemibody weakness contralateral to the side of their tumors, with 3 patients confined to wheelchairs at presentation. Their ages ranged from 25 to 64 years. Tumor volumes ranged from 14 to 93 cm3. More than 50% resection of each tumor was achieved during surgery. In 2 cases, approximately 90% resection was achieved. Motor strength improved in 1 patient who presented with hemiplegia. Two patients required ventriculoperitoneal shunting for complications related to hydrocephalus. At the writing of this article, 2 of our patients were still alive, functional, and free of tumor progression. We present the results of our attempts to resect large gliomas infiltrating the basal ganglia in 4 patients. Our technique combined a contralateral, transcallosal approach with awake neuromonitoring. Our results suggest it is possible to remove these tumors with reasonable outcomes.

Dual-Use Intraoperative MRI in Glioblastoma Surgery: Results of Resection, Histopathologic Assessment, and Surgical Site Infections.

To achieve maximal resection in glioblastoma (GBM) surgery, intraoperative imaging is important. An intraoperative magnetic resonance imaging (iMRI) suite used for both diagnostic and intraoperative imaging is considered being a reasonable concept for modern hospital management. It is still discussed if the dual use increases the risk of surgical site infections (SSI). This article assesses the rate of gross total resection (GTR), extent of resection (EOR), and histopathology after iMRI-guided resections in patients with GBM. The rate of surgical site infections (SSIs) is evaluated. In all, 79 patients with GBM were operated on with iMRI. Additional resection was performed if iMRI depicted contrast enhancing tissue suggestive of residual tumor. GTR and EOR were determined by segmentation and volumetric analysis of the MR images. SSIs and the role of intravenous only or intravenous plus intrathecal antibiotics were evaluated. Statistical analysis was performed to detect the sensitivity, specificity, positive predictive value, and negative predictive value of iMRI-guided extended resections. Pearson's two-tailed chi-square test was performed to evaluate the rates of GTR and variables associated with SSI. GTR was achieved in 59 patients (74.68%). Rate of GTR was 35.44% before iMRI and additional resections (p < 0.0001). Mean EOR was 96.27%. Positive predictive value for tumor cells in the additionally resected tissue was 88.6%, negative predictive value was 100%, sensitivity was 100%, and specificity was 70. 6%. Rate of SSIs was 5.06% (n = 4). Two superficial SSIs, one subdural empyema and one cerebritis, were seen. SSI rates with parenteral only and additional intrathecal antibiotics were 0% and 8%, respectively (p = 0.133). Increase of extent of tumor resection using iMRI is evident. SSI rate is within the normal range of neurosurgical procedures. A dual-use iMRI suite is a safe concept.

Between-hospital variation in mortality and survival after glioblastoma surgery in the Dutch Quality Registry\xa0for Neuro Surgery

PurposeStandards for surgical decisions are unavailable, hence treatment decisions can be personalized, but also introduce variation in treatment and outcome. National registrations seek to monitor healthcare quality. The goal of the study is to measure between-hospital variation in risk-standardized survival outcome after glioblastoma surgery and to explore the association between survival and hospital characteristics in conjunction with patient-related risk factors.MethodsData of 2,409 adults with first-time glioblastoma surgery at 14 hospitals were obtained from a comprehensive, prospective population-based Quality Registry Neuro Surgery in The Netherlands between 2011 and 2014. We compared the observed survival with patient-specific risk-standardized expected early (30-day) mortality and late (2-year) survival, based on age, performance, and treatment year. We analyzed funnel plots, logistic regression and proportional hazards models.ResultsOverall 30-day mortality was 5.2% and overall 2-year survival was 13.5%. Median survival varied between 4.8 and 14.9 months among hospitals, and biopsy percentages ranged between 16 and 73%. One hospital had lower than expected early mortality, and four hospitals had lower than expected late survival. Higher case volume was related with lower early mortality (P = 0.031). Patient-related risk factors (lower age; better performance; more recent years of treatment) were significantly associated with longer overall survival. Of the hospital characteristics, longer overall survival was associated with lower biopsy percentage (HR 2.09, 1.34–3.26, P = 0.001), and not with academic setting, nor with case volume.ConclusionsHospitals vary more in late survival than early mortality after glioblastoma surgery. Widely varying biopsy percentages indicate treatment variation. Patient-related factors have a stronger association with overall survival than hospital-related factors.

Awake surgery for glioblastoma can preserve independence level, but is dependent on age and the preoperative condition.

Lately, awake surgery has been frequently adapted for glioblastoma (GBM). However, even with awake surgery, the expected long-term independence levels may not be achieved. We studied the characteristics of independence levels in GBM patients, and investigated the usefulness and parameter thresholds of awake surgery from the standpoint of functional outcomes. Totally, 60 GBM patients (awake group, n = 30; general anesthesia group, n = 30) who underwent tumor resection surgery were included. We collected preoperative and 1- and 3-month postoperative Karnofsky Performance Status (KPS) scores, and analyzed causes of low KPS scores from the aspect of function, brain region, and clinical factors. Then, we focused on the operative method, and investigated the usefulness of awake surgery. Finally, we explored the parameter standards of awake surgery in GBM considering independence levels. Postoperative KPS were significantly lower than preoperative scores. Responsible lesions for low KPS scores were deep part of the left superior temporal gyrus and the right posterior temporal gyri that may be causes of aphasia and neuropsychological dysfunctions, respectively. Additionally, operative methods influenced on low independence level; long-term KPS scores in the awake group were significantly higher than those in the general anesthesia group, but they depended on age and preoperative KPS scores. Receiver operating characteristic curve analysis showed preoperative KPS = 90 and age = 62years as the cutoff values for preservation of long-term KPS scores in awake group. Awake surgery for GBM is useful for preserving long-term independence levels, but outcomes differ depending on age and preoperative KPS scores.

The utility of surgery in butterfly glioblastoma: A case-control study.

e13529 Background: Glioblastoma is the most common primary brain tumour and may rarely infiltrate the corpus callosum. Such ‘butterfly’ glioblastomas (BGBM) are believed to confer a poorer prognosis than their non-callosal counterparts. We aimed to determine the impact of surgery on overall survival (OS) and postoperative morbidity in butterfly glioblastomas. Methods: Retrospective analysis was performed on all case notes of patients histologically diagnosed with GBM from January 2011 to January 2017 at The Walton Centre NHS Foundation Trust, Liverpool. Data was collected under the following headings: demographics, tumour characteristics, surgical data, adjuvant therapy and survival data. A case-matched control group was produced according to age, sex and 1o resection. Univariate analysis was performed. Results: 632 glioblastoma patients were identified. 37 patients were diagnosed with butterfly BGBM, with a median age of 62.7 years and a gender split of 24 males (64.9%) to 13 females (35.1%). Median tumour volume was 31700mm3, with 24 (56%) tumours involving the genu and 13 (22%) the splenium of the callosum. Kaplan-Meier analysis with log-rank testing demonstrated a significant (p = 0.04) decrease in median OS in those with BGBM (100 days (95%CI 57-142)) vs controls (276 days (95%CI 224-327)). Resection of BGBMs resulted in longer median OS than biopsy alone (296 days (95%CI 229-363) vs 81 (66-96)), though this was a non-significant difference (p = 0.36). Multifocal disease occurred significantly more often in BGBM patients (p = 0.01), the exclusion of which from analysis demonstrated a significant survival benefit with resection (427 days (95%CI 207-647)) compared to biopsy (221 days (95%CI 151-291)) (p = 0.04). Postoperative complications did not occur significantly more often in BGBM resections than controls (7/36 (19.4%) vs 5/36 (13.9%) (p = 0.257)). Conclusions: Overall, butterfly glioblastomas confer a worse prognosis than those without callosal involvement. A greater prevalence of multifocal disease is seen in butterfly glioblastoma, warranting further investigation. Resection offers a significant improvement in OS in solitary butterfly glioblastomas without a significant increase in postoperative morbidity, and should therefore be considered an efficacious and safe treatment option.

Association of Surgical Resection, Disability, and Survival in Patients with Glioblastoma.

Extent of resection (EOR) and Karnofsky Performance Status (KPS) are at odds in glioblastoma (GBM) surgery, that is, the anticipated postoperative disability limits the EOR. This study analyzes the correlation of different surgical modalities with the resulting physical status and survival of patients with GBM. A total of 565 patients with primary GBM were operated on in a single institution between 2006 and 2014. Possible surgical modalities comprised supratotal resection (SLR), gross total resection (GTR; ≥ 95% by volume), tumor debulking (TDB; ≤ 95% by volume), and stereotactic biopsy (SB). Pre- and postoperative KPS before and up to 4 weeks after surgery as well as overall survival (OS) rate were determined retrospectively. Hazard ratio (HR) and 95% confidence intervals were calculated using a Cox proportional hazards model. Median postoperative KPS was ≥ 70, irrespective of surgical modality. Mean OS was 12.5 months. Multivariate analysis revealed age ≥ 70 years (HR: 1.93), preoperative KPS < 70 (HR: 2.15), and unmethylation in MGMT promoter (HR: 1.27) as independent factors for worse OS. Regarding surgical modality, SB was associated with the worst survival (HR: 2.3) followed by TDB (HR: 1.36). SLR was inferior to GTR (HR: 1.27). Higher EOR in patients with GBM does not seem inevitably correlated with increasing functional impairment, but better survival, provided there is a balanced preoperative indication. Nevertheless, SLR does not seem to be superior to GTR. Whenever possible, maximal safe resection should be considered in patients with GBM, even if an EOR ≥ 95% is not possible.