tbuckley/cabot-search huggingface dataset:
Early outcomes of a pilot study of neoadjuvant chemotherapy with S-1 plus oxaliplatin at dose of 130mg/m2 (nacG-SOX130) in stage III gastric cancer
Authors: S. Konishi, D. Manaka, H. An, Y. Nishikawa, T. Ota, R. Kudo, K. Kawaguchi, S. Hamasu, R. Nishitai
Journal: Annals of Oncology (2018)

Introduction: Post-operative adjuvant chemotherapy with S-1 is a widely used standard-of-care in pStage II/III gastric cancer in Japan. However, S-1 monotherapy for 1 year is demonstrated to be not sufficient for the high risk group of recurrence, i.e. stage III. In addition, patients(pts) may not pursuit adjuvant doublet chemotherapy because of the poor postoperative compliance induced by surgical stress. In this pilot trial, we evaluated the safety and efficacy of nacG-SOX130 in Stage III gastric cancer. Methods: A histologically proven resectable gastric cancer with stage IIIa-IIIc (JCGC 14th edition) were eligible. All pts were explored by laparoscopy before treatments to exclude tumor dissemination (CY0, P0). Pts were treated with two-cycles of nacG-SOX130 (S-1 80-120 mg/day according to BSA for 2 weeks, l-OHP 130 mg/m 2 on day 1, every 3 weeks), and radical gastrectomy with D2 lymphadenectomy were performed. Results: From January 2016 to September 2017, 20 pts were enrolled. There were 15 males and 5 females with median age of 66 years (40 to 80). All pts were available for evaluating the clinical response. The completion rate of the protocol treatment was 100%. Relative dose intensity was 89.9% in S-1 (95% CI: 84.7-95.1) and 95.8% in oxaliplatin (95% CI: 91.8-99.4). Non-hematological toxicities were mostly the peripheral sensory neuropathy (Grade 1; 60%, Grade 2; 5%, Grade 3; 0%), and the most frequent hematological toxicity was neutropenia (Grade 1; 0%, Grade 2; 20%, Grade 3; 0%). Clinical response rate was 85% (95% CI: 52.7-82.6), complete response in 3 pts (15%) and partial response in 14 pts (70%). 3 pts had stable disease (15%) and no progressive disease was observed, which lead to the disease control rate of 100% (95% CI: 87-100). 3 pts were finally revealed as a pathological complete response (15%). Histological evaluation of therapeutic effect more than Grade 2 was 45%. Every patient was performed a curative resection (curative resection rate: 100%). No postoperative complications were observed more than G1 of Clavien-Dindo classification. Conclusion: NacG-SOX130 in Stage III gastric cancer was well-tolerated and resulted in high rates of clinical and pathological responses without impairing the surgical treatment. nacG-SOX130 would be a promising choice of neoadjuvant chemotherapy in Stage III gastric cancer. Clinical trial information: UMIN000031388.
New Platform Showcases Scientific Research From Africa
Authors: M.J. Friedrich
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
NFM-12. ENHANCING BRAIN LESIONS IN CHILDREN WITH NEUROFIBROMATOSIS TYPE 1
Authors: Mariana Fernandes, João Passos, Daniela Garcez, Manuela Mafra, Sofia Nunes, Duarte Salgado
Journal: Neuro-Oncology (2018)

Children with Neurofibromatosis type 1 (NF1) are at an increased risk of developing glial tumors. Gadolinium enhancement signals blood-brain barrier breakdown and implies tumor activity. In an attempt to determine the prevalence and outcome of enhancing brain lesions in children with NF1, we performed a retrospective analyses of all patients with NF1 followed in a Pediatric Neuro-Oncology department with periodic brain MRI. Of 67 patients whose follow up included neuroimaging studies (optic pathway gliomas 62, other low grade gliomas 3, enhancing lesion 1, T2 hyperintensity 1), 17(25,3%) showed evidence of enhancing brain lesions (median age at diagnosis 8 years). A total of 25 lesions were identified, mainly in the posterior cranial fossa compartment (60%). Four lesions (4 patients) were symptomatic. One symptomatic patient (mesencephalic lesion), underwent solely a ventriculostomy. Three symptomatic and 3 asymptomatic patients (based on imagiological progression) underwent chemotherapy (complete response obtained in 3 patients, partial response in 2, 1 patient under treatment). In patients who didn’t underwent chemotherapy, spontaneous regression was observed in 8 lesions (7 patients), the others remain imagiological stable. Mean follow up time 4,5 years. In our experience, enhancing brain lesions are prevalent in children with NF1, and although gadolinium enhancement suggests glioma, the proliferative potential remains questionable. The best approach of this lesions is far from being determined. We admit that symptomatic lesions should be treated. In asymptomatic lesions, watchful surveillance may be appropriate and decision to treat must take in consideration multiple aspects, namely imagiological progression.
LGG-48. MULTI-STATE-ANALYSIS FOR PEDIATRIC PATIENTS WITH LOW-GRADE GLIOMA
Authors: Anna-Maria Goebel, Astrid K Gnekow, Daniela Kandels, Olaf Witt, Rene Schmidt, Pablo Hernáiz Driever
Journal: Neuro-Oncology (2018)

Low-grade-glioma (LGG) is often a chronic disease requiring multiple treatment-interventions. The multi-state-model (MSM) analyzes almost unlimited disease-states that patients may undergo. We analyzed disease-state probability of German LGG-patients within the SIOP-LGG 2004 study. Starting-state was defined as “diagnosis” and final-state as “death” with in-between “disease-states”, i.e. surgery, chemotherapy or radiation. We then evaluated clinical risk factors associated with multiple interventions. We identified 1587 patients and a total of 23 different states (median follow-up 6.2 years). For robust statistical calculation, we reduced the model to 10 states. Five years after diagnosis state probabilities of patients were as follows: 0.11 no therapy at all, 0.49 one and 0.10 two surgeries-only, 0.19 one, 0.04 two and 0.02 even three non-surgical interventions with or without prior surgery, 0.005 had developed a malignant tumor and 0.02 had deceased. Risk-group analysis revealed higher probability for multiple interventions for infants (0.40), tumor location in supratentorial midline (0.21) or cerebellum (0.20), astrocytic tumors (0.22) and degree of resection, i.e. partial resection (0.31) and biopsy-only (0.35) five years after diagnosis. Probabilities for patients with neurofibromatosis type-1 were most likely not to be treated at all (0.36) or to receive non-surgical therapy, if needed (0.45). Sex had no influence. This is the first MSM analysis of a LGG clinical trial cohort reflecting natural history and transitions to multiple interventions. A substantial number of patients is at risk for successive treatments with associated neurotoxicity. This underscores the necessity that LGG-management attempts to save function.
Personalised perioperative care by e-health after intermediate-grade abdominal surgery: a multicentre, single-blind, randomised, placebo-controlled trial
Authors: Eva van der Meij, Johannes R Anema, Wouter K G Leclercq, Marlies Y Bongers, Esther C J Consten, Steven E Schraffordt Koops, Peter M van de Ven, Caroline B Terwee, Johanna M van Dongen, Frederieke G Schaafsma, Wilhelmus J H J Meijerink, Hendrik J Bonjer, Judith A F Huirne
Journal: The Lancet (2018)
HGG-33. PATIENT DERIVED CELL LINES TO STUDY ATRX AND ALT IN PEDIATRIC BRAIN TUMORS
Authors: Heba Ijaz, Robert Dilley, Mateusz Koptra, Gonzalo Garcia, Yuankun Zhu, Bo Zhang, Valerie Baubet, Jennifer Mason, Adam Resnick, Krutika Gaonkar, Angela Waanders, Pichai Raman, Roger Greenberg, Kristina Cole
Journal: Neuro-Oncology (2018)

All cancers acquire a mechanism of telomere maintenance (TMM) for genomic stability and unlimited replicative potential. Some cancers, including a subset of pediatric brain tumors, use the TMM of alternative lengthening of telomeres (ALT). However, there are few cancer cell lines with ALT, representing a mixture of histotypes. We aim to generate patient derived pediatric brain tumor cell lines with and without ALT for downstream analyses. The Children’s Brain Tumor Tissue Consortium (CBTTC) database was queried for pediatric brain tumor types likely to have ALT and tumor in freezing media. Patient derived cell lines were generated as adherent and suspension lines. Corresponding primary tumor samples were analyzed for ALT by c-circle assay (CCA) and WGS for targeted gene mutations and estimated telomere length. 38 high-grade glioma and PNET samples were processed into patient derived cell lines. To date, at least one line from 25 of the 38 tumors are growing well in various stages of development and validation, with 10 having the expected somatic mutations, including 3 with ALT. Analysis of the cell lines corresponding primary tumor revealed that 13/37 (35%) are ALT (CCA) positive. Targeted H3.3 sequencing showed that 3/3 (100%) of G34R mutant, 3/8 (37%) of K27M mutant and 7/26 (27%) of H3.3 wild-type tumors are ALT positive. WGS was available for 29 tumors, including 10 with ALT. The ALT positive tumors have damaging mutations in TP53 (6/10), ATRX (6/10), H3.3 (6/10) and IDH1 (1/10) and are computationally predicted to have long telomeres (p=0.03).
ATRT-27. A PHASE II STUDY OF PANOBINOSTAT IN PAEDIATRIC PATIENTS WITH SOLID TUMORS INCLUDING MALIGNANT RHABDOID TUMOR/ATYPICAL TERATOID RHABDOID TUMOURS
Authors: Paul Wood, Jayesh Desai, Nick Gottardo, Jason Cain, David Ashley
Journal: Neuro-Oncology (2018)

Low-dose panobinostat treatment has been shown to terminally differentiate malignant rhabdoid tumor (MRT)/atypical teratoid rhabdoid tumors (ATRT) in pre-clinical models. This will be an open label, phase II study, of panobinostat in patients with newly diagnosed MRT/ATRT, aimed to define the anti-tumour activity of panobinostat. To define the anti-tumour activity of low dose continuous panobinostat. To define and describe the associated toxicities of panobinostat. To define the anti-tumor activity of low dose, continuous panobinostat using functional imaging techniques. To assess the biologic activity of low dose panobinostat by measuring histone acetylation status in peripheral mononuclear cells (PMNC) and markers of differentiation in fresh tumour tissue specimens in all patients (when available). Pediatric patients with newly diagnosed MRT/ATRT will be eligible to be enrolled. Following initial cycles of chemotherapy and/or radiation treatment panobinostat will be administered as a continuous daily oral dose starting at 10mg/m2. There will be a three-week wash out period between therapies. Real-time acetylation status, using acetylated H3 & H4 on PMNC, will determine biological activity of panobinostat in the first two patients enrolled. A second analysis will be performed after nine patients have been enrolled. The regimen will be considered worthy of further study if disease stability of more than three of the first nine patients, with less than 30% of patients experiencing grade 3 and/ or 4 adverse events, at four months. If this is achieved the study will proceed to recruit a total of 20 patients.
IMMU-01. DURABLE RESPONSE TO NIVOLUMAB IN A PEDIATRIC PATIENT WITH REFRACTORY GLIOBLASTOMA AND CONSTITUTIONAL BIALLELIC MISMATCH REPAIR DEFICIENCY
Authors: Musa AlHarbi, Nahla Ali Mobark, Latifa Al-Mubarak, Rasha Alaljelaify, Mariam AlSaeed, Amal Almutairi, Fatmah Alqubaishi, Emarat Hussain, Lamia AlSubaie, Saeed AlShieban, Nada alTassan, Shakti H Ramkissoon, Malak Abedalthagafi
Journal: Neuro-Oncology (2018)

Constitutional biallelic mismatch repair deficiency CMMR-D is a rare childhood cancer predisposition syndrome. Detection of CMMR-D in pediatric HGG is crucial and can improve patient outcome due to the fact that CMMR-D is responsive to immune checkpoint inhibitors like Nivolumab. A 5 years old girl not known to have any medical illness before presented KFMC (a tertiary pediatric cancer center in Saudi Arabia) with history of headache, vomiting, left eye squint and lethargy. Parents are first degree relatives with strong family history of malignancy. Her brother died at the age of 8 years with refractory non-Hodgkin lymphoma. Imaging showed large intra-axial left frontal complex mass. GTR achieved and pathology revealed glioblastoma. She received radiation and TMZ therapy but her tumor relapsed quickly. Molecular testing performed and revealed germline pathogenic mutation in MSH6 gene which confirmed the diagnosis of CMMRD. After the first 6 doses of Nivolumab, imaging showed regression of the tumor with very good tolerance of the therapy. We tried to avoid doing early MRI scanning as long as our patient continued to be clinically stable to avoid misinterpretation of initial immunotherapy-specific tumor flare. Unanswered question is the optimal duration of immunotherapy. We are planning to continue Nivolumab therapy as long she continues her excellent general condition in the absence of significant progression or severe toxicity with the possibility of second surgical excision in the future if the tumor become more localized.
Epidemiology, treatment modalities and prognostic factors of pancreatic cancer: A retrospective study
Authors: W. Khechine, I. Belaid, F. Ezzairi, A. El Ghali, A. Bedioui, N. Bouzid, F. Bouzaiene, M. Ben Mabrouk, Y. Bencheick, I. Chabchoub, M. Hochlaf, L. Ben Fatma, S. Ben Ahmed
Journal: Annals of Oncology (2018)

Background: Pancreatic cancer is considered a challenge in digestive cancers. Even with early diagnosis, mortality rates are high explaining why, despite the low incidence, it ranks eighth in the world listing of cancer mortality. The aim of this study was to report the epidemiologic profile of patients with pancreatic cancer, to see the different modalities of treatment of this pathology and to identify prognostic factors. Methods: A single-center series of 130 patients treated between January 2001 and December 2016 in a department of Medical Oncology in Tunisia was retrospectively investigated. Results: Median age was 58.7 years [32-81] and sex ratio was 1.8. A family history of cancer was found in 4% of the patients. 38.5% had diabetes, 10% were obese and 2% had a chronic pancreatitis. 39 % of patients were smokers and alcohol consumption was noted in 20% of the cases. Most common complaints at diagnosis were abdominal pain (55%) and jaundice (33%). Tumors were mainly located in the head of the pancreas (59%). 30 % of the patients had a localized tumor, 28.5% patients had a locally advanced disease and 41.5% were metastatic at diagnosis. The liver was the main site of metastases (67%). 32% of the patients had a curative surgery while 23% underwent palliative surgery. 14% had an adjuvant chemotherapy. Neoadjuvant chemotherapy was administered in 15% but it did not lead to surgery in any of the patients. 52% of the cases received palliative chemotherapy for a metastatic disease. 8.5% patients were unfit for chemotherapy and received best supportive care. Response rates after first and second line chemotherapy were respectively 14% and 11%. Relapse rate after curative treatment was 27 % with a mean time to relapse of 12.6 months. 63% received a palliative chemotherapy for their relapse. Median overall survival was 6 months and median progression-free survival was 4 months. A ten-year survival rate was 10%. Prognostic factors significantly related to better survival rates were: female gender (p=0.013), performance status WHO (0-1) (p<0.0001), localization of tumor in the head of the pancreas (p=0.054), localized stage at diagnosis (p<0.0001), curative surgery (p<0.0001), adjuvant chemotherapy (p<0.0001) and palliative chemotherapy (p<0.0001). Conclusion: Pancreatic cancer remains one of the deadliest tumors. Etiology of pancreatic cancer remains elusive. Our study confirms that smoking, diabetes, obesity, alcohol consumption and chronic pancreatitis are associated with an increased risk of pancreatic cancer. Chemotherapy is the mainstay of therapy in the majority of the patients whereas resection is the only chance of cure but not usually possible. Curative surgery in localized stage and adjuvant chemotherapy are correlated with better survival rates.
Prevalence and prognostic impact of non‐cardiac co‐morbidities in heart failure outpatients with preserved and reduced ejection fraction: a community‐based study
Authors: Annamaria Iorio, Michele Senni, Giulia Barbati, Stephen J. Greene, Stefano Poli, Elena Zambon, Concetta Di Nora, Giovanni Cioffi, Luigi Tarantini, Antonello Gavazzi, Gianfranco Sinagra, Andrea Di Lenarda
Journal: European Journal of Heart Failure (2018)
QOL-42. BETTER SOCIAL, COGNITIVE, AND ACADEMIC OUTCOMES AMONG PEDIATRIC BRAIN TUMOR SURVIVORS TREATED WITH PROTON VERSUS PHOTON RADIATION THERAPY
Authors: Emily Warren, Amanda Child, Paul Cirino, David Grosshans, Anita Mahajan, Arnold Paulino, Murali Chintagumpala, Fatih Okcu, M Douglas Ris, Charles Minard, Andres Viana, Johanna Bick, Steven Woods, Jessica Orobio, Judy Xue, Lisa Kahalley
Journal: Neuro-Oncology (2018)

Proton beam radiotherapy (PBRT) reduces exposure of healthy tissue to radiation, which may minimize late effects in pediatric brain tumor patients. This study compared social, cognitive, and academic outcomes in children treated with PBRT versus photon radiotherapy (XRT). Survivors who were >1 year post-radiation (M=6.5, SD=3.27 years) completed cognitive (processing speed, working memory, language, attention, executive function, memory) and academic (reading, writing, math fluency) testing. Parents completed questionnaires assessing survivors' social functioning. XRT (n=29) and PBRT (n=54) groups did not differ on demographic/clinical variables (68.7% male, M age-at-treatment=7.8 years, 51.8% infratentorial tumor, 55.0% craniospinal RT, median RT dose to tumor=54.0 Gy), except for age-at-evaluation (PBRT M=13.23 years, XRT M=16.39 years; p=0.01) and follow-up interval (PBRT M=5.05 years, XRT M=8.59 years; p<0.01). Tumor types included: 21.7% glioma, 38.6% PNET/medulloblastoma, 13.3% ependymoma, 15.7% germ cell, 10.8% other. The PBRT group performed within normal limits (+/-1SD) on most cognitive measures, while the XRT group performed <-1SD on measures of working memory, language, executive function, and memory. Both groups performed <-1SD on measures of processing speed and motor dexterity. On ANCOVA tests, controlling for group differences on age-at-evaluation and follow-up interval, survivors treated with PBRT outperformed those treated with XRT on all cognitive (p<0.001 to 0.032) and academic tasks (p<0.001), except attention (p>0.05). The PBRT group was also rated as having better social functioning (p<0.05). Findings suggest PBRT may provide a meaningful benefit over XRT for social, cognitive, and academic outcomes in pediatric brain tumor survivors.
Short-term and low-dose IL-2 therapy restores the Th17/Treg balance in the peripheral blood of patients with primary Sjögren’s syndrome
Authors: Miao Miao, Zhenye Hao, Yingying Guo, Xiaoying Zhang, Shengxiao Zhang, Jing Luo, Xiangcong Zhao, Chen Zhang, Xiaoqing Liu, Xiaoyan Wu, Dan Xu, Jinfang Zhao, Xuechun Lu, Chong Gao, Xiaofeng Li
Journal: Annals of the Rheumatic Diseases (2018)

Based on evidence that low-dose interleukin-2 (IL-2) increases CD4+CD25+FOXP3+ Treg (CD4Treg) cells in patients with graft-versus-host disease, induction of autoimmune tolerance has been proposed as a treatment.1 However, evidence-based guidelines for the management of primary Sjogren’s syndrome (pSS) are lacking.2 Using a modified method of flow cytometry, we aimed to revaluate the exact levels of Th17 and CD4Treg cells in the peripheral blood (PB) of patients with pSS and explore the effects of short-term and low-dose IL-2.3 4

A total of 190 patients with pSS (169, treated with immunosuppressants; 21, new-onset (sampled as treated or new pSS patients below)) consented at enrolment to donate PB samples for comprehensive immunophenotyping (see online supplementary table S1 and figure S1). In the study, BD Trucount tubes were used to determine the absolute counts of total CD4+ T cells in the PB, and then, the absolute number of CD4+ T subsets, such as CD4Treg cells, were calculated. Detailed methods and statistical analysis is in online version (see online supplementary text). 

### Supplementary file 11

[annrheumdis-2018-213036-SP11.docx]

Among the CD4+ T subsets in the PB of the healthy control …
RONC-22. IMPACT OF RADIOTHERAPY MODALITY ON NEUROPSYCHOLOGICAL OUTCOMES OF PEDIATRIC BRAIN TUMOR PATIENTS
Authors: Jeffrey Gross, Stephanie Powell, Frank Zelko, William Hartsell, Stewart Goldman, Jason Fangusaro, Rishi Lulla, Natasha Pillay-Smiley, John Chang, Vinai Gondi
Journal: Neuro-Oncology (2018)

To evaluate predictors of neuropsychological outcomes for pediatric brain tumor patients undergoing x-ray radiotherapy (XRT) or proton radiotherapy (PRT). 125 patients received treatment for tumors located in the supratentorial (17.6%), midline (28.8%) or posterior fossa (53.6%) compartments. All received age-appropriate neuropsychological assessment of intelligence quotient (IQ), processing speed (PS), visual motor integration (VMI), executive function, memory and parent-reported function. Median age at diagnosis was 7.0 years; median time from treatment to last assessment was 4.0 years. Patients receiving PRT had higher socioeconomic status (SES), differing distributions of race and tumor locations, as well shorter median follow-up time compared to XRT (9.5 vs. 5.0 years, p<0.001). Univariate and multivariate analyses with tests for interaction of treatment group and follow-up identified higher verbal IQ (β=0.84 points/year, p=0.02) and full-scale IQ (β=1.03, p=0.01) for older patients; lower PS (β=-15.9 points, p=0.04) and VMI (β=-14.0, p=0.006) following CSI; and higher full-scale IQ (β=10.6 points, p=0.048), PS (β=12.6, p=0.02), and parent-reported practical function (β=13.8, p=0.049) following PRT relative to XRT. VMI was higher in those with higher SES (β=1.2 points/$10,000 household income, p=0.04), but lower following receipt of vincristine chemotherapy (β=-16.6, p=0.01). Parent-reported practical function was lower in those with posterior fossa tumors (β=-10.8, p=0.048). Neuropsychological outcomes of pediatric brain tumor patients are impacted by age, SES, receipt of CSI or vincristine chemotherapy, and tumor location. Relative to XRT, PRT is associated with favorable neuropsychological outcomes in terms of full-scale IQ, PS, and parent-reported practical function.