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"Freyschlag, Christian"
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The Clinical Frailty Scale as predictor of overall survival after resection of high-grade glioma
by
Krigers, Aleksandrs
,
Freyschlag, Christian F.
,
Kerschbaumer, Johannes
in
Aged
,
Brain cancer
,
Clinical Study
2022
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.
Journal Article
Mind the gap—the use of sodium fluoresceine for resection of brain metastases to improve the resection rate
by
Krigers, Aleksandrs
,
Freyschlag, Christian F.
,
Spinello, Antonio
in
Brain - pathology
,
Brain cancer
,
Brain Neoplasms - pathology
2023
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.
Journal Article
Socioeconomic influences on survival outcome in idh-wildtype glioma patients: examining the role of age, education, and lifestyle factors
2025
Background
Socioeconomic factors influence survival in different cancer types. This study aimed to assess the impact of various socioeconomic factors, including education, marital status, lifestyle, and social network, on survival in patients with Isocitrate dehydrogenase (IDH) wildtype gliomas.
Methods
We conducted a retrospective analysis of 309 adult patients with de novo diagnosed IDH wildtype gliomas who underwent surgical treatment at our institution between 2014 and 2022. Socioeconomic factors, including education, marital status, employment, language, lifestyle (alcohol abuse, smoking, BMI), and social network were assessed. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan–Meier and Cox regression models.
Results
Education, alcohol abuse, and age significantly influenced OS. Patients with higher education had significantly lower tumor volumes (
p
= 0.037) and longer survival (
p
= 0.001). Alcohol abuse was associated with significantly shorter OS (8.6 vs. 17.9 months,
p
= 0.034). Patients aged over 65 years showed significantly shorter OS in this study (14.9 months vs 33.2 months,
p
< 0.001). Native and non-native German speakers had similar outcomes. Marital status did not significantly affect survival.
Conclusion
Socioeconomic and lifestyle factors, especially higher education and alcohol abuse, significantly impact survival in IDH wildtype glioma patients. These findings suggest that, in addition to molecular features and oncological treatment, socioeconomic and lifestyle factors also play a crucial role in influencing the prognosis of patients with IDH wildtype gliomas.
Journal Article
Audencel Immunotherapy Based on Dendritic Cells Has No Effect on Overall and Progression-Free Survival in Newly Diagnosed Glioblastoma: A Phase II Randomized Trial
by
Oberndorfer, Stefan
,
Stockhammer, Günther
,
Von Campe, Gord
in
Antigen-presenting cells
,
Antigens
,
Brain cancer
2018
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%, p = 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; p = 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.
Journal Article
Age is associated with unfavorable neuropathological and radiological features and poor outcome in patients with WHO grade 2 and 3 gliomas
by
Krigers, Aleksandrs
,
Freyschlag, Christian F.
,
Demetz, Matthias
in
631/67/1922
,
631/67/2324
,
Brain tumors
2021
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.
Journal Article
Influence of preoperative corticosteroid treatment on rate of diagnostic surgeries in primary central nervous system lymphoma: a multicenter retrospective study
by
Oberndorfer, Stefan
,
Pfisterer, Wolfgang
,
Freyschlag, Christian F.
in
Biomedical and Life Sciences
,
Biomedicine
,
Biopsy
2021
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.
Journal Article
The Clinical Frailty Scale as useful tool in patients with brain metastases
by
Krigers, Aleksandrs
,
Freyschlag, Christian F.
,
Pichler, Nadine
in
Aged
,
Brain cancer
,
Brain Neoplasms - surgery
2022
Purpose
The Clinical Frailty Scale (CFS) evaluates patients’ level of frailty on a scale from 1 to 9 and is commonly used in geriatric medicine, intensive care and orthopedics. The aim of our study was to reveal whether the CFS allows a reliable prediction of overall survival (OS) in patients after surgical treatment of brain metastases (BM) compared to the Karnofsky Performance Score (KPS).
Methods
Patients operated for BM were included. CFS and KPS were retrospectively assessed pre- and postoperatively and at follow-up 3–6 months after resection.
Results
205 patients with a follow-up of 22.8 months (95% CI 18.4–27.1) were evaluated. CFS showed a median of 3 (“managing well”; IqR 2–4) at all 3 assessment-points. Median KPS was 80 preoperatively (IqR 80–90) and 90 postoperatively (IqR 80–100) as well as at follow-up after 3–6 months. CFS correlated with KPS both preoperatively (r = − 0.92; p < 0.001), postoperatively (r = − 0.85; p < 0.001) and at follow-up (r = − 0.93; p < 0.001).
The CFS predicted the expected reduction of OS more reliably than the KPS at all 3 assessments. A one-point increase (worsening) of the preoperative CFS translated into a 30% additional hazard to decease (HR 1.30, 95% CI 1.15–1.46; p < 0.001). A one-point increase in postoperative and at follow-up CFS represents a 39% (HR 1.39, 95% CI 1.25–1.54; p < 0.001) and of 42% risk (HR 1.42, 95% CI 1.27–1.59; p < 0.001).
Conclusion
The CFS is a feasible, simple and reliable scoring system in patients undergoing resection of brain metastasis. The CFS 3–6 months after surgery specifies the expected OS more accurately than the KPS.
Journal Article
Impact of postoperative blood pressure management on postoperative hemorrhage after resection of intraparenchymal brain tumors
This study aimed to assess the relationship between postoperative blood pressure and other common radiological and epidemiological factors in relation to the incidence of postoperative hemorrhage.
This retrospective analysis included all patients who underwent surgery between 2016 and 2023 at our institution for an intraparenchymal intracranial tumor. We evaluated blood pressure both intraoperatively and postoperatively for the first 12 postoperative hours. We compared a cohort that experienced postoperative hemorrhage with a cohort that did not require intervention. ROC-analysis were performed to find thresholds for postoperative blood pressure.
453 patients were included. In 35 cases (7.7%), further treatment was necessary due to postoperative hemorrhage. Of these, nine patients required revision surgery, while 26 patients were managed conservatively. Both intra- (p < 0.05) and postoperative (p < 0.001) blood pressure influenced the risk of postoperative hemorrhage significantly. We identified a threshold of 140 mmHg of systolic blood pressure to minimize the risk of postoperative hemorrhage.
Maintaining systolic blood pressure below 140 mmHg after surgery seems to be crucial, as patients with postoperative hemorrhage experienced significantly longer durations of elevated systolic pressure (62 min > 140 mmHg and 17 min > 160 mmHg), highlighting its strong influence on hemorrhage risk.
Journal Article
Same but different. Incidental and symptomatic lower grade gliomas show differences in molecular features and survival
by
Krigers, Aleksandrs
,
Freyschlag, Christian F.
,
Demetz, Matthias
in
2-Methylisoborneol
,
Adult
,
Brain Neoplasms - diagnostic imaging
2023
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.
Journal Article
Risk Factors for Radiation Necrosis in Patients Undergoing Cranial Stereotactic Radiosurgery
by
Krigers, Aleksandrs
,
Freyschlag, Christian F.
,
Kerschbaumer, Johannes
in
Edema
,
Gadolinium
,
Magnetic resonance imaging
2021
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.
Journal Article