tbuckley/cabot-search huggingface dataset:
The use of NLR, PLR and CA19.9 as prognostic markers for locally advanced pancreatic cancer
Authors: A. Dean, D. Higgs, A. Das, S. Fennessy, M. Rogers-Seeley, C. McGarvey, M. McNulty
Journal: Annals of Oncology (2018)

Introduction: The routine use of gemcitabine with nab-paclitaxel and FOLFIRINOX is changing the approach to locally advanced pancreatic cancer. This study aims to assess the accuracy of pre-treatment CA19.9, neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) as markers of prognosis patients with locally advanced pancreatic cancer. Methods: A retrospective cohort study was conducted for 66 patients with locally advanced pancreatic cancer who received chemotherapy only (C), chemotherapy plus radiotherapy (CRT) or chemotherapy plus radiotherapy then surgery (CRTS) between January 2014 and February 2017. After excluding 31 patients' due to insufficient data, 35 of them were analysed for full blood count, NLR and PLR, prior to starting treatment and CA19.9 level before and during treatment. Patients were divided according to the type of treatment they received (C [n = 15], CRT [n = 12] or CRTS [n = 15]). Results: Using the C only patients as a control group, there was a significant difference in the mean PLR between C and CRT (196.7 vs 121.0, p = 0.008), and C and CRTS groups (196.7 vs 129.1, p = 0.025). No significant difference in means seen between CRT and CRTS for PLR, nor for NLR amongst the three groups. The pre-treatment level of CA19.9 did not appear to correlate if a patient who underwent chemotherapy, progresses to radiotherapy or surgery. Median survival for the C group was 17 months, CRT was 26 months and CRTS group has not yet been reached. Conclusion: This retrospective study showed that the platelet lymphocyte ratio was the only predictor of prognosis in our locally advanced pancreatic cancer cohort. Once median survival has been reached in the group receiving trimodality therapy (CRTS) we may be able to provide further data on PLR, NLR and rate of change in CA19.9 in predicting resection and survival. We aim to further expand our locally advanced cohort and hope to develop a novel formula may be predictive of prognosis and likelihood of resection.
TBIO-27. GABRIELLA MILLER KIDS FIRST DATA RESOURCE CENTER ADVANCING GENETIC RESEARCH IN CHILDHOOD CANCER AND STRUCTURAL BIRTH DEFECTS THROUGH LARGE SCALE INTEGRATED DATA-DRIVEN DISCOVERY AND CLOUD-BASED PLATFORMS FOR COLLABORATIVE ANALYSIS
Authors: Allison P Heath, Pichai Raman, Yuankun Zhu, Jena V Lilly, Deanne Taylor, Phillip B Storm, Angela J Waanders, Sam Volchenboum, Lincoln Stein, Kyle Ellrott, Adam Margolin, Brandi Davis-Dusenbery, Robert Grossman, Vincent Ferretti, Sabine Mueller, Javad Nazarian, Adam C Resnick
Journal: Neuro-Oncology (2018)

Childhood cancers and structural birth share a common context of context in developmental biology that remains poorly defined. Indeed, epidemiologically, pediatric central nervous system tumors are some of the most frequently co-occurring cancers in children with birth defects. While researchers have been increasingly identifying the underlying biological causes of these conditions, the role of genetics and/or shared pathways across cancer and birth defects is not yet fully understood. A better understanding of a common developmental setting could spur advancements in prevention, early detection, and therapeutic interventions that will improve the lives of the children and families impacted by these conditions. The Common Fund’s Gabriella Miller Kids First Pediatric Research Program represents a national initiative focused on developing a large-scale genomic data supported by a data resource center (DRC) that will empower collaborative discovery and shared resources for research. The DRC will allow researchers everywhere access to vast amounts of childhood cancer and structural birth defects through cloud-based computational and analytics portals including CAVATICA (cavatica.org). Approximately 8,000 patient samples will be ready for analysis at the launch this year including a data cohort of more than 2000 pediatric brain tumor WGS/RNAseq provided by the Children’s Brain Tumor Tissue Consortium (CBTTC) and the Pacific Pediatric Neuro-Oncology Consortium (PNOC). More than 25,000 WGS are expected to be processed by 2019, making the Kids First Data Resource Center the largest pediatric data cohort of its kind.
Innate Lymphoid Cell Development: A T Cell Perspective
Authors: Dylan E. Cherrier, Nicolas Serafini, James P. Di Santo
Journal: Immunity (2018)

Innate lymphoid cells (ILCs) and natural killer (NK) cells have garnered considerable interest due to their unique functional properties in immune defense and tissue homeostasis. Our current understanding of how these cells develop has been greatly facilitated by knowledge of T cell biology. Models of T cell differentiation provided the basis for a conceptual classification of these innate effectors and inspired a scheme of their activation and regulation. In this review, we discuss NK cell and ILC development from a "T cell standpoint" in an attempt to extend the analogy between adaptive T cells and their innate ILC and NK cell counterparts. Innate lymphoid cells (ILCs) and natural killer (NK) cells have garnered considerable interest due to their unique functional properties in immune defense and tissue homeostasis. Our current understanding of how these cells develop has been greatly facilitated by knowledge of T cell biology. Models of T cell differentiation provided the basis for a conceptual classification of these innate effectors and inspired a scheme of their activation and regulation. In this review, we discuss NK cell and ILC development from a "T cell standpoint" in an attempt to extend the analogy between adaptive T cells and their innate ILC and NK cell counterparts.
Association Between Inherited Germline Mutations in Cancer Predisposition Genes and Risk of Pancreatic Cancer
Authors: Chunling Hu, Steven N. Hart, Eric C. Polley, Rohan Gnanaolivu, Hermela Shimelis, Kun Y. Lee, Jenna Lilyquist, Jie Na, Raymond Moore, Samuel O. Antwi, William R. Bamlet, Kari G. Chaffee, John DiCarlo, Zhong Wu, Raed Samara, Pashtoon M. Kasi, Robert R. McWilliams, Gloria M. Petersen, Fergus J. Couch
Journal: JAMA (2018)

Individuals genetically predisposed to pancreatic cancer may benefit from early detection. Genes that predispose to pancreatic cancer and the risks of pancreatic cancer associated with mutations in these genes are not well defined.To determine whether inherited germline mutations in cancer predisposition genes are associated with increased risks of pancreatic cancer.Case-control analysis to identify pancreatic cancer predisposition genes; longitudinal analysis of patients with pancreatic cancer for prognosis. The study included 3030 adults diagnosed as having pancreatic cancer and enrolled in a Mayo Clinic registry between October 12, 2000, and March 31, 2016, with last follow-up on June 22, 2017. Reference controls were 123 136 individuals with exome sequence data in the public Genome Aggregation Database and 53 105 in the Exome Aggregation Consortium database.Individuals were classified based on carrying a deleterious mutation in cancer predisposition genes and having a personal or family history of cancer.Germline mutations in coding regions of 21 cancer predisposition genes were identified by sequencing of products from a custom multiplex polymerase chain reaction-based panel; associations of genes with pancreatic cancer were assessed by comparing frequency of mutations in genes of pancreatic cancer patients with those of reference controls.Comparing 3030 case patients with pancreatic cancer (43.2% female; 95.6% non-Hispanic white; mean age at diagnosis, 65.3 [SD, 10.7] years) with reference controls, significant associations were observed between pancreatic cancer and mutations in CDKN2A (0.3% of cases and 0.02% of controls; odds ratio [OR], 12.33; 95% CI, 5.43-25.61); TP53 (0.2% of cases and 0.02% of controls; OR, 6.70; 95% CI, 2.52-14.95); MLH1 (0.13% of cases and 0.02% of controls; OR, 6.66; 95% CI, 1.94-17.53); BRCA2 (1.9% of cases and 0.3% of controls; OR, 6.20; 95% CI, 4.62-8.17); ATM (2.3% of cases and 0.37% of controls; OR, 5.71; 95% CI, 4.38-7.33); and BRCA1 (0.6% of cases and 0.2% of controls; OR, 2.58; 95% CI, 1.54-4.05).In this case-control study, mutations in 6 genes associated with pancreatic cancer were found in 5.5% of all pancreatic cancer patients, including 7.9% of patients with a family history of pancreatic cancer and 5.2% of patients without a family history of pancreatic cancer. Further research is needed for replication in other populations.
PETACC-6: Preop chemoradiation and postop chemotherapy (capecitabine +/- oxaliplatin) in locally advanced rectal cancer: Overall survival after long term follow-up
Authors: H. Schmoll, K. Haustermans, T. Price, B. Nordlinger, R. Hofheinz, J. Daisne, J. Janssens, B. Brenner, P. Schmidt, H. Reinel, S. Hollerbach, K. Caca, F. Fauth, C. Hannig, J. Zalcberg, N. Tebbutt, M. Mauer, S. Marreaud, M. Lutz, E. Van Cutsem
Journal: Annals of Oncology (2018)

Introduction: The PETACC-6 trial investigated the role of oxaliplatin in combination with preoperative capecitabine-based chemoradiation (CRT) and postoperative capecitabine (CT) to improve disease-free and overall survival (DFS, OS) in locally advanced rectal cancer. Methods: 1090 patients with locally advanced rectal cancer (within 12 cm from the anal verge, T3/4 and/or node-positive, no metastatic disease, potentially resectable) have been randomized between 11/2008 and 09/2011 in Europe and Australia. The primary analysis was intent-to-treat adjusted for stratification factors (clinical T category, nodal status, distance from the tumor to the anal verge, method of locoregional staging). Results: 1069 patients are evaluable. DFS has been reported (Schmoll H et al, Proc ASCO 2014) after a medium follow-up of 31 months, without difference: HR: 1.036 (CI 0.806 – 1.331, p 0.78); 3yrs DFS 74.5% vs 73.9%. However, there was a striking difference in outcome with significant improvement of DFS by oxaliplatin for the subgroup of non-German (N = 353) vs. the German patients (N = 728), with a reciprocal effect with borderline significant superior DFS for the control group. Conclusion: The overall survival analysis was planned, as specified in the protocol, after a minimum follow-up of 5 years from the last "patient in". The survival data are now available after a minimum follow-up of 5 years and a maximum of 10 years (data lock 02/18). Evaluation of all data including DFS and OS for all subgroups and multivariate analysis for prognostic factors, with particular reference to the German and non-German group is ongoing. The final outcome data of the trial will be presented at the meeting.
Case 19-2018: A 15-Year-Old Girl with Acute Kidney Injury
Authors: Ann Y. Kao, Pallavi Sagar, Jean E. Klig, Amita Sharma, Kristen J. Tomaszewski
Journal: New England Journal of Medicine (2018)

A 15-year-old girl presented with acute kidney injury. Eight days earlier, bloody diarrhea and abdominal cramping had developed. On admission, the creatinine level was 7.71 mg per deciliter, and anemia and thrombocytopenia were present. A diagnosis was made.
Brigatinib in Patients With Alectinib-Refractory ALK-Positive NSCLC
Authors: Jessica J. Lin, Viola W. Zhu, Adam J. Schoenfeld, Beow Y. Yeap, Ashish Saxena, Lorin A. Ferris, Ibiayi Dagogo-Jack, Anna F. Farago, Angela Taber, Anne Traynor, Smitha Menon, Justin F. Gainor, Jochen K. Lennerz, Andrew J. Plodkowski, Subba R. Digumarthy, Sai-Hong Ignatius Ou, Alice T. Shaw, Gregory J. Riely
Journal: Journal of Thoracic Oncology (2018)
QOL-39. NEUROCOGNITIVE LATE EFFECTS OF POSTERIOR FOSSA TUMORS. PSYCHOLOGICAL RISK AND PROTECTIVE FACTORS
Authors: Justyna Korzeniewska, Marta Perek-Polnik, Bozenna Dembowska-Bagińska
Journal: Neuro-Oncology (2018)

Long-term brain tumor survivors present challenging neurocognitive problems, that limit their educational achievement and social independence. This motivates to seek effective ways of limiting the negative consequences of brain tumors and anticancer treatment, as well as increasing their quality of life. Group of patients with posterior fossa tumor treated in our center, has been divided into two subgroups: with or without cognitive and physical stimulation during and after treatment. Next we randomly chose from each of group 30 patients, aged 8-14. Assessed groups did not differ on demographic or clinical variables. Three years after finishing treatment we assessed intelligence quotient, executive function, attention, visuospatial skills, processing speed, short-term memory and language in both groups. Social functioning were assessed according to definition of adaptive behavior (Vineland Adaptive Behavior Scales). All medical factors and treatment methods, especially the dose of irradiation, were also analyzed. Very important in these studies was the ecological aspect, which means bringing the forms of stimulation closer to the natural conditions and activities, typical for children in this group of age. We observed significant differences between neurocognitive outcome and educational achievement between subgroups, which allowed us prepare recommendation for stimulation of development pediatric brain tumors survivors. The most common objection to cognitive stimulation is the instability of effects. That’s why we studied patients three years after the end of treatment. In addition, we combined cognitive training with physical exercises.
NURS-06. EFFECT OF INTENSIVE NUTRITION INTERVENTION ON PEDIATRIC PATIENTS WITH CENTRAL NERVOUS SYSTEM TUMORS WITH CONCURRENT RADIOCHEMOTHERAPY
Authors: Yangqiong Zhang, Xiulan Wu, Minting Ye, Mingyao Lai, Linbo Cai
Journal: Neuro-Oncology (2018)

Pediatric patients with central nervous system (CNS) tumors undergoing chemoradiotherapy are at high risk of malnutrition. The goal of this study was to investigate the effects of intensive nutrition intervention on the pediatric patients with CNS tumors receiving concurrent chemoradiotherapy. We analysed retrospectively the clinical outcomes of 28 CNS tumor patients who were received early nutritional intervention (nutrition intervention group, NG) before they were treated with chemoradiotherapy. The outcomes of these patients were compared to that of 39 patients who received chemoradiotherapy without any early nutritional intervention (control group, CG). There are no significant differences between two groups in hemoglobin, platelet, prealbumin, globulin, and albumin before they were treated with chemoradiotherapy. However, the white cell count in control group was larger than that in NG (6.07 ± 1.35 vs. 8.87 ± 5.10, p<0.05) (109/L). There are no significant differences between two groups in prealbumin, globulin and albumin after they were treated with chemoradiotherapy. The body mass percentage (5.08 ± 10.67 % vs. -0.49 ± 5.41%), white cell count (2.86 ± 1.00 vs. 2.31 ± 0.76) (109/L), hemoglobin count (120.20 ± 39.70 vs. 100.62 ± 14.44) (109/L) and platelet count (141.36 ± 47.95 vs. 101.11 ± 27.00) (109/L) in NG were higher than that in CG after they were treated with chemoradiotherapy. And the radiotherapy interruption time)0.35 ± 1.20 vs. 2.07 ± 2.98 days) in NG were shorter than that in CG after they were treated with chemoradiotherapy. Early nutrition intervention can effectively improve the nutritional status of pediatric patients when they were treated with chemoradiotherapy. These results suggested that nutritional intervention must be initiated before chemoradiotherapy.
Comment on Redondo et al. Racial/Ethnic Minority Youth With Recent-Onset Type 1 Diabetes Have Poor Prognostic Factors. Diabetes Care 2018;41:1017–1024
Authors: Benjamin U. Nwosu
Journal: Diabetes Care (2018)

I read with interest an article by Redondo et al. (1) that reported a significantly lower rate of partial clinical remission in African Americans (AAs) compared with non-Hispanic whites (NHWs) in the first 3 years of diagnosis with type 1 diabetes and no differences in the lipid profile between the groups.

This interesting report may represent a key drawback of the gold-standard test for partial clinical remission, the insulin dose–adjusted hemoglobin A1c (IDAA1c) of ≤9.0%. The IDAA1c has been criticized for its shortcomings, including the underestimation of the prevalence of partial clinical remission in older, obese European girls who are more insulin resistant (2), as it cannot discriminate between insulin sensitivity and insulin secretion (2). The …
HGG-34. EARLY PRECLINICAL OUTCOMES OF INTRATUMORAL MODULATION THERAPY FOR DIFFUSE INTRINSIC PONTINE GLIOMA AND GLIOBLASTOMA
Authors: Andrew Deweyert, Hu Xu, Eugene Wong, Sussane Schmid, Matthew Hebb
Journal: Neuro-Oncology (2018)

Diffuse intrinsic pontine glioma (DIPG) is a common, malignant childhood central nervous system (CNS) cancer with dismal treatment outcomes. Glioblastoma (GBM) is another rapidly fatal glial tumor that occurs throughout the CNS in children and adults. We are pioneering a novel treatment strategy, called Intratumoral Modulation Therapy (IMT), to exploit the vulnerability of glioma cells to non-ablative, locoregional electrotherapy. IMT delivers low intensity, titratable therapeutic electric fields across the tumor-infiltrated CNS using an implantable bioelectrode system. We previously reported the in vitro efficacy of IMT in adult GBM and now speculate that this innovative approach may also be effective in vivo and offer new treatment potential for DIPG. This study evaluated the efficacy of IMT in patient-derived DIPG and GBM cells using customized in vitro and in vivo preclinical treatment models. DIPG and GBM cells were treated with a standardized regime of sham, IMT, temozolomide (TMZ) chemotherapy or IMT plus TMZ, followed by metabolic and immunocytological viability analyses. A custom-designed rodent IMT model was used for electric field mapping in the brain and evaluating the in vivo efficacy of IMT against GBM. Patient DIPG cells exhibited a robust ~40% viability loss with IMT monotherapy and synergistic response of 60-80% reduction using the combination of IMT and TMZ. The rodent model demonstrated in vivo IMT efficacy, showing tumor volume reductions of 22-40% using IMT monotherapy delivered with a pilot treatment system. IMT is a novel locoregional electrotherapeutic strategy that shows significant preclinical efficacy against DIPG and GBM.
Prognostic factors in patients with advanced biliary tract cancer treated with first-line gemcitabine plus cisplatin chemotherapy: retrospective analysis of 142 patients
Authors: H. Engin
Journal: Annals of Oncology (2018)

Introduction: Biliary tract cancer (BTC) is a heterogeneous group comprising intrahepatic and extrahepatic cholangiocarcinoma and gallbladder cancer. Although gemcitabine plus cisplatin (GEMCIS) has been established as the standard first-line chemotherapy for advanced biliary tract cancer based on the ABC-02 trial, more data are needed to define the clinical course of BTC and its prognostic factors with the standard GEMCIS treatment. Methods: Between May 2010 and June 2017, 142 patients with histologically documented cholangiocarcinoma and gallbladder cancer were treated with first-line GEMCIS in Bülent Ecevit University Oncology Center, Zonguldak, Turkey. Results: In 97 patients with measurable disease (68.3%), the objective response rate was 19.6% (n = 19) and there was no significant difference between primary tumor sites (p = 0.52). With a median follow-up duration of 28.2 months (95% CI 23.8-31.5), the median progression-free survival (PFS) and overall survival (OS) were 6.3 months (95% CI 5.2-7.1) and 12.1 months (95% CI 10.6-12.9), respectively. In multivariate analysis, male gender (female versus male, hazard ratio HR 0.73), baseline CA 19-9 level (elevated versus normal, HR 1.31), baseline CEA level (elevated versus normal, HR 1.27), metastatic disease (versus locally advanced disease, HR 1.82), poor performance status (2 versus 0-1, HR 1.35), and measurable disease by RECIST criteria (versus non-measurable, HR 1.40) were significantly associated with a poorer OS (all p < 0.05). Conclusion: Our retrospective analysis found comparable efficacy outcomes to the ABC-02 trial. The prognostic factors identified here may help to predict clinical outcomes and design future clinical trials for advanced BTC.
IMMU-17. HEMATOPOIETIC STEM CELL-DERIVED DENDRITIC CELLS REPROGRAM THE BRAIN TUMOR MICROENVIRONMENT
Authors: Tyler Wildes, Catherine Flores, Bayli DiVita, Kyle Dyson, Adam Grippin, Duane Mitchell
Journal: Neuro-Oncology (2018)

Despite multimodality treatment, patients with malignant gliomas only achieve a median survival of 18 months. Our group has pioneered an adoptive T cell immunotherapy that utilizes total tumor RNA-pulsed dendritic cells to expand polyclonal tumor-reactive T cells ex-vivo. The strongest anti-tumor efficacy of adoptive T cell immunotherapy is achieved when combined with syngeneic hematopoietic stem and progenitor cell (HSPC) transplant. The inclusion of HSPCs leads to a doubling of median survival and 40% long-term cures in treatment-resistant murine malignant glioma, brainstem glioma, and medulloblastoma. In this study, we evaluated the HYPOTHESIS that adoptive T cell immunotherapy drives the differentiation of HSPCs into dendritic cells within the brain tumor microenvironment. We evaluated HSPC differentiation and function in the context of immunotherapy in tumor-bearing animals and HSPC proliferation and differentiation in-vitro using a T cell co-culture system. The differentiation of HSPCs into CD11c+MHCII+CD86+ dendritic cells in the tumor microenvironment depended on tumor-reactive T cell-released IFN-γ. Additionally, HPSC-derived dendritic cells cross-presented tumor-derived antigens to tumor-reactive T cells, increasing T cell activation within the tumor. When evaluating the impact of HSPCs on host intratumoral immunity, we determined that HSPC transfer strongly supplants host myeloid-derived suppressor cells and downregulates suppressive genes. We have made novel observations that HSPCs significantly enhance immunotherapy by supplanting host immunity and synergizing with T cells in the tumor microenvironment. A phase I trial evaluating the impact of HSPC transfer on adoptive immunotherapy in pediatric high-grade gliomas is on schedule to open this year (ACTION– FDA IND#BB-17298).