tbuckley/cabot-search huggingface dataset:
DEV-14. IMPACT OF A LATIN AMERICA-WIDE TELECONFERENCED BRAIN TUMOR BOARD
Authors: Diana S Osorio, Alvaro Lassaletta, Andres E Morales la Madrid, Joseph Stanek, Ute Bartels, Ibrahim Qaddoumi, Jonathan L Finlay
Journal: Neuro-Oncology (2018)

Pediatric-cancer cure rates are ~80% in high-income countries (HIC) however, 80% of children with cancer live in low-to-middle income countries (LMIC) where chances for cure are much lower. Pediatric neuro-oncology requires a multi-disciplinary effort challenging to achieve in LMIC. We started a pediatric neuro-oncology teleconference to help improve healthcare disparities for children in Latin America (LA) with brain tumors, herein we summarize our efforts. Utilizing a web-portal provided by cure4kids.org we connect HIC-global-pediatric neuro-oncologists with LA pediatric-subspecialists. Weekly, real-time, 60-minute sessions are held in Spanish. Minutes are sent in Spanish after each meeting to solidify recommendations and education. In 2013, we started with one country and 6 members. Substantial growth and data acquisition occurred to include 20-countries throughout LA with growing membership, 2015: 44, 2016: 121, and 2017: 199; and participation, median of 17 (range: 9–22) in 2016 to 25 (range: 11–40) in 2017 (p=0.0005). This required more sessions 2015: 13, 2016: 34, 2017: 47. The total number of cases reviewed were, 2015: 22, 2016: 73, 2017: 132; demonstrating 2017 had statistically more cases per session, on average, than 2016 (p=0.0049) and 2015 (p=0.0075). The growing size of our program demonstrates a reassuring response by LA. We provide systematic and effective communication among LA providers in their language. We succeeded in connecting LA institutions of differing resources and experience with global-pediatric neuro-oncologists from leading cancer-centers in HIC to help improve the care of children with brain tumors in LA and promote continuing education for their providers.
HGG-24. MOLECULAR, PATHOLOGICAL, RADIOLOGICAL AND IMMUNE PROFILING OF NON-BRAINSTEM PAEDIATRIC HIGH GRADE GLIOMA FROM THE HERBY PHASE II RANDOMISED TRIAL
Authors: Alan Mackay, Anna Burford, Valeria Molinari, David Jones, Elisa Izquierdo, Juriaan Brouwer-Visser, Felice Giangaspero, Christine Haberler, Torsten Pietsch, Thomas Jacques, Dominique Figarella-Branger, Daniel Rodriguez, Paul Morgan, Pichai Raman, Angela Waanders, Adam Resnick, Maura Massimino, Maria Luisa Garre, Helen Smith, David Capper, Stefan Pfister, Thomas Wurdinger, Rachel Tam, Josep Garcia, Meghna Das Thakur, Giles Vassal, Jacques Grill, Tim Jaspan, Pascale Varlet, Chris Jones
Journal: Neuro-Oncology (2018)

The HERBY trial was a phase-II open-label, randomised, multicentre trial evaluating bevacizumab in addition to temozolomide/radiotherapy in patients with newly-diagnosed non-brainstem high-grade glioma between the ages of 3-18 years. We collected specimens from 89/113 patients consenting to translational research, and carried out comprehensive molecular analysis integrated with pathology, radiology and immune profiling. 7/89 patients harboured H3F3A_G34R/V mutations (diffusely infiltrative with predominant deep left temporoparietal involvement), whilst 24/89 harboured H3F3A_K27M, both conferring a worse outcome. Of the latter, two patients had distinct, separate lesions in the thalamus and hypothalamus, whilst the remaining had symmetrical central thalamic and midbrain localization. Four older patients had tumours harbouring IDH1 mutations, whilst three younger patients had tumours which by methylation profiling resembled low grade lesions; both of these hemispheric subgroups had a significantly longer survival. Hypermutator tumours (driven by mismatch repair deficiency and somatic POLE / POLD1 mutations) and those biologically resembling pleomorphic xanthoastrocytoma (PXA-like, driven by BRAF_V600E or NF1 mutation) had an elevated immune response in the form of CD8-positive tumour infiltrating lymphocytes (p=0.0018), and had longer overall survival in the bevacizumab arm (p=0.0489). Histone H3 subgroups (hemispheric G34R/V and midline K27M) had a worse outcome and were immune cold. Although the experimental arm did not improve survival across the whole cohort, we identify disease subgroups with MAPK activation to harbour an enhanced immune response and derive benefit from the addition of bevacizumab to standard temozolomide/radiotherapy.
Computational Characterization of Suppressive Immune Microenvironments in Glioblastoma
Authors: Suvi Luoto, Ismaïl Hermelo, Elisa M. Vuorinen, Paavo Hannus, Juha Kesseli, Matti Nykter, Kirsi J. Granberg
Journal: Cancer Research (2018)

The immunosuppressive microenvironment in glioblastoma (GBM) prevents an efficient antitumoral immune response and enables tumor formation and growth. Although an understanding of the nature of immunosuppression is still largely lacking, it is important for successful cancer treatment through immune system modulation. To gain insight into immunosuppression in GBM, we performed a computational analysis to model relative immune cell content and type of immune response in each GBM tumor sample from The Cancer Genome Atlas RNA-seq data set. We uncovered high variability in immune system-related responses and in the composition of the microenvironment across the cohort, suggesting immunologic diversity. Immune cell compositions were associated with typical alterations such as IDH mutation or inactivating NF1 mutation/deletion. Furthermore, our analysis identified three GBM subgroups presenting different adaptive immune responses: negative, humoral, and cellular-like. These subgroups were linked to transcriptional GBM subtypes and typical genetic alterations. All G-CIMP and IDH-mutated samples were in the negative group, which was also enriched by cases with focal amplification of CDK4 and MARCH9. IDH1-mutated samples showed lower expression and higher DNA methylation of MHC-I-type HLA genes. Overall, our analysis reveals heterogeneity in the immune microenvironment of GBM and identifies new markers for immunosuppression. Characterization of diverse immune responses will facilitate patient stratification and improve personalized immunotherapy in the future.Significance: This study utilizes a computational approach to characterize the immune environments in glioblastoma and shows that glioblastoma immune microenvironments can be classified into three major subgroups, which are linked to typical glioblastoma alterations such as IDH mutation, NF1 inactivation, and CDK4-MARCH9 locus amplification.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/19/5574/F1.large.jpg Cancer Res; 78(19); 5574-85. ©2018 AACR.
Feasibility of docetaxel, cisplatin and S-1 chemotherapy in elderly patients: Comparison with younger
Authors: Y. Nakamura, T. Nishimaki, H. Shimoji, H. Karimata
Journal: Annals of Oncology (2018)

Introduction: Choice of the therapy for esophageal cancer(EC) is often decided on a consideration of patient’s age as well as performance status. Elderly patients sometimes tend to be undertreated for safety reasons, therefore the best practice for them is unknown. Standard therapy for unresectable EC in Japan is any of chemotherapy, radiotherapy or concurrent chemoradiotherapy. But the clinical outcome is still limited. Recently, some study showed the effectiveness of triplet induction chemotherapy with docetaxel, cisplatin and fluorouracil(DCF). By taking those results, we have treated EC patients with docetaxel, cisplatin and oral fluorouracil prodrug S-1(DCS) chemotherapy since 2010. In this study, we retrospectively assess the efficacy and safety of this triplet regimen for unresectable EC patients, especially for the elderly. Methods: We enrolled the patients who received DCS for unresectable esophageal cancer. Patients received docetaxel (35mg/m2) plus cisplatin (35mg/m2) intravenously on day1 and 15, and S-1 (80mg/m2) on days 1-14, of a 28-day cycle. If the adverse event was tolerable, patients continued receiving cycles until the progression of the disease was observed or the tumor turned to be resectable. Response rate (RR), progression-free survival (PFS), overall survival (OS), and adverse events(AE) were compared between two age groups. Results: Between May 2011 to November 2017, 55 patients were treated with the systemic regimen. Median age was 63 years (range 47-85). Eleven patients (20%) were more than 70 years old (elderly group) and forty-four were below 70 years (young group). Reasons for unresectable were locally advanced (74.5%), distant metastasis (16.4%) and recurrence (9.1%). The median number of therapy cycles applied was 3. The best clinical response to DCS in elderly group were complete response 0%, partial response 62.5% and stable disease 27.2% (RR 54.5%). Those in young group were 11.4%, 63.6% and 18.2%, respectively (RR 75.0%). Twelve patients of all were converted to surgery. The median PFS in all was 6.7 months (5.3 months in elderly group and 6.7 months in young group, p = 0.85). The median OS was 25.2 months (15.0 months vs 25.3 months, p = 0.4). Grade 3-4 toxicity were observed 90.9% of elderly group and 81.8% of young group, there was no statistical significance between two groups(p = 0.47). There was no treatment related death. Conclusion: In our study, DCS therapy in elderly patients was as effective and feasible as in young. High grade adverse events were observed regardless of age, but still manageable.
Diagnostic and therapeutic efficacy of endoscopic enucleation for subepithelial tumors originating from muscularis propria layer
Authors: B. Bang, E. Ko, K. Kwon, Y. Shin, H. Kim
Journal: Annals of Oncology (2018)

Introduction: Gastric subepithelial tumors originated from the muscularis propria (MP) are partly benign tumors, but some MP tumors have malignant potential, especially gastrointestinal stromal tumors (GISTs). Therefore, accurate diagnosis of MP tumor is essential. The aim of this study was to evaluate the utility of endoscopic enucleation for the diagnosis and treatment of MP tumors. Methods: From January 2010 to February 2018, eighty-seven patients with gastric MP tumor underwent endoscopic enucleation. Before endoscopic resection, all patients performed endoscopic ultrasound to determine the layer of origin and the accurate size. According to tumor size (12mm or 12mm), band ligation and resection (BLR) or endoscopic submucosal resection (ESD) was performed. Tumor characteristics, procedure time, complete resection rate and recurrence were analyzed. Results: A total 87 patients were eligible for inclusion in this study. BLR method was used in 44 patients. Median procedure time was 10.5 minutes (range 3-85) and complete resection rate was 90.9% (40/44). Perforation was developed in four patients, which was closed by endoscopic clipping. ESD method was used in 43 patients. The median procedure time was 45 minutes (range 10 – 300) and complete resection rate was 86.0% (37/43). Nine cases were complicated by perforation. Five patients were treated using metal clips and four patient received surgery. Among 35 patients who were diagnosed as GIST, 30 patients showed low risk and very low risk. The mean follow-up time was 24.4 months (range 1-66) and recurrence was not developed in any patients during follow-up period. Conclusion: Endoscopic enucleation appears to be effective and relatively safe method for the histologic diagnosis and removal of subepithelial tumor originating from MP layer. Especially, BLR is an effective, less time-consuming and relatively safe treatment for small MP tumor (12 mm).
Second-line chemotherapy for advanced biliary tract cancer after failure of the gemcitabine-platinum combination: A single center experience
Authors: H. Engin
Journal: Annals of Oncology (2018)

Introduction: Few data are available on second-line chemotherapy (CT2) for advanced biliary tract cancer (ABTC). The aim of this retrospective study was to describe the CT2 regimens used, the response rates, and the outcomes of patients treated with various CT2 regimens. Methods: Patients who received CT2 for ABTC at Bülent Ecevit University Oncology Institute after the failure of the gemcitabine-platinum combination were retrospectively studied. Progression-free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method. Cox models were used for multivariate analyses. Results: Among 142 patients who received first-line chemotherapy (CT1) for ABTC, 96 received CT2: 5-fluorouracil (5-FU) and irinotecan (n = 30), 5-FU and oxaliplatin (n = 25), 5-FU and cisplatin (n = 16), 5-FU or capecitabine (n = 25). Among the 60 assessable patients, there were 7 partial responses and 17 stabilizations. After a median follow-up of 23.4 months, the median PFS and OS were 3.3 and 7.0 months, respectively. There was no significant difference in PFS or OS between CT2 regimens. Fluoropyrimidine-based doublet chemotherapy was not superior to fluoropyrimidine alone in terms of OS and PFS. In a multivariate analysis, a performance status of 0 to 1, disease control with CT1, a carbohydrate antigen 19-9 (CA 19-9) level ≤ 300 IU/mL, and age <50 years were significantly associated with longer PFS and OS. Conclusion: CT2 might provide disease control for selected patients with ABTC after the failure of gemcitabine-platinum, but the prognosis remains poor. No particular regimen seems superior to others.
A Randomized Controlled Trial of Parent-Child Psychotherapy Targeting Emotion Development for Early Childhood Depression
Authors: Joan L. Luby, Deanna M. Barch, Diana Whalen, Rebecca Tillman, Kenneth E. Freedland
Journal: American Journal of Psychiatry (2018)

Objective: Clinical depression in children as young as age 3 has been validated, and prevalence rates are similar to the school-age disorder. Homotypic continuity between early and later childhood depression has been observed, with alterations in brain function and structure similar to those reported in depressed adults. These findings highlight the importance of identifying and treating depression as early as developmentally possible, given the relative treatment resistance and small effect sizes for treatments later in life. The authors conducted a randomized controlled trial of a dyadic parent-child psycho-therapy for early childhood depression that focuses on enhancing the child’s emotional competence and emotion regulation. Method: A modified version of the empirically tested parent-child interaction therapy with a novel “emotion development” module (PCIT-ED) was compared with a waiting list condition in a randomized controlled trial in 229 parent-child dyads with children 3–6.11 years of age. Both study arms lasted 18 weeks. Results: Children in the PCIT-ED group had lower rates of depression (primary outcome), lower depression severity, and lower impairment compared with those in the waiting list condition (Cohen’s d values, >1.0). Measures of child emotional functioning and parenting stress and depression were significantly improved in the PCIT-ED group. Conclusions: The findings from this randomized controlled trial of a parent-child psychotherapy for early childhood depression suggest that earlier identification and intervention in this chronic and relapsing disorder represents a key new pathway for more effective treatment. Manualized PCIT-ED, administered by master’s-level clinicians, is feasible for delivery in community health settings.
QOL-22. THE EFFECTS OF FATIGUE ON DAILY LIVING ACTIVITIES AND QUALITY OF LIFE IN CHILDREN WITH BRAIN TUMOR
Authors: Muberra Tanriverdi, Fatma Karantay Mutluay, Fatma Betul Cakir
Journal: Neuro-Oncology (2018)

Brain tumors are second most common childhood cancer, and most common type of solid tumors. Our aim of study is to investigate effect of fatigue on Daily Living Activities(DLA) and Quality of Life(QoL) in children with brain tumor. Demographic information of children was recorded. Fatigue was assessed by "Visuel Analogue Scale" (VAS) and Borg fatigue scales verbally asked, DLA by WeeFIM, and QoL by PODCI. Ten (40%) girls, 15(60%) boys, totally 25 children with brain tumors were included. Mean age of children were 10.08 ± 3.639years, height 1.29 ± 0.197meters, weight 30.70 ± 10.634kg, diagnosis age 7.52 ± 3.917years, chemotherapy 7 ± 2.598cure, radiotherapy 31.80 ± 8.836sessions, surgical age 7.76 ± 3.992years and last surgical age 2.32 ± 1,145years. According to VAS results, 3.64 ± 1.655(1-7), Borg fatigue before walking 0.22 ± 0.614(0-3), after walking 1.82 ± 1.870(0-7) and fifth minute recovery 0.34 ± 0.608(0-2) was found. WeeFIM result was 119.08 ± 24.338(82-199), PODCI subscale scores showed that upper extremity 84.76 ± 11.395(58-100), transfer/basic movement 91.68 ± 11.153(59-100), sport/physical function 71 ± 23.518(16-100), pain/comfort 71.8 ± 25.290 (22-100), happiness 83.28 ± 16.739(25-100) and general function 79.68 ± 15.294(48-97). While there was a statistically significant relationship between fatigue of children and sex(r=-0.433; p=0.031), height(r=-0.397; p=0.049), radiotherapy sessions(r=0.610; p=0.001), PODCI upper extremity(r=-0.483;p=0.015), PODCI sport/physical function(r=-0.476; p=0.016), PODCI happiness(r=-0.504;p=0.010); there was no statistically significant difference between WeeFIM score and PODCI pain/comfort(r=-0.396;p=0.050). Fatigue in children with brain tumors is not only a symptom of illness, but also a result of treatment. It also affects DLA and QoL as well as activity. We think that functional capacity should be increased in order for fatigue to occur later.
Abstract 17846: Temporal Shift Towards Left Ventricular Sources of Idiopathic Ventricular Ectopy in Patients Referred for Ablation
Authors: Charles Rouse, Medhat Abdelmessih, Amarnath Annapureddy, Ralph DeBiasi, Alan Enriquez, Mark Marieb
Journal: Circulation (2016)

Introduction:  Historically the focus of ectopy in idiopathic ventricular tachycardia (VT) or premature ventricular contractions (PVC) showed a heavy bias towards right ventricular origins. The purpose of this study is to characterize the incidence of right vs left ventricular origins of idiopathic VT/PVC in patients referred for ablation in a modern cohort of patients.   Hypothesis:  There has been a temporal shift towards more left ventricular locations in patients who present for idiopathic VT/PVC ablation.   Methods:  The study population includes all patients referred for VT or PVC ablation at two sites within the Yale-New Haven Health System from January 1, 2011 to June 30, 2015. Patients were excluded if there was a history of cardiomyopathy or other structural heart disease. For each patient, clinical characteristics, medical history, ECGs, cardiac imaging, stress testing and Holter monitors were reviewed. Operative reports from the ablation procedure were reviewed. Location of the VT/PVC was defined as the site where ablation resulted in termination of the arrhythmia.   Results:  There were 67 cases included in the final analysis. There were no significant differences in baseline patient characteristics such as age, gender or body mass index between right and left ventricular locations. Right vs left ventricular location for the first vs second half of the time period are summarized in the figure. In the first half of the time period there was 95% vs 5% for right and left ventricular location respectively. In the second half there was 59% vs 41% for right vs left ventricular location respectively. (p=0.003)   Conclusions:  There has been a shift over time toward more left ventricular locations for idiopathic VT/PVC that present for ablation. No risk factors were identified that may contribute to this change. Confounders such as referral bias, environmental factors or improved recognition of left sided foci at ablation may contribute to this change and deserves further study.
Ultra-selection of metastatic colorectal cancer patients using next-generation sequencing to improve clinical efficacy of anti-EGFR therapy
Authors: J. Vidal, B. Bellosillo, C. Santos Vivas, P. García-Alfonso, A. Carrato, M.T. Cano, R. García-Carbonero, E. Élez, F. Losa, B. Massutí, M. Valladares-Ayerbes, J.M. Viéitez, J.L. Manzano, D. Azuara, J. Gallego, S. Pairet, G. Capellá, R. Salazar, J. Tabernero, E. Aranda, C. Montagut
Journal: Annals of Oncology (2019)

Extended RAS analysis is mandatory in metastatic colorectal cancer (mCRC) patients. The optimal threshold of RAS mutated subclones to identify patients most likely to benefit from antiepidermal growth factor receptor (EGFR) therapy is controversial. Our aim was to assess the clinical impact of detecting mutations in RAS, BRAF, PIK3CA and EGFRS492R in basal tissue tumour samples by using a highly sensitive next-generation sequencing (NGS) technology in mCRC patients treated with chemotherapy plus anti-EGFR or anti-vascular endothelial growth factor.Five hundred and eighty-one tumour samples from untreated mCRC patients from 7 clinical studies were collected. Mutational analysis was carried out by standard-of-care (therascreen pyro) with a sensitivity detection of 5% mutant allele fraction (MAF), and compared with NGS technology using 454GS Junior platform (Roche Applied Science, Germany) with a sensitivity of 1%. Molecular results were correlated with clinical outcomes.After quality assessment, 380 samples were evaluable for molecular analysis. Standard-of-care mutational analysis detected RAS, BRAFV600E or PIK3CA mutations in 56.05% of samples compared with 69.21% by NGS (P = 0.00018). NGS identified coexistence of multiple low-frequency mutant alleles in 96 of the 263 mutated cases (36.5%; range 2-7). Response rate (RR), progression-free survival (PFS) and overall survival (OS) were increasingly improved in patients with RAS wild-type, RAS/BRAF wild-type or quadruple (KRAS/NRAS/BRAF/PIK3CA) wild-type tumours treated with anti-EGFR, assessed by standard-of-care. No additional benefit in RR, PFS or OS was observed by increasing the detection threshold to 1% by NGS. An inverse correlation between the MAF of the most prevalent mutation detected by NGS and anti-EGFR response was observed (P = 0.039). EGFRS492Rmutation was not detected in untreated samples.No improvement in the selection of patients for anti-EGFR therapy was obtained by adjusting the mutation detection threshold in tissue samples from 5% to 1% MAF. Response to anti-EGFR was significantly better in patients with quadruple wild-type tumours.