Supratentorial Glioblastoma Research Articles

Cerebellar glioblastoma in adults: a comparative single-center matched pair analysis and systematic review of the literature

PurposeThe rarity of cerebellar glioblastoma presents a significant challenge in clinical practice due to the lack of extensive prognostic data on long-term survival rates, rendering it an underrepresented entity compared to its supratentorial counterpart. This study aims to analyze potential differences in survival outcome between patients with cerebellar and supratentorial glioblastomas.MethodsFrom 2009 to 2020, 8 patients underwent surgical treatment for cerebellar glioblastoma at the authors’ institution. These patients were individually matched with a cohort of 205 consecutive patients from our institutional database with supratentorial glioblastoma, taking into account key prognostic parameters. Progression-free survival (PFS) and overall survival (OS) rates were compared. Additionally, we performed a systematic literature review to compile further survival data on cerebellar glioblastoma patients.ResultsThe median OS for cerebellar glioblastoma patients was 18 months (95% CI 11–25). The balanced matched-pair analysis showed no significant difference in survival when compared to patients with supratentorial glioblastoma, exhibiting a median OS of 23 months (95% CI 0–62) (p = 0.63). Respective values for PFS were 8 months (95% CI 4–12) for cerebellar and 7 months (95% CI 0–16) for supratentorial glioblastoma (p = 0.2). The systematic review revealed that median OS for cerebellar glioblastoma in current literature ranges from 7 to 21 months.ConclusionsThe present findings indicate that patients with supra- and infratentorial glioblastoma do not significantly differ in regard to survival outcome parameters. This similarity in prognosis might encourage clinicians to consider surgical interventions for both supra- and infratentorial glioblastoma in a similar manner.

Protocol digest of a phase III randomized trial of gross total resection versus possible resection of fluid-attenuated inversion recovery-hyperintense lesion on MRI for newly diagnosed supratentorial glioblastoma: JCOG2209 (FLAMINGO).

The goal of surgery for patients with newly diagnosed glioblastoma (GBM) is maximum safe resection of the contrast-enhancing (CE) lesion on magnetic resonance imaging. However, there is no consensus on the efficacy of FLAIRectomy, which is defined as the possible resection of fluid-attenuated inversion recovery (FLAIR)-hyperintense lesions surrounding the CE lesion. Although retrospective analyses suggested the potential benefits of FLAIRectomy, such outcomes have not been confirmed by prospective studies. Therefore, we planned a multicenter, open-label, randomized controlled phase III trial to evaluate the efficacy of FLAIRectomy compared with gross total resection of CE lesions in patients with newly diagnosed GBM. The primary endpoint is overall survival. In total, 130 patients will be enrolled from 47 institutions over 5years. This trial has been registered at the Japan Registry of Clinical Trials (study number jRCT1031230245).

Machine learning-based nomogram for distinguishing between supratentorial extraventricular ependymoma and supratentorial glioblastoma.

To develop a machine learning-based nomogram for distinguishing between supratentorial extraventricular ependymoma (STEE) and supratentorial glioblastoma (GBM). We conducted a retrospective analysis on MRI datasets obtained from 140 patients who were diagnosed with STEE (n=48) and GBM (n=92) from two institutions. Initially, we compared seven different machine learning algorithms to determine the most suitable signature (rad-score). Subsequently, univariate and multivariate logistic regression analyses were performed to identify significant clinical predictors that can differentiate between STEE and GBM. Finally, we developed a nomogram by visualizing the rad-score and clinical features for clinical evaluation. The TreeBagger (TB) outperformed the other six algorithms, yielding the best diagnostic efficacy in differentiating STEE from GBM, with area under the curve (AUC) values of 0.735 (95% CI: 0.625-0.845) and 0.796 (95% CI: 0.644-0.949) in the training set and test set. Furthermore, the nomogram incorporating both the rad-score and clinical variables demonstrated a robust predictive performance with an accuracy of 0.787 in the training set and 0.832 in the test set. The nomogram could serve as a valuable tool for non-invasively discriminating between STEE and GBM.

Long-term survivors in 976 supratentorial glioblastoma, IDH-wildtype patients.

Glioblastoma, isocitrate dehydrogenase (IDH)-wildtype is the most aggressive glioma with poor outcomes. The authors explored survival rates and factors associated with long-term survival in patients harboring a glioblastoma, IDH-wildtype. In an observational, retrospective, single-center study, the authors examined the medical records of 976 adults newly diagnosed with supratentorial glioblastomas, IDH-wildtype between January 2000 and January 2021. They analyzed clinical-, imaging-, and treatment-related factors associated with 2-year and 5-year survival. The median overall survival was 11.2 months (12.2 months for patients included after 2005 and the introduction of standard combined chemoradiotherapy). The median progression-free survival was 9.4 months (10.0 months for patients included after 2005). Overall, 17.6% of patients reached a 2-year overall survival, while 2.2% of patients reached a 5-year overall survival. Furthermore, 6.6% of patients survived 2 years without progression, while 1.1% of patients survived 5 years without progression. Two factors that were consistently associated with 2-year and 5-year survival were first-line oncological treatment with standard combined chemoradiotherapy and methylated O6-methylguanine-DNA methyltransferase promoter. Other factors that were significantly associated with 2-year or 5-year survival were age at diagnosis ≤ 60 years, headaches or signs of raised intracranial pressure at diagnosis, cortical contact of contrast enhancement, no contrast enhancement crossing the midline on initial imaging, total or subtotal tumor resection, and a second line of oncological treatment at recurrence. Within 21 cases of 5-year survival, 18 were confirmed to be glioblastomas, IDH-wildtype, and 7 of the 5-year survivors (38.9%) had additional genetic alterations: 3 cases had an FGFR mutation or fusion, 3 cases had a PIK3CA mutation, 1 case had a PTPN11 mutation, and 1 case had a PMS2 mutation in the context of constitutional mismatch repair deficiency syndrome. Five-year overall survival in patients with glioblastoma, IDH-wildtype is extremely low. Predictors of a longer survival are mostly treatment factors, emphasizing the importance of a complete oncological treatment plan, when achievable. Glioblastoma, IDH-wildtype 5-year survivors could be screened for actionable targets in case of recurrence.

AB012. A phase III randomized trial of gross total resection versus possible resection of fluid-attenuated inversion recovery (FLAIR) hyperintensity lesion on magnetic resonance image for newly diagnosed supratentorial glioblastoma (JCOG2209).

Complete resection of contrast-enhanced lesions [gross total resection (GTR)] without severe neurological deficits has been generally accepted as the goal of surgery. However, it remains unclear if additional resection of surrounding fluid-attenuated inversion recovery (FLAIR) hyper-intense lesions combined with GTR (FLAIRectomy) has survival advantage of primary glioblastoma patients. Multicenter, open-label, randomized phase III trial was commenced to confirm the superiority of FLAIRectomy to GTR alone followed by radiotherapy with concomitant and adjuvant temozolomide in terms of overall survival (OS) for primary glioblastoma IDH-wildtype patients. This trial investigates not only survival but also postoperative neurological and neurocognitive deficits in detail. We assumed a 2-year OS of 50% in the GTR arm and expected a 15% improvement in the FLAIRectomy arm. A total of 130 patients is required with a one-sided alpha of 5%, power of 70%, and will be accrued from 49 Japanese institutions in 4 years and follow-up will last 2.5 years. Patients aged 18-75 years will be registered and randomly assigned to each arm with 1:1 allocation. The primary endpoint is OS, and the secondary endpoints are progression-free survival, frequency of adverse events, proportion of Karnofsky performance status preservation, proportion of National Institutes of Health stroke scale preservation, proportion of mini-mental state examination preservation and proportion of health-related quality of life preservation. The Japan Clinical Oncology Group Protocol Review Committee approved this study protocol in May 2023. Ethics approval was granted by the National Cancer Center Hospital Certified Review Board. Patient enrollment began in July 2023. If FLAIRectomy is superior to GTR alone, aggressive surgery will become a standard surgical treatment for glioblastoma with resectable contrast-enhanced lesion. Registry number: jRCT1031230245. Date of registration: 19/July/2023. Date of first participant enrollment: 28/July/2023.

Symptomatic spinal metastasis of a supratentorial glioblastoma in a pediatric patient: a case report and comprehensive review of the literature

Spinal metastasis of Glioblastoma is a rare occurrence, especially in pediatric patients, and extremely rare to become symptomatic. The pathology is poorly understood and remains with unclear dissemination mechanisms. The treatment approaches are varied and multimodal therapy (surgery, chemotherapy, and radiotherapy) can be employed to manage this type of metastasis. We report a case of a 17-year-old female who underwent a gross-total resection of a right frontal glioblastoma and had adjuvant therapy with chemo- and radiotherapy. In the sixth month of follow-up, the patient presented a paraparesis, and a distant recurrence at T7-T8 was detected. The patient was treated with gross-total resection of the tumor through a laminectomy. The histopathological results were consistent with an isocitrate dehydrogenase (IDH) wildtype GBM metastasis. The patient was treated with multimodal therapy, including surgery, radiotherapy, and chemotherapy. A complementary comprehensive review of current available literature on this topic is also presented.

Impact of frailty on survival glioblastoma, IDH-wildtype patients.

Frailty increases the risk of mortality among patients. We studied the prognostic significance of frailty using the modified 5-item frailty index (5-mFI) in patients harboring a newly diagnosed supratentorial glioblastoma, IDH-wildtype. We retrospectively reviewed records of patients surgical treated at a single neurosurgical institution at the standard radiochemotherapy era (January 2006 - December 2021). Inclusion criteria were: age ≥ 18, newly diagnosed glioblastoma, IDH-wildtype, supratentorial location, available data to assess the 5-mFI index. A total of 694 adult patients were included. The median overall survival was longer in the non-frail subgroup (5-mFI < 2, n = 538 patients; 14.3 months, 95%CI 12.5-16.0) than in the frail subgroup (5-mFI ≥ 2, n = 156 patients; 4.7 months, 95%CI 4.0-6.5 months; p < 0.001). 5-mFI ≥ 2 (adjusted Hazard Ratio (aHR) 1.31; 95%CI 1.07-1.61; p = 0.009) was an independent predictor of a shorter overall survival while age ≤ 60 years (aHR 0.78; 95%CI 0.66-0.93; p = 0.007), KPS score ≥ 70 (aHR 0.71; 95%CI 0.58-0.87; p = 0.001), unilateral location (aHR 0.67; 95%CI 0.52-0.87; p = 0.002), total removal (aHR 0.54; 95%CI 0.44-0.64; p < 0.0001), and standard radiochemotherapy protocol (aHR 0.32; 95%CI 0.26-0.38; p < 0.0001) were independent predictors of a longer overall survival. Frailty remained an independent predictor of overall survival within the subgroup of patients undergoing a first-line oncological treatment after surgery (n = 549) and within the subgroup of patients who benefited from a total removal plus adjuvant standard radiochemotherapy (n = 209). In newly diagnosed supratentorial glioblastoma, IDH-wildtype patients treated at the standard combined radiochemotherapy era, frailty, defined using a 5-mFI score ≥ 2 was an independent predictor of overall survival.

ALA-RDT in GBM: protocol of the phase I/II dose escalation trial of radiodynamic therapy with 5-Aminolevulinic acid in patients with recurrent glioblastoma

BackgroundDespite improvements in surgical as well as adjuvant therapies over the last decades, the prognosis for patients with glioblastoma remains poor. Five-Aminolevulinic acid (5-ALA) induced porphyrins are already used for fluorescence-guided resection and as photosensitizer for photodynamic therapy. New findings reveal their potential use as sensitizing agents in combination with ionizing radiation.MethodsWe initiated a phase I/II dose escalation study, treating patients with recurrence of glioblastoma with oral 5-ALA concurrent to radiotherapy (RT). This prospective single-center study based in the University Hospital Münster aims to recruit 30 patients over 18 years of age with histologically verified recurrence of supratentorial glioblastoma in good performance status (KPS ≥ 60). Following a 3 + 3 dose-escalation design, patients having undergone re-resection will receive a 36 Gy RT including radiodynamic therapy fractions (RDT). RDT constitutes of oral administration of 5-ALA before the irradiation session. Two cohorts will additionally receive two fractions of neoadjuvant treatment three and two days before surgery. To determine the maximum tolerated dose of repeated 5-ALA-administration, the number of RDT-fractions will increase, starting with one to a maximum of eight fractions, while closely monitoring for safety and toxicity. Follow-up will be performed at two and five months after treatment. Primary endpoint will be the maximum tolerated dose (MTD) of repeated ALA-administration, secondary endpoints are event-free-, progression-free-, and overall-survival. Additionally, 5-ALA metabolites and radiobiological markers will be analysed throughout the course of therapy and tissue effects after neoadjuvant treatment will be determined in resected tissue. This protocol is in accordance with the SPIRIT guidelines for clinical trial protocols.DiscussionThis is the protocol of the ALA-RDT in GBM-study, the first-in-man evaluation of repeated administration of 5-ALA as a radiosensitizer for treatment of recurrent glioblastoma.Trial registrationThis study was approved by the local ethics committee of the Medical Association of Westphalia-Lippe and the University of Münster on 12.10.2022, the German federal institute for Drugs and medical devices on 13.10.2022 and the federal office for radiation protection on 29.08.2022. This trial was registered on the public European EudraCT database (EudraCT-No.: 2021-004631-92) and is registered under www.cliniclatrials.gov (Identifier: NCT05590689).

Efficacy and Safety of Carmustine Wafer Implantation After Ventricular Opening in Glioblastomas, Isocitrate Dehydrogenase-Wildtype, in Adults.

We assessed the impact of ventricular opening on postoperative complications and survival of carmustine wafer implantation during surgery of newly diagnosed supratentorial glioblastomas, isocitrate dehydrogenase (IDH)-wildtype in adults. We performed an observational, retrospective, single-center cohort study at a tertiary surgical neuro-oncological center between January 2006 and December 2021. One hundred ninety-four patients who benefited from a first-line surgical resection with carmustine wafer implantation were included. Seventy patients (36.1%) had a ventricular opening. We showed that ventricular opening (1) did not increase overall postoperative complication rates (P = .201); (2) did not worsen the early postoperative Karnofsky Performance Status score (P = .068); (3) did not increase the time interval from surgery to adjuvant oncological treatment (P = .458); (4) did not affect the completion of the standard radiochemotherapy protocol (P = .164); (5) did not affect progression-free survival (P = .059); and (6) did not affect overall survival (P = .142). In this study, ventricular opening during first-line surgical resection did not affect the survival and postoperative complications after use of carmustine wafer implantation in adult patients with a newly diagnosed supratentorial glioblastoma, IDH-wildtype. This warrants a prospective and multicentric study to clearly assess the impact of the ventricular opening after carmustine wafer implantation in glioblastoma, IDH-wildtype.

Characteristics and Prognosis of Tumor-Related Epilepsy During Tumor Evolution in Patients With IDH Wild-Type Glioblastoma.

Tumor-related epilepsy is a well-known symptom of glioblastoma. However, the particular characteristics of epileptic seizures related to glioblastoma, isocitrate dehydrogenase (IDH)-wild-type is almost unexplored longitudinally during the whole course of the disease. We assessed tumor-related epilepsy and seizure control during tumor evolution and the prognostic significance of tumor-related epilepsy. We performed an observational, retrospective single-center study at one tertiary referral neuro-oncology surgical center (2000-2020). We included adult patients treated for a newly diagnosed supratentorial glioblastoma, IDH-wild-type with available preoperative and postoperative MRI and with available epileptic seizure status at diagnosis. To determine factors associated with tumor-related epilepsy or seizure control, univariate analyses were performed using the χ2 or Fisher exact tests for categorical variables and the unpaired t test or Mann-Whitney rank-sum test for continuous variables. Predictors associated with tumor-related epilepsy and seizure control in unadjusted analysis were entered into backward stepwise logistic regression models. One thousand six patients were enrolled. The cumulative incidence of tumor-related epilepsy increased during tumor evolution (33.1% at diagnosis, 44.7% after oncologic treatment, 52.4% at progression, and 51.8% at the end-of-life phase) and is related to tumor features (cortex involvement, no necrosis, and small volume). Uncontrolled epileptic seizures increased during tumor evolution (20.1% at diagnosis, 32.0% after oncologic treatment, 46.7% at progression, and 41.1% at the end-of-life phase). Epileptic seizure control after oncologic treatment was related to seizure features (uncontrolled before oncologic treatment and focal-to-bilateral tonic-clonic seizures) and to the extent of resection. Epileptic seizure control at tumor progression was related to seizure features (presence at diagnosis and uncontrolled after oncologic treatment) and to the time to progression. Tumor-related epilepsy at diagnosis was a predictor of a longer overall survival (adjusted hazard ratio, 0.78; 95% CI 0.67-0.90; p < 0.001) independent of age, Karnofsky Performance Status score, tumor location and volume, extent of resection, standard combined chemoradiotherapy, levetiracetam use, and MGMT promoter methylation. The progression of tumor-related epilepsy with the evolution of glioblastoma, IDH-wild-type and the effects of surgery on seizure control argue for proper antiseizure medication and maximal safe resection. Tumor-related epilepsy is an independent predictor of a longer survival.

10074-COT-10 A NEW PREOPERATIVE PREDICTIVE SCORING SYSTEM FOR SUPRATENTORIAL NEWLY DIAGNOSED ISOCITRATE DEHYDROGENASE-WILD TYPE GLIOBLASTOMA TREATED WITH RADIOTHERAPY PLUS CONCOMITANT AND ADJUVANT TEMOZOLOMIDE

Abstract We aimed to evaluate the usefulness of a preoperative predictive score for assessing overall survival in patients with supratentorial newly diagnosed isocitrate dehydrogenase (IDH)-wild type glioblastoma (GBM) treated with radiotherapy plus concomitant and adjuvant temozolomide. In this study, 104 patients with newly diagnosed supratentorial IDH-wild type GBM were enrolled between May 2007 and April 2021. Four prognostic factors were evaluated preoperatively: age, initial symptoms, neutrophil/lymphocyte ratio (NLR), and contact of the tumor with the ventricles on magnetic resonance imaging (MRI). A scoring system of 0-6 points was created, with 2, 1, 2, and 1 points assigned to age &amp;gt; 75 years, no seizure onset, NLR &amp;gt; 2.23, and ventricular c ontact. The median follow-up period after surgery was 15 months (range: 1-146 months). The total score was 0, 1, 2, 3, 4, 5, and 6 points for 6, 6, 18, 15, 43, 6, and 10 patients respectively. Patients with 0-2, 3-4, and 5-6 points were assigned to groups 1, 2, and 3, respectively. The median survival time from surgery was 20 months in the entire cohort and 34, 19, and 10 months in groups 1, 2, and 3, respectively. The three groups showed significant differences in the median survival time (p&amp;lt; 0.001), with lower scores corresponding to longer survival times. We propose a new preoperative prognostic scoring system for newly diagnosed patients with supratentorial IDH-wild GBM. The prognostic information obtained using this system can help determine the intensity of treatment for the patient.

10094-MPC-8 MOLECULAR PATHOLOGICAL ANALYSIS OF RADIATION-INDUCED GLIOBLASTOMA AFTER PEDIATRIC CEREBELLAR MEDULLOBLASTOMA TREATMENT

Abstract INTRODUCTION The number of long-term survivors of pediatric medulloblastoma has been increasing due to improved treatment options. However, secondary cancer can be an issue for long-term survivors. We report the molecular pathological evaluation of two cases of radiation-induced glioblastoma. Patients: Of the 27 patients with cerebellar medulloblastoma treated at our institution, two who were 3 years old and 11 years old at the time of medulloblastoma diagnosis and both were girls, developed cerebellar glioblastomas after the initial treatment at five years and 11 months and 22 years and eight months, respectively. These two cerebellar glioblastomas were clinically diagnosed as radiation-induced secondary cancer. RESULTS Both of the two cases we clinically diagnosed as radiation-induced glioblastoma had negative IDH-1, EGFR expression and positive p53 expression in immunohistochemistry. DISCUSSION It has been reported that EGFR expression is negative as a molecular feature of radiation-induced glioblastoma, and the two cases we experienced were consistent with radiation-induced secondary cancers. In general, primary glioblastoma is positive for EGFR expression in the supratentorial region and negative in the infratentorial region. Therefore, in the case of supratentorial glioblastoma, it is useful to evaluate EGFR expression to distinguish primary glioblastoma from secondary glioblastoma.

The role of acute normovolemic hemodilution in reducing allogeneic blood transfusion in glioblastoma surgery: a case–control study

BackgroundAcute normovolemic hemodilution (ANH) was first introduced in glioblastoma surgery, and its role in reducing allogeneic blood transfusion was investigated in this study.MethodsThis study enrolled supratentorial glioblastoma patients who received total resection. In the ANH group, the patients were required to draw blood before the operation, and the blood will be transfused back to the patient during the operation. The association between ANH and clinical features was investigated.ResultsSixty supratentorial glioblastoma patients were enrolled in this study, 25 patients were allocated in the ANH group, and another 35 patients were included in the control group. ANH dramatically reduced the need for allogeneic blood transfusion (3 [12%] vs 12 [34.3%], P = 0.049), and the blood transfusion per total of patients was dramatically decreased by the application of ANH (0.40 ± 1.15 units vs 1.06 ± 1.59 units, P = 0.069). Furthermore, ANH also markedly reduced the requirement of fresh frozen plasma (FFP) transfusion (2 [8%] vs 11 [31.4%], P = 0.030) and the volume of FFP transfusion per total of patients (32.00 ± 114.46 mL vs 115.71 ± 181.00 mL, P = 0.033). The complication rate was similar between the two groups.ConclusionsANH was a safe and effective blood conservation technique in glioblastoma surgery.

EPID-07. DISTANT PROGRESSION TO THE POSTERIOR FOSSA IN SUPRATENTORIAL GLIOBLASTOMA: A REPORT OF THREE CASES DURING TUMOR TREATING FIELDS THERAPY

Abstract BACKGROUND Distant progression of supratentorial glioblastoma (GBM) to the posterior fossa is rare. We report three cases in which such distant progression was observed during Tumor Treating Fields (TTFields) therapy. CASES: All three cases involved solitary supratentorial tumors. Biopsy was performed in case 1 (61-year-old male) and partial resection in cases 2 (69-year-old female) and 3 (73-year-old male). The diagnosis was IDH-wildtype GBM in all three cases. TTFields therapy was performed following chemoradiotherapy. In case 1, distant progression was observed in the dorsal side of the medulla oblongata at 7 postoperative months and in the left cerebellum at 23 postoperative months. The patient died 5 months later. In case 2, distant progression was evident in the pons at 41 postoperative months and the patient died 3 months later. In case 3, distant progression was observed in the cerebellum at 5 postoperative months and the patient died 3 months later. Autopsy was performed in case 1 and revealed multiple separate GBM lesions in the supra- and infratentorial space. Although there was histological heterogeneity within lesions, there was no clear histological difference between supra- and infratentorial lesions. DISCUSSION In the EF-14 trial, although there were no cases of GBM progression to the posterior fossa in the control group who did not receive TTFields therapy (0/122 cases), such progression occurred in 3.6% (11/306) of cases in the TTFields-treated group (p&amp;lt; 0.001). Even though TTFields therapy affords good local control of GBM, distant progression might occur in the posterior fossa, where the electric field effect is poor. Further accumulation and analysis of such cases is warranted.

P15.05.B THE IMPACT OF IOMRI ON GLIOBLASTOMA RESECTION AND CLINICAL OUTCOMES IN A STATE-OF-THE-ART NEURO-ONCOLOGICAL SETUP

Abstract BACKGROUND Intraoperative magnetic resonance imaging (ioMRI) is applied to improve the extent of resection in patients suffering from primary brain tumors, especially glioblastoma (GBM). While some older randomized trials reported data on safety and feasibility, ioMRI’s actual impact in a modern neurosurgical setting has not been sufficiently investigated. We therefore aimed to evaluate the effect of ioMRI on tumor resection and progression-free survival (PFS) in GBM patients in a modern high-volume center. MATERIAL AND METHODS Patients undergoing ioMRI for resection of supratentorial GBM were prospectively included between March 2018 and June 2020. In all cases, ioMRI was performed after complete macroscopic tumor resection. The extent of resection (EOR) was determined by volumetric analysis. Gross total resection (GTR) was defined as EOR ≥95%. Furthermore, progression-free survival (PFS) was analyzed through univariate and multivariate Cox proportional regression analysis. RESULTS Overall, 172 patients were enrolled in this study. The mean EOR increased from 93·9% on ioMRI to 98·3% (p&amp;lt;0·0001) on postoperative MRI, with residual tumor volume decreasing from 1·3 ± 4·2 cm3 to 0·6 ± 2·5 cm3(p=0·0037). The GTR rate increased from 78·5% to 93·0% (p=0·0002). Logistic regression revealed recurrent GBM (odds ratio [OR] =3·047, 95% confidence interval [CI] 1·165-7·974, p=0·023) and tumor volume less than 15 cm3 (OR=3·031, 95% CI 1·062-8·651, p=0·038) as independent risk factors leading to STR. Tumor resection performed additionally after ioMRI lead to equally long PFS compared to patients with complete tumor removal achieved before ioMRI (HR=0·898, 95%CI 0·543-1·483, p=0·67). CONCLUSION ioMRI serves as a valuable tool in a modern neurosurgical setting, severely decreasing residual tumor volume. ioMRI considerably helps to achieve comparable PFS even in cases, where an unexpected tumor residual is found on ioMRI after initial resection.

A multicenter, randomized, placebo-controlled phase IIb trial of an autologous formalin-fixed tumor vaccine for newly diagnosed glioblastomas.

An autologous formalin-fixed tumor vaccine (AFTV) derived from resected glioblastoma (GBM) tissue can be used against unidentified tumor antigens. Thus, the authors conducted a multicenter double-blind phase IIb trial to investigate the efficacy of an AFTV. Eligible patients were adults with supratentorial GBMs, 16-75 years of age, with Karnofsky Performance Scale (KPS) scores ≥ 60%, and no long-term steroid administration. An AFTV comprising fixed paraffin-embedded tumor tissue with immune adjuvants or an identical placebo without fixed tumor tissue was injected intradermally over three courses before and after chemoradiotherapy. The primary and secondary end points were overall survival (OS), progression-free survival (PFS), and 3-year survival rate. Sixty-three patients were enrolled. The average patient age was 61 years. The median KPS score was 80%, and the median resection rate was 95%. The full analysis set of 57 patients indicated no significant difference in OS (p = 0.64) for the AFTV group (median OS 25.6 months, 3-year OS rate 38%) compared with the placebo group (31.5 months and 41%, respectively) and no difference in PFS (median PFS 13.3 months in both groups, p = 0.98). For patients with imaging-based total tumor removal, the 3-year PFS rate was 81% in the AFTV group versus 46% in the placebo group (p = 0.067), whereas the 3-year OS rate was 80% versus 54% (p = 0.16), respectively. Similar results were obtained in the p53-negative subgroups. Severe adverse effects were not observed. The AFTV may have potential effects in certain patient subgroups. A phase III study for patients with total tumor removal remains warranted to confirm these findings. Clinical trial registration no.: UMIN000010602 (UMIN Clinical Trials Registry).

The Impact of ioMRI on Glioblastoma Resection and Clinical Outcomes in a State-of-the-Art Neuro-Oncological Setup.

Intraoperative magnetic resonance imaging (ioMRI) aims to improve gross total resection (GTR) in glioblastoma (GBM) patients. Despite some older randomized data on safety and feasibility, ioMRI's actual impact in a modern neurosurgical setting utilizing a larger armamentarium of techniques has not been sufficiently investigated to date. We therefore aimed to analyze its effects on residual tumor, patient outcome, and progression-free survival (PFS) in GBM patients in a modern high-volume center. Patients undergoing ioMRI for resection of supratentorial GBM were enrolled between March 2018 and June 2020. ioMRI was performed in all cases at the end of resection when surgeons expected complete macroscopic tumor removal. Extent of resection (EOR) was performed by volumetric analysis, with GTR defined as an EOR ≥ 95%, respectively. Progression-free survival (PFS) was analyzed through univariate and multivariate Cox proportional regression analyses. In total, we enrolled 172 patients. Mean EOR increased from 93.9% to 98.3% (p < 0.0001) due to ioMRI, equaling an increase in GTR rates from 78.5% to 93.0% (p = 0.0002). Residual tumor volume decreased from 1.3 ± 4.2 cm3 to 0.6 ± 2.5 cm3 (p = 0.0037). Logistic regression revealed recurrent GBM as a risk factor leading to subtotal resection (STR) (odds ratio (OR) = 3.047, 95% confidence interval (CI) 1.165-7.974, p = 0.023). Additional resection after ioMRI led to equally long PFS compared to patients with complete tumor removal before ioMRI (hazard ratio (HR) = 0.898, 95%-CI 0.543-1.483, p = 0.67). ioMRI considerably reduces residual tumor volume and helps to achieve comparable PFS, even in patients with unexpected residual tumor after initial resection before ioMRI.

The benefit of complete resection of contrast enhancing tumor in glioblastoma patients: A population-based study.

New treatment modalities have not been widely adopted for patients with glioblastoma (GBM) after the addition of temozolomide to radiotherapy. We hypothesize that increased extent of resection (EOR) has resulted in improved survival for surgically treated patients with glioblastoma at the population level. Retrospective analysis of adult patients operated for glioblastoma in the population of South-Eastern Norway. Patients were stratified into Pre-temozolomide- (2003-2005), temozolomide- (2006-2012), and resection-focused period (2013-2019) and evaluated according to age and EOR. The study included 1657 adult patients operated on for supratentorial glioblastoma. The incidence of histologically confirmed glioblastoma increased from 3.7 in 2003 to 5.3 per 100 000 in 2019. The median survival was 11.4 months. Complete resection of contrast-enhancing tumor (CRCET) was achieved in 386 patients, and this fraction increased from 13% to 32% across the periods. Significant improvement in median survival was found between the first 2 periods and the last (10.5 and 10.6 vs. 12.3 months; P < .01), with a significant increase in 3- and 5-year survival probability to 12% and 6% (P < .01). Patients with CRCET survived longer than patients with non-CRCET (16.1 vs. 10.8 months; P < .001). The median survival doubled in patients ≥70 years and (12.1 months). Survival was similar between the time periods in patients where CRCET was achieved. We demonstrate an improved survival of GBM patients at the population level associated with an increased fraction of patients with CRCET. The data support the importance of CRCET to improve glioblastoma patient outcomes.

Primary glioblastoma of cerebellopontine angle: The diagnostic dilemma of this rare case

Supratentorial glioblastoma is a common primary intracranial tumor in adults. High-grade glioma in cerebellopontine angle (CPA) is rare. We describe a case of adult-type diffuse high-grade glioma of CPA in a 49-year-old female that was managed surgically at our institute. Glioblastoma is an infiltrating type of glioma (WHO grade 4). MRI helped in characterizing the lesion; however, diagnosis was confirmed on histopathology. This report aims at the imaging pattern of primary adult-type diffuse high-grade glioma (WHO grade 4) at cerebellopontine angle.

Interstitial photodynamic therapy for newly diagnosed glioblastoma

PurposeInnovative, efficient treatments are desperately needed for people with glioblastoma (GBM).MethodsSixteen patients (median age 65.8 years) with newly diagnosed, small-sized, not safely resectable supratentorial GBM underwent interstitial photodynamic therapy (iPDT) as upfront eradicating local therapy followed by standard chemoradiation. 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX was used as the photosensitizer. The tumors were irradiated with light at 635 nm wavelength via stereotactically implanted cylindrical diffuser fibers. Outcome after iPDT was retrospectively compared with a positively-selected in-house patient cohort (n = 110) who underwent complete tumor resection followed by chemoradiation.ResultsMedian progression-free survival (PFS) was 16.4 months, and median overall survival (OS) was 28.0 months. Seven patients (43.8%) experienced long-term PFS > 24 months. Median follow-up was 113.9 months for the survivors. Univariate regression revealed MGMT-promoter methylation but not age as a prognostic factor for both OS (p = 0.04 and p = 0.07) and PFS (p = 0.04 and p = 0.67). Permanent iPDT-associated morbidity was seen in one iPDT patient (6.3%). Patients treated with iPDT experienced superior PFS and OS compared to patients who underwent complete tumor removal (p < 0.01 and p = 0.01, respectively). The rate of long-term PFS was higher in iPDT-treated patients (43.8% vs. 8.9%, p < 0.01).ConclusioniPDT is a feasible treatment concept and might be associated with long-term PFS in a subgroup of GBM patients, potentially via induction of so far unknown immunological tumor-controlling processes.