tbuckley/cabot-search huggingface dataset:
RONC-04. PROSPECTIVE, LONGITUDINAL STUDY OF NEUROCOGNITIVE CHANGE IN PEDIATRIC BRAIN TUMOR PATIENTS TREATED WITH PROTON BEAM RADIOTHERAPY VERSUS SURGERY ONLY
Authors: Lisa S Kahalley, Anita Mahajan, M Fatih Okcu, Murali Chintagumpala, M Douglas Ris, Arnold C Paulino, Charles Minard, William Whitehead, Emily A Warren, Jessica Orobio, Judy J Xue, David R Grosshans
Journal: Neuro-Oncology (2018)

Proton radiotherapy (PRT) reduces the volume of normal tissue receiving radiation dose, which may lead to better neurocognitive outcomes. We examined change in neurocognitive scores over time in pediatric brain tumor patients treated with craniospinal PRT (P-CSI), focal PRT (P-Focal), or Surgery Only (SO). Patients received annual neurocognitive evaluations for up to 5 years. We examined Full Scale IQ (FSIQ), Verbal Comprehension (VC), Perceptual Reasoning (PR), Working Memory (WM), and Processing Speed (PS) scores. Separate general linear mixed models examined change in scores over time by treatment group. 83 patients (19 P-CSI, 26 P-Focal, 38 SO) were examined. Groups were compared on demographic/clinical variables (49.4% male, 34.9% infratentorial, mean age-at-treatment=9.7 years, mean follow-up interval=2.8 years). Tumor types included: 54.2% glioma, 18.1% PNET/medulloblastoma, 6.0% ependymoma, 7.2% germ cell, 7.2% craniopharyngioma, and 7.2% other. Median RT dose to tumor bed was 54.0 Gy (P-CSI) and 50.4 Gy (P-Focal). All index scores remained stable in P-Focal and SO groups (all p>0.05). WM, PS, and FSIQ scores declined significantly in the P-CSI group (p=0.04, 0.01, 0.02). The P-CSI group showed significantly greater decline in PS and FSIQ scores compared to P-Focal and SO groups (all p<0.05). Within early survivorship, P-Focal was not associated with significant cognitive decline, even in radiosensitive domains. Outcomes were similar whether patients received P-Focal or no radiotherapy. P-Focal and SO group means were within normal limits for age across all indexes and time points. CSI emerged as a cognitive risk factor, consistent with photon outcomes research.
Use of gemcitabine and nab-paclitaxel as a third-line treatment following failure of first line gemcitabine for advanced pancreatic adenocarcinoma
Authors: M. McNulty, A. Dean, A. Das, M. Gordon
Journal: Annals of Oncology (2018)

Introduction: First line treatment for advanced pancreatic adenocarcinoma is well documented and typically involves therapy with FOLFIRINOX or gemcitabine plus nab-paclitaxel. The CONKO-003 trial demonstrated efficacy of 2nd line treatment with the OFF regimen (oxaliplatin, 5-fluorouracil and folinic acid) and more recently the phase III trial, NAPOLI-1, established a tolerable and effective 2nd line treatment option, combining nal-irinotecan with 5-fluorouracil and leucovorin. Despite these advances, there remains minimal amount of data regarding the options for or the efficacy of 3rd line treatment in these patients. This retrospective analysis assessed the use of gemcitabine plus nab-paclitaxel as a 3rd line treatment option in a single hospital settling. Methods: Using an electronic database, we conducted a retrospective analysis of 20 patients with locally advanced or metastatic adenocarcinoma of the pancreas who received third line treatment with gemcitabine and nab-paclitaxel between 2013 and 2017. We selected patients who had received first line gemcitabine-based therapy, to assess the subsequent outcome of retreatment with gemcitabine and nab-paclitaxel (800 mg/m2 and 125 mg/m2 respectively, on days 1, 8 and 15 every four weeks). Overall survival (OS) was estimated by the Kaplan-Meier method. Results: Twenty patients were reviewed. Median age was 70 years (range, 44 – 81). 55% of the patients were females. Majority of the studied patients had locally advanced cancer at diagnosis (85%). The median OS was 6.0 months (95% CI, 4.0 – 26.0) from re-initiation of gemcitabine plus nab-paclitaxel. Conclusion: This retrospective study showed that retreatment of advanced pancreatic adenocarcinoma patients with gemcitabine plus nab-paclitaxel could be a suitable third-line treatment option. In order to evaluate the actual efficacy of this third-line chemotherapy regimen, phase III trials would need to be conducted to compare gemcitabine plus nab-paclitaxel with other chemotherapeutic agents.
Efficacy of Dialectical Behavior Therapy for Adolescents at High Risk for Suicide
Authors: Elizabeth McCauley, Michele S. Berk, Joan R. Asarnow, Molly Adrian, Judith Cohen, Kathyrn Korslund, Claudia Avina, Jennifer Hughes, Melanie Harned, Robert Gallop, Marsha M. Linehan
Journal: JAMA Psychiatry (2018)

Suicide is a leading cause of death among 10- to 24-year-old individuals in the United States; evidence on effective treatment for adolescents who engage in suicidal and self-harm behaviors is limited.
FOLFOX/bevacizumab +/- irinotecan in advanced colorectal cancer (CHARTA): Long term outcome
Authors: H. Schmoll, B. Garlipp, C. Junghanß, A. Vogel, U. Kaiser, A. Florschütz, S. Kanzler, C. Hannig, F. Meinert, F. Cygon, A. Stein
Journal: Annals of Oncology (2018)

Introduction: FOLFOXIRI/bevacizumab (Bev) was superior to FOLFIRI/Bev in the TRIBE trial. However the comparison with FOLFOX/Bev as the alternative standard was not proven. The CHARTA trial was developed in parallel to TRIBE, but with FOLFOX/Bev as control arm; for comparison reasons TRIBE and CHARTA used the same dose and schedule. Methods: From 7/11 to 12/14 250 patients were randomized, including ECOG 0-2, ≥ 1 measurable lesion > 1cm, stratified by ESMO-Group 1,2,3. Induction: 6 months, maintenance capecitabine+Bev until progression or max. 12 months, at P reinduction by investigators decision. 25% dose reduction was allowed in cycle 1 + 2 on the investigator's discretion. Primary EP: significant improvement of PFS-rate @ 9 months (p < 0.1, 2-sided Fisher's-exact test); secondary EP: RR, PFS, OS, toxicity. Results: 241 pts (1 not elig., 8 prot. violation) are evaluable and have been previously presented after a follow up of 31.4 (0.1-51) months (Schmoll et al, World GI 2017). The Primary Endpoint was met: PFS @ 9 months 56% vs. 68%, p = 0.086. PFS was improved: 9.8 vs. 12.0 months, HR 0.7 (ns.), identical to TRIBE with 9.7 vs. 12.1 months. Response rate (A/B): CR: 5%/5%, CR/PR 60%/70%, SD 25%/21%, PD 14%/9%. OS was not significant different (24 vs 28). Toxicity was low to moderate without major differences except grade ¾ diarrhea (12%/16%) and neutrophils (14%/20%). Clinical/molecular prognostic or predictive factors are equally distributed (stratified by ESMO groups). PFS was significantly improved (p = 0.027) in the subgroup of pts. with synchronous metastases (91% of pts); the strongest improvement by the 4-drug combination was shown in those pts. with synchronous mets., who never had resection of the primary (52% of the pts.): 17 vs. 26.5 mos. (p < 0.01). In the subgroup of "liver/lung only" there was no difference, however with a long OS in both arms (45.3 / 44.2 mos.). In univariate analysis there are major, but mostly not significant differences in RR/ PFS in most subgroups (borderline significant: risk score high HR 0.66; ESMO group 3 HR 0.62; BRAF HR 0.72; right location HR 0.73), however, not strong enough to safely identify patients with high potential to benefit from the 4-drug combination. Conclusion: After 12 further months of follow-up with a median of 38 with a maximum of 7 years. All data for PFS and OS are mature and ready for final evaluation, including clinical and molecular subgroup and multivariate analyses as well data on reinduction and salvage treatments. Translational research is ongoing. The final clinical data will be available at the meeting.
Analysis of echoendoscopic punctures of a solid pancreatic lesions in a private institution in Brazil
Authors: T. Pessoa, A. Pessoa, P. Aguiar, R. Pessoa, A. Moura, D. Ferreira, F. Távora, F. Pessoa, R. Pessoa
Journal: Annals of Oncology (2018)

Introduction: In the last 10 years echoendoscopy has been consolidated as a major weapon for the diagnosis of pancreatic diseases. The improvement in radiological exams (tomography and MRI) increases the number of nodules detected in asymptomatic patients. And it is important to establish diagnoses by cytology or histology. Echoendoscopy is better than conventional ultrasound to guide puncture because of the retroperitoneal localization. This study aimed to analyze the result of punctures performed in solid lesions in pancreas. Methods: It is a retrospective study, quantitative, carried out in a private clinic in Northeast of Brazil, comprising 99 patients who underwent pancreatic puncture during the years 2016 and 2017 using a single needle (22 gauge), Fanning maneuver and technique by Negative pressure and capillarity, depending on the doctor's choice, without rose. GraphPad software was used for the statistical analysis efficiency of the punctures, the lesions (size and location), confirmation of the form of collection and degree of similarity of the results with those described in the literature. We divided the size of the lesions in three groups: less than 1 cm; 1 to 3 cm and larger than 3 cm. 5% significance was adopted. Results: In 86.86% of the cases, the final pathologic diagnosis confirmed the clinical suspicion. Ninety nine (99) pancreatic punctures were performed, 65.66% in the head of the pancreas; 23.24% in the body; 8.08% in the tail and 3.02% in the uncinate process. The major part of the punctures (54.55%) had 1 to 3 cm; 37.37% were greater than 3cm and 8.08% less than 1 cm. Sixty three percent (63.07%) of the punctures of head nodules were positive. 68.29% of them had between 1 to 3cm; 24.40% were greater than 3cm and 9.75% less than 1cm. Eighty two percent of the punctured in the body were positive, 68.42% of them had between 1 to 3 cm; 21,05% was greater than 3cm and 10.52% less than 1cm. In the tail, 50% of the punctures were positive, 62.50% of them were greater than 3cm and 37.50% (1 to 3 cm). In uncinate process, punctures were positive in 66.66%, and 66.67% were greater than 3 cm, while 33.33% had between 1 to 3 cm. Of the 13.13% negative nodules, 56.92% were in the head (1 to 3 cm); 20.01% in the Body (83.24% -1 to 3 cm and 16.76% greater than 3cm); 7.69% in the Tail (1 to 3 cm) and 15.38% in the uncinate process (greater than 3cm). Conclusion: It is concluded that our study coincided with the literature as we had 86.86% of sensitivity and 100% of specificity. The negative results were more frequent in lesions in the head of the pancreas and smaller than 1 cm.
MBCL-02. CURRENT ISSUES IN THE MANAGEMENT OF DESMOPLASTIC NODULAR MEDULLOBLASTOMA IN YOUNG CHILDREN
Authors: Mohamed AbdelBaki, Daniel Boué, Jonathan Finlay, Mark Kieran
Journal: Neuro-Oncology (2018)

Children with desmoplastic nodular medulloblastoma (DNMB) have excellent survival, leading multiple groups globally to attempt reduction of treatment-related morbidity. In 2013, the Children’s Oncology Group began a clinical trial (ACNS1221) eliminating both radiation therapy (RT) and intraventricular methotrexate for children under 3 years of age with localized DNMB, aiming to build upon the excellent outcomes of the German (HIT) trials. ACNS1221 has recently closed due to increased incidence of recurrences noted at the 2-year interim analysis, raising important questions regarding optimal therapy for DNMB. A review of major clinical trials that included children with DNMB was performed through July 2017. One hundred and eighty eight DNMB patients enrolled on 11 prospective clinical trials were identified. The use of marrow-ablative chemotherapy and autologous hematopoietic cell rescue (AuHCR), or treatment with intraventricular methotrexate has been associated with excellent outcomes. RT was usually required for patients with evidence of disease at the end of therapy. The minimal intensity and duration of chemotherapy required to maximally cure children with DNMB without need of RT, remains unknown. Further trials are required to better identify a subset of DNMB patients who can be cured without marrow-ablative chemotherapy or intraventricular methotrexate.
Abstract 18719: Reduction of Right Ventricular Pressure Overload by Lung Transplantation Reverses Right Ventricular Function and Remodeling in Patients With End-Stage Pulmonary Arterial Hypertension
Authors: Toshihiro Sarashina, Kazufumi Nakamura, Kentaro Ejiri, Satoshi Akagi, Hiroki Oe, Hiroshi Ito
Journal: Circulation (2016)

Introduction: Right ventricular (RV) dysfunction has been regarded as an independent determinant of the worse outcome in patients with pulmonary arterial hypertension (PAH). Although several PAH-sp...
Transcribed ultraconserved regions Uc160 and Uc346 in colon cancer progression
Authors: A. Kottorou, C. Sirinian, F. Dimitrakopoulos, A. Antonacopoulou, T. Makatsoris, H. Kalofonos
Journal: Annals of Oncology (2018)

Introduction: Expression of Transcribed Ultra Conserved Regions (Transcribed Ultra Conserved Regions, T-UCRs) is often deregulated in many types of cancer, including colorectal cancer (CRC). Our previous results showed that T-UCRs Uc160 and Uc346 are methylated in CRC. Additionally, their tumor methylation is associated with time to disease progression (TTP) and appears to be a promising biomarker for CRC. However, their role in CRC progression has not been elucidated to date. Methods: Aim of the study was to investigate the role of Uc160 and Uc346 in proliferation, motility and migration in colon cancer cells. For that purpose, Uc160 and Uc346 were cloned into plasmids and three colon cancer cell lines (HT-29, Caco-2 and DLD-1) were transiently transfected. After overexpression of Uc160 and Uc346, proliferation (ΜΤΤ assay), motility (scratch wound healing assay) and migration (transwell migration assay) rates were evaluated. Results: Proliferation rates, 48h after overexpression, were higher in the transfected cell in all cell lines, compared with the control cells (mock transfected). The most significant differences in proliferation rates were noticed for Uc160 overexpression in Caco-2 (p = 0.008) and Uc346 overexpression in DLD-1 cells (p = 0.033). Similar results were observed in motility assay, with cells overexpressing Uc160 or Uc346 having higher motility rates compared to control cells in all cell lines. More specifically, most significant differences in motility rates were observed in HT-29 and DLD-1 cells overexpressing Uc160 or Uc346 (p = 0.017, p = 0.041 and p = 0.023, p = 0.004 respectively). Further analysis of DLD-1 cells migration confirmed the above results, with higher number of Uc160 or Uc346 overexpressing cells migrating compared to the control cells (p = 0.005 for both T-UCRs). Conclusion: T-UCRs Uc160 and Uc346 appear to affect the proliferation, motility and migration rates of colon cancer cells, implicating a complex role in CRC progression.
Functional Multichannel Poly(Propylene Fumarate)‐Collagen Scaffold with Collagen‐Binding Neurotrophic Factor 3 Promotes Neural Regeneration After Transected Spinal Cord Injury
Authors: Xi Chen, Yannan Zhao, Xing Li, Zhifeng Xiao, Yuanjiang Yao, Yun Chu, Balázs Farkas, Ilaria Romano, Fernando Brandi, Jianwu Dai
Journal: Advanced Healthcare Materials (2018)

Abstract Many factors contribute to the poor axonal regrowth and ineffective functional recovery after spinal cord injury (SCI). Biomaterials have been used for SCI repair by promoting bridge formation and reconnecting the neural tissue at the lesion site. The mechanical properties of biomaterials are critical for successful design to ensure the stable support as soon as possible when compressed by the surrounding spine and musculature. Poly(propylene fumarate) (PPF) scaffolds with high mechanical strength have been shown to provide firm spatial maintenance and to promote repair of tissue defects. A multichannel PPF scaffold is combined with collagen biomaterial to build a novel biocompatible delivery system coated with neurotrophin‐3 containing an engineered collagen‐binding domain (CBD‐NT3). The parallel‐aligned multichannel structure of PPF scaffolds guide the direction of neural tissue regeneration across the lesion site and promote reestablishment of bridge connectivity. The combinatorial treatment consisting of PPF and collagen loaded with CBD‐NT3 improves the inhibitory microenvironment, facilitates axonal and neuronal regeneration, survival of various types of functional neurons and remyelination and synapse formation of regenerated axons following SCI. This novel treatment strategy for SCI repair effectively promotes neural tissue regeneration after transected spinal injury by providing a regrowth‐supportive microenvironment and eventually induces functional improvement.
Efficacy and safety of tislelizumab, an anti-PD-1 antibody, versus sorafenib as first-line treatment in patients with advanced hepatocellular carcinoma in a phase 3, randomized, open-label, multicenter study - Trial in progress
Authors: S. Qin, R. Finn, M. Kudo, T. Meyer, A. Vogel, M. Ducreux, T. Macarulla, G. Tomasello, F. Boisserie, J. Hou, C. Li, J. Song, A. Zhu
Journal: Annals of Oncology (2018)

Introduction: Unresectable hepatocellular carcinoma (HCC) accounts for 70% of diagnosed HCC. Tislelizumab (previously known as BGB-A317) is a humanized, IgG4 monoclonal antibody with high affinity and binding specificity for programmed cell death receptor-1 (PD-1). Furthermore, tislelizumab was specifically engineered to minimize FcgR binding on macrophages, thereby abrogating antibody-dependent phagocytosis, a potential mechanism of T-cell clearance. A first-in-human, phase 1A/1B study (NCT02407990) demonstrated that single-agent tislelizumab was generally well tolerated and showed evidence of antitumor activity in patients with advanced solid tumors, including HCC. A recommended phase 3 dose of 200 mg administered intravenously (IV) every 3 weeks (Q3W) has been established for tislelizumab. Methods: This global, phase 3, randomized, multicenter study (NCT03412773) was designed to evaluate the efficacy and safety of tislelizumab compared with sorafenib as a first-line treatment of unresectable HCC. Adult patients, aged ≥18 years, with unresectable, histologically confirmed HCC, an ECOG score ≤1, Child-Pugh A classification, BCLC Stage C disease or BCLC Stage B disease that has relapsed after loco-regional therapy, and who have not received prior systemic therapy, are being enrolled. Approximately, 640 patients from 100 international centers will be randomized (1:1) to receive tislelizumab 200 mg IV Q3W or sorafenib 400 mg orally BID. The primary outcome of this non-inferiority study is overall survival (OS) of patients treated with tislelizumab compared with OS of patients treated with sorafenib; secondary outcomes include objective response rate, progression-free survival, duration of response, time to progression, and quality-of-life outcomes. Safety/tolerability assessments include monitoring adverse events (AEs), including immune-related AEs, as well as physical examinations, vital signs, and electrocardiograms. Exploratory endpoints include assessment of potential predictive biomarkers, characterization of the tislelizumab pharmacokinetic profile in patients with HCC, and to determine host immunogenicity against tislelizumab.
Analysis of clinical outcomes of two antiEGFR antibodies, cetuximab and panitumumab, in the 1st line chemotherapy of RAS wild metastatic colorectal cancer, by neutrophil-to-lymphocyte ratio (NLR) kinetics
Authors: D. Manaka, R. Nishitai, S. Konishi, T. Ota, Y. Nishikawa, R. Kudo, K. Kawaguchi, H. An, S. Hamasu
Journal: Annals of Oncology (2018)

Introduction: mFOLFOX6+antiEGFR antibody is a standard-of-care in the 1st line chemotherapy of metastatic colorectal cancer. Two molecular targeted drugs, i.e. cetuximab (Cet) and panitumumab (Pani), are the choices of antiEGFR antibody, but the proper use of these drugs are not clarified yet. Cet, IgG subclass1 antibody, is demonstrated to have ADCC activity and other immune, inflammatory functions. Differences of the activities of these two antibodies could be analyzed from this standpoint using the kinetic evaluations of neutrophil-to-lymphocyte ratio (NLR), which is the indicator of cancer-related immune and inflammatory activities. Methods: 50 pts with RAS wild metastatic colorectal cancer were enrolled and treated with mFOLFOX6+antiEGFR antibody (25 pts with Cet, 25 pts with Pani). NLR was measured at the points of pre-treatment (preT), early-tumor-shrinkage (ETS) and progression of disease (PD). The associations of NLR and clinical outcomes were evaluating by Spearman's rank correlation coefficient, and two-sample Mann-Whitney U tests were performed with several variants between Cet and Pani pts. Results: The median follow-up time for censored cases was 28 months (m) (IQR, 14-52). Progression free survival (PFS) and overall survival (OS) were 10.9m (95% C.I;7.9-12.6) and 30.0m (95% CI; 20.4-41.2), respectively. PFS and OS of Cet and Pani pts were not different significantly different [PFS: 12.0m (95% CI; 7.2-16.2) vs 9.5m (95% CI; 7.8-12.1), p = 0.23; OS: 30.0m (95% CI; 21-49.9) vs 33.1m (95% CI; 13-41.9), p = 0.202]. NLR at preT and PD were significantly correlated with OS, -0.291(p = 0.0422) and -0.347 (p = 0.0413), respectively. Correlation of PFS with NLR at ETS and with the difference of NLR between preT and ETS, were -0.415 (p = 0.0391) and -0.355 (p = 0.0816) in Cet pts, whereas there were no significant trends of correlation in Pani pts, 0.272 (p = 0.209) and 0.598 (p = 0.002), respectively. Conclusion: Our results suggest that NLR kinetics could reflect the treatment outcomes and kinetic analysis would lead to the stratification of clinical use of Cet and Pani. Cet, rather than Pani, might have more immune and inflammatory associations in the 1st line chemotherapy of RAS wild metastatic colorectal cancer. Clinical trial information: UMIN000031535.
NSRG-02. UNUSUAL DISSEMINATED DYSEMBRYOPLASTIC NEUROEPITHELIAL TUMOR INDICATING ROSETTE-FORMING GLIONEURAL TUMOR
Authors: Taku Uchiyama, Rie Nagayama, Junji Shibahara, Noriyoshi Fukushima, Daisuke Matsubara, Kensuke Kawai, Akira Gomi
Journal: Neuro-Oncology (2018)

Dysembryoplastic neuroepithelial tumor (DNT) is usually a localized tumor in the temporal or frontal lobe, and dissemination or progression of DNT is very rare. Few reports have described multifocal DNTs. Here we present a case of disseminated, progressive tumor with DNT features. A 9-year-old boy was referred to our hospital with headache and epilepsy. MRI indicated left medial temporal tumor involving the cerebral cortex, which showed T1-weighted hypointensity and T2-weighted hyperintensity without gadolinium contrast enhancement. The tumor gradually enlarged, and initial surgery comprising partial resection was therefore performed at 10 years old. The initial pathological diagnosis was DNT. Disseminated lesions on the lateral ventricle walls were identified and the residual temporal lesion gradually enlarged. At 15 years old, the residual tumor involving the hippocampus and amygdala underwent subtotal removal. Histopathological findings from the second surgery mainly comprised specific glioneuronal elements indicating DNT. However, islands of high cellularity containing neurocytic rosettes were also observed. No pilocytic astrocytoma-like component was observed. No mitosis was detected. We finally diagnosed rosette-forming glioneural tumor (RGNT) with DNT background. Recently, some reports of mixed tumors comprising RGNT and DNT have been published. Those tumors often showed CSF dissemination. Tumors with DNT features and disseminated lesions may represent RGNT, and neurocytic rosette should be looked for in such cases.