Publications by authors named "Anna S Berghoff"

116 Publications

Thyroid Hormone Replacement Therapy Is Associated with Longer Overall Survival in Patients with Resectable Gastroesophageal Cancer: A Retrospective Single-Center Analysis.

Cancers (Basel) 2021 Oct 9;13(20). Epub 2021 Oct 9.

Department of Medicine I, Division of Oncology, Medical University of Vienna, 1090 Vienna, Austria.

Introduction: As thyroid hormones modulate proliferative pathways it is surmised that they can be associated with cancer development. Since the potential association of gastroesophageal cancer and thyroid disorders has not been addressed so far, the aim of this study was to investigate the association of thyroid hormone parameters with the outcome of these patients, so novel prognostic and even potentially therapeutic markers can be defined.

Material And Methods: Clinical and endocrinological parameters of patients with resectable gastroesophageal cancer treated between 1990 and 2018 at the Vienna General Hospital, Austria, including history of endocrinological disorders and laboratory analyses of thyroid hormones at first cancer diagnosis were investigated and correlated with the overall survival (OS).

Results: In a total of 865 patients, a tendency towards prolonged OS in hypothyroid patients (euthyroid, = 647: median OS 29.7 months; hyperthyroid, = 50: 23.1 months; hypothyroid, = 70: 47.9 months; = 0.069) as well as a significant positive correlation of thyroid hormone replacement therapy with the OS was observed (without, = 53: median OS 30.6 months; with, = 67: 51.3 months; = 0.017). Furthermore, triiodothyronine (T3) levels were also associated with the OS (median OS within the limit of normal: 23.4, above: 32.4, below: 9.6 months; = 0.045).

Conclusions: Thyroid disorders and their therapeutic interventions might be associated with the OS in patients with resectable gastroesophageal cancer. As data on the correlation of these parameters is scarce, this study proposes an important impulse for further analyses concerning the association of thyroid hormones with the outcome in patients with gastroesophageal tumors.
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http://dx.doi.org/10.3390/cancers13205050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534173PMC
October 2021

Integrated Molecular-Morphologic Meningioma Classification: A Multicenter Retrospective Analysis, Retrospectively and Prospectively Validated.

J Clin Oncol 2021 Dec 7;39(34):3839-3852. Epub 2021 Oct 7.

Department of Neurosurgery, NYU Langone Hospital, New York, NY.

Purpose: Meningiomas are the most frequent primary intracranial tumors. Patient outcome varies widely from benign to highly aggressive, ultimately fatal courses. Reliable identification of risk of progression for individual patients is of pivotal importance. However, only biomarkers for highly aggressive tumors are established ( and ), whereas no molecularly based stratification exists for the broad spectrum of patients with low- and intermediate-risk meningioma.

Methods: DNA methylation data and copy-number information were generated for 3,031 meningiomas (2,868 patients), and mutation data for 858 samples. DNA methylation subgroups, copy-number variations (CNVs), mutations, and WHO grading were analyzed. Prediction power for outcome was assessed in a retrospective cohort of 514 patients, validated on a retrospective cohort of 184, and on a prospective cohort of 287 multicenter cases.

Results: Both CNV- and methylation family-based subgrouping independently resulted in increased prediction accuracy of risk of recurrence compared with the WHO classification (c-indexes WHO 2016, CNV, and methylation family 0.699, 0.706, and 0.721, respectively). Merging all risk stratification approaches into an integrated molecular-morphologic score resulted in further substantial increase in accuracy (c-index 0.744). This integrated score consistently provided superior accuracy in all three cohorts, significantly outperforming WHO grading (c-index difference = .005). Besides the overall stratification advantage, the integrated score separates more precisely for risk of progression at the diagnostically challenging interface of WHO grade 1 and grade 2 tumors (hazard ratio 4.34 [2.48-7.57] and 3.34 [1.28-8.72] retrospective and prospective validation cohorts, respectively).

Conclusion: Merging these layers of histologic and molecular data into an integrated, three-tiered score significantly improves the precision in meningioma stratification. Implementation into diagnostic routine informs clinical decision making for patients with meningioma on the basis of robust outcome prediction.
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http://dx.doi.org/10.1200/JCO.21.00784DOI Listing
December 2021

Humoral Immune Response in Hematooncological Patients and Health Care Workers Who Received SARS-CoV-2 Vaccinations.

JAMA Oncol 2021 Sep 30:1-8. Epub 2021 Sep 30.

Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.

Importance: To our knowledge, little is known about antibody development after SARS-CoV-2 vaccination in immunocompromised individuals, such as patients with cancer.

Objective: To determine whether hematooncological patients develop anti-SARS-CoV-2 antibodies after vaccination.

Design, Setting, And Participants: This retrospective cohort study included 2 independent cohorts of patients who were treated for hematological and solid malignant tumors between October 2020 and May 2021, comprising 901 samples from 595 patients and 58 health care workers (HCWs). Serum samples were collected from patients who were treated at an academic center and a community hospital in a rural area and a control group of HCWs, all of whom received SARS-CoV-2 vaccination.

Main Outcomes And Measures: Total anti-SARS-CoV-2 nucleocapsid (anti-NC) and antispike protein (anti-S) antibodies were measured retrospectively.

Results: In total, 595 patients (320 women [53.8%] and 275 men [46.2%]; median [range] age, 67 [19-96] years) and 58 HCWs (40 women [69.0%] and 18 men [31.0%]; median [range] age, 42 [24-60] years) were included. Previous SARS-CoV-2 infection was documented in 43 of 595 (7.2%), while anti-NC antibodies that suggested previous infections were observed in 49 of 573 evaluable patients (8.6%). In both cohorts, anti-S antibody levels were higher in fully vaccinated patients compared with patients who received 1 dose. After the first vaccination, patients with hematological cancer who received B cell-targeting agents had lower anti-S levels (median, 1.6 AU/mL; range: 0-17 244 AU/mL) than patients who received other therapies (median, 191.6 AU/mL; range, 0-40 000; P < .001) or patients with solid tumors (median, 246.4 AU/mL; range, 0-40 000 AU/mL; P < .001). Anti-S levels after the first vaccination differed according to ongoing antineoplastic treatment modalities, with the lowest median levels in patients who received chemotherapy alone (157.7 AU/mL; range, 0-40 000 AU/mL) or in combination with immunotherapy (118.7 AU/mL; range, 14.1-38 727 AU/mL) and the highest levels in patients with no ongoing antineoplastic treatment (median, 634.3 AU/mL; range, 0-40 000 AU/mL; P = .01). Antibody levels after full immunization were higher in HCWs (median, 2500 U/mL; range, 485-2500 U/mL) than in patients with cancer (median, 117.0 U/mL; range, 0-2500 U/mL; P < .001).

Conclusions And Relevance: In this cohort study of patients with hematooncological diseases and a control group of HCWs, anti-SARS-CoV-2 antibodies after vaccination could be detected in patients with cancer. Lower antibody levels compared with HCWs and differences in seroconversion in specific subgroups underscore the need for further studies on SARS-CoV-2 vaccination in patients with hematooncological disease.
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http://dx.doi.org/10.1001/jamaoncol.2021.5437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485209PMC
September 2021

SARS-CoV-2 screening in cancer outpatients during the second wave of the COVID-19 pandemic : Conclusions for crisis response at a high-volume oncology center.

Wien Klin Wochenschr 2021 Sep 19;133(17-18):909-914. Epub 2021 Aug 19.

Division of Oncology, Department of Medicine I, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Background: During the second wave of the coronavirus disease 2019 (COVID-19) pandemic Austria suffered one of the highest severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rates worldwide. We report performance parameters of a SARS-CoV‑2 screening program established for cancer outpatients at our center.

Methods: Institutional policy recommended routine biweekly SARS-CoV‑2 testing. Adherence to the testing recommendation during the second wave of the COVID-19 pandemic between 1 October and 30 November 2020 was analyzed. The SARS-CoV‑2 infection rate during first wave period (21 March to 4 May 2020) was compared to the one during second wave.

Results: A total of 1577 cancer patients were seen at our outpatient clinic during the second wave. In 1079/1577 (68.4%) patients, at least 1 SARS-CoV2 test was performed. Overall 2833 tests were performed, 23/1577 (1.5%, 95% confidence interval, CI 1.0-2.2%) patients were tested positive for SARS-CoV‑2, which indicates a significant increase compared to the first wave (4/1016; 0.4%, 95% CI 0.1-1.0%) with an odds ratio of 3.9 (95% CI 1.5-10.1; p < 0.005). Patients undergoing active anticancer treatment (172/960; 17.9% not tested) were more likely to have undergone a SARS-CoV‑2 test than patients in follow-up or best supportive care (326/617; 52.8% not tested p < 0.001). Furthermore, patients with only 1 visit within 4 weeks were more likely to not have undergone a SARS-CoV‑2 test (386/598; 64.5%) compared to patients with 2 or more visits (112/979; 11.4%; p < 0.001). The projected number of patients with undetected SARS-CoV‑2 infection during the study period was 5.

Conclusion: We identified clinical patient parameters influencing SARS-CoV‑2 testing coverage in cancer outpatients. Our data can provide information on generation of standard operating procedures and resource allocation during subsequent infection waves.
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http://dx.doi.org/10.1007/s00508-021-01927-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375465PMC
September 2021

Development of Randomized Trials in Adults with Medulloblastoma-The Example of EORTC 1634-BTG/NOA-23.

Cancers (Basel) 2021 Jul 9;13(14). Epub 2021 Jul 9.

Erasmus Medical Center Cancer Institute, Department of Neuro-Oncology, 3015 GD Rotterdam, The Netherlands.

Medulloblastoma is a rare brain malignancy. Patients after puberty are rare and bear an intermediate prognosis. Standard treatment consists of maximal resection plus radio-chemotherapy. Treatment toxicity is high and produces disabling long-term side effects. The sonic hedgehog (SHH) subgroup is highly overrepresented in the post-pubertal and adult population and can be targeted by smoothened (SMO) inhibitors. No practice-changing prospective randomized data have been generated in adults. The EORTC 1634-BTG/NOA-23 trial will randomize patients between standard-dose vs. reduced-dosed craniospinal radiotherapy and SHH-subgroup patients between the SMO inhibitor sonidegib (Odomzo, Sun Pharmaceuticals Industries, Inc., New York, USA) in addition to standard radio-chemotherapy vs. standard radio-chemotherapy alone to improve outcomes in view of decreased radiotherapy-related toxicity and increased efficacy. We will further investigate tumor tissue, blood, and cerebrospinal fluid as well as magnetic resonance imaging and radiotherapy plans to generate information that helps to further improve treatment outcomes. Given that treatment side effects typically occur late, long-term follow-up will monitor classic side effects of therapy, but also health-related quality of life, cognition, social and professional outcome, and reproduction and fertility. In summary, we will generate unprecedented data that will be translated into treatment changes in post-pubertal patients with medulloblastoma and will help to design future clinical trials.
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http://dx.doi.org/10.3390/cancers13143451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303185PMC
July 2021

Androgen Receptor is Expressed in Breast Cancer Brain Metastases.

Appl Immunohistochem Mol Morphol 2021 Nov-Dec 01;29(10):728-733

Department of Medicine I, Division of Oncology.

Background: Androgen receptor (AR) expression is a potential therapeutic target in breast cancer (BC) as it is frequently expressed in the luminal A and B subtypes and in approximately one third of basal-like cancers. As AR-positive BC displays a distinct biological behavior, we aimed to analyze AR expression in the particular context of BC brain metastases (BM).

Materials And Methods: Patients with newly diagnosed BC BM treated with neurosurgical resection were identified from the Vienna Brain Metastasis Registry and clinical data including patient characteristics, biological tumor subtypes and overall survival were obtained by retrospective chart review. Formalin-fixed and paraffin-embedded specimen containing BM tissue were retrieved from the Neuro-Biobank. Immunohistochemical staining of AR was performed and AR expression in the tumor-cell nucleus was evaluated.

Results: Fifty-seven BM samples from 57 individual patients with BC were available for this analysis. AR expression of ≥1% tumor cells was evident in 20/57 (35.1%) BM specimens; the median AR-expression rate was 10% (range: 1% to 60%). AR expression was observed in 11/21 (52.4%) BM of the luminal/human epidermal growth factor receptor 2 (HER2)-negative subtype, 3/13 (23.1%) of the luminal/HER2-positive subtype, 2/7 (28.6%) of the HER2-positive subtype and 4/16 (25.0%) of the triple-negative subtype (P=0.247). Median survival from diagnosis of BM was 10 months (range: 0 to 104 mo) in the entire cohort. No significant association of overall survival and AR expression ≥1% was observed (15 vs. 13 mo; P>0.05).

Conclusion: AR is expressed in more than one third of BC BM with the highest rates among the luminal/HER2-negative BC subtype and may therefore be a potential prognostic and predictive biomarker in this particular BC population.
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http://dx.doi.org/10.1097/PAI.0000000000000952DOI Listing
November 2020

5-ALA Fluorescence Is a Powerful Prognostic Marker during Surgery of Low-Grade Gliomas (WHO Grade II)-Experience at Two Specialized Centers.

Cancers (Basel) 2021 May 21;13(11). Epub 2021 May 21.

Department of Neurosurgery, Medical University of Vienna, 1090 Vienna, Austria.

The prediction of the individual prognosis of low-grade glioma (LGG) patients is limited in routine clinical practice. Nowadays, 5-aminolevulinic acid (5-ALA) fluorescence is primarily applied for improved intraoperative visualization of high-grade gliomas. However, visible fluorescence is also observed in rare cases despite LGG histopathology and might be an indicator for aggressive tumor behavior. The aim of this study was thus to investigate the value of intraoperative 5-ALA fluorescence for prognosis in LGG patients. We performed a retrospective analysis of patients with newly diagnosed histopathologically confirmed LGG and preoperative 5-ALA administration at two independent specialized centers. In this cohort, we correlated the visible intraoperative fluorescence status with progression-free survival (PFS), malignant transformation-free survival (MTFS) and overall survival (OS). Altogether, visible fluorescence was detected in 7 (12%) of 59 included patients in focal intratumoral areas. At a mean follow-up time of 5.3 ± 2.9 years, patients with fluorescing LGG had significantly shorter PFS (2.3 ± 0.7 vs. 5.0 ± 0.4 years; 0.01), MTFS (3.9 ± 0.7 vs. 8.0 ± 0.6 years; = 0.03), and OS (5.4 ± 1.0 vs. 10.3 ± 0.5 years; = 0.01) than non-fluorescing tumors. Our data indicate that visible 5-ALA fluorescence during surgery of pure LGG might be an already intraoperatively available marker of unfavorable patient outcome and thus close imaging follow-up might be considered.
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http://dx.doi.org/10.3390/cancers13112540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196836PMC
May 2021

Circulating PD-L1 levels change during bevacizumab-based treatment in recurrent glioma.

Cancer Immunol Immunother 2021 Dec 6;70(12):3643-3650. Epub 2021 May 6.

Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria.

Purpose: In primary brain tumors, the efficacy of immune-modulating therapies is still under investigation as inflammatory responses are restricted by tight immunoregulatory mechanisms in the central nervous system. Here, we measured soluble PD-L1 (sPD-L1) in the plasma of patients with recurrent glioblastoma (GBM) and recurrent WHO grade II-III glioma treated with bevacizumab-based salvage therapy.

Methods: Thirty patients with recurrent GBM and 10 patients with recurrent WHO grade II-III glioma were treated with bevacizumab-based salvage therapy at the Medical University of Vienna. Prior to each treatment cycle, EDTA plasma was drawn and sPD-L1 was measured applying a sandwich ELISA with a lower detection limit of 0.050 ng/ml. Leukocyte counts and C-reactive protein (CRP) levels were measured according to institutional practice.

Results: Median number of sPD-L1 measurements was 6 per patient (range: 2-24). At baseline, no significant difference in sPD-L1 concentrations was observed between WHO grade II-III glioma and GBM. Intra-patient variability of sPD-L1 concentrations was significantly higher in WHO grade II-III glioma than in GBM (p = 0.014) and tendentially higher in IDH-mutant than in IDH-wildtype glioma (p = 0.149) In WHO grade II-III glioma, sPD-L1 levels were significantly lower after one administration of bevacizumab than at baseline (median: 0.039 ng/ml vs. 0.4855 ng/ml, p = 0.036). In contrast, no significant change could be observed in patients with GBM.

Conclusions: Changes in systemic inflammation markers including sPD-L1 are observable in patients with recurrent glioma under bevacizumab-based treatment and differ between WHO grade II-III glioma and GBM.
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http://dx.doi.org/10.1007/s00262-021-02951-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571215PMC
December 2021

Tumor DNA methylation profiles correlate with response to anti-PD-1 immune checkpoint inhibitor monotherapy in sarcoma patients.

J Immunother Cancer 2021 03;9(3)

Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.

Background: Some sarcomas respond to immune checkpoint inhibition, but predictive biomarkers are unknown. We analyzed tumor DNA methylation profiles in relation to immunological parameters and response to anti-programmed cell death 1 (anti-PD-1) immune checkpoint inhibitor (ICI) therapy in patients with sarcoma.

Patients And Methods: We retrospectively identified adult patients who had received anti-PD-1 ICI therapy for recurrent sarcoma in two independent centers. We performed (1) blinded radiological response evaluation according to immune response evaluation criteria in solid tumors (iRECIST) ; (2) tumor DNA methylation profiling of >850,000 probes using Infinium MethylationEPIC microarrays; (3) analysis of tumor-infiltrating immune cell subsets (CD3, CD8, CD45RO, FOXP3) and intratumoral expression of immune checkpoint molecules (PD-L1, PD-1, LAG-3) using immunohistochemistry; and (4) evaluation of blood-based systemic inflammation scores (neutrophil-to-lymphocyte ratio, leucocyte-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio). Response to anti-PD-1 ICI therapy was bioinformatically and statistically correlated with DNA methylation profiles and immunological data.

Results: 35 patients (median age of 50 (23-81) years; 18 females, 17 males; 27 soft tissue sarcomas; 8 osteosarcomas) were included in this study. The objective response rate to anti-PD-1 ICI therapy was 22.9% with complete responses in 3 out of 35 and partial responses in 5 out of 35 patients. Adjustment of DNA methylation data for tumor-infiltrating immune cells resulted in identification of methylation differences between responders and non-responders to anti-PD-1 ICI. 2453 differentially methylated CpG sites (DMPs; 2043 with decreased and 410 with increased methylation) were identified. Clustering of sarcoma samples based on these DMPs revealed two main clusters: methylation cluster 1 (MC1) consisted of 73% responders and methylation cluster 2 (MC2) contained only non-responders to anti-PD-1 ICI. Median progression-free survival from anti-PD-1 therapy start of MC1 and MC2 patients was 16.5 and 1.9 months, respectively (p=0.001). Median overall survival of these patients was 34.4 and 8.0 months, respectively (p=0.029). The most prominent DNA methylation differences were found in pathways implicated in Rap1 signaling, focal adhesion, adherens junction Phosphoinositide 3-kinase (PI3K)-Akt signaling and extracellular matrix (ECM)-receptor interaction.

Conclusions: Our data demonstrate that tumor DNA methylation profiles may serve as a predictive marker for response to anti-PD-1 ICI therapy in sarcoma.
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http://dx.doi.org/10.1136/jitc-2020-001458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993298PMC
March 2021

LAG-3 expression in the inflammatory microenvironment of glioma.

J Neurooncol 2021 May 2;152(3):533-539. Epub 2021 Mar 2.

Division of Oncology and Christian Doppler Laboratory for Personalized Immunotherapy, Department of Medicine I, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Purpose: Immune modulatory therapies including immune checkpoint inhibitors have so far failed to result in clinically meaningful efficacy in glioma. We aimed to investigate lymphocyte activation gene 3 (LAG-3), an inhibitory receptor on immune cells and target of second-generation immune checkpoint inhibitors, in glioma.

Methods: 97 patients with diffuse glioma (68 with glioblastoma, 29 with WHO grade II-III glioma) were identified from the Neuro-Biobank of the Medical University of Vienna. LAG-3 expression in the inflammatory microenvironment was assessed by immunohistochemistry (monoclonal anti-LAG-3 antibody, clone 17B4) and correlated to CD3+ , CD8+ , CD20+ and PD-1+ tumor-infiltrating lymphocytes (TILs) and PD-L1 expression on tumor cells.

Results: LAG-3+ TILs could be observed in 10/97 (10.3%) IDH-wildtype samples and in none of the included IDH-mutant glioma samples (p = 0.057). Further, LAG-3+ TILs were only observed in WHO grade IV glioblastoma, while none of the investigated WHO grade II-III glioma presented with LAG-3+ TILs (p = 0.03). No association of O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation and presence of LAG-3+ TILs was observed (p = 0.726). LAG-3 expression was associated with the presence of CD3+ (p = 0.029), CD8+ (p = 0.001), PD-1+ (p < 0.001) TILs and PD-L1+ tumor cells (p = 0.021), respectively. No association of overall survival with LAG-3+ TIL infiltration was evident (median OS 9.9 vs. 14.2 months, p = 0.95).

Conclusions: LAG-3 is only rarely expressed on TILs in IDH-wildtype glioma and associated with active inflammatory milieu as defined by higher TIL density. Immune microenvironment diversity should be considered in the design of future immunotherapy trials in glioma.
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http://dx.doi.org/10.1007/s11060-021-03721-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084780PMC
May 2021

Degradation of BRD4 - a promising treatment approach not only for hematologic but also for solid cancer.

Am J Cancer Res 2021 1;11(2):530-545. Epub 2021 Feb 1.

Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna Austria.

Bromodomain (BRD) and extra-terminal (BET) proteins are epigenetic readers that regulate gene expression and promote cancer evolution. Pharmacological inactivation of BRD4 has recently been introduced as a promising anti-neoplastic approach that targets MYC oncogene expression. However, resistance against BRD4-targeting drugs has been described. We compared the efficacy of the small-molecule-type BET BRD inhibitor JQ1 with the recently developed BET protein degraders dBET1 and dBET6 in colon, breast, melanoma, ovarian, lung and prostate cancer cell lines. As determined by qPCR, all BRD4 targeting drugs dose-dependently decreased MYC expression, with dBET6 introducing the strongest downregulation of MYC. This correlated with the anti-proliferative activity of these drugs, which was at least one order of magnitude higher for dBET6 (IC 0.001-0.5 µM) than for dBET1 or JQ1 (IC 0.5-5 µM). Interestingly, when combined with commonly used cytotoxic therapeutics, dBET6 was found to promote anti-neoplastic effects and to counteract chemoresistance in most cancer cell lines. Moreover, JQ1 and both BET degraders strongly downregulated baseline and interferon-gamma induced expression of the immune checkpoint molecule PD-L1 in all cancer cell lines. Together, our data suggest that dBET6 outperforms first-generation BRD4 targeting drugs like dBET1 and JQ1, and decreases chemoresistance and immune resistance of cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868748PMC
February 2021

Prognostic Value of 5-ALA Fluorescence, Tumor Cell Infiltration and Angiogenesis in the Peritumoral Brain Tissue of Brain Metastases.

Cancers (Basel) 2021 Feb 3;13(4). Epub 2021 Feb 3.

Department of Neurosurgery, Medical University Vienna, Vienna General Hospital, Waehringer Guertel 18-20, 1090 Vienna, Austria.

Complete resection is an indispensable treatment option in the management of brain metastases (BM). 5-aminolevulinic acid (5-ALA) fluorescence is used for improved intraoperative visualization of tumor tissue in gliomas and was recently observed in BM. We investigated the potential of 5-ALA fluorescence to visualize the infiltrative growth of BM in the peritumoral brain tissue and its histopathological correlate. Patients with BM resection after 5-ALA administration and collection of tissue samples from peritumoral brain tissue were included. Each tissue sample was histopathologically investigated for tumor cell infiltration and angiogenesis. Altogether, 88 samples were collected from the peritumoral brain tissue in 58 BM of 55 patients. Visible 5-ALA fluorescence was found in 61 (69%) of the samples, tumor infiltration in 19 (22%) and angiogenesis in 13 (15%) of samples. Angiogenesis showed a significant correlation with presence of fluorescence ( = 0.008). Moreover, angiogenesis was related to visible 5-ALA fluorescence and showed an association with patient prognosis since it was significantly correlated to shorter time to local progression/recurrence ( = 0.001) and lower one-year survival ( = 0.031). Consequently, angiogenesis in the peritumoral brain tissue of BM might be a novel prognostic marker for individualized perioperative treatment concepts in the future.
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http://dx.doi.org/10.3390/cancers13040603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913757PMC
February 2021

Evaluation of the Temporal Muscle Thickness as an Independent Prognostic Biomarker in Patients with Primary Central Nervous System Lymphoma.

Cancers (Basel) 2021 Feb 2;13(3). Epub 2021 Feb 2.

Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.

In this study, we assessed the prognostic relevance of temporal muscle thickness (TMT), likely reflecting patient's frailty, in patients with primary central nervous system lymphoma (PCNSL). In 128 newly diagnosed PCNSL patients TMT was analyzed on cranial magnetic resonance images. Predefined sex-specific TMT cutoff values were used to categorize the patient cohort. Survival analyses, using a log-rank test as well as Cox models adjusted for further prognostic parameters, were performed. The risk of death was significantly increased for PCNSL patients with reduced muscle thickness (hazard ratio of 3.189, 95% CI: 2-097-4.848, < 0.001). Importantly, the results confirmed that TMT could be used as an independent prognostic marker upon multivariate Cox modeling (hazard ratio of 2.504, 95% CI: 1.608-3.911, < 0.001) adjusting for sex, age at time of diagnosis, deep brain involvement of the PCNSL lesions, Eastern Cooperative Oncology Group (ECOG) performance status, and methotrexate-based chemotherapy. A TMT value below the sex-related cutoff value at the time of diagnosis is an independent adverse marker in patients with PCNSL. Thus, our results suggest the systematic inclusion of TMT in further translational and clinical studies designed to help validate its role as a prognostic biomarker.
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http://dx.doi.org/10.3390/cancers13030566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867149PMC
February 2021

Systemic inflammation scores correlate with survival prognosis in patients with newly diagnosed brain metastases.

Br J Cancer 2021 03 21;124(7):1294-1300. Epub 2021 Jan 21.

Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria.

Background: Systemic inflammation measured by the neutrophil-to-lymphocyte ratio (NLR), leucocyte-to-lymphocyte ratio (LLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR) and CRP/albumin ratio (CRP/Alb) was shown to impact the survival prognosis in patients with extracranial solid cancer.

Methods: One thousand two hundred and fifty patients with newly diagnosed brain metastases (BM) were identified from the Vienna Brain Metastasis Registry.

Results: PLR and CRP/Alb were higher in patients with progressive extracranial disease and lower in patients with no evidence of extracranial disease. Lower NLR (cut-off = 5.07; 9.3 vs. 5.0 months), LLR (cut-off = 5.76; 10.0 vs. 5.3 months), PLR (cut-off = 335; 8.0 vs. 3.8 months), MLR (cut-off = 0.53; 6.0 vs. 3.5 months) and CRP/Alb (cut-off = 2.93; 8.5 vs. 3.7 months; p < 0.05) were associated with longer overall survival (OS). In multivariate analysis with graded prognostic assessment (hazard ratio (HR) 1.45; 95% confidence interval (CI): 1.32-1.59; p = 1.62e - 13, NLR (HR 1.55; 95% CI: 1.38-1.75; p = 1.92e - 11), LLR (HR 1.57; 95% CI: 1.39-1.77; p = 1.96e - 11, PLR (HR 1.60; 95% CI: 1.39-1.85; p = 2.87955e - 9), MLR (HR 1.41; 95% CI: 1.14-1.75; p = 0.027) and CRP/Alb (HR 1.83; 95% CI: 1.54-2.18; p = 2.73e - 10) remained independent factors associated with OS at BM diagnosis.

Conclusions: Systemic inflammation, measured by NLR, LLR, PLR, MLR and CRP/Alb, was associated with OS in patients with BM. Further exploration of immune modulating therapies is warranted in the setting of BM.
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http://dx.doi.org/10.1038/s41416-020-01254-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007827PMC
March 2021

Identification and Characterization of Cancer Cells That Initiate Metastases to the Brain and Other Organs.

Mol Cancer Res 2021 04 22;19(4):688-701. Epub 2020 Dec 22.

Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Specific biological properties of those circulating cancer cells that are the origin of brain metastases (BM) are not well understood. Here, single circulating breast cancer cells were fate-tracked during all steps of the brain metastatic cascade in mice after intracardial injection over weeks. A novel two-photon microscopy methodology was developed that allowed to determine the specific cellular and molecular features of breast cancer cells that homed in the brain, extravasated, and successfully established a brain macrometastasis. Those BM-initiating breast cancer cells (BMIC) were mainly originating from a slow-cycling subpopulation that included only 16% to 20% of all circulating cancer cells. BMICs showed enrichment of various markers of cellular stemness. As a proof of principle for the principal usefulness of this approach, expression profiling of BMICs versus non-BMICs was performed, which revealed upregulation of NDRG1 in the slow-cycling BMIC subpopulation in one BM model. Here, BM development was completely suppressed when NDRG1 expression was downregulated. In accordance, in primary human breast cancer, NDRG1 expression was heterogeneous, and high NDRG1 expression was associated with shorter metastasis-free survival. In conclusion, our data identify temporary slow-cycling breast cancer cells as the dominant source of brain and other metastases and demonstrates that this can lead to better understanding of BMIC-relevant pathways, including potential new approaches to prevent BM in patients. IMPLICATIONS: Cancer cells responsible for successful brain metastasis outgrowth are slow cycling and harbor stemness features. The molecular characteristics of these metastasis-initiating cells can be studied using intravital microscopy technology.
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http://dx.doi.org/10.1158/1541-7786.MCR-20-0863DOI Listing
April 2021

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

Neuro Oncol 2021 07;23(7):1100-1112

Department of Neurology, Clinical Neuroscience Center and Comprehensive Cancer Center, University Hospital and University of Zurich, Zurich, Switzerland.

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.
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http://dx.doi.org/10.1093/neuonc/noaa298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301235PMC
July 2021

Local blood coagulation drives cancer cell arrest and brain metastasis in a mouse model.

Blood 2021 03;137(9):1219-1232

Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany.

Clinically relevant brain metastases (BMs) frequently form in cancer patients, with limited options for effective treatment. Circulating cancer cells must first permanently arrest in brain microvessels to colonize the brain, but the critical factors in this process are not well understood. Here, in vivo multiphoton laser-scanning microscopy of the entire brain metastatic cascade allowed unprecedented insights into how blood clot formation and von Willebrand factor (VWF) deposition determine the arrest of circulating cancer cells and subsequent brain colonization in mice. Clot formation in brain microvessels occurred frequently (>95%) and specifically at intravascularly arrested cancer cells, allowing their long-term arrest. An extensive clot embedded ∼20% of brain-arrested cancer cells, and those were more likely to successfully extravasate and form a macrometastasis. Mechanistically, the generation of tissue factor-mediated thrombin by cancer cells accounted for local activation of plasmatic coagulation in the brain. Thrombin inhibition by treatment with low molecular weight heparin or dabigatran and an anti-VWF antibody prevented clot formation, cancer cell arrest, extravasation, and the formation of brain macrometastases. In contrast, tumor cells were not able to directly activate platelets, and antiplatelet treatments did reduce platelet dispositions at intravascular cancer cells but did not reduce overall formation of BMs. In conclusion, our data show that plasmatic coagulation is activated early by intravascular tumor cells in the brain with subsequent clot formation, which led us to discover a novel and specific mechanism that is crucial for brain colonization. Direct or indirect thrombin and VWF inhibitors emerge as promising drug candidates for trials on prevention of BMs.
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http://dx.doi.org/10.1182/blood.2020005710DOI Listing
March 2021

A basic review on systemic treatment options in WHO grade II-III gliomas.

Cancer Treat Rev 2021 Jan 13;92:102124. Epub 2020 Nov 13.

Division of Oncology, Department of Medicine I, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. Electronic address:

WHO grade II-III gliomas are rare primary brain tumors occurring at a median age of about 35-55 years. Median survival is longer in WHO grade II-III glioma compared with WHO grade IV glioblastoma as survival times of up to 10 years and longer can be observed. Maximal safe resection and adjuvant therapies including chemotherapy and radiotherapy are the mainstay of treatment. Clinical trials in WHO grade II-III tumors are challenging due to the rarity and the long follow up times. The 2016 WHO Classification of Central Nervous Tumours introduced a new diagnostic framework relying on molecular characteristics, providing the definition of prognostically more homogenous subgroups compared to the histopathological analysis. Most available evidence on the adjuvant treatment of WHO II-III gliomas was generated in the pre-molecular era, challenging the interpretation of study results. The present review therefore summarizes the available data from prospective trials on systemic treatment options in WHO grade II-III glioma, considering molecular markers, recently published results and future outlooks in the field.
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http://dx.doi.org/10.1016/j.ctrv.2020.102124DOI Listing
January 2021

Assessment of Central Nervous System Lymphoma Based on CXCR4 Expression In Vivo Using 68Ga-Pentixafor PET/MRI.

Clin Nucl Med 2021 Jan;46(1):16-20

From the Division of Oncology, Department of Medicine I.

Purpose Of The Report: F-FDG PET is limited for assessment of central nervous system lymphoma (CNSL) due to physiologic tracer accumulation in the brain. We prospectively evaluated the novel PET tracer Ga-pentixafor, which targets the C-X-C chemokine receptor 4 (CXCR4), for lesion visualization and response assessment of CNSL.

Materials And Methods: Seven CNSL patients underwent Ga-pentixafor PET/MRI with contrast enhancement (CE-MRI) and diffusion-weighted sequences. The accuracy of Ga-pentixafor PET for CNSL lesion detection relative to the CE-MRI reference standard was determined. Standardized uptake values (SUVmean and SUVmax), PET-based (PTV) and MRI-based (VOLMRI) tumor volumes, and apparent diffusion coefficients (ADCs) were assessed, and correlation coefficients were calculated. Three SUVmax thresholds (41%, 50%, and 70%) were evaluated for PTV definitions (PTV41%, PTV50%, and PTV70%) and tested against VOLMRI using paired sample t tests.

Results: Twelve Ga-pentixafor PET/MRI examinations (including 5 follow-up scans) of 7 patients were evaluated. Ga-pentixafor PET demonstrated 18 lesions, all of which were confirmed by CE-MRI; there were no false-positive lesions on PET (accuracy, 100%). PTV41% showed the highest concordance with lesion morphology, with no significant difference compared with VOLMRI (mean difference, -0.24 cm; P = 0.45). The correlation between ADCmean and SUVmean41% (r = 0.68) was moderate. Changes in PTV41% on follow-up PET/MRI showed the same trend as VOLMRI changes, including progression of 1 lesion each in patient 1 (+456.0% PTV41% and +350.8% VOLMRI) and patient 3 (+110.4% PTV41% and +85.1% VOLMRI).

Conclusions: Ga-pentixafor PET may be feasible for assessment and follow-up of CNSL. Future studies need to focus on testing its clinical value to distinguish between glioma and CNSL, and between radiation-induced inflammation and viable residual tumor.
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http://dx.doi.org/10.1097/RLU.0000000000003404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385649PMC
January 2021

Brain metastases in metastatic cancer: a review of recent advances in systemic therapies.

Expert Rev Anticancer Ther 2021 03 30;21(3):325-339. Epub 2020 Nov 30.

Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.

: Brain metastases (BM) are a frequent complication of metastatic cancer. Due to the wider availability and application of screening procedures, an increasing fraction of patients are diagnosed at the asymptomatic stage. The introduction of immune checkpoint inhibitors and targeted therapies has revolutionized treatment in several frequently BM-causing entities like metastatic lung cancer, melanoma and breast cancer. However, registered trials of new targeted and immunotherapy mostly excluded patients with BM resulting in limited knowledge of the intracranial efficacy of new systemic agents.: The present review highlights recent advances in systemic therapies for the treatment and prophylaxis of the three leading BM causing tumors: NSCLC, melanoma and breast cancer.: High intracranial efficacy was observed for several next-generation tyrosine kinase inhibitors as well as immune checkpoint inhibitors, especially in patients with asymptomatic disease. Ongoing discussions addressed the need for local therapies in patients with asymptomatic BM and the availability of systemic therapy with high intracranial efficacy. Further BM-specific studies as well as BM-specific endpoints in registered trials are needed to define the role of systemic monotherapies in patients with BM.
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http://dx.doi.org/10.1080/14737140.2021.1851200DOI Listing
March 2021

Soluble PD-L1 is associated with local and systemic inflammation markers in primary and secondary brain tumours.

ESMO Open 2020 11;5(6):e000863

Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria. Electronic address:

Background: Immune-modulatory treatments have so far shown limited clinical activity in primary brain tumours. We aimed to investigate soluble programmed death receptor ligand 1 (sPD-L1) as systemic inflammation parameter in patients with brain tumour.

Methods: EDTA plasma was collected from 81 glioma (55 glioblastoma (GBM), 26 lower-grade glioma (LGG)), 17 meningioma and 44 brain metastasis (BM) patients and 24 controls. sPD-L1 concentrations were determined by ELISA. Correlations with the local tumour microenvironment were assessed by immunohistochemical analysis for PD-L1, CD3 and CD8.

Results: sPD-L1 was detected in 62 out of 166 (37.7%) patients (glioma: 41/81, 50.6%; meningioma: 5/17, 29.4%; BM: 7/44, 15.9%; controls: 9/24, 37.5%; p=0.002). sPD-L1 concentrations were lower in BM than in LGG (p=0.003) or GBM (p<0.001). Membranous PD-L1 expression on tumour cells was not associated with sPD-L1 concentrations (p=0.953). sPD-L1 concentration was inversely correlated with the density of CD8+ (r=-0.713, p=0.001) and CD3+ (r=-0.484, p=0.042) tumour-infiltrating lymphocytes in LGG. sPD-L1 is correlated with neutrophil counts (r=-0.318, p=0.045) and C reactive protein levels (r=-0.363, p=0.008) in GBM. sPD-L1+ patients had longer overall survival in GBM (p=0.006) and worse OS in LGG (p=0.028).

Conclusions: sPD-L1 is detectable in a fraction of patients with brain tumour. Although it is not correlated with tissue PD-L1 expression, correlations with other local and systemic inflammation parameters could be detected in LGG and GBM.
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http://dx.doi.org/10.1136/esmoopen-2020-000863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662140PMC
November 2020

Evaluation of an Assay for MGMT Gene Promoter Methylation in Glioblastoma Samples.

Anticancer Res 2020 Nov;40(11):6229-6236

Department of Pathology and Knight Cancer Institute, Oregon Health and Science University, Portland, OR, U.S.A.

Background/aim: To compare the GeneXpert® O6-methylguanine DNA methyltransferase (MGMT) methylation prototype (GX MGMT) assay with pyrosequencing in glioblastomas.

Materials And Methods: The MGMT methylation status was retrospectively assessed in formalin-fixed paraffin embedded (FFPE) tumor blocks from 262 glioblastoma patients obtained from three independent cohorts using either a standard of care pyrosequencing laboratory developed test or the GX MGMT assay.

Results: The concordance rate was 92.1% (58/63) for Oregon Health and Science University (OSHU) samples, 91.7% (88/96) for Medical University of Vienna (MUV) samples, and 82.5% (85/103) for Kepler University Hospital (KUH) samples. Patients with MGMT promoter hypermethylation assessed by pyrosequencing or the GX MGMT test had a significantly longer overall survival compared to patients without hypermethylation (HR=0.43, 95%CI=0.26-0.72, p=0.001 and HR=0.51, 95%CI=0.31-0.84, p=0.008, respectively).

Conclusion: Standardized, simplified, and on-demand testing of MGMT promoter methylation by the GX MGMT assay is feasible.
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http://dx.doi.org/10.21873/anticanres.14643DOI Listing
November 2020

Thirteen-year analyses of medical oncology outpatient day clinic data: a changing field.

ESMO Open 2020 10;5(5):e000880

Division of Oncology, Department for Medicine I, Medical University of Vienna, Wien, Austria.

Background: Novel treatment modalities like targeted therapy and immunotherapy are currently changing treatment strategies and protocols in the field of medical oncology.

Methods: Numbers of patients and patient contacts admitted to medical oncology day clinics of a large European academic cancer centre in the period from 2006 to 2018 were analysed using our patient administration system.

Results: A patient cohort of 9.870 consecutive individual patients with 125.679 patient contacts was descriptively and retrospectively characterised. Mean age was 59.9 years. A substantial increase in both individual patients treated per year (+45.4%; 2006: 1.100; 2018: 1.599) and annual patient contacts (+63.3%; 2006: 8.857; 2018: 14.467) between 2006 and 2018 was detected. Hence and most interestingly, the ratio of visits per patient increased by approximately one visit per patient per year over the last 12 years (+12.4%; 2006: 8.0; 2018: 9.0). Further, a decrease of patient contacts in more prevalent entities like breast cancer was found, while contacts for orphan diseases like myeloma and sarcoma increased substantially. Interestingly, female patients showed more per patient contacts as compared with men (13.5 vs 11.9). Lastly, short-term safety data of outpatient day clinic admissions are reported.

Conclusions: We present a representative and large set of patient contacts over time that indicates an increasing load in routine clinical work of outpatient cancer care. Increases observed were highest for orphan diseases, likely attributed to centralisation effects and increased treatment complexity.
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http://dx.doi.org/10.1136/esmoopen-2020-000880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555099PMC
October 2020

Nintedanib and a bi-specific anti-VEGF/Ang2 nanobody selectively prevent brain metastases of lung adenocarcinoma cells.

Clin Exp Metastasis 2020 12 12;37(6):637-648. Epub 2020 Sep 12.

Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.

Brain metastases (BM) are an ever-increasing challenge in oncology, threatening quality of life and survival of many cancer patients. The majority of BM originate from lung adenocarcinoma, and stage III patients have a risk of 40-50% to develop BM in the first years of disease onset. As therapeutic options are limited, prevention of their occurrence is an attractive concept. Here we investigated whether Nintedanib (BIBF 1120), a tyrosine kinase inhibitor (TKI) targeting the VEGF pathway approved for lung adenocarcinoma, and the dual anti-VEGF-A/Ang2 nanobody BI836880 have the potential to prevent BM formation. A mouse model of brain metastasis from lung adenocarcinoma was used in which tumor cells were injected intracardially. Metastases formation occurred inside and outside of the brain and was followed by MRI, IVIS, and immunohistochemistry. BM were reduced in volume and number by both Nintedanib and the dual anti-VEGF-A/Ang2 nanobody, which translated into improved survival. Both compounds were able to normalize cerebral blood vessels at the site of brain metastatic lesions. Extracranial metastases, however, were not reduced, and meningeal metastases only partially. Interestingly, unspecific control IgG also lead to brain vessel normalization and reduction of brain and meningeal metastases. This data indicates a brain-specific group effect of antiangiogenic compounds with respect to metastasis prevention, most likely by preventing an early angiogenic switch. Thus, Nintedanib and BI836880 are promising candidates for future BM preventive study concepts in lung adenocarcinoma patients.
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http://dx.doi.org/10.1007/s10585-020-10055-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666285PMC
December 2020

SARS-CoV-2 Testing in Patients With Cancer Treated at a Tertiary Care Hospital During the COVID-19 Pandemic.

J Clin Oncol 2020 10 14;38(30):3547-3554. Epub 2020 Aug 14.

Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.

Purpose: To analyze the prevalence of SARS-CoV-2 infection in patients with cancer in hospital care after implementation of institutional and governmental safety measurements.

Methods: Patients with cancer routinely tested for SARS-CoV-2 RNA by nasal swab and real-time polymerase chain reaction between March 21 and May 4, 2020, were included. The results of this cancer cohort were statistically compared with the SARS-CoV-2 prevalence in the Austrian population as determined by a representative nationwide random sample study (control cohort 1) and a cohort of patients without cancer presenting to our hospital (control cohort 2).

Results: A total of 1,688 SARS-CoV-2 tests in 1,016 consecutive patients with cancer were performed. A total of 270 of 1,016 (26.6%) of the patients were undergoing active anticancer treatment in a neoadjuvant/adjuvant and 560 of 1,016 (55.1%) in a palliative setting. A total of 53 of 1,016 (5.2%) patients self-reported symptoms potentially associated with COVID-19. In 4 of 1,016 (0.4%) patients, SARS-CoV-2 was detected. At the time of testing at our department, all four SARS-CoV-2-positive patients were asymptomatic, and two of them had recovered from symptomatic COVID-19. Viral clearance was achieved in three of the four patients 14-56 days after testing positive. The estimated odds ratio of SARS-CoV-2 prevalence between the cancer cohort and control cohort 1 was 1.013 (95% CI, 0.209 to 4.272; = 1), and between control cohort 2 and the cancer cohort it was 18.333 (95% CI, 6.056 to 74.157).

Conclusion: Our data indicate that continuation of active anticancer therapy and follow-up visits in a large tertiary care hospital are feasible and safe after implementation of strict population-wide and institutional safety measures during the current COVID-19 pandemic. Routine SARS-CoV-2 testing of patients with cancer seems advisable to detect asymptomatic virus carriers and avoid uncontrolled viral spread.
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http://dx.doi.org/10.1200/JCO.20.01442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571795PMC
October 2020

Postoperative Magnetic Resonance Imaging After Surgery of Brain Metastases: Analysis of Extent of Resection and Potential Risk Factors for Incomplete Resection.

World Neurosurg 2020 11 27;143:e365-e373. Epub 2020 Jul 27.

Department of Neurosurgery, Medical University Vienna, Vienna, Austria; Comprehensive Cancer Center, Medical University Vienna, Vienna, Austria. Electronic address:

Background: Extent of resection (EOR) constitutes a crucial factor for patient prognosis in surgery of brain metastases (BMs). According to early studies using postoperative magnetic resonance imaging (MRI), an unexpected residual tumor was not uncommon. Knowledge of potential risk factors for incomplete BM resection would be of major importance to optimize surgical strategies. The aim of this study was to evaluate EOR in a large cohort and analyze potential risk factors for incomplete BM resection.

Methods: Patients with BM resection and available postoperative MRI were included. Intraoperative estimation of EOR by the neurosurgeon was noted. Additionally, EOR was determined by postoperative MRI. Potential risk factors for incomplete resection were investigated.

Results: There were 145 patients with 163 BMs included. According to postoperative MRI, complete resection was achieved in 103 (63%) BMs, and resection was incomplete in 44 (27%) BMs. Postoperative MRI detected unexpected residual tumor in 32 (25%) BMs, and a misjudgment of the EOR by the neurosurgeon was found in 29% of cases. Regarding risk factors for incomplete resection, preoperative tumor volume was significantly larger in incompletely resected BMs compared with completely resected BMs (P = 0.011). All other analyzed risk factors had no significant influence on EOR.

Conclusions: Our data indicate that postoperative MRI is able to detect a high portion of unexpected residual tumors after surgery of BMs. Preoperative tumor volume in particular represents an important risk factor for incomplete resection, and hence neurosurgeons should pay special attention to avoid residual tumor tissue.
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http://dx.doi.org/10.1016/j.wneu.2020.07.150DOI Listing
November 2020
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