Glioma Espionage From Longitudinal CSF Proteomics

alexandrossfakianakis shared this article with you from Inoreader Glioma Espionage From Longitudinal CSF Proteomics via # Neuro-Oncology Current Issue Abstract AIMS Rapid, detailed feedback is needed to understand the individualized biological impacts of novel glioma therapies. We are performing glioma biomarker discovery by serial cerebrospinal fluid (CSF) sampling from Ommaya reservoirs to determine how the CSF proteome can reveal early longitudinal intelligence regarding glioma status, biology, and therapeutic response. METHOD Global proteomic analysis of CSF was performed on the Somalogic platform – an aptamer-based technology for highly sensitive and specific analysis of over 7,000 proteins. Discovery analysis comprised of the top-500 ranked proteins in CSF from seven patients with high-grade gliomas (HGG) versus non-glioma controls. The top-500 HGG proteins were then preliminarily filtered to include only proteins that met two additional criteria of decrease with resection and increase with recurrence in individual paired patient samples. RESULTS Proteomic enrichment analysis revealed a conserved HGG CSF proteomic signature defined by 79 proteins, including ones known to be over-expressed in solid tumor malignancies, such as retinoblastoma binding protein 4, heat shock protein 90, and sorcin. The HGG proteomic signature was consistently enriched in an independent validation cohort consisting of 13 gliomas diverse in primary versus recurrent status, subtype, and grade, when compared to control CSF samples. Encouragingly, proteins in the HGG signature decreased in the two patients for whom CSF was collected prior to and after resection (both at POD16 and POD18) with decreased tumor burden. CONCLUSION Our data demonstrate the ability to gain detailed, individualized insights regarding glioma biology, tumor burden, and evolution through global CSF proteomics acquired from longitudinal access to gliomas via Ommaya reservoirs. View on Web

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IDHwt Glioblastomas Show Opposing Resistance Mechanisms Across Patients in Response to Standard Treatment

alexandrossfakianakis shared this article with you from Inoreader IDHwt Glioblastomas Show Opposing Resistance Mechanisms Across Patients in Response to Standard Treatment via # Neuro-Oncology Current Issue Abstract AIMS Glioblastoma (GBM) is the most common primary malignant brain tumour in adults. Despite aggressive treatment, a resistant tumour recurs in practically all patients. We therefore aimed to better understand the mechanisms driving this treatment resistance through investigating changes in gene expression across pairs of primary and recurrent GBM tumours. METHOD We generated or acquired bulk tumour RNA sequencing data for primary and first recurrent tumours from 107 patients who received standard treatment. Differential expression analysis between primary and recurrent samples found that the most dysregulated genes were involved in neurodevelopment and neurodifferentiation. We therefore used a publicly available ChIP-seq database to identify DNA binding factors for which binding sites are enriched in the promotors of genes with the largest expression changes from primary to recurrent. RESULTS Jumonji and AT-Rich Inter acting Domain 2 (JARID2) was the most strongly enriched for binding to promotors of dysregulated genes. 65 patients showed an up-regulation and 42 showed a down-regulation of genes bound by this protein. The same set of JARID2 bound genes were found to be dysregulated in each direction, and correlated with the largest source of variation between samples in their response to treatment. Further enrichment analyses indicated that 'Up' responders may resist treatment through reduced proliferation and increased interaction with the tumour microenvironment, whereas 'Down' responders instead rely on a shift to mesenchymal cell states. CONCLUSION These results indicate that GBM tumours can be split into two subtypes that transcriptionally reprogramme in different directions through treatment and may benefit from different treatment approaches. View on Web

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Palliative Carboplatin Chemotherapy in Previously Treated High-Grade Glioma: Real-World Efficacy and Safety

alexandrossfakianakis shared this article with you from Inoreader Palliative Carboplatin Chemotherapy in Previously Treated High-Grade Glioma: Real-World Efficacy and Safety via # Neuro-Oncology Current Issue Abstract AIMS Effective third-line chemotherapy options for patients after temozolomide (TMZ) and nitrosourea-based chemotherapy for high-grade glioma (HGG) are not well defined. The use of carboplatin is limited due to uncertainly around its effectiveness and tolerability. METHOD Patients with HGG treated with single-agent carboplatin chemotherapy between 2005-2021 were identified from our institutional database. Patient and treatment-related details were acquired from electronic hospital records. SPSS Statistics for Windows, (Version 23.0, IBM Corp.) was used for data analysis. RESULTS A total of 16 HGG patients were identified. This included 9 glioblastoma (GBM) and 3 anaplastic astrocytomas (AA). These 12 patients were used for further analysis. The median age was 48 (22-73) years. All patients initially received a flat dose of 450 mg intravenous carboplatin every 3-4 weeks. All had previously received high dose RT (54-60 G y), and temozolomide and lomustine-based chemotherapy. Carboplatin was used as 3rd or 4th line treatment. The median number of cycles given was 3 (range: 1-12). Five had rapid decline in performance status after 1-3 cycles. Five patients required dose/ cycle length adjustment due to grade 1 or 2 haematological toxicity. Other than cumulative fatigue, no other >/= grade 2 toxicities were reported. None required inpatient management for treatment toxicities. Median progression-free survival on carboplatin was 3 months (range 1-11 months) and overall survival was 8 months (range 1–26 months). CONCLUSION Carboplatin is a viable treatment option for HGG with acceptable toxicity rates. However, careful patient selection remains key to attaining maximum benefit. View on Web

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Stereotactic Radiosurgery for Brainstem Metastases

alexandrossfakianakis shared this article with you from Inoreader Stereotactic Radiosurgery for Brainstem Metastases via # Neuro-Oncology Current Issue Abstract AIMS Limited data exists on outcomes following SRS for brainstem metastases (BSM). The purpose of this audit was to explore the use of SRS using Cyberknife for BSM at a single centre; reporting rates of toxicity and survival outcomes. METHOD Patients undergoing SRS for BSM from 2013 to 2021 were identified from a prospective database. Clinical characteristics were collected including; gender, age, histology and KPS. The use of previous WBRT, the volume and the dose delivered to the BSM were also recorded. All target volumes were peer reviewed by a neuro-radiologist. RESULTS 41 patients with a BSM were identified. The median age was 62 years (range 35-78). Histology was lung 15 (36.6%), breast 13 (31.7%) and other 13(31.7%). The median brainstem target volume was 0.36cc (range 0.01 – 5.63cc). 32 patients had single fraction (dose range 14.5 to 18Gy) and 9 patients had 3 fractions (dose range 17-24Gy). 7 patients had p revious WBRT. Median overall survival was 242 days (range 19-1213). A radiological response or stable disease was seen in 26 out of 30 patients with post SRS imaging available for review. 2 patients developed a 6th nerve palsy. 12 patients required a prolonged course of dexamethasone. No statistically significant relationship was observed between patient age, brainstem lesion size or fractionation and the need for prolonged use of dexamethasone but there was a trend with lung cancer patients requiring prolonged dexamethasone (p=0.06). CONCLUSION Brainstem SRS is viable option with an acceptable late toxicity profile. Updated information on survival and local control will be presented. View on Web

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Tecovirimat therapy for severe monkeypox infection: Longitudinal assessment of viral titers and clinical response pattern – A first case‐series experience

alexandrossfakianakis shared this article with you from Inoreader Tecovirimat therapy for severe monkeypox infection: Longitudinal assessment of viral titers and clinical response pattern – A first case‐series experience via Journal of Medical Virology Abstract Tecovirimat is the only antiviral with conditional and emergency approval for treatment of monkeypox by the European Medicines Agency. We present longitudinal virologic data of three patients with severe monkeypox treated with Tecovirimat. These patients presented with underlying comorbidities (ulcerative colitis; acute syphilis; HIV infection) and higher baseline monkeypox viremia compared to patients with less severe disease courses. Tecovirimat was well-tolerated, and clinical improvement was observed. In median viremia decreased by more than 2 logs within one week of therapy. This article is protected by copyright. All rights reserved. View on Web

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Development of chemiluminescent lab‐on‐fiber immunosensor for rapid point‐of‐care testing of anti‐SARS‐CoV‐2 antibodies and evaluation of longitudinal immune response kinetics following three‐dose inactivation virus vaccination

alexandrossfakianakis shared this article with you from Inoreader Development of chemiluminescent lab‐on‐fiber immunosensor for rapid point‐of‐care testing of anti‐SARS‐CoV‐2 antibodies and evaluation of longitudinal immune response kinetics following three‐dose inactivation virus vaccination via Journal of Medical Virology Abstract Developing reliable, rapid, and quantitative point-of-care testing (POCT) technology of SARS-CoV-2 specific antibodies and understanding longitudinal vaccination response kinetics are highly required to restrain the ongoing Coronavirus Disease 2019 (COVID-19) pandemic. We demonstrate a novel portable, sensitive, and rapid chemiluminescent lab-on-fiber detection platform for detection of anti-SARS-CoV-2 antibodies: the c-LOFI. Using SARS-CoV-2 Spike S1 RBD protein functionalized fiber bio-probe, the c-LOFI can detect anti-SARS-CoV-2 IgG and IgM antibodies with high sensitivity based on their respective HRP labeled secondary antibodies. The limits of detection of anti-SARS-CoV-2 IgG and IgM antibodies were 0.6 ng/mL and 0.3 ng/mL, respectively. The c-LOFI was successfully applied for direct detection of anti-SARS-CoV-2 antibodies in whole blood samples with simple dilution, which can serve as a finger prick test to rapidly detect antibodies. Furthermore, the l ongitudinal immune response (>12 months) kinetics following three-dose inactivated virus vaccines was evaluated based on anti-SARS-CoV-2 IgG detection results, which can provide importance significance for understanding the immune mechanism against COVID-19 and identify individuals who may benefit from the vaccination and booster vaccination. The c-LOFI has great potential to become a sensitive, low-cost, rapid, high-frequency POCT tool for the detection of both SARS-CoV-2 specific antibodies and other biomarkers. This article is protected by copyright. All rights reserved. View on Web

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Partial laryngectomy for naïve pT3N0 laryngeal cancer: Systematic review on oncological outcomes

alexandrossfakianakis shared this article with you from Inoreader Partial laryngectomy for naïve pT3N0 laryngeal cancer: Systematic review on oncological outcomes via Head & Neck Abstract The first aim was to define the oncologic outcomes of open partial laryngectomy (OPL) in naïve pT3 laryngeal cancer. The second aim was to analyze the outcomes after OPL versus total laryngectomy (TL). A literature search was conducted in three databases (MEDLINE, EMBASE, and Cochrane Library) until January 2022. In 805 patients treated with OPL, 5-year OS, DSS, DFS and LFS were 80.5% (95% CI 70.6–87.6), 83.4% (95% CI 75.7–89), 77.4% (95% CI 66.3–85.7) and 77.9% (95% CI 68.7–85), respectively. Three articles compared TL versus OLP: 5-year OS, DSS and DFS risk difference were 0.100 (95% CI −0.092 to 0.291), 0.067 (95% CI −0.085 to 0.220) and 0.018 (95% CI −0.164 to 0.201) respectively. OPL for selected pT3 laryngeal cancer is able to guarantee a high percentage of oncological success. Accurate patient selection is of utmost importance to differentiate advanced disease amenable to conservative surgery. View on Web

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