tbuckley/cabot-search huggingface dataset:
NRG Oncology/NSABP B-51/RTOG 1304: Phase III trial to determine if chest wall and regional nodal radiotherapy (CWRNRT) post mastectomy (Mx) or the addition of RNRT to breast RT post breast-conserving surgery (BCS) reduces invasive breast cancer recurrence free interval (IBCRFI) in patients (pts) with positive axillary (PAx) nodes who are ypN0 after neoadjuvant chemotherapy (NC).
Authors: Eleftherios P. Mamounas, Hanna Bandos, Julia R. White, Thomas B. Julian, Atif J. Khan, Simona Flora Shaitelman, Mylin Ann Torres, Frank Vicini, Patricia A. Ganz, Susan Ann McCloskey, Soonmyung Paik, Nilendu Gupta, X. Allen Li, Dominic J. DiCostanzo, Walter John Curran, Norman Wolmark
Journal: Journal of Clinical Oncology (2017)

TPS589 Background: This phase III post-NC trial evaluates if CWRNRT post-Mx or whole breast irradiation (WBI) with RNRT after BCS significantly reduces the IBCR-FI rate in pts with PAx nodes that are negative after NC. Secondary aims are OS, LRR-FI, DR-FI, DFS-DCIS, second primary cancer, and comparison of RT effect on cosmesis in reconstructed Mx pts. Correlative science examines RT effect by tumor subtype, molecular outcome predictors for residual disease pts, and predictors for the degree of reduction in locoregional recurrence. Methods: Clinical T1-3, N1 IBC PAx nodes (FNA or core needle biopsy) pts complete ≥12 weeks of NC (anthracycline and/or taxane). HER2+ pts receive anti-HER2 therapy. Following NC BCS or Mx, sentinel node biopsy (≥3 nodes) and/or Ax dissection with histologically negative nodes is performed. ER/PR and HER-2neu status before NC is required. Pts receive required systemic therapy. Radiation credentialing with a facility questionnaire/case benchmark is required. Random assignment for Mx pts is to no CWRNRT or CWRNRT and for BCS pts to WBI or WBI RNRT. Statistics: 1636 pts to be enrolled over 5 yrs (definitive analysis at 7.5 yrs). Study is powered at 80% to test that RT reduces the annual hazard rate of events for IBCR-FI by 35% for an absolute risk reduction of 4.6% (5-yr cumulative rate). Intent-to-treat analysis with 3 interim analyses (43, 86, and 129 events) and a 4th/final analysis at 172 events. Pt-reported outcomes focusing on RT effect will be provided by 736 pts before random assignment and at 3, 6, 12, and 24 mos. Accrual as of 2-2-17 is 534 (32.64%). Contacts: Questions: NRG Oncology Pgh Clin Coord Dpt: 1-800-477-7227 or ccd@nsabp.org . Support: U10 CA-2166; -180868, -180822; 189867; Elekta Clinical trial information: NCT01872975.
WHO downgrades oseltamivir on drugs list after reviewing evidence
Authors: Zosia Kmietowicz
Journal: BMJ (2017)

Oseltamivir (Tamiflu) has been downgraded in the World Health Organization’s list of essential medicines from a “core” drug to one that is “complementary”—a category encompassing drugs that are deemed less cost effective.

Fiona Godlee, The BMJ ’s editor in chief, welcomed the move as a victory for the journal’s campaign for evidence based medicine. “WHO’s decision is a vote for evidence based policy making, which will save money and harm. It is also …
Abstract #194: The role of CD133 on tumorigenesis of pancreatic cancer cell lines.
Authors: Sonshin Takao, Ding Qiang, Tomomi Hayashi, Shuichiro Matsubara, Toshinobu Fujiyoshi, Toru Obara, Hiroyuki Shinchi, Shoji Natsugoe
Journal: Cancer Research (2009)

Objectives: In the last AACR meeting, we reported that CD133 expression was significantly associated with lymphatic metastases, VEGF-C expression and prognosis in patients with pancreatic cancer. This time, our aims are to investigate whether CD133 plays a role as a marker of tumor-initiating cells in pancreatic cancer cell lines. Materials and Methods: 1) Seven cell lines: Capan-1, SUIT2, Panc-1, et al. 2) FACS analysis; CD133, CD44, CD24, CXCR4, ESA, et al. 3) Isolation of CD133-positive/negative cells by a FACSAria. 4) Sphere formation assay 5) RT-PCR 6) Tumorigenicity assay using NOD/SCID mice 7) migration & invasion assay 8) DNA microarray 9) Immunohistochemical study Results: 1) According to CD133 expression, 5 cell lines showed less than 1%, whereas 2 cell lines, Capan-1 and SUIT2, with high expressions around 70%. 2) In DMEM-F12 containing EGF, bFGF and B27 supplements as a stem cell culture condition, Capan-1, SUIT2 and Panc-1 showed sphere forms for 5 - 10 days culture. 3) Under the confocal laser scanning microscopy. CD133 and CD44 expressions on cell surface of composed cells of sphere form were observed. 4) CD133+ population cells of Capan-1 showed stronger capabilities of inducing tumor formation in NOD/SCID mice compared to CD133- population (Table). 5) CD133, CD44 and CXCR4 expressions in vivo vs. in vitro showed the different distributions. 6) CD133+ cells showed higher potential of migration and invasion compared to CD133- cells. 7) Several overexpressed genes associated with CD133+ cells of Capan-1 and SUIT2 identified by microarray. Conclusions: CD133 plays an important role as a marker on tumorigenesis in Capan-1 indicating that Capan-1 may be useful as a therapeutic model for pancreatic cancer stem cells. Results of tumorigenicity assay $$table_{7CF5552D-C083-4812-8F16-57ED27401658}$$  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 194.
A phase 2 study of napabucasin with weekly paclitaxel in previously treated metastatic breast cancer.
Authors: William Jeffery Edenfield, Carlos Becerra, Adrian Langleben, Alexander I. Spira, Fadi S. Braiteh, Kimiko Kossler, Yuan Gao, Youzhi Li, Matthew Hitron, Chiang Li
Journal: Journal of Clinical Oncology (2017)

1084 Background: Napabucasin is a first-in-class cancer stemness inhibitor, identified by its ability to inhibit STAT3-driven gene transcription and spherogenesis of cancer stem cells (Li et al PNAS 112 (6):1839, 2015). Napabucasin has shown potent synergistic preclinical anti-tumor activity with paclitaxel (PTX). In a phase Ib dose escalation study in patients (pts) with advanced solid tumors, Napabucasin plus weekly paclitaxel was well tolerated. A phase II expansion cohort was opened for pts with previously treated metastatic breast cancer (MBC). Methods: Pts with metastatic MBC for whom weekly PTX was a reasonable treatment option received Napabucasin 240, 480, or 500 mg orally, twice daily in combination with paclitaxel 80 mg/m2 IV weekly on 3 of every 4 weeks. Adverse events were evaluated using CTCAE v4.03 and objective tumor assessments were obtained every 8 weeks per RECIST 1.1 criteria. Results: A total of 50 pts were enrolled including 34 with triple-negative disease (negative for estrogen receptor [ER], progesterone receptor [PR], and Her2 and no prior history of positive receptor status). There were 9 pts positive for ER, PR, or Her2 and refractory to targeted agents, and 7 pts with conversion to triple-negative disease from pathology previously positive for ER, PR or Her2. Pts were heavily pre-treated, having received a median of 5 prior lines of systemic therapy. All but 3 patients had received previous systemic treatment with a taxane. Napabucasin + PTX was well tolerated. Grade 3 AE occurring in ≥ 5% patients was diarrhea (n = 4), and 1 pt had grade 4 diarrhea. The objective response rate (ORR), disease control rate (DCR), median progression free survival (mPFS), and median overall survival (mOS) for all pts and for each sub-group are summarized in the table. Conclusions: Napabucasin (BBI-608) plus weekly paclitaxel has demonstrated safety, tolerability, and encouraging signs of anti-cancer activity in pts with pretreated metastatic breast cancer. Further clinical evaluation of this combination regimen in controlled trials is warranted. Clinical trial information: NCT01325441. [Table: see text]
Correlation of Breast Cancer Index (BCI) prognostic and predictive results to Ki67 and tumor grade in early stage HR+ breast cancer.
Authors: Carla Isadora Falkson, Jeffrey Kepes, Graham M. Poage, Junmei Liu, Catherine A. Schnabel
Journal: Journal of Clinical Oncology (2017)

e12075 Background: Markers of tumor proliferative status, e.g., Ki67 and grade (G), are prognostic for early distant recurrence (DR) in HR+ breast cancer and integrated in adjuvant chemotherapy decisions; however, their impact on late DR and extended endocrine therapy (EET) decisions is less clear. BCI is a genomic assay that provides 2 results: BCI Predictive, based on HoxB13/IL17BR (H/I ratio), reports a prediction of likelihood of benefit from EET; BCI Prognostic, based on the algorithmic combination of H/I and proliferation genes, reports risk of late DR. In this study, BCI results were examined within clinicopathologic risk categories based on Ki67 and G. Methods: The BCI Clinical Database for Correlative Studies is an IRB-approved de-identified database that contains &gt; 50 clinicopathologic and molecular variables from cases submitted for BCI testing in clinical practice (N = 14,463). Clinicopathologic variables were abstracted from pathology reports, and were available for a subset of cases. High Ki67 was defined as ≥14%. Chi-squared tests were used to compare BCI results between Ki67 and G subgroups. Results: Analyses included 3395 LN- pts (median age 59.1y; 73% ≥ 50y). BCI Prognostic showed a wide distribution of individual risk assessments in pts with high or low Ki67. A greater proportion of pts with high Ki67 was classified by BCI as high risk of late DR compared to low Ki67 (68.2% vs 26.5%; P &lt; 0.0001); however, substantial proportions of high Ki67 pts were classified as BCI low risk (31.8%) and pts with low Ki67 classified as BCI high risk (26.5%). Overall, there was a moderate correlation between individual BCI Scores and individual Ki67 scores (Correlation = 0.519). 45.5% of pts with high Ki67 were classified as High BCI Predictive (H/I) compared to 35.5% of pts with low Ki67 (p &lt; 0.001). Both BCI Prognostic and BCI Predictive (H/I) classified increasing proportions of pts as high risk or high benefit with increasing G (P &lt; 0.0001). Conclusions: These findings help characterize differential stratification based on tumor biology vs Ki67/G for pts considering EET. While moderately correlated, both BCI Prognostic and BCI Predictive (H/I) identified distinct populations compared to Ki67 and G.
French comment on article Development and validation of a training module on the use of acetic acid for the detection of Barrett’s neoplasia1 Développement et validation d’un module de formation pour l’utilisation de l’acide acétique pour la détection de néoplasie sur muqueuse de Barrett
Journal: Endoscopy (2017)

Il est indispensable d’améliorer la reconnaissance des zones dysplasiques des œsophages de Barret puisque les biopsies selon Seattle manquent 40 % des diagnostics. Parmi les techniques de détection/caractérisation, celle utilisant l’acide acétique est prometteuse et peu couteuse. En effet, l’acide acétique améliore la vision des reliefs muqueux, mais fait perdre la lecture des vaisseaux par magnification et filtres électroniques.
Coroner calls for GPs to be allowed to order urgent CT scans after patient death
Authors: Clare Dyer
Journal: BMJ (2017)

A coroner has demanded a change in rules that stop NHS GPs in some areas ordering urgent computerised tomography (CT) scans, after the death of a 37 year old woman from a brain tumour.

Lisa Hashmi, area coroner for Manchester North, gave the warning in a report sent to Bury clinical commissioning group on the death of Elaine Talbot, whose brain tumour was missed by her GP and hospital doctors. Coroners have a statutory duty to send a report to the person or institution they believe should take action, if the evidence shows a risk …
Influence of marital status on risk of mortality for 23,493 cases of triple negative breast cancer for four mutually exclusive race/ethnicities.
Authors: Carol Parise, Vincent Caggiano
Journal: Journal of Clinical Oncology (2017)

1098 Background: Marital status has been associated with better breast cancer survival. However, breast cancer is a heterogeneous disease and it has not been determined whether marital status is a survival advantage for women with triple negative breast cancer (TNBC) and if this advantage holds for all race/ethnicities. The purpose of this study was to determine if being unmarried resulted in an increased risk of mortality for TNBC for four mutually exclusive race/ethnicities. Methods: We identified 23,493 cases of TNBC from the California Cancer Registry 2000-2014. Marital status at time of diagnosis was defined as: 1) married, 2) single, never married; 3) separated; 4) divorced; 5) widowed. Race/ethnicity was defined as white (n = 13,241), black (n = 2,775), Hispanic (n = 5,059), and Asian/Pacific Islander (API) (n = 2,418). Kaplan-Meier Survival Analysis and Cox Regression were used to assess the risk of mortality associated with marital status using married as the reference category. Marital status was considered a risk for mortality and hazard ratios (HR) and 95% confidence intervals reported if the Wald χ 2 was statistically significant (p &lt; 0.05). Models were adjusted for AJCC stage, age, grade, socioeconomic status, and treatment. Separate analyses were conducted for each race/ethnicity. Results: For allraces, single women had statistically significantly worse unadjusted survival (p &lt; 0.05) than married women. However adjusted analyses showed that single (HR = 1.13; 1.01-1.27) and widowed (HR = 1.43; 1.27-1.61) white women had increased mortality when compared with married women. Single (HR = 1.50; 1.14-1.96) and divorced (HR = 1.75; 1.23-2.48) API women had an increased risk of mortality compared with married women. For black and Hispanic women, marital status was not associated with risk of mortality. Conclusions: Being married at the time of diagnosis of TNBC is a survival advantage only for white and API women but not for black and Hispanic women.
Genome-wide Pleiotropy Between Parkinson Disease and Autoimmune Diseases
Authors: Aree Witoelar, Iris E. Jansen, Yunpeng Wang, Rahul S. Desikan, J. Raphael Gibbs, Cornelis Blauwendraat, Wesley K. Thompson, Dena G. Hernandez, Srdjan Djurovic, Andrew J. Schork, Francesco Bettella, David Ellinghaus, Andre Franke, Benedicte A. Lie, Linda K. McEvoy, Tom H. Karlsen, Suzanne Lesage, Huw R. Morris, Alexis Brice, Nicholas W. Wood, Peter Heutink, John Hardy, Andrew B. Singleton, Anders M. Dale, Thomas Gasser, Ole A. Andreassen, Manu Sharma
Journal: JAMA Neurology (2017)

Recent genome-wide association studies (GWAS) and pathway analyses supported long-standing observations of an association between immune-mediated diseases and Parkinson disease (PD). The post-GWAS era provides an opportunity for cross-phenotype analyses between different complex phenotypes.To test the hypothesis that there are common genetic risk variants conveying risk of both PD and autoimmune diseases (ie, pleiotropy) and to identify new shared genetic variants and their pathways by applying a novel statistical framework in a genome-wide approach.Using the conjunction false discovery rate method, this study analyzed GWAS data from a selection of archetypal autoimmune diseases among 138 511 individuals of European ancestry and systemically investigated pleiotropy between PD and type 1 diabetes, Crohn disease, ulcerative colitis, rheumatoid arthritis, celiac disease, psoriasis, and multiple sclerosis. NeuroX data (6927 PD cases and 6108 controls) were used for replication. The study investigated the biological correlation between the top loci through protein-protein interaction and changes in the gene expression and methylation levels. The dates of the analysis were June 10, 2015, to March 4, 2017.The primary outcome was a list of novel loci and their pathways involved in PD and autoimmune diseases.Genome-wide conjunctional analysis identified 17 novel loci at false discovery rate less than 0.05 with overlap between PD and autoimmune diseases, including known PD loci adjacent to GAK, HLA-DRB5, LRRK2, and MAPT for rheumatoid arthritis, ulcerative colitis and Crohn disease. Replication confirmed the involvement of HLA, LRRK2, MAPT, TRIM10, and SETD1A in PD. Among the novel genes discovered, WNT3, KANSL1, CRHR1, BOLA2, and GUCY1A3 are within a protein-protein interaction network with known PD genes. A subset of novel loci was significantly associated with changes in methylation or expression levels of adjacent genes.The study findings provide novel mechanistic insights into PD and autoimmune diseases and identify a common genetic pathway between these phenotypes. The results may have implications for future therapeutic trials involving anti-inflammatory agents.
Association between weight gain during adjuvant chemotherapy (CTx) for early-stage breast cancer (BC) and survival outcomes.
Authors: Angelica M. Gutierrez-Barrera, Gustavo Schvartsman, Juhee Song, Naoto T. Ueno, Susan K. Peterson, Banu Arun
Journal: Journal of Clinical Oncology (2017)

e12057 Background: Obese and overweight women have an increased risk of BC and worse outcomes at the time of diagnosis compared to those at normal weight. Studies suggest that women tend to gain weight after BC cancer diagnosis and during CTx for early-stage disease, which may in turn increase risk for worse outcomes. We examined if weight gained during adjuvant CTx was associated with worse outcomes. Methods: We queried the prospectively maintained UT MD Anderson Cancer Center Breast Cancer (UTMDACC) Database for data on patients (pts) who received adjuvant third-generation CTx for early-stage BC cancer, including: demographics; tumor characteristics; and, body mass index (BMI) at diagnosis, pre- and post-CTx and one year after completion of treatment. Univariate and multivariate analysis (MA) by Cox regression were performed for survival outcomes across 3 categories according to BMI variation from start to end of CTx: &gt;0.5-point loss or gain and stable BMI (± 0.5). Results: We included 1998 pts in this study. Women over 50 years old and post-menopausal were more likely to lose weight during adjuvant CTx, whereas women under 30 years old gained more weight (p&lt;0.0001). At one year post-CTx, all pts tended to return to their original weight (ρ=0.3, p&lt;0.0001). On MA, a BMI increase of 0.5 points was o associated with increased loco regional recurrence risk for both the entire cohort (HR 2.4; 95% CI, 1.122-5.166; p=0.0241) adjusting for grade and stage and for post-menopausal women (HR 3.774, 95% CI 1.241-11.447, p=0.0193) adjusting for Her2 status. Age &lt;30 years old (HR, 2.52; 95% CI, 1.009-6.293; p=0.0478) and tumor stage 3 comparing to 1 (HR, 4.598; 95% CI, 2.754-7.677; p&lt;0.0001) were associated with increased risk of death and tumor grade 2 (vs 3; HR, 0.547; 95% CI, 0.353-0.847; p=0.0069) was a protective factor on MA for the entire cohort. Conclusions: Weight gain during adjuvant CTx was associated with increased loco regional recurrence for the entire cohort and post-menopausal women, including pts who at year 1 returned to their normal weight. The effect of increased BMI during CTx on breast stroma, molecular profile and how it affects local recurrence is intriguing and needs to be further evaluated.
Abstract TMEM-029: AGING INCREASES SUSCEPTIBILITY TO OVARIAN CANCER METASTASIS IN A MURINE ALLOGRAFT MODEL
Authors: Elizabeth Loughran, Annemarie Leonard, Ryan Phan, Laura Tarwater, Tyvette Hilliard, Marwa Asem, Yueying Liu, Jing Yang, Yuliya Klymenko, Jeff Johnson, Zonggao Shi, Matthew Leevy, Matthew Ravosa, M. Sharon Stack
Journal: Clinical Cancer Research (2017)

Abstract Ovarian cancer (OvCa) is the leading gynecological malignancy in women in the United States. OvCa metastasizes uniquely, spreading through the peritoneal cavity and generating widespread metastatic sites. The vast majority of OvCa cases occur in women over 40 and the median age at diagnosis is 63 (SEER). Despite age being a significant risk factor for the development of OvCa, there is a paucity of studies addressing the role of aging in OvCa metastasis. To our knowledge, there are no reports utilizing old mice to investigate the effects of age on metastasis in vivo. We designed a study using a C57BL/6 model of aging where young (Y) mice are 3-6 months of age and aged (A) mice are 20-23 months of age, corresponding to young (20-30 years) and aged (60-67 years) humans. Using the C57BL/6 syngeneic ID8 mouse ovarian surface epithelial cell line, we tested the effect of aging on metastatic success in vivo. An allograft study was carried out with Y and A mice that were intraperitoneally injected with 3.7x106 ID8 RFP-tagged cells. The mice were imaged once a week starting at 4.5 weeks post injection and were sacrificed for dissection at 8 weeks post injection. Live imaging suggested OvCa metastasis was more efficient in the aged animals than in the young animals. After dissection, the abdominal organs were imaged ex vivo and tumor burden was quantified. The aged mice displayed heavier tumor burden in the gonadal fat compared to the young. Interestingly, no difference in metastasis to the omentum was detected. To investigate why gonadal fat is more receptive to metastasis in the aged animals, periovarian adipose from 4 young and 4 aged healthy non-tumor bearing mice was isolated for RNAseq analysis. Several immune pathways involving B cells were found to be significantly upregulated in the RNA from aged animals. Studies will be conducted to elucidate the status of B cells in aging periovarian adipose, including immunohistochemistry for CD45 and other B cell markers upregulated in the RNAseq dataset. Citation Format: Elizabeth Loughran, Annemarie Leonard, Ryan Phan, Laura Tarwater, Tyvette Hilliard, Marwa Asem, Yueying Liu, Jing Yang, Yuliya Klymenko, Jeff Johnson, Zonggao Shi, Matthew Leevy, Matthew Ravosa and M. Sharon Stack. AGING INCREASES SUSCEPTIBILITY TO OVARIAN CANCER METASTASIS IN A MURINE ALLOGRAFT MODEL [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr TMEM-029.
Kinase-Activating Fusions in Pediatric High-Risk B-Lineage Acute Lymphoblastic Leukemia (ALL): a Report from the Dana-Farber Cancer Institute (DFCI) ALL Consortium
Authors: Thai Hoa Tran, Marian H. Harris, Jonathan V. Nguyen, Traci M. Blonquist, Kristen E. Stevenson, Eileen Stonerock, Barbara L. Asselin, Uma H. Athale, Luis A. Clavell, Peter D. Cole, Kara M. Kelly, Caroline Laverdiere, Jean-Marie Leclerc, Bruno Michon, Marshall A. Schorin, Jennifer J.G. Welch, Shalini C. Reshmi, Donna S. Neuberg, Stephen E. Sallan, Mignon L. Loh, Lewis B. Silverman
Journal: Blood (2016)