tbuckley/cabot-search huggingface dataset:
MBCL-25. OUTCOME OF CHILDREN WITH MEDULLOBLASTOMA AT TERTIARY CARE HOSPITAL IN PAKISTAN
Authors: Syed Ahmer Hamid, Maria Idrees Dawson, Rahil Khan, Muhammad Shamvil Ashraf, Ibrahim Qaddoumi
Journal: Neuro-Oncology (2018)

Brain tumours have been attributed as the leading cause of childhood cancer mortality and major problems faced by developing countries in term of poor survival rate. MATERIALS AND A retrospective chart review. Total number of 63 patients, ranging from 0 - 18 years, with medulloblastoma out of 341 patients with brain tumor at Indus Hospital. Data collected from June 1997 to November 2016. The data analyzed using SPSS 21 to calculate the survival rate of patients and frequency of outcomes. The total percentage of children with medulloblastoma is 19% among all children with brain tumors in our centre 63/341. Average age of presentation was 8 years. Male to female ratio was 2:1. The most common symptom was headache (20%) followed by vomiting 19%. Time interval from the first symptom till surgery was on average 4 months with a maximum delay of 17 months. A significant percentage of children presented with metastatic disease 38%. Leptomeningeal spread was the most common site (23%). Only 47/63 were risk stratified (75%). Among them standard risks were 19% and high risk were 56%. Among the whole cohort 42 (67%) were actively treated .23/42 (55%) completed treatment, 12/42(29%) are alive and off treatment. 8/42(19%) are on treatment at the time of analysis. Outcome in children who were actively treated was 20/42 (48%).Overall outcome in whole cohort is 32%. Significant delay in the diagnosis, poor socio-economic status, advance disease, abondonment are major challenges. Developing multidisciplinary services, dedicated neuro-oncological expertise will help in improving the overall outcome.
Commentary: New Zealand’s full decriminalisation means police and sex workers collaborate to try to reduce violence
Authors: Catherine Healy
Journal: BMJ (2018)

I was hired as a receptionist in a massage parlour in 1987 in Wellington, New Zealand, naively believing massage was the nature of the work. Soon after I became a masseuse, as sex workers were called to avoid associations with the laws prohibiting sex work (or prostitution as it was known), and related activities, such as brothel keeping, living on the earnings, procuring, and soliciting.

Tips on working safely were whispered to the new masseuses as they started. The helpful advice I received was, “Don’t forget to massage his feet, and you might need this,” as I was given a condom. The police would turn up periodically …
Evaluation of the prognostic value of lymph-node ratio in patients with colon cancer in the oxaliplatin era
Authors: B. Bird, D. Connell, D. O’Connor
Journal: Annals of Oncology (2018)

Introduction: N stage for colon cancer is based on the absolute number of cancer-positive lymph nodes removed at surgery. Lymph node ratio (LNR) is the ratio of the number of cancer-positive nodes to the total number of lymph nodes removed. In patients receiving adjuvant 5-fluorouracil (5-FU), LNR has been shown to be a more accurate prognostic indicator than N stage. However, a combination of adjuvant oxaliplatin and 5-FU has now become the new standard of care. There is limited evidence to show LNR retains its prognostic significance in this setting. The aim of this project is to determine if LNR retains its prognostic significance for colon cancer when patients are treated with oxaliplatin. Methods: Data was collected for all patients with stage 3 colon cancer treated with adjuvant oxaliplatin at a single institution between 2000 and 2015. End points were overall survival and disease-free survival. Based on previous work patients were stratified into three groups according to LNR (LNR1 < 0.11; LNR2 0.11 - 0.27; LNR3 >0.27). These categories were related to the endpoints using Kaplan-Meier curves and Cox regression analysis. Results: 142 patients met the inclusion criteria. Using LNR1 as the reference category, the hazard ratios for overall survival were 1.54 (p = 0.26) for LNR2 and 0.53 (p = 0.23) for LNR3. The hazard ratios for disease-free survival were 1.95 (p = 0.68) and 1.12 (p = 0.79) for LNR2 and LNR3, respectively. The Kaplan-Meier curves did not show a statistically significant relationship between LNR and overall survival (p = 0.10) or disease-free survival (p = 0.13). The hazard ratios for N2 compared to N1 were 0.8 (p = 0.578) and 1.65 (p = 0.124) for overall survival and disease-free survival, respectively. The Kaplan-Meier curves did not show a statistically significant relationship between N stage and overall survival (p = 0.58) or disease-free survival (p = 0.12). Conclusion: LNR is not a useful prognostic indicator for colon cancer treated with 5-FU and oxaliplatin.
DIPG-26. MOLECULAR DETERMINANTS OF RESPONSE TO RADIOTHERAPY IN DIPG: A CLINICAL AND IN VITRO STUDY
Authors: Coralie Werbrouck, Cláudia C S Evangeslista, Emilie Barret, Stéphanie Puget, Jacques Grill, Marie-Anne Debily, David Castel
Journal: Neuro-Oncology (2018)

Diffuse intrinsic pontine gliomas (DIPG) are the most severe and common form of malignant brain tumours in children and adolescent. Radiotherapy is the only validated treatment, albeit only bringing a transient symptom relief followed by a constant subsequent progression within a variable delay. We previously identified a heterogeneous response to radiotherapy at diagnosis in DIPG patients depending on the type of mutated histone H3 (Castel et al., 2015 & 2016). We thus hypothesized that there are possible molecular determinants of this initial response, and evaluated the radiosensitivity of a compendium of 13 treatment-naïve cellular models of DIPG deriving from stereotactic biopsies at diagnosis. Our results show a heterogeneous response of DIPG cells to RT in vitro correlating with the duration of the clinical response in the corresponding patients. This phenomenon thus implies a cell-autonomous response, and we decided to confront radioresistance with the molecular profiles of the corresponding cells. It appears that the main driver of resistance to irradiation in DIPG is the inactivation of TP53, and not the type of mutated histone per se. We are currently validating this result in isogenic DIPG cells with or without functional TP53, and studying the underlying molecular mechanisms that could explain the differences in radiosensitivity of these tumour cells. By confronting tumour molecular data with clinical responses to RT in a monocentric retrospective cohort, we are able to consolidate our in vitro prediction and propose new possible stratifications in DIPG with respect to response to therapy.
71-Year-Old Man With Recurrent Dyspnea Following Transcatheter Aortic Valve Replacement
Authors: Timothy F. Simpson
Journal: JAMA Cardiology (2018)

A 71-year-old man presents with subacute progressive dyspnea on exertion after having undergone transcatheter aortic valve replacement 12 months earlier for symptomatic aortic stenosis. What would you do next?
Berberine inhibits the migration and invasion depending on HNF4αvia Wnt/beta-catenin pathway in gastric cancer
Authors: Q. Hu, P. Yi
Journal: Annals of Oncology (2018)

Introduction: Metastasis and invasion of cancer cells are important features of advanced gastric cancer. WNT/β-catenin signaling plays an important role in the metastasis and invasion of tumor cells. Previous studies found the relationship between the expression of HNF4α and gastric cancer invasion and metastasis, berberine can down-regulate the expression of HNF4α in gastric cancer cells. Therefore, this study attempts to explain the anti-tumor effect of berberine by inhibiting the metastasis and invasion of gastric cancer cells. Methods: In order to illustrate the expression of HNF4α, WNT5a and β-catenin in gastric cancer tissues, we used immunohistochemistry to detect 53 cases of pathological sections. In addition, AMPK, p-AMPK, HNF4α, WNT5a and β-catenin in SGC7091 and AGS cells which were treated with berberine were detected by western blotting. Transwell assays were used to detect the migration and invasion of gastric cancer cell AGS in the group of berberine, LV-HNF4A-RNAi and control. Results: HNF4α, WNT5a and β-catenin expression were significantly higher in gastric cancer tissues than in adjacent tissues and in normal stomach tissues (P < 0.01), but HNF4α, WNT5a and β-catenin expression in gastric cancer were not related to tumor classification, tumor differentiation, lymph node metastasis and TNM staging. Furthermore, berberine can upregulate the expressions of p-AMPK and downregulate the expressions of HNF4α, WNT5a and β-catenin in gastric cancer cells. Further analysis revealed that berberine and LV-HNF4A-RNAi reduce gastric cancer cell metastasis and invasive ability (P < 0.01). Conclusion: The AMPK/HNF4α/WNT5a/β-catenin pathway plays an important role in gastric cancer metastasis and invasion. It is through this pathway that berberine exerts its effect on the metastasis and invasion of gastric cancer cells.
ATRT-08. IDENTIFYING AND ACCELERATING POTENTIAL NEW DRUG THERAPIES FOR PEDIATRIC ATYPICAL TERATOID RHABDOID TUMORS (ATRTs) THROUGH DRUG REPURPOSING
Authors: Nicole Wood, Kevin Ginn, Anuradha Roy, Coral Huntley, Scott Weir, Prabhu Ramamoorthy, Shrikant Anant
Journal: Neuro-Oncology (2018)

CNS ATRTs are rare, aggressive tumors occurring in very young children and have a poor prognosis and high morbidity. Even with aggressive multi-modal therapy, the cure rate remains less than 50%. New therapy approaches are desperately needed. The broad objective of this project is to accelerate new treatments for ATRT by employing drug repurposing strategies. A high throughput screening (HTS) assay was developed to interrogate our curated library of FDA-approved and industry-abandoned drugs. Two ATRT cell lines from the Children’s Oncology Group were used for the primary HTS. 3,574 FDA-approved and abandoned drugs were screened using a well-established CellTiter-Glo® Luminescent Cell Viability Assay to determine drug effect on ATRT cell line viability and 122 active drugs were identified. Based on demonstrated systems pharmacology data, drug development and regulatory science considerations, and the ability of agents to cross the blood brain barrier, 9 drugs were selected for in vitro studies. Drug effects on cell proliferation, colony formation, spheroid formation, cell cycle, migration, invasion, and cell signaling pathways will be characterized in human control and ATRT cell lines. Based on resulting mechanistic data, in vitro combination studies will be conducted to determine additive or synergistic anticancer activity in the ATRT cell lines. Building upon our extensive track record of advancing 12 repurposed FDA-approved drugs to cancer experimental therapeutics clinical trials over the past seven years, we will employ innovative drug development and regulatory science strategies to rapidly translate promising new treatments identified through this research to ATRT patients.
NURS-11. IMPACT OF A CENTRAL NERVOUS SYSTEM (CNS) TUMOR PATIENT AND FAMILY EVENT
Authors: Meghan Belongia, Suzanne Novak, Jeffrey Knipstein
Journal: Neuro-Oncology (2018)

Annually, 40-50 new patients with a central nervous system (CNS) tumor are managed at Children’s Hospital of Wisconsin (CHW). In 2013, our neuro-oncology team recognized a need for these patients, their parents, and survivors to connect with one another while learning more about the impact a CNS tumor has on the child and family. The first event was planned following a needs assessment completed by our patients and families. The aims of the event are 1) to educate our patients/families about CNS tumors and their related clinical and supportive care, 2) to provide a place to allow families to network and connect with one another, and 3) to address long-term transition and reintegration of patients into the community after treatment is complete. We have continued to build each year, extending the invitation to include patients and families within the state of Wisconsin as well as those that take care of these patients in the community such as teachers, therapists, and referring physicians. As a result, the event has outgrown the hospital auditorium and moved last year to a local water park where we supported over 90 attendees. We will describe the event planning, identify educational content, and share the feedback from participants. This information may assist other programs in developing similar events at their home institutions.
Allogeneic haematopoietic stem cell transplantation eliminates alloreactive inhibitory antibodies after liver transplantation for bile salt export pump deficiency
Authors: Florian Brinkert, Ieva Pukite, Dorothee Krebs-Schmitt, Andrea Briem-Richter, Jan Stindt, Dieter Häussinger, Verena Keitel, Ingo Müller, Enke Grabhorn
Journal: Journal of Hepatology (2018)
NFM-07. SPRINT: PHASE II STUDY OF THE MEK 1/2 INHIBITOR SELUMETINIB (AZD6244, ARRY-142886) IN CHILDREN WITH NEUROFIBROMATOSIS TYPE 1 (NF1) AND INOPERABLE PLEXIFORM NEUROFIBROMAS (PN)
Authors: Andrea Gross, Pamela Wolters, Andrea Baldwin, Eva Dombi, Michael J Fisher, Brian Weiss, AeRang Kim, Jaishri Blakeley, Patricia Whitcomb, Marielle Holmblad, Staci Maritin, Marie Claire Roderick, Scott M Paul, Janet Therrien, Kara Heisey, Austin Doyle, Malcolm Smith, John Glod, Seth Steinberg, Brigitte C Widemann
Journal: Neuro-Oncology (2018)

PN in NF1 cause substantial morbidity. In a phase I trial of selumetinib, 17/24 patients had a partial response (PR). This study evaluates the PR rate of PN to selumetinib and changes in PN-related morbidities. Patients 2-18 years with NF1, inoperable PN and ≥ 1 PN-related morbidity received continuous 28-day cycles of selumetinib (25 mg/m2 PO BID). Response (volumetric MRI analysis; PR = PN volume decrease ≥20%) and PN-related morbidities were assessed after every 4 cycles. Fifty children (30 male, median age 10.2 years, range 3.5, 17.4) enrolled. Disfigurement (n=44), motor dysfunction (n=33) and pain (n=28) were the most frequent PN-related morbidities. As of November 5, 2017: median cycle number 19.5 (range 0, 29); median change in PN volume -27.7% (range -50.6%, 2.2%). Best response PR (36 patients, 72%), stable disease (12 patients, 24%); 2 (4%) had no re-staging evaluations. Of the 36 PR, 32 were confirmed on ≥ two consecutive restaging studies. Pain intensity and interference scores improved significantly (p <0.01) over one year, as did strength (0-5 scale) and range of motion (degrees) (p < 0.01). Most frequent toxicities: gastrointestinal, asymptomatic creatine kinase increase, acneiform rash and paronychia. Selumetinib dose was reduced in 12 patients, of which 5 were removed from treatment. The response rate from this study (72%) confirms our previously observed rate (71%). Most responses have lasted ≥6 months. Improvements in PN-related pain and motor impairment demonstrate that selumetinib can provide clinical benefit. Data validation and further analyses are ongoing.
Antibiotic susceptibility testing and species identification of Nocardia isolates: a retrospective analysis of data from a French expert laboratory, 2010–2015
Authors: D. Lebeaux, E. Bergeron, J. Berthet, J. Djadi-Prat, D. Mouniée, P. Boiron, O. Lortholary, V. Rodriguez-Nava
Journal: Clinical Microbiology and Infection (2018)
CRAN-37. MOLECULAR HETEROGENEITY OF SUBEPENDYMAL GIANT CELL ASTROCYTOMAS IN PATIENTS WITH MILD-PHENOTYPE TUBEROUS SCLEROSIS COMPLEX
Authors: Cody Nesvick, Amulya Nageswara Rao, Aditya Raghunathan, David Daniels
Journal: Neuro-Oncology (2018)

Subependymal giant cell astrocytomas (SEGAs) are rare central nervous system tumors that are almost pathognomonic of tuberous sclerosis complex (TSC). These lesions are World Health Organization (WHO) grade-I tumors that arise in the lateral ventricles near the foramen of Monro and almost always contain detectable mutations in TSC1 or TSC2. We present three children with TSC in whom a diagnosis of SEGA was the presenting feature and who displayed a mild TSC phenotype. All patients underwent surgery for tumor resection. Following surgical resection, germline testing for TSC1 and TSC2 mutations was performed, and pathologic specimens subsequently underwent molecular analysis using chromosomal microarray and a 50-gene next-generation sequencing. There were two males and one female with an age range of 12 to 18 years. All patients had evidence of cortical tubers on brain MRI, and two had hypomelanotic macules; no other manifestations of TSC were present. None of these patients were found to have detectable germline mutations in TSC1 or TSC2. One tumor specimen contained copy-neutral loss of heterozygosity (cnLOH) of chromosome 9q34 affecting TSC1 and NOTCH1. The second specimen contained cnLOH of chromosome 16p12-13 affecting TSC2; DNA sequencing confirmed a known pathogenic mutation in TSC2 in this patient. A third specimen was cytogenetically normal but contained a missense mutation in NOTCH2 of unknown significance. These data demonstrate that SEGAs in patients with a mild TS phenotype are molecularly heterogeneous, sometimes containing genetic alterations in TSC1 or TSC2 but also containing mutations in other pathways associated with growth, development and neoplasia.
Definitive chemoradiation in esophageal squamous-cell carcinoma: Carboplatin/paclitaxel versus cisplatin/5-FU
Authors: N. Tavares, M. Ribeiro, S. Meireles, D. Almeida, L. Águas, A. Costa, P. Fontes, M. Damasceno
Journal: Annals of Oncology (2018)

Introduction: Patients with Esophageal squamous-cell carcinoma (ESCC) carry a bad prognosis. Definitive chemoradiation (dQRT) is a curative intent treatment for inoperable or unresectable tumors. Data suggests that treatment with carboplatin/paclitaxel (CP) is less toxic than cisplatin/5FU (CF) but it is currently unknown if there is any survival difference between these protocols. This study tried to compare overall survival (OS) and toxicity profiles in ESCC patients submitted to dQRT with CP or CF. Methods: Retrospective cohort of patients with ESCC diagnosed between June 2011 and February 2016 in a tertiary university hospital and treated with CP (weekly carboplatin AUC 2 + paclitaxel 50 mg/m2) or CF (cisplatin 75 mg/m2 + 5-FU 1g/m2 in a 96h perfusion on days 1 and 29) and concomitant radiation therapy (45 Gy in fractions of 1.8 Gy). OS was estimated by Kaplan-Meier method and a significant level of 0.05 was chosen to assess the statistical significance. Results: 30 patients were included, 90% (n = 27) of male gender with a median age at diagnosis of 63 years. Tumors were mainly located in the middle (53.3%, n = 16) or upper third (40%, n = 12) of the esophagus. Only two cases were located in the lower third (6.7%). Eighteen patients (60%) were treated with CP and 12 (40%) with CF. Overall survival was 7.6 months (CI 95% 2.8–12.4 months). There were no difference in OS between the two groups (CP 7.6 months vs. CF 6.8 months, p = 0.829). Twenty one patients had an ECOG=0 (CP = 11 vs. CF = 10) and 7 had an ECOG=1 (CP = 6 vs. CF = 1). All patients with cardiovascular comorbidities (n = 4) were treated with CP. Most common grade ≥3 toxicities were oral mucositis (CP = 7, CF = 1), fatigue (CP = 5, CF = 1), febrile neutropenia (CP = 3, CF = 1) and anemia (CP = 2, CF = 2). Fourteen patients (46.7%) didn't managed to perform all planned chemotherapy cycles: 6 due to grade ≥3 toxicity, 6 due to infections (2 of whom died) and 2 due to patient refusal to proceed. Patients treated with CP were more frequently unable to complete chemotherapy (CP = 12 vs. CF = 2; p = 0.007). Disease progression was confirmed in 86.7% of patients (n = 26) and only 23.1% of these (n = 6) were treated with a subsequent line of chemotherapy (3 patients treated with CP in first line and 3 patients treated with CF). Conclusion: Inoperable or unresectable ESCC remains an entity with scarce treatment strategies and this study confirmed that these patients have a bad prognosis. There wasn't a statistically significant difference in OS between CP and CF protocols. Patients treated with CP seemed to have higher rates of toxicity and treatment withdrawal. This is probably due to preferential allocation of patients with more comorbidities and unfavorable performance status to a traditionally considered better tolerated scheme, still without any apparent impact on OS.
Pancreatic ductal adenocarcinoma (PDAC) and type 2 diabetes mellitus: Cause or consequence? Analysis of the prevalence of alterations in glucose metabolism (AGM) in a patients’ cohort with PDAC
Authors: L. Medina Rodriguez, C. Sanchez Cendra, M. Pantin Gonzalez, D. Gutierrez Abad, I. Juez Martel, M. De Torres Olombrada
Journal: Annals of Oncology (2018)

Introduction: Type 2 diabetes mellitus is likely the third modifiable risk factor for pancreatic cancer (PDAC) after cigarette smoking and obesity. Epidemiological investigations have found that long-term type 2 diabetes mellitus is associated with a 1.5- to 2.0-fold increase in the risk of PDAC. On the other hand, new-onset diabetes may indicate subclinical PDAC, and patients with new-onset diabetes may constitute a population in whom PDAC can be detected early. Use of the antidiabetic drugs, such as metformin, has been associated with reduced risk of PDAC in diabetics and recognized as an antitumor agent with the potential to prevent and treat this cancer. Several ongoing clinical trials are exploring this potential benefit in different settings of PDAC. Methods: We aimed to study the prevalence of AGM in patients diagnosed by PDAC at our service and explore their potential interactions between other known risk factors for PDAC. This is an observational and retrospective study based on clinical data from 60 patients diagnosed by PDAC between January 2013 to December 2017. Clinical and epidemiological variables were collected as well as variables associated to risk factors for PDAC. Overall survival (OS) and progression-free survival (PFS) were estimated with the use of the Kaplan–Meier method. Results: Data from 60 patients were analysed. The median age at the diagnosis was 61 years. Male represented 55% of the total, and female the 45%. 86% of the patients presented metastatic (M1) disease at the analysis moment and 70% of the patients had died. The median OS was 26 months for early stage tumours and 16 months for metastatic setting. The PFS for M1 patients was 6,1 months. From all patients, 55% showed AGM, and between these patients, the 55% were diagnosed “de novo”, and the 28% suffered from long-term hyperglycaemia or diabetes. This trend was maintained in M1 patients. Only in M1 patients, we observed that about 60% of the patients experienced a worsening of AGM during the disease showing a tendency to statistical significance between this worsening and progression disease (p = 0,06). Between patients with AGM only 41% had received corticoid treatment during the disease. Use of corticoids does not seem to be associated with AGM evolution. Only the 20% of patients with were referred to the Endocrinology Department for control. Conclusion: The relationship between PDAC and diabetes is very complex. Frequently, de novo alterations in glucose metabolism are underdiagnosed and trivialized. Based on our results we are starting a prospective observational study in collaboration with Endocrinology Department to evaluate PDAC patients with AGM in order to optimize the diabetes treatment and explore its influence in tumour natural history.