tbuckley/cabot-search huggingface dataset:
P14.101 Glioblastoma survival outcomes related to cortical/neural stem cells regions
Authors: T Kazda, R Jancalek, R Belanova, P Pospisil, P Burkon, L Hynkova, P Slampa, R Lakomy
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Subventricular brain zone (SVZ) and hippocampal regions are supposed to harbor astrocyte-like neural stem cells. While some tumors may arise from transformed SVZ stem cells, other may be initiated by neo-plastic transformation of non-SVZ progenitor cells or mature glial cells. Lim′s et al classification (Neuro-Oncology 2007) of initial glioblastoma location, related to these neural stem cells regions, was predictive for invasive and multifocal tumor phenotype. The aim of this retrospective single-institutional study is to evaluate the relations of this Lim classification on survival parameters in unselected cohort of glioblastoma patients. MATERIAL AND METHODS Patients treated between 2014–2017 were grouped according to initial location of their contrast enhancing lesion as follows: Lim1 (SVZ+⋯SVZ/hippocampal involvement and Cortex+⋯cortex involvement), Lim2 (SVZ+ and Cortex-), Lim3 (SVZ- and Cortex+) and Lim4 (SVZ- and Cortex-). All patients underwent radiotherapy, some patients were indicated to full treatment according to Stupp regimen (at least 3 cycles of adjuvant chemotherapy after postsurgery chemoradiotherapy). RESULTS In total, 144 patients were analyzed (94 men, mean age 59 years). 47 patients (30.5%) were treated according to Stupp regimen. Lim1 classification was presented in 74 (48%) patients, Lim2 in 22 (14.3%), Lim3 in 50 (32.5%) and Lim4 in 8 (5.2%) patients. Cortical structures (Lim1 and Lim3) were involved in 124 (80.5%) patients. Median overall survival was significantly better in patients treated according to Stupp regimen (23.3 vs. 8.6 months, p&lt;0.001). Median overall survival differs in respective Lim groups: 12.3, 5.6, 11.8 and 6.6 months (p=0.07). Better survival was in patients with cortical involvement (Lim1+Lim3): 12.3 vs. 6.4 months (p=0.02), especially in subgroup of patients who were not treated according to Stupp regimen (8.9 vs. 4.4 months, p=0.02) vs. those after Stupp regimen (23 vs. 23.4 months, p=0.7). CONCLUSION Initial location of enhancing glioblastoma was prognostic for overall survival, with better outcomes in patients presented by involvement of cortical structures comparing to subventricular/hippocampal zones. Molecular patterns may further clarify potential effects of neural stem cells in glioma genesis mirrored in different clinical behavior and location of initial tumor. Supported by Ministry of Health of the Czech Republic, grant No. 18-03-00469
Replication in selective systems: Multiplicity of carriers, variation of information, iteration of encounters
Authors: George N. Reeke
Journal: Behavioral and Brain Sciences (2001)

An analysis of biological selection aimed at deriving a mechanism-independent definition removes Hull et al.'s obligatory requirement for replication of the carriers of information, under conditions, such as those obtaining in the nervous system, where the information content of a carrier can be modified without duplication by an amount controlled by the outcome of interactions with the environment.
OS1.3 Tumor cell-free DNA detection in CSF for primary CNS lymphoma diagnosis
Authors: V Rimelen, G Ahle, E Pencreach, N Zinniger, A Debliquis, L Zalmaï, I Harzallah, R Hurstel, I Alamome, F Lamy, A Brinet, J Voirin, B Drénou
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Primary CNS lymphoma (PCNSL) is a rare disease accounting for around 3% of the primary brain tumors. In the vast majority of cases, PCNSL are classified as diffuse large B-cell lymphoma according to the WHO classification. The diagnosis is based on cranial MRI, in combination with a brain biopsy. In case of classical MRI findings, the identification of lymphoma cells in the cerebrospinal (CSF) or vitreous fluid by cytology and flow cytometry might obviate brain biopsy. The presence of the somatic mutation p.Leu265Pro (L265P) in MYD88 is detectable in 50 to 80% of PCNSL, and might also be helpful to confirm the diagnosis. The aim of our study was to evaluate the contribution of a highly sensitive digital droplet PCR, targeting the mutation L265P MYD88, for the detection of tumoral circulating DNA from CSF supernatant. MATERIAL AND METHODS We identified 9 PCNSL expressing the L265P mutation at diagnosis or relapse. The mutation was found by an allele specific PCR technique either on biopsy or in CSF cells. Circulating DNA was isolated from CSF supernatant with the « QiaAmp® circulating nucleic acid» kit. The quantity of DNA collected was estimated by quantitative PCR for a reference gene (albumine) with 7900HT (Life technologies™) device. Subsequently, the L265P MYD88 mutation was quantified by digital droplet PCR Biorad™: The droplets generated were amplified by PCR, detected with the QX200 Reader, and analyzed with the QuantaSoft™ software. RESULTS The circulating DNA concentration was low, varying between 0 and 2.2 ng/mL of CSF. However, the mutation was detected in the circulating DNA from CSF supernatant in 6 out of 9 cases (66%). The fractional abundance varied from 2.6 to 85%. In 3 cases, the mutation was detected even though cytology and flow cytometry did not reveal leptomeningeal disease. For 3 other cases, the mutation was not detected: The genome copy number was below 1 copy/µL, indicating a low analytical sensitivity for theses samples. CONCLUSION This study shows that circulating DNA is present in low concentration in CSF and can be amplified by a sensitive digital PCR for the L265P MYD88 mutation. The detection of circulating PCNSL DNA in CSF is possible and might be used to improve the non-invasive diagnosis of PCNSL. It might also help to select patients for targeted therapies.
P14.10 Endoscopic skull base surgery for tumors invading internal carotid artery
Authors: S Geng
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Internal carotid artery (ICA) injury is a disaster in endoscopic skull base surgery, so protection of internal carotid artery is an essential task. We use 3-dimensional multimodal imaging (3D-MMI) and intraoperative navigation (ION) in endoscopic skull base surgery to locate ICA and decrease ICA injury. MATERIAL AND METHODS 26 patients underwent endoscopic skull base surgery (pituitary adenomas, chordomas, neurinomas and other tumors invading internal carotid artery) guided by 3D-MMI and ION techniques to locate ICA. RESULTS In all patients, the 3D-MMI and ION techniques enabled adequate visualization of vascular structures stereoscopically, especially the relationship between lesion and ICA, and suplly real-time navigation to locate ICA during endoscopic skull base surgery. No ICA injury happened and neurosurgeons removed tumors with relaxed mind. CONCLUSION 3D-MMI and ION techniques were found to be helpful to locate internal carotid artery and decrease ICA injury during endoscopic skull base surgery.
A phase I/II study of pembrolizumab (Pem) and doxorubicin (Dox) in treating patients with metastatic/unresectable sarcoma.
Authors: Seth Pollack, Mary Weber Redman, Michael Wagner, Elizabeth Trice Loggers, Kelsey K. Baker, Sabrina McDonnell, Jeffrey Gregory, Vanessa C. Copeland, Kathryn J. Hammer, Rylee Johnson, Roxanne Moore, Michael Shahnazari, Steven Matthew Townson, Robin Lewis Jones, Lee D. Cranmer
Journal: Journal of Clinical Oncology (2019)

11009 Background: Patients with advanced soft tissue sarcomas (STS) treated with single agent Dox have a median progression-free survival (PFS) of 4.6 months (mo) and response rate (RR) of 14%. Dox sensitizes tumors to Pem through calreticulin release and killing of immunosuppressive cells. Thus we hypothesize that combining Dox + Pem will improve patient outcomes. Methods: A phase I/II trial (NCT02888665) evaluating Dox+Pem was designed for Dox naïve STS and select bone sarcomas with a 1° endpoints of safety (CTCAE v4.03) and response rate (RR) by RECIST 1.1. Patients received one “priming” dose of Pem (200mg IV) prior to starting Dox+Pem Q3wks. Dox+Pem was continued for up to 6 cycles, followed by Pem monotherapy for up to 2 years or progression. The phase I portion used a 3+3 design with 2 Dox doses (45 &amp; 75 mg/m 2 ), followed by a Simon 2-stage expansion. A retrospective study of patients treated at our center on non-ifosfamide containing Dox trials (DoxT) was performed in order to compare our observed PFS with a comparable historic population. Results: Treatment was well tolerated; detailed safety data will be presented. No additional cardiac risk was observed. No DLTs were observed during phase I and 75mg/m 2 was selected as the phase 2 Dox dose. The study met criteria for expansion to the 2nd stage. Though the planned enrollment was 41, the study closed after 37 as it was clear that the RR (22% , including phase I patients) would not meet the phase 2 RR target of 29%. However, 59% of patients had stable disease (disease control rate = 81%) with tumor regression in a majority of patients. The median PFS on Dox + Pem was 8.1 mo (95% CI: 6.3, 10.8). Patients treated with Dox + Pem had a significantly longer median PFS compared to the DoxT cohort (4.1 mo, 95%CI 3.0 – 6.6, p &lt; 0.001). Conclusions: Dox+Pem is well-tolerated. While this study failed to meet its 1° RR endpoint, a highly significant improvement in PFS was observed compared with historical controls. This is consistent with findings in other cancers, such as head &amp; neck, where improved clinical outcomes were observed without significant increase in RR by RECIST. A randomized trial of Dox +/- Pem should be carefully considered in light of recent negative trials in STS. Clinical trial information: NCT02888665.
Adverse Childhood Experiences: Implications for Offspring Telomere Length and Psychopathology
Authors: Kyle C. Esteves, Christopher W. Jones, Mark Wade, Keegan Callerame, Alicia K. Smith, Katherine P. Theall, Stacy S. Drury
Journal: American Journal of Psychiatry (2019)

Adverse childhood experiences (ACEs) are associated with mental and physical health risks that, through biological and psychosocial pathways, likely span generations. Within an individual, telomere length (TL), an established marker of cellular stress and aging, is associated with both ACE exposure and psychopathology, providing the basis for an emerging literature suggesting that TL is a biomarker of the health risks linked to early-life adversity both within and across generations. The authors tested the effect of maternal ACEs on both the trajectory of infant TL and infant social-emotional problems at 18 months of age.
Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-MOmentum): a double-blind, randomised placebo-controlled phase 2/3 trial
Authors: Bruce A C Cree, Jeffrey L Bennett, Ho Jin Kim, Brian G Weinshenker, Sean J Pittock, Dean M Wingerchuk, Kazuo Fujihara, Friedemann Paul, Gary R Cutter, Romain Marignier, Ari J Green, Orhan Aktas, Hans-Peter Hartung, Fred D Lublin, Jorn Drappa, Gerard Barron, Soraya Madani, John N Ratchford, Dewei She, Daniel Cimbora, Eliezer Katz
Journal: The Lancet (2019)
Surgeon who performed wrong knee surgery is suspended for 12 months
Authors: Clare Dyer
Journal: BMJ (2019)

A consultant orthopaedic and trauma surgeon has been suspended from the UK medical register for 12 months for dishonesty after he performed the wrong knee surgery on a patient, then tried to cover it up with revision surgery which was not clinically indicated.

Alan Norrish’s misconduct would never have come to light had he not reported himself to the General Medical Council, said Neil Dalton, chairing the medical practitioners’ tribunal in Manchester.

This, along with his genuine remorse, glowing testimonials from colleagues, and a strong record of charity work convinced the tribunal not to strike him off, said Dalton.

Norrish was a senior consultant at Addenbrooke’s Hospital in Cambridge when in January 2018 he carried out a medial uni-compartmental knee replacement on a patient at the private Nuffield …
Identification of genomic alterations by circulating tumor DNA in leiomyosarcoma: A molecular analysis of 73 patients.
Authors: Junaid Arshad, Ali Roberts, Jared Addison Cotta, Jonathan C. Trent
Journal: Journal of Clinical Oncology (2019)

11044 Background: Leiomyosarcoma is a malignant mesenchymal tumor of cells of smooth muscle lineage arising commonly in retroperitoneum, uterus, large veins, and the limbs. In contrast to many sarcomas, the genetics of leiomyosarcomas are complex and there is very limited understanding of common driver mutations. Circulating Tumor DNA (ctDNA) offers a rapid and non-invasive method of next-generation sequencing (NGS) that could be utilized for diagnosis, therapy and detection of recurrence. Methods: ctDNA testing was performed using Guardant360, which detects single nucleotide variants, amplifications, fusions, and specific insertion/deletion mutations in 73 genes utilizing NGS. Blood samples from patients with leiomyosarcoma were analyzed, and results from December 2014-December 2018 were reviewed. Results: Of the 90 samples collected and analyzed, alterations were detected in 73 ctDNA samples. After exclusion of variants of uncertain significance (VUS), 63 ctDNA samples harbored cancer-associated genomic alterations. Of 73 patients, 59 were found to have one or more cancer-associated genomic alteration. 76% (45) were female with a median age of 63 (range, 38-87) years. All samples were designated metastatic. The following table shows common alterations and types of mutations. The other alterations included RAF1, ERBB2, MET, PTEN, TERT, APC and NOTCH1. In 24 of the 73 patients (33%) the genomic alterations detected by ctDNA are potentially targetable by an FDA-approved or clinical trial therapy. There were 4 (5%) patients who were found to have incidental germline TP53 mutations. Conclusions: NGS of ctDNA allows identification of genomic alterations in plasma from patients with leiomyosarcoma. Unfortunately, there is limited activity of targeted agents in leiomyosarcomas. These results suggest opportunities to develop therapy against TP53, cell cycle, and kinase signaling pathways. Further validation and prospective evaluation is warranted to investigate the clinical utility of ctDNA for patients with leiomyosarcoma.[Table: see text]
Colour: An exosomatic organ?
Authors: B. A. C. Saunders, J. van Brakel
Journal: Behavioral and Brain Sciences (1997)

Sections R1 to R3 attempt to take the sting out of hostile commentaries. Sections R4 to R5 engage Berlin and Kay and the World Color Survey to correct the record. Section R6 begins the formulation of a new theory of colour as an engineering project with a technological developmental trajectory. It is recommended that the colour space be abandoned.
P04.14 Loss of oligodendroglial features at recurrence in five diffuse low-grade glioma patients treated with repeated surgery
Authors: A Darlix, H Duffau, V Rigau, C Gozé
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Diffuse low-grade gliomas (DLGG) are characterized by a continuous growth and an unavoidable anaplastic transformation. IDH mutation and 1p19q codeletion have been integrated to the 2016 WHO classification to define the oligodendroglioma entity. Whenever feasible, neurosurgical resection is the first treatment option. At recurrence, a second surgical resection is proposed in selected cases. The consistency of molecular patterns (IDH mutation, 1p19q codeletion) at recurrence has been poorly studied in DLGG. MATERIAL AND METHODS We conducted a retrospective study on consecutive DLGG patients treated at our institution with repeated surgery (2006–2017). Clinical and biological data were collected for both the initial and subsequent surgery. Additional immunohistochemistry (including tumor morphology, ATRX and p53) and genetic analyses (TERT promoter mutation, CIC mutation, CGHa) were also performed on tumors with joint loss of IDH mutation and of 1p19q codeletion at recurrence. RESULTS A total of 71 patients were identified. Analyses were carried out on 56 patients (molecular data missing: n=15). Nine patients (16.1%) presented with a loss of their IDH mutation at second surgery. Five of them (8.9%) had an additional loss of their 1p19q codeletion. These five cases (3 men, median age 36.6 years) were all treated with surgery as the first oncological treatment. The first surgery revealed in all cases tumors with morphological oligodendroglial features, IDH mutation and 1p19q codeletion. Further molecular analysis strengthened the diagnosis of oligodendroglioma (TERT promoter and CIC mutations, no ATRX loss, no expression of p53). Four patients were followed-up after the first surgery; one patient received Temozolomide 14 months later due to FLAIR tumor volume growth. Because of the regrowth of the residual FLAIR tumor volume, a second surgery was performed in all patients, after a median time of 38.9 months. The morphological oligodendroglial features were lost, and the genetic analyses revealed in all cases no IDH mutation, no 1p19q codeletion, no ATRX loss and no expression of p53. No evidence of anaplasia was found histologically or by CGHa analysis in these recurrent tumors. CONCLUSION We describe five DLGG patients with a shared histo-molecular evolution characterized by the loss of the initial IDH mutation and of oligodendroglial features at second surgery. While rare, this possible evolution must be acknowledged as it can impact the subsequent therapeutic strategy. This observation is the first of a loss of founder alterations in DLGG genesis (i.e. IDH mutation and 1p19q codeletion); the involved mechanism likely differs from the previously described oligoclonal selection caused by spontaneous tumor genetic drift and/or pressure of chemotherapy, and could be linked with the Darwinian selection of a subpopulation of tumor cells after the first surgery.
Low-dose post-transplant cyclophosphamide and anti-thymocyte globulin as an effective strategy for GVHD prevention in haploidentical patients
Authors: Yu Wang, De-Pei Wu, Qi-Fa Liu, Lan-Ping Xu, Kai-Yan Liu, Xiao-Hui Zhang, Wen-Jing Yu, Yang Xu, Fen Huang, Xiao-Jun Huang
Journal: Journal of Hematology & Oncology (2019)

Low-dose post-transplant cyclophosphamide (PTCy) in conjunction with anti-thymocyte globulin (ATG) appears as a potentially effective graft-versus-host disease (GVHD) prevention strategy in haploidentical hematopoietic cell transplant (haplo-HCT). Our study aims to assess the efficacy of this regimen.We extended our prospective study in patients treated with low-dose PTCy (14.5 mg/kg on days 3 and 4) in ATG/granulocyte colony-stimulating factor (G-CSF)-based regimen and compared the results to the contemporary cohort of patients without low-dose PTCy (ATG cohort). Both study cohort and control are transplanted from maternal donor or collateral relatives.We identified 239 consecutive patients (ATG-PTCy cohort = 114; ATG cohort = 125). All patients but one in ATG cohort achieved myeloid engraftment by day 30 post-HCT. We found that both the cumulative incidence of 100-day grade III-IV aGvHD and non-relapse-mortality (NRM) in the ATG-PTCy cohort was significantly reduced than that in the ATG group (5% vs 18%; P = 0.003; and 6% vs 15%; P= 0.045); the 2-year cumulative incidences of relapse and overall survival were comparable between the two cohorts (13% vs 14%; P = 0.62; and 83% vs 77%; P = 0.18, respectively). Furthermore, GVHD-free, relapse-free survival (GRFS) was significantly improved in the ATG-PTCy arm (63% vs 48%; P = 0.039). In multivariate analysis, the joint treatment resulted in lower grade II-IV acute GVHD (HR 0.58; P = 0.036), grade III-IV aGvHD (HR 0.28; P = 0.006), chronic GVHD (HR 0.60; P = 0.047), NRM (HR 0.26; P = 0.014), and higher GRFS (HR 0.59; P = 0.021) but slower myeloid and platelet recovery (HR 0.29 and 0.30; both P < 0.001).These results suggested that ATG/PTCy (low-dose) can reduce both acute and chronic GVHD as compared with standard ATG-based prophylaxis using maternal donor or collateral relatives at particular high GVHD risk.
Robot assisted surgery is blamed for heart patient’s death
Authors: Clare Dyer
Journal: BMJ (2018)

A coroner overseeing an inquest into the death of a 69 year old man after a pioneering robotic heart operation went wrong has concluded that a risk of further deaths will remain unless additional safeguards are introduced.

The coroner, Karen Dilks, said that the death of retired music teacher Stephen Pettitt came as a “direct consequence of the operation and its complications.” She added, “Mr Pettitt died due to complications of an operation to treat mitral valve disease and, in part, because the operation was undertaken with robotic assistance.”

The inquest heard that the operation in February 2015 at the Freeman Hospital in Newcastle was the first of its kind in the UK. The surgeon, Sukumaran Nair, had observed other surgeons using …
Combined focal radiotherapy (FRT) and temozolomide (TEM) in the management of high grade malignant gliomas (HGMG): Romanian single centre experience
Authors: L. Bujor, C. Oprea, M. Pop, R. Perin, C. Vasile
Journal: Journal of Clinical Oncology (2006)

11526 Background: Standard treatment of HGMG is surgical resection followed by adjuvant FRT; chemotherapy is under investgation in postoperative setting combined with external FRT. The phase III study of Stupp et al favours the combined TEM and FRT for newly diagnosed HGMG with encouraging results in terms of both survival and disease free survival. We present the experience achieved in our centre with 18 consecutive patients with HGMG treated with FRT and TEM either concomitant or sequential. Methods: In the period January 2004–January 2006 eighteen consecutive adult patients age range 25–72 years, median 55 years, sex ratio M/F 10/8 with histologically proven HGMG have been refferd in our centre for adjuvant treatment. Most of the patients had deep situated tumors that precluded complete resection which has been performed in 6 out of 18 patients. For the remaining patients stereotaxic biopsy was the procedure of diagnosis. A maximum dose of 60 Gy FRT was delivered with dual energy photon (6–15 MV) linear accelerator over six weeks in 30 sessions. TEM was administered concomitant in continuous low daily doses 75 mg/sqm in five patients (all males) followed by maintenance 150–200 mg/sqm for up to six cycles. For three patients TEM was co-administered for two cycles of 200 mg/sqm during the days 1–5 and 29–33 of radiotherapy course and whereas for the remaining patients the TEM was given sequentially after the completion of FRT up to six cycles in 5/28 days schedule. Results: With a median follow-up of 11.5 months the overall survival was 9.7 months and the survival rate of 78.5%. Clinical examination was performed every week during FRT with neurological improvement and a decrease in the need of anticonvulsivants in all patients. According to CTC criteria no grade 3 and 4 grade toxicities were recorded. After the completion of FRT imaging evaluation (CT/MRI) was performed at 6 weeks time period with tumor regression in 75% of the patients and early recurrence in only 2 cases. Conclusions: Concomitant FRT and TEM is a safe and promising treatment in newly diagnosed cases of HGMG. Our preliminary experience confirms the data from literature and we will present updated results by the ASCO meeting time. No significant financial relationships to disclose.
Abstract 16246: Versican Secretion from Endocardium is Required for Chamber Formation via The Recruitment of Cardiac Progenitors
Authors: Sung-Han Yoon, Yuta Higashikuse, Toshimi Kageyama, Mayumi Oda, Ruri Kaneda, Motoaki Sano, Shinsuke Yuasa, Misato Fujita, Atsushi Kawakami, Atsushi Shimizu, Sonoko Hatano, Hideto Watanabe, Akira Kudo, Shinji Makino, Keiichi Fukuda
Journal: Circulation (2012)

Background: Linear heart tube from the primary heart field develops into a multi-chambered heart through the addition of new cardiomyocytes. Transcription factors involved in the secondary heart fi...