Background
The Clinical Frailty Scale (CFS) describes the general level of fitness or frailty and is widely used in geriatric medicine, intensive care and orthopaedic surgery. This study was ...conducted to analyze, whether CFS could be used for patients with high-grade glioma.
Methods
Patients harboring high-grade gliomas, undergoing first resection at our center between 2015 and 2020 were retrospectively evaluated. Patients’ performance was assessed using the Rockwood Clinical Frailty Scale and the Karnofsky Performance Scale (KPS) preoperatively and 3–6 months postoperatively.
Results
289 patients were included. Pre- as well as postoperative median frailty was 3 CFS points (IqR 2–4) corresponding to “managing well”. CFS strongly correlated with KPS preoperatively (r = − 0.85; p < 0.001) and at the 3–6 months follow-up (r = − 0.90; p < 0.001). The reduction of overall survival (OS) was 54% per point of CFS preoperatively (HR 1.54, CI 95% 1.38–1.70; p < 0.001) and 58% at the follow-up (HR 1.58, CI 95% 1.41–1.78; p < 0.001), comparable to KPS. Patients with IDH mutation showed significantly better preoperative and follow-up CFS and KPS (p < 0.05). Age and performance scores correlated only mildly with each other (r = 0.21…0.35; p < 0.01), but independently predicted OS (p < 0.001 each).
Conclusion
CFS seems to be a reliable tool for functional assessment of patients suffering from high-grade glioma. CFS includes non-cancer related aspects and therefore is a contemporary approach for patient evaluation. Its projection of survival can be equally estimated before and after surgery. IDH-mutation caused longer survival and higher functionality.
Dendritic cells (DCs) are antigen-presenting cells that are capable of priming anti-tumor immune responses, thus serving as attractive tools to generate tumor vaccines. In this multicentric ...randomized open-label phase II study, we investigated the efficacy of vaccination with tumor lysate-charged autologous DCs (Audencel) in newly diagnosed glioblastoma multiforme (GBM). Patients aged 18 to 70 years with histologically proven primary GBM and resection of at least 70% were randomized 1:1 to standard of care (SOC) or SOC plus vaccination (weekly intranodal application in weeks seven to 10, followed by monthly intervals). The primary endpoint was progression-free survival at 12 months. Secondary endpoints were overall survival, safety, and toxicity. Seventy-six adult patients were analyzed in this study. Vaccinations were given for seven (3⁻20) months on average. No severe toxicity was attributable to vaccination. Seven patients showed flu-like symptoms, and six patients developed local skin reactions. Progression-free survival at 12 months did not differ significantly between the control and vaccine groups (28.4% versus 24.5%,
= 0.9975). Median overall survival was similar with 18.3 months (vaccine: 564 days, 95% CI: 436⁻671 versus control: 568 days, 95% CI: 349⁻680;
= 0.89, harzard ratio (HR) 0.99). Hence, in this trial, the clinical outcomes of patients with primary GBM could not be improved by the addition of Audencel to SOC.
Abstract
With the rising life expectancy and availability of neuroimaging, increased number of older patients will present with diffuse and anaplastic gliomas. The aim of our study was therefore to ...investigate age-related prognostic clinical, neuropathological and radiological features of lower-grade gliomas. All consecutive patients with diffuse or anaplastic glioma WHO grade 2 and 3 who underwent first tumor resection between 2010 and 2018, were selected from the institutional neuro-oncological database and evaluated. The mean age of 55 males and 44 females was 46 years (SD ± 16). Wild-type IDH1 (p = 0.012), persistent nuclear ATRX expression (p = 0.012) and anaplasia (p < 0.001) were significantly associated with higher age. The CE volume before resection was found to be increased in older patients (r = 0.42, p < 0.0001), and CE rate was higher in the IDH wild-type population only (p = 0.02). The extent of resection did not differ with age. Overall, one year of life resulted in a PFS reduction of 9 days (p = 0.047); in IDH sub-group analysis, this dependency was confirmed only in wild-type tumors (p = 0.05). OS was significantly reduced in older patients (p = 0.033). In conclusion, behavior and prognosis of WHO grade 2 and 3 glioma were unfavorable in correlation to patient’s age, even if the extent of resection was comparable. Older age imparted a poorer PFS and higher CE rate only in the IDH wild-type population.
Introduction and purpose
Brain metastases appear to be well resectable due to dissectable tumor margins, but postoperative MRI quite often depicts residual tumor with potential influence on tumor ...control and overall survival. Therefore, we introduced sodium fluoresceine into the routine workflow for brain metastasis resection. The aim of this study was to evaluate whether the use of fluorescence-guided surgery has an impact on postoperative tumor volume and local recurrence.
Material and methods
We retrospectively included patients who underwent surgical resection for intracranial metastases of systemic cancer between 11/2017 and 05/2021 at our institution. Tumor volumes were assessed pre- and postoperatively on T1-CE MRI. Clinical and epidemiological data as well as follow-up were gathered from our prospective database.
Results
Seventy-nine patients (33 male, 46 female) were included in this study. Median preoperative tumor volume amounted to 11.7cm
3
and fluoresceine was used in 53 patients (67%). Surgeons reported an estimated gross total resection (GTR) in 95% of the cases, while early postoperative MRI could confirm GTR in 72%. Patients resected using fluoresceine demonstrated significantly lower postoperative residual tumor volumes with a difference of 0.7cm
3
(
p
= 0.044) and lower risk of local tumor recurrence (
p
= 0.033). The use of fluorescence did not influence the overall survival (OS). Postoperative radiotherapy resulted in a significantly longer OS (
p
= 0.001).
Discussion
While GTR rates may be overrated, the use of intraoperative fluorescence may help neurosurgeons to achieve a more radical resection. Fluoresceine seems to facilitate surgical resection and increase the extent of resection thus reducing the risk for local recurrence.
Purpose
Data on differences in overall survival and molecular characteristics between incidental (iLGG) and symptomatic lower grade Glioma (sLGG) are limited. The aim of this study was to investigate ...differences between patients with iLGG and sLGG.
Methods
All adult patients with a histologically proven diffuse (WHO°II) or anaplastic (WHO°III) glioma who underwent their first surgery at the authors’ institution between 2010 and 2019 were retrospectively included. Tumor volume on pre- and postoperative MRI scans was determined. Clinical and routine neuropathological data were gained from patients’ charts. If IDH1, ATRX and EGFR were not routinely assessed, they were re-determined.
Results
Out of 161 patients included, 23 (14%) were diagnosed as incidental findings. Main reasons for obtaining MRI were: headache(n = 12), trauma(n = 2), MRI indicated by other departments(n = 7), staging examination for cancer(n = 1), volunteering for MRI sequence testing(n = 1). The asymptomatic patients were significantly younger with a median age of 38 years (IqR28-48) vs. 50 years (IqR38-61), p = 0.011. Incidental LGG showed significantly lower preoperative tumor volumes in T1 CE (p = 0.008), FLAIR (p = 0.038) and DWI (p = 0.028). Incidental LGG demonstrated significantly lower incidence of anaplasia (p = 0.004) and lower expression of MIB-1 (p = 0.008) compared to sLGG. IDH1-mutation was significantly more common in iLGG (p = 0.024). Incidental LGG showed a significantly longer OS (mean 212 vs. 70 months, p = 0.005) and PFS (mean 201 vs. 61 months, p = 0.001) compared to sLGG.
Conclusion
Our study is the first to depict a significant difference in molecular characteristics between iLGG and sLGG. The findings of this study confirmed and extended the results of previous studies showing a better outcome and more favorable radiological, volumetric and neuropathological features of iLGG.
Distant intercellular communication in gliomas is based on the expansion of tumor microtubuli, where actin forms cytoskeleton and GAP-43 mediates the axonal conus growth. We aimed to investigate the ...impact of GAP-43 and actin expression on overall survival (OS) as well as crucial prognostic factors. FFPE tissue of adult patients with diffuse and anaplastic gliomas, who underwent first surgery in our center between 2010 and 2019, were selected. GAP-43, Cx43 and actin expression was analyzed using immunohistochemistry and semi-quantitatively ranked. 118 patients with a median age of 46 years (IqR: 35-57) were evaluated. 48 (41%) presented with a diffuse glioma and 70 (59%) revealed anaplasia. Tumors with higher expression of GAP-43 (p = 0.024, HR = 1.71/rank) and actin (p < 0.001, HR = 2.28/rank) showed significantly reduced OS. IDH1 wildtype glioma demonstrated significantly more expression of all proteins: GAP-43 (p = 0.009), Cx43 (p = 0.003) and actin (p < 0.001). The same was confirmed for anaplasia (GAP-43 p = 0.028, actin p = 0.029), higher proliferation rate (GAP-43 p = 0.016, actin p = 0.038), contrast-enhancement in MRI (GAP-43 p = 0.023, actin p = 0.037) and age (GAP-43 p = 0.004, actin p < 0.001; Cx43 n.s. in all groups). The intercellular distant communication network in diffuse and anaplastic gliomas formed by actin and GAP-43 is associated with a negative impact on overall survival and with unfavorable prognostic features. Cx43 did not show relevant impact on OS.
Glioblastoma is the most common malignant brain tumor in adults. Standard treatment includes tumor resection, radio-chemotherapy and adjuvant chemotherapy with temozolomide (TMZ). TMZ methylates DNA, ...whereas O6-methylguanine DNA methyltransferase (MGMT) counteracts TMZ effects by removing the intended proteasomal degradation signal. Non-functional MGMT mediates the mismatch repair (MMR) system, leading to apoptosis after futile repair attempts. This study investigated the associations between
promoter methylation, MGMT and MMR protein expression, and their effect on overall survival (OS) and progression-free survival (PFS) in patients with glioblastoma.
promoter methylation was assessed in 42 treatment-naïve patients with glioblastoma WHO grade IV by pyrosequencing. MGMT and MMR protein expression was analyzed using immunohistochemistry.
promoter methylation was present in 52%, whereas patients <70 years of age revealed a significantly longer OS using a log-rank test and a significance threshold of
≤ 0.05. MGMT protein expression and methylation status showed no correlation. MMR protein expression was present in all patients independent of MGMT status and did not influence OS and PFS. Overall,
promoter methylation implicates an improved OS in patients with glioblastoma aged <70 years. In the elderly, the extent of surgery has an impact on OS rather than the
promoter methylation or protein expression.
Purpose: single-staged stereotactic radiosurgery (SRS) is an established part of the multimodal treatment in neuro-oncology. Radiation necrosis after high-dose irradiation is a known complication, ...but there is a lack of evidence about the risk factors. The aim of this study was to evaluate possible risk factors for radiation necrosis in patients undergoing radiosurgery. Methods: patients treated with radiosurgery between January 2004 and November 2020 were retrospectively analyzed. The clinical data, imaging and medication were gathered from electronic patient records. The largest diameter of the tumors was measured using MRI scans in T1 weighted imaging with gadolinium and the edema in T2 weighted sequences. The diagnosis of a radiation necrosis was established analyzing imaging criteria combined with clinical course or pathologically confirmed by subsequent surgical intervention. Patients developing radiation necrosis detected after SRS were compared to patients without evidence of an overshooting irradiation reaction. Results: 388 patients were included retrospectively, 61 (15.7%) of whom developed a radiation necrosis. Median follow-up was 24 (6–62) months with a radiation necrosis after 8 (6–12) months. The most frequent tumors were metastases in 47.2% of the cases, followed by acoustic neuromas in 32.2% and meningiomas in 13.4%. Seventy-three (18.9%) patients already underwent one or more previous radiosurgical procedures for different lesions. The mean largest diameter of the tumors amounted to 16.3 mm (±6.1 mm). The median—80%—isodose administered was 16 (14–25) Gy. Of the radiation necroses, 25 (43.1%) required treatment, in 23 (39.7%) thereof, medical treatment was applied and in 2 (3.4%) cases, debulking surgery was performed. In this study, significantly more radiation necroses arose in patients with higher doses (HR 1.3 CI 1.2; 1.5, p < 0.001) leading to a risk increment of over 180% between a radiation isodose of 14 and 20 Gy. The maximum diameter was a second significant risk factor (p = 0.028) with an HR of 1065 for every 1 mm increase in multivariate analysis. Conclusion: large diameter and high doses were reliable independent risk factors leading to more frequent radiation necroses, regardless of tumor type in patients undergoing radiosurgery. Alternative therapeutic procedures may be considered in lesions with large volume and an expected high radiation doses due to the increased risk of developing radiation necrosis.
Atypical and anaplastic meningiomas account for 20% of all meningiomas. An irregular tumor shape on preoperative MRI has been associated with WHO grade II-III histology. However, this subjective ...allocation does not allow quantification or comparison. An objective parameter of irregularity could substantially influence resection strategy toward a more aggressive approach. Therefore, the aim of this study was to objectively quantify the level of irregularity on preoperative MRI and predict histology based on WHO grade using this novel approach.
A retrospective study on meningiomas resected between January 2010 and December 2018 was conducted at two neurosurgical centers. This novel approach relies on the theory that a regularly shaped tumor has a smaller surface area than an irregularly shaped tumor with the same volume. A factor was generated using the surface area of a corresponding sphere as a reference, because for a given volume a sphere represents the shape with the smallest surface area possible. Consequently, the surface factor (SF) was calculated by dividing the surface area of a sphere with the same volume as the tumor with the surface area of the tumor. The resulting value of the SF ranges from > 0 to 1. Finally, the SF of each meningioma was then correlated with the corresponding histopathological grading.
A total of 126 patients were included in this study; 60.3% had a WHO grade I, 34.9% a WHO grade II, and 4.8% a WHO grade III meningioma. Calculation of the SF demonstrated a significant difference in SFs between WHO grade I (SF 0.851) and WHO grade II-III meningiomas (SF 0.788) (p < 0.001). Multivariate analysis identified SF as an independent prognostic factor for WHO grade (OR 0.000009, 95% CI 0.000-0.159; p = 0.020).
The SF is a proposed mathematical model for a quantitative and objective measurement of meningioma shape, instead of the present subjective assessment. This study revealed significant differences between the SFs of WHO grade I and WHO grade II-III meningiomas and demonstrated that SF is an independent prognostic factor for WHO grade.
Background Corticosteroid therapy (CST) prior to biopsy may hinder histopathological diagnosis in primary central nervous system lymphoma (PCNSL). Therefore, preoperative CST in patients with ...suspected PCNSL should be avoided if clinically possible. The aim of this study was thus to analyze the difference in the rate of diagnostic surgeries in PCNSL patients with and without preoperative CST. Methods A multicenter retrospective study including all immunocompetent patients diagnosed with PCNSL between 1/2004 and 9/2018 at four neurosurgical centers in Austria was conducted and the results were compared to literature. Results A total of 143 patients were included in this study. All patients showed visible contrast enhancement on preoperative MRI. There was no statistically significant difference in the rate of diagnostic surgeries with and without preoperative CST with 97.1% (68/70) and 97.3% (71/73), respectively (p = 1.0). Tapering and pause of CST did not influence the diagnostic rate. Including our study, there are 788 PCNSL patients described in literature with an odds ratio for inconclusive surgeries after CST of 3.3 (CI 1.7-6.4). Conclusions Preoperative CST should be avoided as it seems to diminish the diagnostic rate of biopsy in PCNSL patients. Yet, if CST has been administered preoperatively and there is still a contrast enhancing lesion to target for biopsy, surgeons should try to keep the diagnostic delay to a minimum as the likelihood for acquiring diagnostic tissue seems sufficiently high. Keywords: Primary central nervous system lymphoma, Corticosteroid therapy, Diagnostic rate
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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