Papers by Marie-therese Forster
Neuro-Oncology
Background Glioblastoma (GB) is incurable at present without established treatment options for re... more Background Glioblastoma (GB) is incurable at present without established treatment options for recurrent disease. In this phase I first-in-human clinical trial we investigated safety and feasibility of adoptive transfer of clonal chimeric antigen receptor (CAR)-NK cells (NK-92/5.28.z) targeting HER2, which is expressed at elevated levels by a subset of glioblastomas. Methods Nine patients with recurrent HER2-positive GB were treated with single doses of 1 × 107, 3 × 107, or 1 × 108 irradiated CAR-NK cells injected into the margins of the surgical cavity during relapse surgery. Imaging at baseline and follow-up, peripheral blood lymphocyte phenotyping and analyses of the immune architecture by multiplex immunohistochemistry and spatial digital profiling were performed. Results There were no dose-limiting toxicities, and none of the patients developed a cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. Five patients showed stable disease after relaps...
Journal of Cancer Research and Clinical Oncology
Purpose With increasing patient self-empowerment and participation in decision making, we hypothe... more Purpose With increasing patient self-empowerment and participation in decision making, we hypothesized that patients with adult-type diffuse gliomas, CNS WHO grade 4 who change sites of treatment differ from patients being entirely treated in one neuro-oncological center. Methods Prospectively collected data from all diffuse glioma grade 4 patients who underwent treatment in our neuro-oncological center between 2012 and 2018 were retrospectively examined for differences between patients having initially been diagnosed and/or treated elsewhere (External Group) and patients having entirely been treated in our neuro-oncological center (Internal Group). Additionally, a matched-pair analysis was performed to adjust for possible confounders. Results A total of 616 patients was analyzed. Patients from the External Group (n = 78) were significantly younger, more frequently suffered from IDH-mutant astrocytoma grade 4, had a greater extent of tumor resection, more frequently underwent adjuva...
Cancers
Current data show that resilience is an important factor in cancer patients’ well-being. We aim t... more Current data show that resilience is an important factor in cancer patients’ well-being. We aim to explore the resilience of patients with lower grade glioma (LGG) and the potentially influencing factors. We performed a cross-sectional assessment of adult patients with LGG who were enrolled in the LoG-Glio registry. By phone interview, we administered the following measures: Resilience Scale (RS-13), distress thermometer, Montreal Cognitive Assessment Test for visually impaired patients (MoCA-Blind), internalized stigmatization by brain tumor (ISBI), Eastern Cooperative Oncological Group performance status (ECOG), patients’ perspective questionnaire (PPQ) and typical clinical parameters. We calculated correlations and multivariate regression models. Of 74 patients who were assessed, 38% of those showed a low level of resilience. Our results revealed significant correlations of resilience with distress (p < 0.001, −0.49), MOCA (p = 0.003, 0.342), ECOG (p < 0.001, −0.602), stigm...
Neuroradiology
Purpose Non-invasive prediction of the tumour of origin giving rise to brain metastases (BMs) usi... more Purpose Non-invasive prediction of the tumour of origin giving rise to brain metastases (BMs) using MRI measurements obtained in radiological routine and elucidating the biological basis by matched histopathological analysis. Methods Preoperative MRI and histological parameters of 95 BM patients (female, 50; mean age 59.6 ± 11.5 years) suffering from different primary tumours were retrospectively analysed. MR features were assessed by region of interest (ROI) measurements of signal intensities on unenhanced T1-, T2-, diffusion-weighted imaging and apparent diffusion coefficient (ADC) normalised to an internal reference ROI. Furthermore, we assessed BM size and oedema as well as cell density, proliferation rate, microvessel density and vessel area as histopathological parameters. Results Applying recursive partitioning conditional inference trees, only histopathological parameters could stratify the primary tumour entities. We identified two distinct BM growth patterns depending on t...
Journal of Neuro-Oncology
Objective The aim of this work is to define competencies and entrustable professional activities ... more Objective The aim of this work is to define competencies and entrustable professional activities (EPAs) to be imparted within the framework of surgical neuro-oncological residency and fellowship training as well as the education of medical students. Improved and specific training in surgical neuro-oncology promotes neuro-oncological expertise, quality of surgical neuro-oncological treatment and may also contribute to further development of neuro-oncological techniques and treatment protocols. Specific curricula for a surgical neuro-oncologic education have not yet been established. Methods We used a consensus-building approach to propose skills, competencies and EPAs to be imparted within the framework of surgical neuro-oncological training. We developed competencies and EPAs suitable for training in surgical neuro-oncology. Result In total, 70 competencies and 8 EPAs for training in surgical neuro-oncology were proposed. EPAs were defined for the management of the deteriorating pat...
Frontiers in Oncology
ObjectivesGliomas are often diagnosed due to epileptic seizures as well as neurocognitive deficit... more ObjectivesGliomas are often diagnosed due to epileptic seizures as well as neurocognitive deficits. First treatment choice for patients with gliomas in speech-related areas is awake surgery, which aims at maximizing tumor resection while preserving or improving patient’s neurological status. The present study aimed at evaluating neurocognitive functioning and occurrence of epileptic seizures in patients suffering from gliomas located in language-related areas before and after awake surgery as well as during their follow up course of disease.Materials and MethodsIn this prospective study we included patients who underwent awake surgery for glioma in the inferior frontal gyrus, superior temporal gyrus, or anterior temporal lobe. Preoperatively, as well as in the short-term (median 4.1 months, IQR 2.1-6.0) and long-term (median 18.3 months, IQR 12.3-36.6) postoperative course, neurocognitive functioning, neurologic status, the occurrence of epileptic seizures and number of antiepilepti...
Frontiers in Oncology
PurposeSurgery of KOOS IV vestibular schwannoma remains challenging regarding the balance of exte... more PurposeSurgery of KOOS IV vestibular schwannoma remains challenging regarding the balance of extent of tumor resection (EoR) and functional outcome. Our aim was to evaluate the outcome of surgical resection and define a cut-off value for safe resection with low risk for tumor regrowth of KOOS IV vestibular schwannoma.MethodsAll patients presenting at the authors’ institution between 2000 and 2019 with surgically treated KOOS IV vestibular schwannoma were included. Outcome measures included EoR, facial/hearing nerve function, surgical complications and progression of residual tumor during the median follow-up period of 28 months.ResultsIn 58 patients, mean tumor volume was 17.1 ± 9.2 cm3, and mean EoR of 81.6 ± 16.8% could be achieved. Fifty-one patients were available for the follow-up analysis. Growth of residual tumor was observed in 11 patients (21.6%) followed by adjuvant treatment with stereotactic radiosurgery or repeat surgery in 15 patients (29.4%). Overall serviceable heari...
Frontiers in Immunology, 2022
BackgroundThe inclusion of immune checkpoint inhibitors (ICIs) in therapeutic algorithms has led ... more BackgroundThe inclusion of immune checkpoint inhibitors (ICIs) in therapeutic algorithms has led to significant survival benefits in patients with various metastatic cancers. Concurrently, an increasing number of neurological immune related adverse events (IRAE) has been observed. In this retrospective analysis, we examine the ICI-induced incidence of cerebral pseudoprogression and propose a classification system.MethodsWe screened our hospital information system to identify patients with any in-house ICI treatment for any tumor disease during the years 2007-2019. All patients with cerebral MR imaging (cMRI) of sufficient diagnostic quality were included. cMRIs were retrospectively analyzed according to immunotherapy response assessment for neuro-oncology (iRANO) criteria.ResultsWe identified 12 cases of cerebral pseudoprogression in 123 patients treated with ICIs and sufficient MRI. These patients were receiving ICI therapy for lung cancer (n=5), malignant melanoma (n=4), glioblast...
Frontiers in Oncology, 2022
Majority of lower grade glioma (LGG) are located eloquently rendering surgical resection challeng... more Majority of lower grade glioma (LGG) are located eloquently rendering surgical resection challenging. Aim of our study was to assess rate of permanent deficits and its predisposing risk factors. We retrieved 83 patients harboring an eloquently located LGGs from the prospective LoG-Glio Database. Patients without surgery or incomplete postoperative data were excluded. Sign rank test, explorative correlations by Spearman ρ and multivariable regression for new postoperative deficits were calculated. Eloquent region involved predominantly motor (45%) and language (40%). At first follow up after 3 months permanent neuro-logical deficits (NDs) were noted in 39%. Mild deficits remained in 29% and severe deficits in 10%. Complete tumor removal (CTR) was successfully in 62% of intended cases. Postoperative and 3-month follow up National Institute of Health Stroke Score (NIHSS) showed significantly lower values than preoperatively (p<0.001). 38% cases showed a decreased NIHSS at 3-month, w...
Journal of Clinical Medicine, 2021
Along with increasing average life expectancy, the number of elderly meningioma patients has grow... more Along with increasing average life expectancy, the number of elderly meningioma patients has grown proportionally. Our aim was to evaluate whether these specific patients benefit from surgery and to investigate a previously published score for decision-making in meningioma patients (SKALE). Of 421 patients who underwent primary intracranial meningioma resection between 2009 and 2015, 71 patients were ≥70 years of age. We compared clinical data including World Health Organization (WHO) grade, MIB-1 proliferation index, Karnofsky Performance Status Scale (KPS), progression free survival (PFS) and mortality rate between elderly and all other meningioma patients. Preoperative SKALE scores (Sex, KPS, ASA score, location and edema) were determined for elderly patients. SKALE ≥8 was set for dichotomization to determine any association with outcome parameters. In 71 elderly patients (male/female 37/34) all data were available. Postoperative KPS was significantly lower in elderly patients (p...
Neuro-Oncology, 2017
NEURO-ONCOLOGY • NOVEMBER 2017 survival in glioblastoma. METHODS: We retrospectively evaluated 12... more NEURO-ONCOLOGY • NOVEMBER 2017 survival in glioblastoma. METHODS: We retrospectively evaluated 127 consecutive patients with newly diagnosed GBM treated at our institution. Forty-seven (37%) had circumferential resection (CR) by the senior author and the other 80(63%) had debulking/piecemeal ("non-circumferential") resection(NCR). All patients underwent adjuvant chemoradiotherapy as per the Stupp protocol. Tumor volumetric analysis was performed using Osirix software. Overall survival and survival as stratified by treatment and extent of resection (EOR) were evaluated using Kaplan-Meier survival analysis. RESULTS: Clinical characteristics between CR and NCR cohorts were similar. Mean age at diagnosis was 59 years and 81(63.9%) were male. Preoperative tumor volume was 31.8 cm 3 vs. 40.6 cm 3 (p=0.05) for CR vs. NCR respectively. Patients who had CR had higher median EOR (100.0 vs. 90.4, p<0.0001). The median OS for the entire cohort was 13.2 months. Median OS for CR and NCR was 17.7 and 11.0 months respectively (p<0.0001). EOR significantly impacted survival. Among the CR cohort, median survival was 22.5 and 11.5 months for >98% and <98% EOR respectively while median survival for the NCR cohort was 14.4 and 9.6 months for >98% and <98% EOR respectively. Post-operative Karnofsky Performance Scale (median, interquartile range) was 80(70-90) and 70(70-90) for CR and NCR patients respectively (p=0.43). CONCLUSION: Circumferential resection helps maximise the extent of resection in glioblastoma surgery and significantly prolongs survival without compromise to functional status.
Scientific Reports, 2020
Due to anticipated postoperative neuropsychological sequelae, patients with gliomas infiltrating ... more Due to anticipated postoperative neuropsychological sequelae, patients with gliomas infiltrating the corpus callosum rarely undergo tumor resection and mostly present in a poor neurological state. We aimed at investigating the benefit of glioma resection in the corpus callosum, hypothesizing neuropsychological deficits were mainly caused by tumor presence. Between 01/2017 and 1/2020, 21 patients who underwent glioma resection in the corpus callosum were prospectively enrolled into this study. Neuropsychological function was assessed preoperatively, before discharge and after 6 months. Gross total tumor resection was possible in 15 patients, and in 6 patients subtotal tumor resection with a tumor reduction of 97.7% could be achieved. During a median observation time of 12.6 months 9 patients died from glioblastoma after a median of 17 months. Preoperatively, all cognitive domains were affected in up to two thirds of patients, who presented a median KPS of 100% (range 60–100%). After ...
Anaesthesiology Intensive Therapy, 2020
Over the last decade, awake craniotomy (AC) has become a commonly performed neurosurgical procedu... more Over the last decade, awake craniotomy (AC) has become a commonly performed neurosurgical procedure for resection of brain tumors in eloquent areas [1]. By cortical and subcortical mapping functional areas can be localized in the awake patient, allowing maximal tumor resection up to functional boundaries [2, 3]. AC has been shown to result in fewer late neurological deficits [4, 5], shorter length of hospital stay [6, 7], and longer overall survival [5], the latter correlating directly with the extent of tumor resection [7]. However, the anesthesiological management for AC shows high variations between centers performing this procedure. So far, different anesthesiological approaches have been reported: asleep-awake-asleep (AAA), asleep-awake (AA), monitored anesthesia care (MAC) and conscious se
Neuro-Oncology, 2019
OBJECTIVE Pursuing a profession is an indispensable component of human happiness. The aim of this... more OBJECTIVE Pursuing a profession is an indispensable component of human happiness. The aim of this study was to analyze patients′ professional, socio-economic and psychological outcomes besides their neuro-oncological and functional evaluation after awake surgery for gliomas in eloquent areas. METHODS The neuro-oncological and functional outcomes of patients with gliomas other than glioblastoma undergoing awake surgery during a period of 5 years were prospectively assessed within our routine oncological follow-up. Repercussions of the disease on their professional status, socio-economic situation, and neurocognitive function were evaluated retrospectively with structured interviews. RESULTS We analyzed data of 37 patients with gliomas (3 WHO Grade I, 6 WHO grade II, 28 WHO grade III). Gross total and subtotal tumor resections were performed in 20 (54.1%) and 11 (29.7%) patients, respectively, whereas in 7 patients (16.2%) resection had to remain partial. Median follow up was 24.1 mon...
Neuro-Oncology, 2019
OBJECTIVE The prognosis especially of older patients with glioblastoma is poor. Novel therapies a... more OBJECTIVE The prognosis especially of older patients with glioblastoma is poor. Novel therapies are usually reserved for patients ≤65 years. As the population is growing older, the challenge remains as to how very elderly patients ≥75 years should be treated. Only limited outcome data exist for this patient subgroup. METHODS Between 2010 and 2018 we treated a total of 977 patients with glioblastoma at our institution. Of these, 144 patients were ≥75 years at diagnosis. The primary procedure was surgery or biopsy followed by adjuvant treatment, if possible. We retrospectively investigated progression-free and overall survival (OS) and looked at potential prognostic factors influencing survival, including Karnofsky performance score (KPS), surgical therapy, adjuvant therapy as well as MGMT promoter methylation status. RESULTS In our very elderly cohort, the median age was 79 years (range: 75–110). Biopsy only was performed in 108 patients, resection was performed in 36 patients. Media...
The Journal of Neuroscience, 2019
The way the human brain represents speech in memory is still unknown. An obvious characteristic o... more The way the human brain represents speech in memory is still unknown. An obvious characteristic of speech is its evolvement over time. During speech processing, neural oscillations are modulated by the temporal properties of the acoustic speech signal, but also acquired knowledge on the temporal structure of language influences speech perception-related brain activity. This suggests that speech could be represented in the temporal domain, a form of representation that the brain also uses to encode autobiographic memories. Empirical evidence for such a memory code is lacking. We investigated the nature of speech memory representations using direct cortical recordings in the left perisylvian cortex during delayed sentence reproduction in female and male patients undergoing awake tumor surgery. Our results reveal that the brain endogenously represents speech in the temporal domain. Temporal pattern similarity analyses revealed that the phase of frontotemporal low-frequency oscillations, primarily in the beta range, represents sentence identity in working memory. The positive relationship between beta power during working memory and task performance suggests that working memory representations benefit from increased phase separation.
Neuro-Oncology Practice, 2018
Background Diffuse low-grade gliomas (DLGGs) are rare and incurable tumors. Whereas maximal safe,... more Background Diffuse low-grade gliomas (DLGGs) are rare and incurable tumors. Whereas maximal safe, functional-based surgical resection is the first-line treatment, the timing and choice of further treatments (chemotherapy, radiation therapy, or combined treatments) remain controversial. Methods An online survey on the management of DLGG patients was sent to 28 expert centers from the European Low-Grade Glioma Network (ELGGN) in May 2015. It contained 40 specific questions addressing the modalities of use of chemotherapy in these patients. Results The survey demonstrated a significant heterogeneity in practice regarding the initial management of DLGG patients and the use of chemotherapy. Interestingly, radiation therapy combined with the procarbazine, CCNU (lomustine), and vincristine regimen has not imposed itself as the gold-standard treatment after surgery, despite the results of the Radiation Therapy Oncology Group 9802 study. Temozolomide is largely used as first-line treatment a...
PloS one, 2018
Stereotactic radiosurgery (SRS) is an established primary treatment for newly diagnosed brain met... more Stereotactic radiosurgery (SRS) is an established primary treatment for newly diagnosed brain metastases with high local control rates. However, data about local re-irradiation in case of local failure after SRS (re-SRS) are rare. We evaluated the feasibility, efficacy and patient selection characteristics in treating locally recurrent metastases with a second course of SRS. We retrospectively evaluated patients with brain metastases treated with re-SRS for local tumor progression between 2011 and 2017. Patient and treatment characteristics as well as rates of tumor control, survival and toxicity were analyzed. Overall, 32 locally recurrent brain metastases in 31 patients were irradiated with re-SRS. Median age at re-SRS was 64.9 years. The primary histology was breast cancer and non-small-cellular lung cancer (NSCLC) in respectively 10 cases (31.3%), in 5 cases malignant melanoma (15.6%). In the first SRS-course 19 metastases (59.4%) and in the re-SRS-course 29 metastases (90.6%) w...
Journal of neuro-oncology, Jan 10, 2018
Imaging studies in diffuse low-grade gliomas (DLGG) vary across centers. In order to establish a ... more Imaging studies in diffuse low-grade gliomas (DLGG) vary across centers. In order to establish a minimal core of imaging necessary for further investigations and clinical trials in the field of DLGG, we aimed to establish the status quo within specialized European centers. An online survey composed of 46 items was sent out to members of the European Low-Grade Glioma Network, the European Association of Neurosurgical Societies, the German Society of Neurosurgery and the Austrian Society of Neurosurgery. A total of 128 fully completed surveys were received and analyzed. Most centers (n = 96, 75%) were academic and half of the centers (n = 64, 50%) adhered to a dedicated treatment program for DLGG. There were national differences regarding the sequences enclosed in MRI imaging and use of PET, however most included T1 (without and with contrast, 100%), T2 (100%) and TIRM or FLAIR (20, 98%). DWI is performed by 80% of centers and 61% of centers regularly performed PWI. A minimal core of ...
Neuro-Oncology Practice, 2017
Diffuse low-grade glioma form a rare entity affecting young people. Despite advances in surgery, ... more Diffuse low-grade glioma form a rare entity affecting young people. Despite advances in surgery, chemotherapy, and radiation therapy, diffuse low-grade glioma are still incurable. According to current guidelines, maximum safe resection, when feasible, is the first line of treatment. Apart from surgery, all other treatment modalities (temozolomide, procarbazine-CCNU-vincristine regimen, and radiation therapy) are handled very differently among different teams, and this in spite of recent results of several phase 3 studies. Based on a European survey, this paper aimed to get a picture of this heterogeneity in diffuse low-grade glioma management, to identify clinically relevant questions raised by this heterogeneity of practice, and to propose new methodological frameworks to address these questions.
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Papers by Marie-therese Forster