tbuckley/cabot-search huggingface dataset:
HGG-43. SUSTAINED RESPONSE OF THREE PEDIATRIC BRAFV600E MUTATED HIGH-GRADE GLIOMAS WITH BRAF AND MEK INHIBITOR THERAPY
Authors: Stephanie Toll, Jennifer Cotter, Alexander Judkins, Benita Tamrazi, Jaclyn Biegel, Palak Patel, Hung N Tran, Robert Cooper, Ashley S Margol
Journal: Neuro-Oncology (2018)

Treating high-grade gliomas in pediatric patients involves multimodal therapy with significant long-term sequelae. Despite this approach, these tumors have a high rate of recurrence. Genetic testing has allowed for targeted therapies to be investigated in tumors with BRAFV600E mutations. While BRAF inhibitors have improved survival among patients with BRAFV600E mutated melanoma, resistance develops quickly leading to trials combining BRAF and MEK inhibitors. The efficacy and side effect profile of this combination has yet to be determined in pediatric high-grade glioma patients. We describe three cases: a 12 year-old female with a high-grade glioma, a 13 year-old male with an astroblastoma and a 6 year-old female with an anaplastic ganglioglioma. All tumors demonstrated a BRAFV600E mutation, and each patient received combined dabrafenib and trametinib therapy. The 12 year-old patient experienced a significant partial response and remains progression-free after a year of combination therapy. The 13 year-old remains disease free post radiation on combination therapy for 8 months. The final patient received combination targeted therapy upfront and after significant tumor response at 3 months, remains progression-free at 1 year. All patients were strictly monitored for side effects and remain free of complications. To our knowledge, this is the first report of sustained responses in pediatric patients with high-grade gliomas following combined BRAF and MEK inhibitor therapy. These responses highlight the potential use of these targeted agents in this population and suggest that targeted combination therapy is a well-tolerated option in pediatric patients with documented BRAFV600E mutated high-grade gliomas.
PDCD5 regulates iNKT cell terminal maturation and iNKT1 fate decision
Authors: Ke Wang, Xinwei Zhang, Yifan Wang, Gaowen Jin, Mingyang Li, Shusong Zhang, Jie Hao, Rong Jin, Xiaojun Huang, Hounan Wu, Jun Zhang, Yingyu Chen, Qing Ge
Journal: Cellular and Molecular Immunology (2018)
TBIO-13. CONSTITUTIONAL MOSAICISM OF CLINICALLY IMPORTANT GENETIC MARKERS IN PEDIATRIC BRAIN TUMORS DETECTED BY NEXT-GENERATION SEQUENCING
Authors: Joanna Trubicka, Malgorzata Rydzanicz, Iwona Filipek, Piotr Iwanowski, Wieslawa Grajkowska, Maciej Pronicki, Rafal Ploski, Bozenna Dembowska-Baginska, Maria Lastowska
Journal: Neuro-Oncology (2018)

The detection of the clinically important genetic markers, including mosaic mutations, is challenging but essential for precise clinical decision making. Next-generation sequencing (NGS) analysis with deep sequence coverage is a reliable approach for detection of genetic variants, including low-level mutations. Here we present usefulness of such approach in the detection of constitutional mosaicism in bilateral choroid plexus carcinoma and glioblastoma. Whole exome sequencing of DNA extracted from probands leukocytes was performed on an Illumina HiSeq 1500 using the Nextera Rapid Capture Enrichment Kit (Illumina). The detected variants were validated by NGS deep amplicon sequencing on the Illumina MiSeq in the patient’s DNA extracted from buccal cells, urine sediment samples and tumor samples. NGS analysis revealed constitutional mutations c.742C>T in TP53 in patient with bilateral choroid plexus carcinoma and c.2392T>C in PSM2 in patient with glioblastoma. They were observed in only 12 of 91 (13.2%) and 37 of 116 (32%) sequencing reads, respectively. Identified TP53 substitution was not found in patient’s parents, indicating an apparent de novo mutation. The presence of allelic imbalance in samples from buccal cells and urine sediment supports the occurrence of constitutional mosaicism. Importantly, TP53 variant was undetectable when Sanger sequencing was applied. Our results highlight the utility of the NGS technology in the detection of mosaic mutations which may not be detectable by Sanger sequencing. This may be important for management of patients and genetic counseling, including a predisposition to other cancers. Funded by National Science Centre, Poland (2016/23/B/NZ2/03064 and 2016/21/B/NZ2/01785)
LGG-22. TREATMENT OUTCOME AND LONG-TERM HEALTH DEFICITS OF PATIENTS WITH LOW-GRADE GLIOMA DIAGNOSED DURING THE FIRST YEAR OF LIFE
Authors: Anthony Liu, Camden Hastings, Shengjie Wu, Johnnie K Bass, Andrew Heitzer, Jason Ashford, Robert Vestal, Mary Hoehn, Jason Chiang, Yahya Ghazwani, Sahaja Acharya, Heather Conklin, Frederick Boop, Amar Gajjar, Ibrahim Qaddoumi
Journal: Neuro-Oncology (2018)
Sodium Thiosulfate for Protection from Cisplatin-Induced Hearing Loss
Authors: Penelope R. Brock, Rudolf Maibach, Margaret Childs, Kaukab Rajput, Derek Roebuck, Michael J. Sullivan, Véronique Laithier, Milind Ronghe, Patrizia Dall’Igna, Eiso Hiyama, Bénédicte Brichard, Jane Skeen, M. Elena Mateos, Michael Capra, Arun A. Rangaswami, Marc Ansari, Catherine Rechnitzer, Gareth J. Veal, Anna Covezzoli, Laurence Brugières, Giorgio Perilongo, Piotr Czauderna, Bruce Morland, Edward A. Neuwelt
Journal: New England Journal of Medicine (2018)

Cisplatin chemotherapy and surgery are effective treatments for children with standard-risk hepatoblastoma but may cause considerable and irreversible hearing loss. This trial compared cisplatin with cisplatin plus delayed administration of sodium thiosulfate, aiming to reduce the incidence and severity of cisplatin-related ototoxic effects without jeopardizing overall and event-free survival.
Staphylococcus aureus impairs sinonasal epithelial repair: Effects in patients with chronic rhinosinusitis with nasal polyps and control subjects
Authors: Fabiana C.P. Valera, Manon Ruffin, Damien Adam, Émilie Maillé, Badr Ibrahim, Julie Berube, Simon Rousseau, Emmanuelle Brochiero, Martin Y. Desrosiers
Journal: Journal of Allergy and Clinical Immunology (2018)
The relationship between primary tumor regression grade and lymph nodes status in local advanced rectal cancer after neoadjuvant chemoradiation therapy
Authors: H. Ju, L. Liu, W. Wu, Y. Cai, X. Lu
Journal: Annals of Oncology (2018)

Introduction: Neoadjuvant chemoradiation therapy may affect the lymph node status in local advanced rectal cancer. In this study, we evaluate the relationship between tumor regression grade and lymph nodes status and prognosis value in local advanced rectal cancer after neoadjuvant chemoradiation therapy. Methods: AJCC-TRG classifications were evaluated on surgical specimens from 201 locally advanced rectal cancer patients receiving CRT. The relationship between tumor regression grade and lymph nodes status were evaluated. The impacts of TRG and lymph node status on survival were estimated using Kaplan–Meier method. Results: Classifications of TRG 0, 1, 2, and 3 were found in 18.9%, 40.8%, 32.3%, and 8.0% of the resected specimens respectively. TRG have significant relationship with harvest lymph node number, positive lymph node number and lymph node metastasis ratio. TRG were significant predictors of OS, DFS, LRFS and DMFS. Positive lymph node number and lymph node metastasis ratio but not total lymph node number have relationship with survival. Conclusion: TRG have significant relationship with lymph node status in local advanced rectal cancer after neoadjuvant chemoradiation therapy. TRG, positive lymph node number and lymph node metastasis ratio have significant predictors of survival, but total lymph node number have little impact on prognosis.
Clinical characteristic of pancreatic cancer
Authors: B. Abdelkader El Hakim, N. Caid, L. Saoudi, R. Benemla, R. Ramoul, S. Rekkache, F. Smaili
Journal: Annals of Oncology (2018)

Introduction: Unfortunately, the majority of cases are diagnosed at an advanced stage, where palliative chemotherapy can be administered to alleviate the symptoms and prolong life. Although pancreatic carcinogenesis has not yet been explained, familial aggregation, tobacco smoking, and hypercaloric intake are associated with pancreatic carcinogenesis. Till date, either prevention or screening programs could yet be proposed. Methods: This is a retrospective study for patients following in medical oncology department of anti-cancer center Blida between January 2010- December 2015. The aims of study are to reported the epidemiologic profile for patients with pancreatic cancer. Although pancreatic carcinogenesis has not yet been explained, familial aggregation, tobacco smoking, and hypercaloric intake are associated with pancreatic carcinogenesis. Till date, either prevention or screening programs could yet be proposed. Results: 110 patients were following in the department, the median age was 60.8 years [21-80], and sex ratio was 2. Family history of cancer was 13.7%, 30.7% Had diabetes in their antecedents, tobacco smoking was present in 46.8% of cases, 32% of obesity, the most common reasons for consultation were pain in 49.2% and jaundice in 18% with an average consultation time of 03 months. The histological type was adenocarcinoma in 95.7% of patients, stage IV and III in 78.5% and 16.3% at diagnosis. Conclusion: As the cancer of the pancreas becomes symptomatic the diagnosis is made with a late stage, which testifies to the gravity of this cancer, to improve this situation prevention keeps an important place by acting on the risk factors such as smoking and the obesity. Around the world significant efforts are being made in order to better understand pancreatic cancer. Detailed epidemiological analyses of pancreatic cancer trends and further analytical epidemiological researches will help guide future cancer control strategies.
Estimating TimeTrees with MEGA and the TimeTree Resource
Authors: Beatriz Mello
Journal: Molecular Biology and Evolution (2018)

The main outcome of molecular dating, the timetree, provides crucial information for understanding the evolutionary history of lineages and is a requirement of several evolutionary analyses. Although essential, the estimation of divergence times from molecular data is frequently regarded as a complicated task. However, establishing biological timescales can be performed in a straightforward manner, even with large, genome-wide data sets. This protocol presents all the necessary steps to estimate a timetree in the program MEGA X. It also illustrates how the TimeTree resource can be a useful tool to obtain chronological information based on previous studies, therefore yielding calibration boundaries.
Nitric Oxide Decreases Acute Kidney Injury and Stage 3 Chronic Kidney Disease after Cardiac Surgery
Authors: Chong Lei, Lorenzo Berra, Emanuele Rezoagli, Binglan Yu, Hailong Dong, Shiqiang Yu, Lihong Hou, Min Chen, Wensheng Chen, Hongbing Wang, Qijun Zheng, Jie Shen, Zhenxiao Jin, Tao Chen, Rong Zhao, Emily Christie, Venkata S. Sabbisetti, Francesco Nordio, Joseph V. Bonventre, Lize Xiong, Warren M. Zapol
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

No medical intervention has been identified that decreases acute kidney injury and improves renal outcome at 1 year after cardiac surgery.
John Denis McGarry, PhD: A Remembrance of a Master Metabolic Physiologist
Authors: Christopher B. Newgard
Journal: Diabetes Care (2018)

John Denis McGarry, PhD (“Denis” to all who knew him), was the most charming and engaging man that I have ever known. He was also one of the most thoughtful and impactful scientists of his generation.

Although remarkably talented, Denis was a humble man. This quality can be traced to his birth and upbringing in Widnes, a working-class town in northwest England near Liverpool. His father Cornelius McGarry was English, and his mother Sarah O’Dell was Irish. Cornelius worked in a chemical production plant making sulfuric acid, and his mother cared for Denis and his two sisters Ann and Pat. They were “quite poor but thrifty,” according to Denis’s wife Angela. Denis went to a local public school until the age of 11 and then won a scholarship to attend St. Francis Xavier’s College Catholic boys school from age 11 until graduation at age 18. During this period, Denis visited a research laboratory at the University of Liverpool and was intrigued by what he saw. Denis was an excellent student and was able to secure scholarships to attend The University of Manchester, where he earned both his Bachelor of Science and PhD degrees, the latter in 1966. His career-long focus on regulation of intermediary metabolism began with his PhD studies with Brian Hodgson at The University of Manchester, where he studied the metabolic fates of radiolabeled propionate in the bacterium Moraxella lwoffi (1,2). He also performed a postgraduate fellowship with Hugh K. King at the University of Liverpool and then moved with Professor King to The University College of Wales, Aberystwyth, where he performed studies on bacterial lipoamide dehydrogenase (3).



Left: Young Denis circa 1944. Right: J. Denis McGarry earns his PhD, The University of Manchester, 1966.



Denis met Angela Caldwell, also from Widnes, through friends, and …
QOL-23. DEVELOPMENT OF AN INTERACTIVE APP FOR DYNAMIC SCREENING OF BASIC SENSORY, COGNITIVE, AND MOTOR ABILITIES OF PAEDIATRIC PATIENTS WITH BRAIN TUMOURS
Authors: Nicola J Pitchford, David Walker, Jair Barbosa, Eduard Moresi, Michel Lopes, Julio Santos, Marcos Morais, Mauricio Júnior, Andre Rodrigues, Luiz Albernaz, Mario Braga
Journal: Neuro-Oncology (2018)

Assessment of basic sensory, cognitive, and motor functions is fundamental for neuropsychological profiling of pediatric patients with brain tumor. Neuropsychological profiling is used to determine extent of functional capacity, pre and post treatment, and in monitoring progression against typical development over time, and in response to intervention. Assessments are usually conducted on an individual basis, with a trained clinical neuropsychologist, using standardized paper and pencil tests, which can take up over an hour to complete. If more than one assessment is required this can result in multiple or lengthy assessment schedules. Standardized assessments are usually normed on typically developing populations from one country, thus limiting their translational utility. Assessments from one publishing house are rarely co-normed with those from another, rendering exploration of associations between assessments/functions unfeasible, without the presence of a typically developing control group. This limits the efficiency and effectiveness of clinical neuropsychology services that are often under-resourced. To address these limitations, we have developed an interactive app, delivered on touch-screen tablets, that has potential to screen for basic sensory, cognitive, and motor abilities of paediatric patients with brain tumours on admission to hospital and to track functional decline or improvements over time, on a self-referenced and/or norm-referenced basis. This could improve the precision of clinical care given to patients, by identifying those most in need of formal clinical neuropsychological assessment and follow up, and directing intervention to targeted domains. In turn, this could enhance the efficiency and effectiveness of service provision within clinical neuropsychology units worldwide.
LGG-50. PROFILE OF LOW GRADE GLIOMAS (LGGs) IN GREEK PATIENTS
Authors: Kleoniki Roka, Maria Filippidou, Georgios Georgoulis, Marios Themistokleous, Natalia Karra, Evangelia Saleptsi, Chrysovalanto Sofia Karatosidi, Kalliopi Stefanaki, Roser Pons, Antonis Kattamis
Journal: Neuro-Oncology (2018)

Low-grade-gliomas(LGGs) encompass a heterogeneous set of tumors of different histologies. They are the most common type of pediatric brain tumors accounting almost 30-50% of them. This is the first attempt to describe characteristics of Greek-LGG-patients diagnosed in the largest Pediatric Brain Tumors National Center. We performed a retrospective review of newly-diagnosed LGG-patients during 2015-2017. Gender, age, symptoms, location, leptomeningeal infiltration, histological type, BRAF-status, NF-status, management and outcome were analysed. During the study period, 42 LGG-patients(22males) were diagnosed. Median age was 6.3years(range:40days-15.8years). Nearly 80% of the patients had symptoms of raised intracranial-pressure (headache/vomiting). The most common locations were: posterior-fossa(38.0%) followed by optic-pathway(26.2%). Surgical intervention was possible in 30 patients(26 subtotal/total excision, 2 partial excision, 2 biopsy). Leptomeningeal infiltration at diagnosis was detected in 2 patients. Histological type was mostly astrocytoma (23pts, 54.8%), especially pilocytic type (69.5% of astrocytomas). NF1 was diagnosed in 23.8% of the patients. In 16non-NF1 patients RT-PCR was performed for KIAA1549/BRAF-fusion and was positive in 5 patients and BRAFV600Emutation was detected in 3 patients. Treatment according to LGG2004-protocol was administered in 13 patients, of which 5 needed treatment-modification (3 due to carboplatin allergic reaction and 2 due to progressive disease) Radiotherapy was administered in 2 patients. One patient had a malignant transformation to glioblastoma multiforme, 16 months after initial diagnosis and died. At the end of treatment, visual and mobility problems were noted in two and one patients respectively. The most common histologic type was pilocytic astrocytoma. Overall survival was 97,6%. Our findings agree with those of internationally published studies.
DIPG-02. H3 K27M-MUTANT GLIOMAS IN ADULTS VS. CHILDREN SHARE SIMILAR HISTOLOGICAL FEATURES AND ADVERSE PROGNOSIS
Authors: Jean Mulcahy Levy, B K Kleinschmidt-DeMasters
Journal: Neuro-Oncology (2018)

The H3 K27M mutation was originally described in pediatric diffuse intrinsic pontine gliomas, but has been recently recognized to also occur in adult midline diffuse gliomas and midline tumors with other morphologies including gangliogliomas (GGs), anaplastic GGs, pilocytic astrocytomas (PAs), and posterior fossa ependymomas. In some patients with H3 K27M-mutant tumors with alternate morphologies, longer survival has been reported, making grading difficult. Additionally, few series include adult tumors. Here, we report our 4-year experience in pediatric and adult patients. Clinical and histological features and survival were evaluated for patients identified with H3 K27M mutations between 01/2013 and 11/10/17. Twenty-eight patients were identified, with equal numbers of adults (13) vs. children (15). For adults, mean and median age was 52 years (range=27–81 years), 2 decades older than a recently-published adult series. Tumors involved thalamic (adult=7; pediatric=7), spinal cord (adult=4; pediatric=2), pons (adult=1; pediatric=6), and hypothalamic (n=1) sites. Other morphologies at presentation included pure GG (n=3, pediatric) and PA (n=1, adult). One adult and 1 pediatric patient each presented with leptomeningeal dissemination or developed leptomeningeal dissemination within 1 year after diagnosis, with transformation from PA or GG histology to glioblastoma. Mean survival was 9.3 (adults) versus 8.9 (pediatric) months. Patients with tumors of other morphologies (GG, PA) did not enjoy extended survival in our cohort. H3 K27M-mutant tumors can affect patients at advanced ages, may show leptomeningeal dissemination at time of presentation, and “pure” GG or PA morphology is not rare. Regardless of patient age or tumor morphology, patients fare equally poorly.
PCLN-08. IN VITRO MODELING OF TUMOR DISSEMINATION FROM HYPOXIC PRIMARY DERIVED CELL LINES (PDCL) SPHEROIDS RECAPITULATED TUMOR DEVELOPMENT AND PROGRESSION IN PATIENTS
Authors: Anne Florence Blandin, Aurelie Durand, Eric Guerin, Isabelle Lelong-Rebel, Monique Dontenwill, Natacha Entz-Werle
Journal: Neuro-Oncology (2018)

Children diagnosed for brain tumors are facing variant prognoses depending mostly on the histological subtypes and their molecular characteristics. Nevertheless, more and more evidence is accumulating on the diffuse infiltrative growth pattern of the tumor, playing its own role in tumor development and progression. This infiltration is reflecting the interaction with tumor microenvironment, which seems to have a profound influence on the functional properties of tumor cells. Accordingly, substantial effort must be devoted to move to three-dimensional like systems that more faithfully recapitulate the hypoxic and in vivo tumor microenvironment. Therefore, we developed PDCL initiated from several pediatric malignant brain tumors (high grade gliomas, medulloblastomas and ependymomas). After establishing stably those PDCLs and exploring their characteristics, we developed spheroid migration assays on fibronectin in hypoxic conditions to recreate both physiological hypoxia of normal brain and tumor hypoxia. In parallel, with these PDCLs, we developed mouse orthotopic xenotransplantations. We were able in all cell lines to perform those spheroid migration assays. The quantification of cells evading from the spheroid and their distance of migration were heterogeneous, not linked to the histological subtypes, but to the in vivo progression of the patient. The cells were preserving mostly their stem-like properties. Surprisingly, we were not able to reproduce the same correlations in the mouse models. Our results present an optimized invasion assay that closely reflects in vivo invasion and might be used as a predictive model for the patient, as well as a new approach to test treatments blocking this brain infiltration.
RONC-16. RISK OF PREMATURE RADIONECROSIS IN PAEDIATRIC PATIENTS WITH HIGH RISK MEDULLOBLASTOMA TREATED WITH PROTONS ON THE CRANIUM SPINAL AXIS
Authors: Giovanna Stefania Colafati, Chiara Carducci, Barbara Rombi, Stefano Lorentini, Andrea Carai, I Paul Voicu, Antonella Cacchione, Angela Mastronuzzi, Maurizio Amichetti, Sabina Vennarini
Journal: Neuro-Oncology (2018)

Proton therapy (PT) is a radiation therapy in increasing use for paediatric cerebral tumours, as in medulloblastoma. Although publications to date are relatively limited, they however include cases of potential development of radionecrosis. The aim of this study has been to compare our experience with data found in literature relating to the insurgence of premature radionecrosis, evaluating incidence, timing, appearance of clinical symptoms, risk factors and radiological characteristics. MATERIALS AND We have retrospectively analysed 10 children with high risk medulloblastoma using protons on the cranio-spinal axis with a dose equal to 36 Gy RBE and with a successive higher dose in the posterior cranial fossa of 18 Gy RBE, at the PT Centre in Trento. All patients underwent PT, post-surgery on the primary tumour and intensive myeloablative chemotherapy: both are two potential risk factors in the appearance of premature radionecrosis. All the patients also underwent MRI on the brain and bone marrow, before and after proton therapy treatment, at an interval of 1 month at the end of PT and then every 3 months. In our clinical records in a median follow up of 4.9 months we did not encounter cases of radionecrosis according to the definition criteria as discussed or published in the consulted publications. The paediatric patients with high risk medulloblastoma undergoing treatment with proton therapy, the subjects of our study, presented a lower risk to premature radionecrosis in respect to the data present in current publications.