Glioblastoma in the oldest old: Clinical characteristics, therapy, and outcome in patients aged 80 years and older.

Background: Incidence rates of glioblastoma in very old patients are rising. The standard of care for this cohort is only partially defined and survival remains poor. The aims of this study were to reveal current practice of tumor-specific therapy and supportive care, and to identify predictors for survival in this cohort. Methods: Patients aged 80 years or older at the time of glioblastoma diagnosis were retrospectively identified in 6 clinical centers in Switzerland and France. Demographics, clinical parameters, and survival outcomes were annotated from patient charts. Cox proportional hazards modeling was performed to identify parameters associated with survival. Results: Of 107 patients, 45 were diagnosed by biopsy, 30 underwent subtotal resection, and 25 had gross total resection. In 7 patients, the extent of resection was not specified. Postoperatively, 34 patients did not receive further tumor-specific treatment. Twelve patients received radiotherapy with concomitant temozolomide, but only 2 patients had maintenance temozolomide therapy. Fourteen patients received temozolomide alone, 35 patients received radiotherapy alone, 1 patient received bevacizumab, and 1 took part in a clinical trial. Median progression-free survival (PFS) was 3.3 months and median overall survival (OS) was 4.2 months. Among patients who received any postoperative treatment, median PFS was 3.9 months and median OS was 7.2 months. Karnofsky performance status (KPS) ≥70%, gross total resection, and combination therapy were associated with better outcomes. The median time spent hospitalized was 30 days, accounting for 23% of the median OS. End-of-life care was mostly provided by nursing homes (n = 20; 32%) and palliative care wards (n = 16; 26%). Conclusions: In this cohort of very old patients diagnosed with glioblastoma, a large proportion was treated with best supportive care. Treatment beyond surgery and, in particular, combined modality treatment were associated with longer OS and may be considered for selected patients even at higher ages.

Prognostic Role of Ventricular Size and Its Dynamics in Patients With Leptomeningeal Metastasis From Solid Tumors.

BACKGROUND AND OBJECTIVES: Hydrocephalus is a common radiologic sign in patients with leptomeningeal metastasis (LM) from solid tumors which can be assessed using the Evans index (EI). Here, we explored the prognostic value of ventricular size in LM. METHODS: We identified patients with LM from solid tumors by chart review at 3 academic hospitals to explore the prognostic associations of the EI at diagnosis, first follow-up, and progression. RESULTS: We included 113 patients. The median age was 58.3 years (interquartile range [IQR] 46.1-65.8), 41 patients (36%) were male, and 72 patients (64%) were female. The most frequent cancers were lung cancer (n = 39), breast cancer (n = 36), and melanoma (n = 23). The median EI at baseline was 0.28 (IQR 0.26-0.31); the EI value was 0.27 or more in 67 patients (59%) and 0.30 or more in 37 patients (33%). Among patients with MRI follow-up, the EI increased by 0.01 or more in 16 of 31 patients (52%), including 8 of 30 patients (30%) without and 10 of 17 patients (59%) with LM progression at first follow-up. At LM progression, an increase of EI of 0.01 or more was noted in 18 of 34 patients (53%). The median survival was 2.9 months (IQR 1-7.2). Patients with a baseline EI below 0.27 had a longer survival than those with an EI of 0.27 or more (5.3 months, IQR 2.4-10.8, vs 1.3 months, IQR 0.6-4.1) (HR 1.70, 95% CI 1.135-2.534, p = 0.0099). The median survival was 3.7 months (IQR 1.4-8.3) with an EI below 0.30 vs 1.8 months (IQR 0.8-4.1) with an EI of 0.30 or more (HR 1.40, 95% CI 0.935-1.243, p = 0.1113). Among patients with follow-up scans available, the overall survival was 9.4 months (IQR 5.6-21.0) for patients with stable or decreased EI at first follow-up as opposed to 5.6 months (IQR 2.5-10.5) for those with an increase in the EI (HR 1.08, 95% CI 0.937-1.243; p = 0.300). DISCUSSION: The EI at baseline is prognostic in LM. An increase of EI during follow-up may be associated with inferior LM progression-free survival. Independent validation cohorts with larger sample size and evaluation of confounding factors will help to better define the clinical utility of EI assessments in LM.

A phase Ib/II randomized, open-label drug repurposing trial of glutamate signaling inhibitors in combination with chemoradiotherapy in patients with newly diagnosed glioblastoma: the GLUGLIO trial protocol.

BACKGROUND: Glioblastoma is the most common and most aggressive malignant primary brain tumor in adults. Glioblastoma cells synthesize and secrete large quantities of the excitatory neurotransmitter glutamate, driving epilepsy, neuronal death, tumor growth and invasion. Moreover, neuronal networks interconnect with glioblastoma cell networks through glutamatergic neuroglial synapses, activation of which induces oncogenic calcium oscillations that are propagated via gap junctions between tumor cells. The primary objective of this study is to explore the efficacy of brain-penetrating anti-glutamatergic drugs to standard chemoradiotherapy in patients with glioblastoma. METHODS/DESIGN: GLUGLIO is a 1:1 randomized phase Ib/II, parallel-group, open-label, multicenter trial of gabapentin, sulfasalazine, memantine and chemoradiotherapy (Arm A) versus chemoradiotherapy alone (Arm B) in patients with newly diagnosed glioblastoma. Planned accrual is 120 patients. The primary endpoint is progression-free survival at 6 months. Secondary endpoints include overall and seizure-free survival, quality of life of patients and caregivers, symptom burden and cognitive functioning. Glutamate levels will be assessed longitudinally by magnetic resonance spectroscopy. Other outcomes of interest include imaging response rate, neuronal hyperexcitability determined by longitudinal electroencephalography, Karnofsky performance status as a global measure of overall performance, anticonvulsant drug use and steroid use. Tumor tissue and blood will be collected for translational research. Subgroup survival analyses by baseline parameters include segregation by age, extent of resection, Karnofsky performance status, O6-methylguanine DNA methyltransferase (MGMT) promotor methylation status, steroid intake, presence or absence of seizures, tumor volume and glutamate levels determined by MR spectroscopy. The trial is currently recruiting in seven centers in Switzerland. TRIAL REGISTRATION: NCT05664464. Registered 23 December 2022.

IV Thrombolysis With or Without Endovascular Treatment for Suspected Ischemic Stroke in Patients With Intracranial Tumors.

BACKGROUND AND OBJECTIVES: IV thrombolysis (IVT) for suspected ischemic stroke in patients with intracranial neoplasms is off-label. However, data on risks of intracranial hemorrhage (ICH) are scarce. METHODS: In a multicenter registry-based analysis within the European Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration, we assessed frequencies of symptomatic and fatal ICH after IVT for suspected ischemic stroke in patients with intracranial tumors by descriptive statistics and analyzed associations with clinical and imaging characteristics by binary logistic regression. Definition of symptomatic ICH was based on the clinical criteria of the European Cooperative Acute Stroke-II trial including hemorrhage at any site in cranial imaging and concurrent clinical deterioration. RESULTS: Screening data of 21,289 patients from 14 centers, we identified 105 patients receiving IVT; among them were 29 patients (28%) with additional endovascular treatment, with suspected, that is, imaging-based, or histologically confirmed diagnosis of intracranial tumors. Among 104 patients with CT or MRI after IVT available, symptomatic and fatal ICH were observed in 9 and 4 patients (9% and 4%, respectively). Among 82 patients with suspected or confirmed meningioma, symptomatic and fatal ICH occurred in 6 and 3 patients (7% and 4%), respectively. In 18 patients with intra-axial suspected or confirmed primary or secondary brain tumors, there was 1 symptomatic nonfatal ICH (6%). Of 4 patients with tumors of the pituitary region, 2 patients (50%) had symptomatic ICH including 1 fatal ICH (25%). Tumor size was not associated with the occurrence of symptomatic ICH (odds ratio 2.8, 95% CI 0.3-24.8, p = 0.34). DISCUSSION: In our dataset from routine clinical care, we provide insights on the safety of IVT for suspected ischemic stroke in patients with intracranial tumors, a population that is commonly withheld thrombolysis in clinical practice and prospective trials. Except for a potential high risk of symptomatic ICH after IVT in patients with tumors of the pituitary region, frequencies of symptomatic ICH in patients with intracranial tumors in our cohort seem to be in the upper range of rates observed in previous studies within the TRISP cooperation. These results may guide individual treatment decisions in patients with acute stroke and intracranial tumors with potential benefit of IVT.

Stroke-associated infections in patients with and without cancer.

Background: Cancer in stroke patients is associated with higher levels of inflammatory biomarkers and unfavorable poststroke outcomes. We thus explored whether there is a link between cancer and stroke-associated infections. Methods: Medical records of patients with ischemic stroke in 2014-2016 registered in the Swiss Stroke Registry of Zurich were retrospectively analyzed. Incidence, characteristics, treatment, and outcome of stroke-associated infections diagnosed within 7 days after stroke onset were tested for an association with cancer. Results: Among 1181 patients with ischemic stroke, 102 patients with cancer were identified. Stroke-associated infections occurred in 179 and 19 patients (17% and 19%) without and with cancer (P = .60), respectively, among them pneumonia in 95 and 10 patients (9% and 10%) and urinary tract infections in 68 and 9 patients (6% and 9%) (P = .74 and P = .32). Use of antibiotics was similar between groups. Levels of C-reactive protein (CRP) (P < .001), erythrocyte sedimentation rate (ESR) (P = .014) and procalcitonin (P = .015) were higher and levels of albumin (P = .042) and protein (P = .031) were lower in patients with cancer than without cancer. Among patients without cancer, higher CRP (P < .001), ESR (P < .001) and procalcitonin (P = .04) and lower albumin (P < .001) were associated with stroke-associated infections. Among cancer patients with or without infections, no significant differences in these parameters were observed. In-hospital mortality was associated with cancer (P < .001) and with stroke-associated infections (P < .001). However, among patients with stroke-associated infections, cancer was not associated with in-hospital mortality (P = .24) or 30-day mortality (P = .66). Conclusions: Cancer does not represent a risk factor for stroke-associated infections in this patient cohort.

A risk model for prediction of diagnosis of cancer after ischemic stroke.

It remains controversial which characteristics may predict occult cancer in stroke patients. Characteristics of patients with ischemic stroke registered in the Zurich Swiss Stroke Registry (2014 to 2016) were tested for associations with cancer diagnosis after stroke with consideration of death as competing risk for cancer diagnosis. Among 1157 patients, 34 (3%) and 55 patients (5%) were diagnosed with cancer within 1 and 3 years after stroke. Levels of white blood cells (WBC) > 9,600/µl (subdistribution hazard ratio (SHR) 3.68, p = 0.014), platelets > 400,000/µl (SHR 7.71, p = 0.001), and d-dimers ≥ 3 mg/l (SHR 3.67, p = 0.007) were independently associated with cancer diagnosis within 1 year after stroke. Occurrence of ischemic lesions in ≥ 2 vascular territories not attributed to cardioembolic etiology was associated with cancer diagnosed within 1 year after stroke in univariable analysis (SHR 3.69, p = 0.001). The area under the curve of a score from these parameters (score sum 0-4) was 0.73. A score of ≥ 2 had a sensitivity of 43% and specificity of 92% for prediction of cancer diagnosis within 1 year after stroke. We suggest further validation of a score of WBC, platelets, d-dimers and multiple ischemic lesions without cardioembolic stroke etiology for prediction of cancer diagnosis after stroke.

Associations of levetiracetam use with the safety and tolerability profile of chemoradiotherapy for patients with newly diagnosed glioblastoma.

Background: Levetiracetam (LEV) is one of the most frequently used antiepileptic drugs (AED) for brain tumor patients with seizures. We hypothesized that toxicity of LEV and temozolomide-based chemoradiotherapy may overlap. Methods: Using a pooled cohort of patients with newly diagnosed glioblastoma included in clinical trials prior to chemoradiotherapy (CENTRIC, CORE, AVAglio) or prior to maintenance therapy (ACT-IV), we tested associations of hematologic toxicity, nausea or emesis, fatigue, and psychiatric adverse events during concomitant and maintenance treatment with the use of LEV alone or with other AED versus other AED alone or in combination versus no AED use at the start of chemoradiotherapy and of maintenance treatment. Results: Of 1681 and 2020 patients who started concomitant chemoradiotherapy and maintenance temozolomide, respectively, 473 and 714 patients (28.1% and 35.3%) were treated with a LEV-containing regimen, 538 and 475 patients (32.0% and 23.5%) with other AED, and 670 and 831 patients (39.9% and 41.1%) had no AED. LEV was associated with higher risk of psychiatric adverse events during concomitant treatment in univariable and multivariable analyses (RR 1.86 and 1.88, P < .001) while there were no associations with hematologic toxicity, nausea or emesis, or fatigue. LEV was associated with reduced risk of nausea or emesis during maintenance treatment in multivariable analysis (HR = 0.80, P = .017) while there were no associations with hematologic toxicity, fatigue, or psychiatric adverse events. Conclusions: LEV is not associated with reduced tolerability of chemoradiotherapy in patients with glioblastoma regarding hematologic toxicity and fatigue. Antiemetic properties of LEV may be beneficial during maintenance temozolomide.

Venous thromboembolic events in glioblastoma patients: An epidemiological study.

BACKGROUND AND PURPOSE: Venous thromboembolic events (VTEs) are a major complication in cancer patients, and therefore, also in brain cancer patients, anticoagulants are considered appropriate in the treatment of VTEs. METHODS: Frequency, risk factors, and treatment of VTEs, as well as associated complications, were assessed in a population-based cohort of glioblastoma patients in the Canton of Zurich, Switzerland. Correlations between clinical data and survival were retrospectively analyzed using the log-rank test and Cox regression models. RESULTS: Four hundred fourteen glioblastoma patients with isocitrate dehydrogenase wild-type status were identified. VTEs were documented in 65 patients (15.7%). Median time from tumor diagnosis to the occurrence of a VTE was 1.8 months, and 27 patients were diagnosed with VTEs postoperatively (within 35 days; 42.2%). History of a prior VTE was more common in patients who developed VTEs than in those who did not (p = 0.004). Bevacizumab treatment at any time during the disease course was not associated with occurrence of VTEs (p = 0.593). Most patients with VTEs (n = 61, 93.8%) were treated with therapeutic anticoagulation. Complications occurred in 14 patients (23.0%), mainly intracranial hemorrhages (n = 7, 11.5%). Overall survival did not differ between patients diagnosed with VTEs and those who had no VTE (p = 0.139). Tumor progression was the major cause of death (n = 283, 90.7%), and only three patients (1.0%) died in association with acute VTEs. CONCLUSIONS: Venous thromboembolic events occurred early in the disease course, suggesting that the implementation of primary venous thromboembolism prophylaxis during first-line chemoradiotherapy could be explored in a randomized setting.

Feasibility of glioblastoma tissue response mapping with physiologic BOLD imaging using precise oxygen and carbon dioxide challenge.

OBJECTIVES: Innovative physiologic MRI development focuses on depiction of heterogenous vascular and metabolic features in glioblastoma. For this feasibility study, we employed blood oxygenation level-dependent (BOLD) MRI with standardized and precise carbon dioxide (CO2) and oxygen (O2) modulation to investigate specific tumor tissue response patterns in patients with newly diagnosed glioblastoma. MATERIALS AND METHODS: Seven newly diagnosed untreated patients with suspected glioblastoma were prospectively included to undergo a BOLD study with combined CO2 and O2 standardized protocol. %BOLD signal change/mmHg during hypercapnic, hypoxic, and hyperoxic stimulus was calculated in the whole brain, tumor lesion and segmented volumes of interest (VOI) [contrast-enhancing (CE) - tumor, necrosis and edema] to analyze their tissue response patterns. RESULTS: Quantification of BOLD signal change after gas challenges can be used to identify specific responses to standardized stimuli in glioblastoma patients. Integration of this approach with automatic VOI segmentation grants improved characterization of tumor subzones and edema. Magnitude of BOLD signal change during the 3 stimuli can be visualized at voxel precision through color-coded maps overlayed onto whole brain and identified VOIs. CONCLUSIONS: Our preliminary investigation shows good feasibility of BOLD with standardized and precise CO2 and O2 modulation as an emerging physiologic imaging technique to detail specific glioblastoma characteristics. The unique tissue response patterns generated can be further investigated to better detail glioblastoma lesions and gauge treatment response.

Hypermetabolism and impaired cerebrovascular reactivity beyond the standard MRI-identified tumor border indicate diffuse glioma extended tissue infiltration.

BACKGROUND: Diffuse gliomas exhibit diffuse infiltrative growth, often beyond the magnetic resonance imaging (MRI)-detectable tumor lesion. Within this lesion, hypermetabolism and impaired cerebrovascular reactivity (CVR) are found, but its exact distribution pattern into the peritumoral environment is unknown. Our aim was to better characterize the extent of diffuse glioma tissue infiltration, beyond the visible lesion (ie, beyond the T1-contrast-enhancing lesion and/or T2/FLAIR-defined tumor border), with metabolic positron emission tomography (PET), and functional MRI CVR (blood oxygenation-level-dependent CVR [BOLD-CVR]) mapping. METHODS: From a prospective glioma database, 18 subjects (19 datasets) with diffuse glioma (n = 2 with anaplastic astrocytoma, n = 10 with anaplastic oligodendroglioma, and n = 7 with glioblastoma) underwent a BOLD-CVR and metabolic PET study between February 2016 and September 2019, 7 of them at primary diagnosis and 12 at tumor recurrence. In addition, 19 matched healthy controls underwent an identical BOLD-CVR study. The tumor lesion was defined using high-resolution anatomical MRI. Volumes of interest starting from the tumor lesion outward up to 30 mm were created for a detailed peritumoral PET and BOLD-CVR tissue analysis. Student's t test was used for statistical analysis. RESULTS: Patients with diffuse glioma exhibit impaired BOLD-CVR 12 mm beyond the tumor lesion (P = .02) with normalization of BOLD-CVR values after 24 mm. Metabolic PET shows a difference between the affected and contralateral hemisphere of 6 mm (P = .05) with PET values normalization after 12 mm. CONCLUSION: We demonstrate hypermetabolism and impaired CVR beyond the standard MRI-defined tumor border, suggesting active tumor infiltration in the peritumoral environment.

Cancer is associated with inferior outcome in patients with ischemic stroke.

BACKGROUND: Whether patients with stroke and cancer exhibit specific characteristics has remained controversial. METHODS: Medical records of patients with ischemic stroke in 2014 or 2015 registered in the Swiss Stroke Registry of Zurich were retrospectively analyzed and integrated with regional cancer registry data. Associations of clinical and outcome parameters with cancer diagnosed up to 5 years prior to stroke were tested. RESULTS: Of 753 patients with ischemic stroke, 59 patients with cancer were identified. History of venous thromboembolism (p < 0.001) was associated with cancer while age and cardiovascular risk factors were not. Higher levels of D-dimers (p = 0.001), erythrocyte sedimentation rate (p = 0.003), C-reactive protein (CRP) (p < 0.001), and lower levels of hemoglobin (p = 0.003) were associated with cancer. For platelets, pathologically low (p = 0.034) or high levels (p < 0.001) were linked to cancer. Modified Rankin scale (mRS) scores ≥ 4 on admission and at follow-up were more frequent in cancer patients (p = 0.038 and p = 0.001). Poor post-stroke survival was associated with cancer (HR 2.2, p < 0.001). Multivariable analysis identified venous thromboembolism (OR 5.1), pathologic platelet count (OR = 2.9), low hemoglobin (OR 2.5) and elevated CRP (OR 1.8) as independently associated with cancer. In multivariable Cox regression, risk for death was associated with cancer (HR 1.7), low hemoglobin (HR 2.6), mRS on admission ≥ 4 (HR 1.9), pathologic platelet count (HR 1.6), female sex (HR 1.7), and elevated CRP (HR 1.4). CONCLUSIONS: Considering cancer as a cofactor for post-stroke outcome may impact clinical decision making.

Distinct Cerebrovascular Reactivity Patterns for Brain Radiation Necrosis.

Background: Current imaging-based discrimination between radiation necrosis versus recurrent glioblastoma contrast-enhancing lesions remains imprecise but is paramount for prognostic and therapeutic evaluation. We examined whether patients with radiation necrosis exhibit distinct patterns of blood oxygenation-level dependent fMRI cerebrovascular reactivity (BOLD-CVR) as the first step to better distinguishing patients with radiation necrosis from recurrent glioblastoma compared with patients with newly diagnosed glioblastoma before surgery and radiotherapy. Methods: Eight consecutive patients with primary and secondary brain tumors and a multidisciplinary clinical and radiological diagnosis of radiation necrosis, and fourteen patients with a first diagnosis of glioblastoma underwent BOLD-CVR mapping. For all these patients, the contrast-enhancing lesion was derived from high-resolution T1-weighted MRI and rendered the volume-of-interest (VOI). From this primary VOI, additional 3 mm concentric expanding VOIs up to 30 mm were created for a detailed perilesional BOLD-CVR tissue analysis between the two groups. Receiver operating characteristic curves assessed the discriminative properties of BOLD-CVR for both groups. Results: Mean intralesional BOLD-CVR values were markedly lower in radiation necrosis than in glioblastoma contrast-enhancing lesions (0.001 ± 0.06 vs. 0.057 ± 0.05; p = 0.04). Perilesionally, a characteristic BOLD-CVR pattern was observed for radiation necrosis and glioblastoma patients, with an improvement of BOLD-CVR values in the radiation necrosis group and persisting lower perilesional BOLD-CVR values in glioblastoma patients. The ROC analysis discriminated against both groups when these two parameters were analyzed together (area under the curve: 0.85, 95% CI: 0.65-1.00). Conclusions: In this preliminary analysis, distinctive intralesional and perilesional BOLD-cerebrovascular reactivity patterns are found for radiation necrosis.

Endoglin and TGF-ß signaling in glioblastoma.

Microvascular proliferation is a key feature of glioblastoma and neovascularization has been implicated in tumor progression. Glioblastomas use pro-angiogenic factors such as vascular endothelial growth factor (VEGF) for new blood vessel formation. Yet, anti-VEGF therapy does not prolong overall survival so that alternative angiogenic pathways may need to be explored as drug targets. Both glioma cells and glioma-associated endothelial cells produce TGF-ß superfamily ligands which bind TGF-ß receptors (TGF-ßR). The TGF-ßR type III endoglin (CD105), is a marker of proliferating endothelium that has already been studied as a potential therapeutic target. We studied endoglin expression in glioblastoma tissue and in glioma-associated endothelial cells in a cohort of 52 newly diagnosed and 10 recurrent glioblastoma patients by immunohistochemistry and by ex vivo single-cell gene expression profiling of 6 tumors. Endoglin protein levels were similar in tumor stroma and endothelium and correlated within tumors. Similarly, endoglin mRNA determined by ex vivo single-cell gene expression profiling was expressed in both compartments. There was positive correlation between endoglin and proteins of TGF-ß superfamily signaling. No prognostic role of endoglin expression in either compartment was identified. Endoglin gene silencing in T98G glioma cells and in human cerebral microvascular endothelial cells (hCMEC) did not affect constitutive or exogenous TGF-ß superfamily ligand-dependent signaling, except for a minor facilitation of pSmad1/5 signaling in hCMEC. These observations challenge the notion that endoglin might become a promising therapeutic target in glioblastoma.

Prognostic validation and clinical implications of the EANO ESMO classification of leptomeningeal metastasis from solid tumors.

BACKGROUND: The EANO ESMO guidelines have proposed a classification of leptomeningeal metastases (LM) from solid cancers based on clinical, magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) cytology presentation. MRI patterns are classified as linear, nodular, both, or neither. Type I LM is defined by positive CSF cytology (confirmed LM) whereas type II LM is defined by typical clinical and MRI signs (probable or possible LM). Here we explored the clinical utility of these LM subtypes. PATIENTS AND METHODS: We retrospectively assembled data from 254 patients with newly diagnosed LM from solid tumors. Survival curves were derived using the Kaplan-Meier method and compared by Log-rank test. RESULTS: Median age at LM diagnosis was 56 years. Typical clinical LM features were noted in 225 patients (89%); 13 patients (5%) were clinically asymptomatic. Tumor cells in the CSF were observed in 186 patients (73%) whereas the CSF was equivocal in 24 patients (9.5%) and negative in 44 patients (17.5%). Patients with confirmed LM had inferior outcome compared with patients with probable or possible LM (P = 0.006). Type I patients had inferior outcome than type II patients (P = 0.002). Nodular disease on MRI was a negative prognostic factor in type II LM (P = 0.014), but not in type I LM. Administration of either intrathecal pharmacotherapy (P = 0.020) or systemic pharmacotherapy (P = 0.0004) was associated with improved outcome in type I LM, but not in type II LM. CONCLUSION: The EANO ESMO LM subtypes are highly prognostic and should be considered for stratification and overall design of clinical trials.

Crossed Cerebellar Diaschisis in Patients with Diffuse Glioma Is Associated with Impaired Supratentorial Cerebrovascular Reactivity and Worse Clinical Outcome.

Crossed cerebellar diaschisis (CCD) can be associated with impaired cerebrovascular reactivity (CVR) and poor clinical outcome, but whether this holds true for patients with diffuse glioma is unknown. With blood oxygenation level-dependent (BOLD)-CVR imaging, we determined the presence of CCD in patients with diffuse glioma and investigated its relationship with cerebrovascular reactivity and clinical outcome. For eighteen enrolled subjects (nineteen datasets) with diffuse glioma, CCD was deferred from BOLD-CVR using a predetermined cerebellar asymmetry index (CAI) cutoff value of 6.0%. A FET-PET study was done as a verification of the CCD diagnosis. BOLD-CVR values as well as clinical performance scores (i.e., Karnofsky performance score (KPS), disability rating scale (DRS), and modified Rankin scale (mRS)) by BOLD-CVR scan at 3-month clinical follow-up were assessed and compared for the CCD-positive and CCD-negative group. CCD was present in 26.3% of subjects and strongly associated with impaired BOLD-CVR of the affected (i.e., the hemisphere harboring the glioma) and unaffected supratentorial hemisphere (CCD(+) vs. CCD(-): 0.08 ± 0.11 vs. 0.18 ± 0.04; p = 0.007 and 0.08 ± 0.12 vs. 0.19 ± 0.04; p = 0.007, respectively). This finding was independent of tumor volume (p = 0.48). Furthermore, poorer initial (by scan) clinical performance scores at follow-up were found for the CCD(+) group. The presence of crossed cerebellar diaschisis in patients with diffuse glioma is associated with impaired supratentorial cerebrovascular reactivity and worse clinical outcome.

Hemodynamic investigation of peritumoral impaired blood oxygenation-level dependent cerebrovascular reactivity in patients with diffuse glioma.

INTRODUCTION: The presence of peritumorally impaired blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) has been unequivocally demonstrated in patients with diffuse glioma, and may have value to better identify tumor infiltration zone. Since BOLD-CVR does not measure hemodynamic changes directly, we performed additional MR perfusion studies to better characterize the peritumoral hemodynamic environment. METHODS: Seventeen patients with WHO grade III and IV diffuse glioma underwent high resolution advanced hemodynamic MR imaging including BOLD-CVR and MR perfusion. The obtained multiparametric hemodynamic factors (i.e., regional cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), mean transit time (MTT), time-to-peak (TTP) and BOLD-CVR, were analyzed within 10 concentric expanding 3 mm volumes of interest (VOIs) up to 30 mm from the tumor tissue mask. RESULTS: BOLD-CVR impairment was found within the tumor tissue mask and the peritumoral VOIs up to 21 mm as compared to the contralateral flipped CVR analysis (p<0.05). In the affected hemisphere, we observed positive spatial correlations including all VOIs between BOLD-CVR and rCBV values (r=0.27; p<0.001), rCBF (r=0.42; p<0.001) and a negative correlation between BOLD-CVR and TTP (r=-0.47; p<0.001). CONCLUSIONS: Peritumorally impaired BOLD-CVR is associated with concomitant hemodynamic alterations with severity correlating to tumor volume. The distribution of these multiparametric hemodynamic MRI patterns may be considered for future studies characterizing the hemodynamic peritumoral environment, thereby better identifying the extent of tumor infiltration.

End-of-life care for glioma patients; the caregivers' perspective.

PURPOSE: Gliomas are primary brain tumors with a life-limiting course of disease, and the last weeks of life are often characterized by neurological deficits that affect communication and personality. End-of-life treatment in this patient group therefore requires specific approaches. To date, little data is available on patients' and caregivers' needs and experiences in the last phase of the disease. METHODS: In this observational study, relatives of patients treated at the University Hospital Zurich, Switzerland and deceased 2015-2017 due to glioma progression were contacted to complete a structured questionnaire assessing caregivers experience within the last weeks of the disease. RESULTS: The survey was sent to 120 relatives of deceased patients with a glioma (WHO grades II-IV) (median patient age: 62 years; 73.8% male). Forty-three questionnaires were returned (37.7%). Approximately half of the patients were taken care of at home in the last 4 weeks of the disease, mainly with the assistance of in-home nursing care, of which eventually 14 patients (63.6%) died at home. While caregivers reported high satisfaction with medical and nursing care, psychological support was rated average to poor on a 10-point scale. Free comment fields were used widely, revealing open questions and needs of the relatives. CONCLUSIONS: This study illustrates the need for a more patient-centered end-of-life care including higher psychological support mechanisms, and a higher inclusion and consideration of relatives and caregivers into the care focus. Earlier discussion of end-of-life preferences could prevent hospitalizations in the last phase of life and could improve patients' and caregivers' quality of life.