tbuckley/cabot-search huggingface dataset:
EPEN-04. RECURRENT EPENDYMOMA: ROLE OF INTRAVENTRICULAR TARGETED RADIOIMMUNOTHERAPY
Authors: Kim Kramer, Neeta Pandit Taskar, John Humm, Pat Zanzonico, Maria Donzelli, Sofia Haque, Yasmin Khakoo, Jason Lewis, Nai-Kong Cheung
Journal: Neuro-Oncology (2018)

Novel treatment strategies are needed for children with recurrent ependymoma. We explored the use of intraventricular targeted immunotherapy with monoclonal antibodies (cRIT-mAb) using 131I-8H9 and 131I-3F8 targeting B7-H3 or GD2, respectively. Patients received 2 mCi cRIT- 131I- mAb for dosimetry with serial CSF sampling and region of interest (ROI) on nuclear scans. Therapy injections were 40 -100 mCi 131I-8H9 or up to 40 mCi 131I-3F8. Brain and spine MRIs, CSF cytology were routinely assessed. Acute toxicities and survival were noted. 11 patients with anaplastic ependymoma (median age 8.5 years, 1–32) suffered 1- 7 recurrences (median 2.9); median age at cRIT was 12.3 years (3–35). 39 injections were delivered (13 131I-3F8; 26 131I-8H9). Transient headache, nausea and vomiting was observed following 131I-3F8; 131I-8H9 was well-tolerated. Mean CSF cGy/mCi by sampling was 37.6 131I-8H9 and 40.1 131I-3F8. Mean ventricular ROI dose was 75.3 cGy/mCi 131I-8H9 and 111 cGy/mCi 131I-3F8 and to spine 20.2 cGy/mCi 131I-8H9 and 18.9 cGy/mCi 131I-3F8. 4/5 patients with radiographic evidence of disease progressed; 1 had spinal disease improvement. Of 5 patients treated in radiographic remission, 2 remain in remission 2.5 and 8 years since cRIT, 1 is alive with disease 2.5 years post; 2 patients died of disease 7 and 13 years post cRIT. cRIT mAb appear safe with a favorable dosimetry therapeutic index and may be considered as a viable therapeutic option for patients with recurrent ependymoma.
DEV-15. MEDULLOBLASTOMA: A DILEMMA IN A TERTIARY CANCER CENTRE IN NEPAL
Authors: Surendra Gauchan, Shivaji Poudel, Ranjan Bhakta Bhandari, Subhas Pandit
Journal: Neuro-Oncology (2018)

Medulloblastoma is a common malignant brain tumors in children with five major histologic variants. Classic, desmoplastic, Large cell, Analplastic and Medulloblastoma with extensive Nodularity (MBEN). The best survival has been reported in patients with desmoplastic or MBEN histology. However other factors intervene the prognosis of the patient like the age and postoperative residual disease and the spread of the disease. The molecular classification of MB is WNT, Sonic Hedgehog(SHH), Group 3 and Group 4. The prognosis is best in WNT subgroup and intermediate in SHH. The Group 3 and group 4 make poor prognosis. All pediatric brain tumor registered on year 2016 & 2017 were retrospectively studied. However only 14 patients were registered with 3 medulloblastomas. The 3 patients were male of 3, 5 and 6 years of age who were referred from other institutes. No further histologic subtypes were reported. No residual disease assessment was made. The diagnosis was only histology with no Immunohistochemistry and no risk assessment, post surgery. Medulloblastoma still remains a dilemma in terms of diagnosis, treatment and prognosis in low income countries.
A phase I/II study of panitumumab combined with TAS-102 in patients (pts) with RAS wild-type (wt) metastatic colorectal cancer (mCRC) refractory to standard chemotherapy: APOLLON study
Authors: K. Yamazaki, H. Yasui, K. Yamaguchi, Y. Kagawa, Y. Kuboki, T. Yoshino, M. Gamoh, Y. Komatsu, H. Satake, M. Goto, H. Tanioka, E. Oki, M. Kotaka, A. Makiyama, T. Denda, J. Soeda, K. Shibya, M. Iwata, K. Oba, T. Kato
Journal: Annals of Oncology (2018)

Introduction: APOLLON is an open-label, single-arm phase I/II study investigating the efficacy and safety of Pmab in combination with TAS-102 (trifluridine/tipiracil) in pts with RAS (KRAS/NRAS) wt mCRC refractory to standard chemotherapy. The recommended phase II dose (RP2D) of this combination was reported in ASCO-GI 2017 as Pmab at 6 mg/kg on Days 1 and 15, every 4 weeks (Q4W) and TAS-102 at 35 mg/m2 twice daily on Days 1–5 and 8–12, Q4W, and was well tolerated without dose-limiting toxicities. Here, we present the efficacy and safety data for pts treated with Pmab with TAS-102 at the RP2D. Methods: Eligible pts were aged 20–74 years (y); ECOG PS 0–1; with RAS wt mCRC; refractory or intolerant to fluoropyrimidines, irinotecan, oxaliplatin and anti-angiogenesis therapy; and had no prior treatment with any anti-EGFR antibody, TAS-102 nor regorafenib. Primary endpoint was investigator-assessed progression-free survival (PFS) rate at 6 months in RP2D treated pts treated at the RP2D (including seven pts in phase I). Secondary endpoints included PFS, response rate (RR), disease control rate (DCR), overall survival (OS) and safety. Using an exact single-stage binomial design, 47 pts were required, with a 6-month PFS rate of 48% deemed promising and 29% unacceptable (one-sided α = 0.05; β = 0.2). Results: From 2015 to 2017, 56 pts (30 male) with a median age of 64 y (range: 38–74 y) were enrolled. Median follow-up was 10.4 months. PFS rate at 6 months (n = 54) was 33.3% (90% CI: 22.8–45.3; p = 0.2414). Median PFS, RR and DCR were 5.8 months (95% CI: 4.5-6.5), 37.0% (95% CI: 24.3-51.3) and 81.4% (95% CI: 68.57-90.75), respectively (n = 54). Median OS was not reached. In subgroup analysis with primary tumour location, left-sided tumors (LT, n = 47) were relatively associated with longer PFS (6.1 vs. 2.9 months) than right-sided tumors (RT, n = 7). RR in LT and RT were 38.3% and 28.6%, respectively. The most common grade (G) 3/4 treatment-emergent adverse events (n = 55) included neutropenia (G3: 30.9%, G4: 16.4%), febrile neutropenia (G3: 10.9%), stomatitis (G3: 9.1%), dermatitis acneiform (G3: 9.1%), fatigue (G3: 3.6%) and hypomagnesemia (G3: 3.6%). There were no treatment-related deaths or unexpected safety signals. Conclusion: The first phase II study of Pmab with TAS-102 at the RP2D showed favourable antitumor activity with an acceptable safety profile for pretreated pts with RAS wt mCRC, although the primary endpoint of PFS rate at 6 months did not meet the prespecified threshold.
Abstract 14922: Urban Atlas and Geographic Information Systems Can be Used to Reveal Mismatch in Automated External Defibrillators Distribution in Residential and Non-Residential Areas of Stockholm, Sweden
Authors: David Fredman, Jan Haas, Yifang Ban, Martin Jonsson, Leif Svensson, Therese Djärv, Jacob Hollenberg, Per Nordberg, Mattias Ringh, Andreas Claesson
Journal: Circulation (2016)

Introduction:  Early defibrillation in OHCA increases survival. International guidelines suggest AEDs to be installed in densely populated areas and locations with many visitors. In many countries the number of AEDs in public places is increasing, but the use is still low. This may be due to long distances from OHCA to nearest AED and that AED placement does not follow the locations of public OHCA incidents. The aim of this study was to investigate if public AED distribution in urban areas of Stockholm County, Sweden follows the incident locations of public OHCA.   Methods:  OHCA data were obtained from the Swedish register for cardio-pulmonary resuscitation and AED data were obtained from the Swedish AED registry. All urban areas in Stockholm County were classified according to the pan-European digital mapping tool, Urban Atlas and further merged into three major classes ( residential, non-residential  and  other areas ). Geographic Information system (GIS) software was used to spatially join and relate public AED and public OHCA data and perform computations on relations.   Results:  Between 2012-01-01 and 2014-12-31 totally 804 OHCA occurred on public locations in Stockholm County and by December 2013, 1828 public AEDs were available. The public OHCA incidence was similar in  residential  (47,3%) and  non-residential areas  (43,4%) but AEDs were less present in  residential areas  (29,4%) compared to  non-residential  (68,8%).   Conclusions:  In conclusion, GIS and Urban Atlas revealed that AED distribution in Stockholm County does not follow incident locations of public OHCA and that AED accessibility was limited in  residential areas . However public OHCA incidence was similarly distributed between  residential  and  non-residential areas.  Our findings indicate that residential areas should be considered targets for AED placement in accordance with international guidelines.
TBIO-05. INTEGRATION OF GENOMIC DATA FROM THE ONCOKIDSSM NEXT GENERATION SEQUENCING PANEL AND CHROMOSOMAL MICROARRAY ANALYSIS FOR DIAGNOSIS AND PROGNOSIS OF PEDIATRIC CNS TUMORS
Authors: Kristiyana Kaneva, Matthew Hiemenz, Jianling Ji, Nathan Robison, Ashley Margol, Girish Dhall, Jennifer Cotter, Debra Hawes, Alexander Judkins, Jaclyn A Biegel
Journal: Neuro-Oncology (2018)

OncoKidsSM is a DNA and RNA-based Ampliseq panel designed at CHLA for clinical evaluation of pediatric hematologic malignancies and solid tumors. The DNA assay is designed to detect mutations in the full coding regions of 44 cancer loci; hotspot mutations in 82 genes; and amplification of 24 genes. The RNA content includes 70 driver genes and 1400 targeted gene fusions. Minimal input of 20ng DNA and RNA from frozen tissue or FFPE is required. To date we have prospectively evaluated 45 CNS tumor samples using OncoKidsSM. Twenty-six of 45 tumors (57%) had at least one variant of strong clinical significance (Tier I). For 33 of the 45 cases (73%) we also performed copy number DNA-based chromosomal microarray (CMA). Results were consistent between the two platforms in 13 of 33 (39%) cases. CMA demonstrated increased clinical utility in 11 (55%) of the remaining cases, while OncoKidsSM provided more clinically useful information in 9 of 20 (45%) cases. For low-grade gliomas, BRAF V600E mutations or KIAA1549-BRAF fusions were detected by both platforms, whereas for high- grade gliomas OncoKidsSM demonstrated diagnostic and prognostic HIST1H3B, FGFR1, ACVR1, and TP53 Tier I mutations. OncoKidsSM analysis also revealed potential germline mutations in cancer predisposition genes. In contrast, CMA had greater utility for embryonal tumors, e.g. medulloblastomas with chromosomal gains and losses consistent with Group 3/4 tumors that were non-informative by OncoKidsSM. Our results demonstrate the clinical utility of CMA and OncoKidsSM analyses for integrated reporting with pathology which have minimal sample requirements and rapid turnaround time.
Patient derived xenografts from American minority gastric cancer patients
Authors: S. Wang, M. Zhu, S. Hammer, J. Shen, I. Nassour, J. Mansour, D. Agarwal, H. Zhu, M. Porembka
Journal: Annals of Oncology (2018)

Introduction: In the United States, race and ethnicity are associated with different gastric cancer epidemiology and outcomes with Black and Hispanic/Latino patients having worse outcomes than White and Asian patients. Notably, Black and Hispanic/Latino patients are significantly underrepresented in large gastric cancer clinical trials and thus it is unclear if currently defined treatment algorithms for gastric cancer are optimized for these patients. Patient derived xenografts (PDX) can be a useful surrogate to model human disease. Methods: Consent was obtained from gastric cancer patients who were undergoing pre-treatment esophagogastroduodenoscopy (EGD) or gastric resection after neoadjuvant therapy. Tumor samples were coated with Matrigel and implanted into the subcutaneous tissue in the flanks of NSG mice. Approximately 10 mg of tumor obtained from EGD biopsies and approximately 100 mm3 obtained from resections were implanted into each flank. Two implants were performed for EGD samples and four implants were performed for resection samples. Tumors were serially measured and passaged when the greatest dimension reached 1.5 cm, or if there was overlying skin necrosis. Results: We implanted EGD biopsies from 70 patients and resection samples from 26. There were 43 Hispanic/Latino and 16 Black patients in the pre-treatment EGD cohort and 15 Hispanic/Latino and 5 Black patients in the post-treatment resection group. The engraftment rates were 43% for EGD biopsies and 62% for resection samples. Median time to first passage was 10 weeks (range: 5.3 to 23) for EGD biopsies and 21 weeks (5.9 to 43) for post-treatment resection samples. Race/ethnicity, presenting clinical stage, Lauren status, tumor differentiation, lymphovascular invasion, perineural invasion, H. pylori status, and Her2 status were not associated with engraftment rates. Histology was generally maintained through passages but mucinous components were lost over time, leaving only solid, poorly differentiated tumor. Almost all samples were able to be serially passaged and reconstituted after deep freeze and thaw. Conclusion: We have established multiple PDX lines from American minority patients. These lines will be a useful platform to investigate biologic factors that contribute to gastric cancer outcome disparities that are associated with race and ethnicity in the United States.
Reply to ‘F508del-CFTR is not corrected by thymosin α1’
Authors: Luigina Romani, Claudia Stincardini, Stefano Giovagnoli, Maurizio Paci, Valeria R. Villella, Luigi Sforna, Giorgia Renga, Marina M. Bellet, Claudio Costantini, Paolo Puccetti, Guido Kroemer, Luigi Maiuri, Mauro Pessia, Allan Goldstein, Enrico Garaci
Journal: Nature Medicine (2018)
DIPG-59. LOW GRADE DIFFUSE INTRINSIC PONTINE GLIOMA? A SINGLE INSTITUTION EXPERIENCE
Authors: Margaret Shatara, Sandeep Sood, Janet M Poulik, Deniz Altinok, Steven Miller, Xuehui Liu, Zhihong Wang
Journal: Neuro-Oncology (2018)

Diffuse Intrinsic Pontine Glioma (DIPG) is an extensively invasive tumor of brainstem. Tumor biopsy was rarely performed until recently, because of the possible complications associated with the procedure, therefore, the data on the DIPG histology is relatively limited. We identified 29 consecutive cases of DIPG diagnosed from 2002 to 2017 at Children’s Hospital of Michigan, and tumor biopsy was performed in 22 cases. The histology was consistent with low grade glioma (LGG) in 4 of the 22 cases (18%). We retrospectively reviewed these 4 cases, including the histology, MRI findings, H3 mutation and BRAF alteration status, treatment and survival. There was one Grade I astrocytoma, one Grade I ganglioglioma, and two grade II astrocytomas. Radiologically, 3 were consistent with typical DIPG, one with atypical DIPG. The testing for H3 mutation and BRAF alteration was performed in two recent cases. One case had H3F3A K27 mutation, but no BRAF alteration was identified in either case. All patients received involved-field external beam radiation as part of their initial treatment. Three patients succumbed to their disease with overall survival of 9–17 months, and one patient is alive with no clinical or radiological sign of disease at 6 months following diagnosis. In summary, histology was consistent with LGG in 4 out of 22(18%) of our biopsied DIPG series. One patient with ganglioglioma was found to have histone H3 mutation, a rare finding in LGG but common in midline high grade glioma, who progressed at 11 months, and died at 17 months following initial diagnosis.
Cost-effectiveness of biomarker testing for treatment choices in advanced non-small cell lung carcinoma: impact of diagnostic strategies and their turnaround times
Authors: Arnaud Uguen
Journal: European Respiratory Journal (2018)

<b>Reducing the turnaround times of molecular analyses in patients with advanced lung cancers could help to reduce the costs of the patients9 management by permitting rapid treatment choices</b>http://ow.ly/Zv7230jAQv4
LGG-41. BEVACIZUMAB FOR PEDIATRIC LOW GRADE GLIOMA
Authors: Keita Terashima, Chikako Kiyotani, Yui Kimura, Tomoo Osumi, Yoko Shioda, Motohiro Kato, Daisuke Tomizawa, Kenichi Usami, Hideki Ogiwara, Hidekazu Aoki, Yoshiyuki Tsutsumi, Rie Irie, Takako Yoshioka, Kimikazu Matsumoto
Journal: Neuro-Oncology (2018)

The treatment of choice for young children with unresectable low grade gliomas (LGG) that occur in the optic nerve, deep midline cerebrum or, brainstem is chemotherapy. Carboplatin and vincristine, or vinblastine are most widely used, and in many cases, tumor control can be obtained safely, but the recurrence rate is high and the symptom may progress. Recently, successful treatment with pediatric LGG by bevacizumab, a monoclonal antibody against vascular endothelial cell growth factor has been reported. Here, we report our experience of bevacizumab treatment for 6 children with unresectable LGG. Mean age at bevacizumab treatment was 6y9m (3y11m-8y4m). Histopathological diagnoses were Pilocytic astrocytoma (2 patients), LGG NOS (2), glioneuronal tumor NOS (1) and no pathology (1). Two patients had neurofibromatosis type 1. The median total doses of bevacizumab in patients who completed the treatment were 10 courses (10-16). The indications for bevacizumab treatment were tumor enlargement (3), amblyopia (2) and homonymous hemianopsia (1). The only observed adverse event was proteinuria in 1 patient. Five out of 6 patients demonstrated decrease of tumor size. Among 4 patients with visual abnormalities, improvement of amblyopia was observed in 1 patient and vision was stabilized in other 3 patients. Bevacizumab treatment for pediatric LGG patients was safe, showed anti-tumor effect and contributed to stabilization of vision.
MBRS-01. A CASE OF MOLECULARLY PROFILED EXTRANEURAL MEDULLOBLASTOMA METASTASES IN A CHILD
Authors: Nahla Ali Mobark, Musa Al-Harbi, Sandro Santagata, Malak Abedalthagafi
Journal: Neuro-Oncology (2018)

We present the case of a young boy with MYC-amplified Medulloblastoma. He received multimodal chemotherapy consisting of gross total resection followed by postoperative craniospinal radiation and adjuvant chemotherapy. The patient developed extraneural metastases 4 months after the end of therapy. Literature review identifies the poor prognosis of MYC-amplified medulloblastomas as well as extraneural metastases; we review the current limitations and future directions of medulloblastoma treatment options. To the best of our knowledge, this is the first molecularly characterized report of extraneural metastases of medulloblastoma in a child.
EPID-02. MALIGNANT PRIMARY BRAIN AND OTHER CENTRAL NERVOUS SYSTEM TUMOURS DIAGNOSED AMONG THE CANADIAN PAEDIATRIC POPULATION FROM 2009 TO 2013
Authors: Emily Walker, Sana Amjad, Faith Davis, The CBTR Surveillance, Reporting Working Group
Journal: Neuro-Oncology (2018)

The Canadian Brain Tumour Registry (CBTR) project was established in 2016 with the aim of enhancing infrastructure for surveillance and clinical research to improve health outcomes for brain tumour patients in Canada. We present a national surveillance report on malignant primary brain and central nervous system (CNS) tumours diagnosed in the Canadian paediatric population from 2009–2013. Patients aged 0–19 years were identified through the Canadian Cancer Registry (CCR); an administrative dataset that includes cancer incidence data from all provinces/territories in Canada. Cancer diagnoses are coded using the ICD-O3 system. Tumour types were classified by site and histology using the Central Brain Tumour Registry of the United States classification; and the International Classification of Childhood Cancer (ICCC). Incidence rates (IR) and 95% confidence intervals (CI) were calculated per 100,000 persons and standardized to the 2011 census population. Overall, 1,130 malignant brain and CNS tumours were diagnosed in the Canadian paediatric population from 2009–2013 (IR: 2.90; 95%CI: 2.74,3.08). Of these, 625 were diagnosed among males (IR: 3.14; 95%CI: 2.89,3.39) and 505 among females (IR: 2.66; 95%CI: 2.43,2.90). The most common ICCC classification was III(b)-Astrocytomas (IR: 1.05; 95%CI: 0.95,1.16). The most common histology by age group was: 0–4 years: Embryonal tumours (IR: 1.07; 95%CI: 0.88,1.30); 5–9 years: Pilocytic Astrocytoma (IR: 0.88; 95%CI: 0.71,1.10); 10–14 years: Pilocytic Astrocytoma (IR: 0.62; 95%CI: 0.49,0.80); and 15–19 years: Pilocytic Astrocytoma (IR: 0.41; 95%CI: 0.31,0.55). The presentation will include: IRs for both classifications, histology groups, geographic distribution and a comparison between Canada and the United States.
Clinic-pathological pattern of hepatocellular carcinoma (HCC) in Egypt
Authors: H. Elghazaly, A. Gaballah, N. Bahie Eldin
Journal: Annals of Oncology (2018)

Introduction: The incidence of liver cancer is one of the highest in the world. HCC represents up to 90% of all liver malignancies. In Egypt, HCC constitutes a significant public health problem. Where it is responsible for 33.63% and 13.54% of all cancers in males and females respectively. Hepatocellular carcinoma occurs in a number of preexisting conditions that commonly includes hepatitis C and B, alcoholic and nonalcoholic cirrhosis. It has a poor prognosis after discovery, which is usually at a late stage of disease. This had been strongly linked to the hepatitis C virus epidemic that affected around 10-15% of the Egyptian population during the last 3 decades, and was reported as the highest prevalence of HCV in the world. Methods: This retrospective study included 300 HCC patients. Clinical and demographic data were collected from medical records during the period between Jan 2011 till end of 2016. Results: Results revealed that 53% of the studied HCC patients were younger than 60 years old, 81.5% male and 18.5% female, 40% of the patients had an a-fetoprotein level of at least 400 ng/ml and 95.7% were positive for hepatitis viral infection, 30% of the patients had Diabetes Mellitus (DM). Majority of the patients were Child Pugh Score A and 96.7% of the cases were diagnosed without tissue biopsy. About 36%of the cases presented with stage IV and 34.8% of the cases had lymph node involvement &vascular invasion radiological. Sorafenib was received by 30% patients as first line or after progression from local therapy. Conclusion: HCC in Egypt occurred in men who developed a cirrhotic liver due to HCV infection. Epidemiological and histopathological data of HCC highlight the importance of an integrated strategy for the prevention and the treatment of viral hepatitis infections and chronic liver disease. Tissue biopsy is not required to make the diagnosis of HCC. There were well-defined tumor markers & imaging criteria for that. Many patients presented with advanced disease beyond curative surgery.