tbuckley/cabot-search huggingface dataset:
PATH-40. STANDARDIZED MOLECULAR ANALYSIS OF PRIMARY CENTRAL NERVOUS SYSTEM (CNS) TUMORS IN A RESEARCH BASED CLINICAL PRACTICE. AN INTRODUCTION TO THE PRIMARY CNS TUMOR NEXT GENERATION SEQUENCING (NGS) PANEL
Authors: Christine Siegel, Terri Armstrong, Hye-Jung Chung, Sonja Crandon, Snehal Patel, Astin Powers, Martha Quezado, Abhik Ray-Chaudhury, Elizabeth Vera, Jing Wu, Liqiang Xi, Mark Raffeld, Mark Gilbert
Journal: Neuro-Oncology (2017)

Combined histological-molecular classification represents a major shift in the diagnosis of CNS tumors, as highlighted in the 4th edition of WHO Classifications. A collaboration between the Laboratory of Pathology and the Neuro-Oncology Branch at the National Institutes of Health devised a Primary CNS Tumor NGS Panel (CNS Panel) for augmentation of histopathologic diagnosis and discovery, that targets small nucleotide variants in 56 genes, copy number alterations in 21 genes, and fusions between 25 gene pairs, all associated with CNS cancer and pathogenesis. Retrospective analysis of CNS panel reports in 129 samples. Clinically significant findings are reported. 144 patients have been enrolled, with 129 samples sequenced and reported to date. Study population is 65% male, with a median age of 48 (19-76 years). 14 patients (10%) have had their histologic diagnosis changed related to findings on the CNS Panel. After identifying a BRAF mutation, 6 high grade gliomas were changed to pilocytic astrocytomas. Findings consistent with oligodendroglioma mutations led to 4 cases being reclassified from oligoastrocytoma. 2 anaplastic ependymomas were diagnosed as glioblastomas with identification of an IDH mutation. An oligodendroglioma changed to glioneuronal tumor after IDH was not confirmed. 1 glioblastoma changed to anaplastic oligodendroglioma when IDH mutation was identified. In 6 additional cases, rationale for targeted treatment and unexpected findings were uncovered: BRAF inhibitors and hedgehog inhibitor drugs, an IDH mutated medulloblastoma, KRAS and FGFR3:TAC3mutations in glioblastomas. The routine use of the CNS Panel in our clinical practice has identified genetic alterations leading to changed diagnoses, targetable mutations for treatment options, and cultivating a database of genetic alterations in CNS tumors, providing opportunities for brain tumor research and the foundation for more precise clinical trials. Further research is ongoing in a larger cohort as accrual to the Natural History Study continues.
Hairy Cell Leukemia, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology
Authors: William G. Wierda, John C. Byrd, Jeremy S. Abramson, Seema Bhat, Greg Bociek, Danielle Brander, Jennifer Brown, Asher Chanan-Khan, Steve E. Coutre, Randall S. Davis, Christopher D. Fletcher, Brian Hill, Brad S. Kahl, Manali Kamdar, Lawrence D. Kaplan, Nadia Khan, Thomas J. Kipps, Jeffrey Lancet, Shuo Ma, Sami Malek, Claudio Mosse, Mazyar Shadman, Tanya Siddiqi, Deborah Stephens, Nina Wagner, Andrew D. Zelenetz, Mary A. Dwyer, Hema Sundar
Journal: Journal of the National Comprehensive Cancer Network (2017)

Hairy cell leukemia (HCL) is a rare type of indolent B-cell leukemia, characterized by symptoms of fatigue and weakness, organomegaly, pancytopenia, and recurrent opportunistic infections. Classic HCL should be considered a distinct clinical entity separate from HCLvariant (HCLv), which is associated with a more aggressive disease course and may not respond to standard HCL therapies. Somatic hypermutation in the IGHV gene is present in most patients with HCL. The BRAF V600E mutation has been reported in most patients with classic HCL but not in those with other B-cell leukemias or lymphomas. Therefore, it is necessary to distinguish HCLv from classic HCL. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of classic HCL.
EPID-10. LONG-TERM SURVIVORS OF GLIOBLASTOMA: A CLOSER LOOK
Authors: Lucy Gately, Sue-Anne McLachlan, Jennifer Philip, Jeremy Ruben, Anthony Dowling
Journal: Neuro-Oncology (2017)

Glioblastoma has a poor prognosis with median survival of 12–14 months. Long-term survivors (LTS) defined as those alive at least 2 years from diagnosis, comprise 13% of this population. This study aims to provide a clinical profile of LTS at two institutions in Melbourne, Australia. Histological diagnosis of glioblastoma from 1st January 2006 to 31st December 2012 were identified from pathology and oncology databases. Demographic, treatment and survival characteristics were recorded, with follow-up to 31st December 2015. Independent sample t-test, chi-squared and fisher exact were used to identify differences between LTS and those surviving less than 2 years. Survival estimated by Kaplan-Meier. 776 patients were identified with 154 (20%) surviving >2 years. Compared with patients surviving < 2 years, LTS were more likely to be younger (median age 56 vs 65yrs, p<.001), have ECOG 0–2 (95% vs 64%, p<.001), unilateral tumours (88% vs 78%, p.004), gross tumour resection (90% vs 61%, p<.001), and receive chemoradiotherapy (69% vs 40%, p<.001). The most common presenting symptoms amongst LTS were headache (42%), seizure (28%) and speech disturbance (16%), with 79% prescribed anticonvulsants. Of LTS, 111 patients (72%) progressed at a median of 20.1 months from diagnosis, with 46% of these undergoing a second craniotomy. Temozolomide was the most common non-surgical second line treatment (41%), followed by radiotherapy (12%). One third of LTS received three or more lines of treatment, and 10% underwent three or more craniotomies. The median overall survival for LTS was 38.3 months, compared with 11.0 months (entire cohort) (p<.001). LTS of glioblastoma (20%) are more likely to be younger, have unilateral tumours, good performance status and undergo multimodality treatment, and multiple lines of therapy. These data may assist in predicting LTS at diagnosis and understanding their clinical journey to facilitate planning of treatment and supportive care.
NIMG-15. VOLUMETRIC 3D MR FINGERPRINTING OF ADULT BRAIN TUMORS: INITIAL RESULTS
Authors: Chaitra Badve, Ozden Kilinc, Louisa Onyewadume, Sara Dastmalchian, Dan Ma, Samuel Frankel, Gregory O’Connor, Jeffrey Sunshine, Marta Couce, Mark Griswold, Vikas Gulani, Jill Barnholtz-Sloan, Andrew Sloan
Journal: Neuro-Oncology (2017)

Magnetic Resonance Fingerprinting (MRF) is a non-invasive multi-parametric quantitative MR imaging technique, which allows rapid and simultaneous quantification of T1 and T2 relaxation times. We have already demonstrated the ability of 2D single-slice MRF-based relaxometry in identifying quantitative differences between various regions in intraaxial brain tumors. 3D volumetric MRF offers the capability to analyze the quantitative features of entire tumor volume, thereby offering the opportunity to capture the heterogeneity of tumor microenvironment. In this IRB approved ongoing study, we assess the utility of the new volumetric 3D MRF technique with whole-brain coverage to differentiate between common intra-axial brain tumors. Volumetric 3D-MRF acquisition was performed in 16 patients (F:9/M:7, mean age 53 ± 15) with untreated intra-axial brain tumors including 8 glioblastomas (GBM), 3 grade lower grade gliomas (LGG), and 6 metastases (METS). Volumetric 3D regions of interest (ROI) were drawn on the solid tumor regions on quantitative MRF maps using Matlab and T1 and T2 values were recorded (The Mathworks, Natick, MA). The statistical comparisons between mean T1 and T2 values were performed using unpaired Student’s t-test across tumor types. Mean T1 values were significantly different between the three groups. Solid tumor region mean T1 value of GBMs (1588 ± 130 ms) differed from metastases and LGGs (p=0.029 and p=0.010 respectively). Solid tumor region mean T1 values were also significantly different between metastases and LGGs (mean 1416 ± 162 ms versus 1784 ± 77 ms respectively, p=0.001). There was no significant difference between mean T2 values of various tumor types. Preliminary data with 3D volumetric MR fingerprinting demonstrates promising differences in T1 values of various tumor types. Further ongoing data collection will allow evaluating the robustness of this technique in differentiating between various tissue types in larger sample size.
Comparative effects of Folfirinox and Gemcitabine/nab-paclitaxel as first and second line chemotherapy for metastatic pancreatic cancer: single choice or sequence
Authors: S. Caponnetto, A. Gelibter, C. Mosillo, V. Magri, S. Scagnoli, G. Pomati, G. Piesco, S. Verkhovskaya, S. Pisegna, G. Sirgiovanni, V. Napoli, D. Buscicchio, G.M. Iannantuono, D. Marinelli, G. Mammone, S. Pannunzio, E. Nicolo', A. Stefani, V. Astorino, M. Mancini, E. Cortesi
Journal: Annals of Oncology (2017)
Guías BICHAT para el manejo clínico de la encefalitis vírica y de la encefalitis vírica relacionada con el bioterrorismo
Authors: P Bossi, A Tegnell, A Baka, F van Loock, A Werner, J Hendriks, H Maidhof, G Gouvras
Journal: Eurosurveillance (2004)

Casi todos los virus que intervienen en la encefalitis son los transmitidos por artropodos, a excepcion del arenavirus que es transmitido por roedores. Pese a la escasa informacion disponible, al parecer casi todos los virus asociados a la encefalitis pueden ser aerosolizados en un ataque bioterrorista. Se ha sugerido la transferencia virica desde la sangre al CNS por via del tracto olfatorio. Otra via de contaminacion posible es a traves de vectores como mosquitos o garrapatas. Los alfavirus son armas biologicas en potencia. El curso clinico de las enfermedades debidas a estos virus no suele ser especifico, pero es posible diferenciarlo con un metodo diagnostico adecuado. No hay farmacoterapias eficaces para tratar estas enfermedades, y el tratamiento es principalmente de cuidados, aunque existen vacunas que protegen contra algunos de estos virus.
Hepatitis B in sub-Saharan Africa: strategies to achieve the 2030 elimination targets
Authors: C Wendy Spearman, Mary Afihene, Reidwaan Ally, Betty Apica, Yaw Awuku, Lina Cunha, Geoffrey Dusheiko, Neliswa Gogela, Chris Kassianides, Michael Kew, Philip Lam, Olufunmilayo Lesi, Marie-Jeanne Lohouès-Kouacou, Papa Saliou Mbaye, Emmanuel Musabeyezu, Betty Musau, Olusegun Ojo, John Rwegasha, Barbara Scholz, Abate B Shewaye, Christian Tzeuton, Mark W Sonderup
Journal: The Lancet. Gastroenterology & hepatology (2017)
BRCA related breast cancer and sporadic tumors: same prognosis or survivorship bias?
Authors: Z. Ballatore, R. Bracci, F. Bianchi, E. Maccaroni, L. Belvederesi, C. Brugiati, A. Murrone, S. Pagliaretta, M. Pistelli, R. Berardi
Journal: Annals of Oncology (2017)
La vigilancia europea de la legionelosis asociada a viajes
Authors: C Joseph
Journal: Eurosurveillance (2004)

Cuando una enfermedad fue adquirida en un pais pero diagnosticada y notificada en otro, es necesaria una cooperacion internacional para controlarla, investigar y evitar que ocurran otros casos. El Sistema Europeo de Vigilancia de la legionelosis asociada a viajes (EWGLINET) fue establecido en 1987 para responder a esta situacion y ha mostrado su eficacia para compartir informacion y coordinar sus acciones.
Robotic versus laparoscopic distal pancreatectomy: A comparative study of clinical outcomes and costs analysis
Authors: Benedetto Ielpo, Hipolito Duran, Eduardo Diaz, Isabel Fabra, Riccardo Caruso, Luis Malavé, Valentina Ferri, J. Nuñez, A. Ruiz-Ocaña, E. Jorge, Sara Lazzaro, Denis Kalivaci, Yolanda Quijano, Emilio Vicente
Journal: International Journal of Surgery (2017)
A pilot study of the immunogenicity of a 9-peptide breast cancer vaccine plus poly-ICLC in early stage breast cancer
Authors: Patrick M. Dillon, Gina R. Petroni, Mark E. Smolkin, David R. Brenin, Kimberly A. Chianese-Bullock, Kelly T. Smith, Walter C. Olson, Ibrahim S. Fanous, Carmel J. Nail, Christiana M. Brenin, Emily H. Hall, Craig L. Slingluff
Journal: Journal for ImmunoTherapy of Cancer (2017)

<h3>Background</h3> Breast cancer remains a leading cause of cancer death worldwide. There is evidence that immunotherapy may play a role in the eradication of residual disease. Peptide vaccines for immunotherapy are capable of durable immune memory, but vaccines alone have shown sparse clinical activity against breast cancer to date. Toll-like receptor (TLR) agonists and helper peptides are excellent adjuvants for vaccine immunotherapy and they are examined in this human clinical trial. <h3>Methods</h3> A vaccine consisting of 9 MHC class I-restricted breast cancer-associated peptides (from MAGE-A1, −A3, and -A10, CEA, NY-ESO-1, and HER2 proteins) was combined with a TLR3 agonist, poly-ICLC, along with a helper peptide derived from tetanus toxoid. The vaccine was administered on days 1, 8, 15, 36, 57, 78. CD8<sup>+</sup> T cell responses to the vaccine were assessed by both direct and stimulated interferon gamma ELIspot assays. <h3>Results</h3> Twelve patients with breast cancer were treated: five had estrogen receptor positive disease and five were HER2 amplified. There were no dose-limiting toxicities. Toxicities were limited to Grade 1 and Grade 2 and included mild injection site reactions and flu-like symptoms, which occurred in most patients. The most common toxicities were injection site reaction/induration and fatigue, which were experienced by 100% and 92% of participants, respectively. In the stimulated ELIspot assays, peptide-specific CD8<sup>+</sup> T cell responses were detected in 4 of 11 evaluable patients. Two patients had borderline immune responses to the vaccine. The two peptides derived from CEA were immunogenic. No difference in immune response was evident between patients receiving endocrine therapy and those not receiving endocrine therapy during the vaccine series. <h3>Conclusions</h3> Peptide vaccine administered in the adjuvant breast cancer setting was safe and feasible. The TLR3 adjuvant, poly-ICLC, plus helper peptide mixture provided modest immune stimulation. Further optimization is required for this multi-peptide vaccine/adjuvant combination. <h3>Trial registration</h3> ClinicalTrials.gov(posted 2/15/2012): NCT01532960. Registered 2/8/2012.https://clinicaltrials.gov/show/NCT01532960
DNA-hypomethylating agents as epigenetic therapy before and after allogeneic hematopoietic stem cell transplantation in myelodysplastic syndromes and juvenile myelomonocytic leukemia
Authors: Christian Flotho, Sebastian Sommer, Michael Lübbert
Journal: Seminars in Cancer Biology (2017)

Myelodysplastic syndrome (MDS) is a clonal bone marrow disorder, typically of older adults, which is characterized by ineffective hematopoiesis, peripheral blood cytopenias and risk of progression to acute myeloid leukemia. Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative neoplasm occurring in young children. The common denominator of these malignant myeloid disorders is the limited benefit of conventional chemotherapy and a particular responsiveness to epigenetic therapy with the DNA-hypomethylating agents 5-azacytidine (azacitidine) or decitabine. However, hypomethylating therapy does not eradicate the malignant clone in MDS or JMML and allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative treatment option. An emerging concept with intriguing potential is the combination of hypomethylating therapy and HSCT. Possible advantages include disease control with good tolerability during donor search and HSCT preparation, improved antitumoral alloimmunity, and reduced risk of relapse even with non-myeloablative regimens. Herein we review the current role of pre- and post-transplant therapy with hypomethylating agents in MDS and JMML.
The Worst of Days
Authors: Charlotte Grinberg
Journal: Annals of Internal Medicine (2017)

On Being a Patient7 November 2017The Worst of DaysCharlotte Grinberg, MDCharlotte Grinberg, MDFrom Mount Auburn Hospital, Cambridge, Massachusetts.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M17-0429 Audio Reading - “The Worst of Days” Audio. Virginia L. Hood, MD, Annals Associate Editor, reads "The Worst of Days," by C. Grinberg. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail I once heard a physician quote Maya Angelou: “I always remind myself that people aren't going to remember what you told them or how you told them, but they will remember how you made them feel.”I went to Walgreens over and over to buy pregnancy tests, even though I knew it was too early to tell. Then, one day, a test turned positive in the beginning of spring, the month of our wedding anniversary.I was coincidentally on my pediatrics rotation. I started to feel a new connection to the mothers and their newborns. I rubbed my abdomen with ... Author, Article, and Disclosure InformationAffiliations: From Mount Auburn Hospital, Cambridge, Massachusetts.Corresponding Author: Charlotte Grinberg, MD, Mount Auburn Hospital, 330 Mount Auburn Street, Cambridge, MA 02138; e-mail, [email protected]harvard.edu. PreviousarticleNextarticle Advertisement Audio Reading - “The Worst of Days” Audio. Virginia L. Hood, MD, Annals Associate Editor, reads "The Worst of Days," by C. Grinberg. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 7 November 2017Volume 167, Issue 9Page: 681-682KeywordsEmergency departmentEmergency medicineFetusesNursesPregnancyTwinsUltrasound imagingUterusVisionVitamins ePublished: 7 November 2017 Issue Published: 7 November 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
A phase 1B study of SNX-5422 plus carboplatin (C) and paclitaxel (P) in patients with advanced non-small-cell lung cancer (NSCLC).
Authors: Martin Gutierrez, Giuseppe Giaccone, Stephen V. Liu, Zhonglin Hao, Christie Hilton, James M Hinson, Everardus Otto Orlemans, Alexander E. Drilon
Journal: Journal of Clinical Oncology (2017)

e20622 Background: SNX-5422 is an orally bioavailable pro-drug of SNX-2112, a highly potent and selective heat shock protein (Hsp) 90 inhibitor with synergy with platinum and paclitaxel. In this study, SNX-5422 + C/P followed by SNX-5422 maintenance therapy was examined in patients (pts) with NSCLC. Preliminary study results from the first 12 pts established the maximum tolerated dose (MTD) for SNX-5422 as 100 mg/m 2 for the combination, with one G3 dose limiting toxicity (DLT) of diarrhea. The updated efficacy and safety results following enrollment completion (N = 20) are presented. Methods: Eligible pts had NSCLC (EGFR wild-type or non-sensitizing mutation) and ≤1 prior line of chemotherapy. Pts received C (AUC 5) and P (175 mg/m 2 ) every 3 weeks for up to 6 cycles and SNX-5422 every other day (starting at 50 mg/m 2 ) for 21 of 28 days, with a standard 3+3 dose escalation design during the combination, followed by SNX-5422 (100 mg/m 2 every other day) monotherapy for maintenance until disease progression. Results: Twenty pts with NSCLC (pathology assessment: 18 adenocarcinoma, 2 squamous cell carcinoma) were enrolled (mean age, 59 yrs), with 19 evaluable for efficacy. Best response was partial response in 37% (7/19) of pts, stable disease in 58% (11/19) of pts, and progressive disease in 5% (1/19) of pts. Twelve of the 19 pts (63%) continued maintenance SNX-5422 monotherapy, and 7 of the 12 (58%) received therapy for ≥8 cycles. Four pts had G3 DLTs with combined therapy (considered possibly related to ≥1 agent): diarrhea (1 pt discontinued), increased alanine aminotransferase/aspartate aminotransferase (ALT/AST) (1), nausea, vomiting, and diarrhea (1), and peripheral sensory neuropathy (1). The most common adverse events considered possibly related to the combination were diarrhea (n = 14), nausea (n = 10), fatigue (n = 8), alopecia (n = 5), and vomiting (n = 5), and the majority of these events were G1/2. Conclusions: SNX-5422 added to C/P was well-tolerated at doses up to 100 mg/m 2 , and preliminary efficacy of this combination in NSCLC warrants further study. Clinical trial information: NCT01892046.
SCDT-45. ANTIBODY-BASED PET IMAGING OF BRAIN CANCER CELLS INFILTRATION
Authors: Gabriel Charest, Otman Sarrhini, David Fortin, Danica Stanimirovic, Reinhard Gabathuler, Brigitte Guérin
Journal: Neuro-Oncology (2017)

Infiltrated glioblastoma (GBM) cells into the brain parenchyma cause recurrences after tumor resection and there is presently no efficient non-invasive method to detect these infiltrated cells. One obstacle is the blood-brain barrier (BBB), which limits the passage of specific radiolabeled antibodies targeting infiltrated cells to the central nervous system, preventing imaging by positron emission tomography (PET). We hereby aimed to conceive bi-specific radiolabeled antibodies acting in two chronological steps: 1- targeting a transporter to allow receptor-mediated transcytosis through the BBB and 2- targeting a specific biomarker of GBM cells for a specific retention and imaging. We will present the first part of the project consisting to demonstrate that the mono-specific radiolabeled antibody targeting BBB-transporter can actively cross the BBB of healthy rat following injection in the right external carotid artery. This method allows for high tracer concentration in the right hemisphere after first passage following the injection. Comparing the specific radiolabeled antibody to a non-specific antibody, we observe that only the BBB-transmigrating antibody is momentary retained at the BBB and then returns in the blood circulation. We will next assess whether this transitory uptake to the BBB is sufficient to let the bi-specific antibody reaches and link a specific antigen present on the migrating GBM cells. This study demonstrates that our radiolabeled antibody allows for a transitory and specific uptake to the BBB. These successful results are promising for the use of bi-specific radiolabeled antibody targeting infiltrated GBM cells thus should enabling for specific PET imaging.
RTHP-22. IMPROVING RADIOTHERAPY FOR GLIOMAS: EXPERIENCE FROM SUNYAT-SEN UNIVERSITY CANCER CENTER
Authors: Yunfei Xia
Journal: Neuro-Oncology (2017)

External radiotherapy or chemoradiotherapy has an important role as an adjuvant treatment to surgery in cerebral glioma patients. Author in this article introduced the situation and experience of radiation treatment for glioma in the Cancer Center of Sun Yatsen University in Mainland of China. It includes the three historical stages: radiation treatment before 1990s, from 1999 to 2005, and from 2006 to now. The author focus on introducing translational study, improving radiation treatment, and clinical trials for glioma in department of radiation oncology of cancer center of SYSYCC in recent years.
Electrochemotherapy in the treatment of cutaneous metastases from breast cancer: a multicenter cohort analysis
Authors: M. Guida, C. Cabula, L.G. Campana, G. Grilz, S. Galuppo, R. Bussone, L. De Meo, A. Bonadies, P. Curatolo, M. De Laurentiis, M. Renne, S. Valpione, T. Fabrizio, N. Solari, A. Santoriello, M. D'Aiuto, R. Agresti
Journal: Annals of Oncology (2017)
223Ra-chloride therapy: the first multidisciplinary and multicenter Italian study
Authors: A. Farnesi, S. Mazzarri, G. Boni, L. Galli, C. Cianci, E. Biasco, A. Sbrana, F. Paolieri, F. Bloise, P. Ghedini, E. Lodi Rizzini, V. Dionisi, E. Borsatti, R. Bortolus, L. Fratino, C. Gobitti, S. Fanti, D. Volterrani, F. Monari, S. Ricci, A. Falcone
Journal: Annals of Oncology (2017)