bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of the AJCC 8th edition prognostic stage in breast cancer.
Authors: Weiss Anna , Chavez-Mac Gregor Mariana , Lichtensztajn Daphne , Yi Min , Clarke Christina A , Giordano Sharon Hermes , Hunt Kelly , Mittendorf Elizabeth Ann 
Published: September 2018

e23186 Background: The 8th edition of the AJCC staging manual introduced a prognostic stage incorporating biologic factors. The goal this study was to validate the prognostic stage in a single institution cohort and large population database. Methods: Patients were identified in a prospective institutional database and the California Cancer Registry (CCR). Factors included were T, N, m stage, grade, estrogen receptor, progesterone receptor and HER2 status. Survival was calculated by Kaplan Meier method. Harrell’s concordance index (C index) was used to quantify models’ predictive performance, and Akaike Information Criterion (AIC) to compare model fits. Results: A total of 3,327 Stage I-IIIC breast cancer patients treated 2007-2013 at a single institution with complete clinicopathologic data were identified. Compared to the anatomic stage, the prognostic stage upstaged 29.5% of patients and downstaged 28.1%. Median follow up was 5 yrs. The prognostic staging system’s C index (0.84) and AIC (816.8) reflect a more accurate model predictive of disease specific survival (DSS) (Table) than the anatomic staging (C index 0.74, P < .0001; AIC 1039.8). A total of 49,767 Stage I-IIIC patients diagnosed 2005-2009 with complete data were identified in the CCR. 31.7% of patients were upstaged and 21.1% downstaged. Median follow up was 7.15 years. Prognostic staging performed better (C index 0.81, AIC 65924.1) than anatomic staging (C index 0.77, P < .0001; AIC 66847.7). Conclusions: The newly released 8th AJCC prognostic staging system, validated in both a single institution and a large population database, provides more accurate prognostic information than the anatomic staging system. [Table: see text]
A genomic signature based in IGF1R-network in breast cancer.
Authors: Gomez Andrea C. , Araujo Jhajaira M. , Flores Claudio J. , Velazco Rodolfo , Gomez Henry Leonidas , Pinto Joseph A. 
Published: September 2018

e23187 Background: The insulin-like growth factor 1 receptor (IGF1R) is a member of the receptor tyrosine kinase family and has been involved in tumor transformation and survival of malignant cells. The evaluations of interactions networks of this protein could be helpful to find new therapeutic targets and prognostic factors. Our aim was to develop a genomic signature for disease-free survival (DFS) based on IGF1R signaling. Methods: We identified in STRING v.10.0 a set of proteins participating in the network of IGF1R. Analysis was done with a high confidence (0.7). We identified GEO datasets of microarray experiments containing gene expression profiling of breast tumors. The end point was DFS. We use one discovery set (GSE25066, N = 508) and two validations sets (GSE42568, N = 121; GSE1456, N = 318). Univariate Coxph identified a first set of genes that were screened in a multivariate analysis and then evaluated in Km-plotter (http://kmplot.com). Genes significantly associated with the DFS were analyzed in a multivariate Coxph to estimate regression coefficients to develop a linear score. Results: Analysis in STRING identified 100 proteins whose coding genes were evaluated in a first univariate analysis identifying 30 genes. The multivariate analysis identified 5 genes associated with the DFS (VCL, IARS, IRS1, IGF1R and MAKP3). The bioinformatics platform Km-plotter selected IRS1, IARS, IGF1R and MAKP3 as predictors for DFS. The multivariate analysis with the stepwise method selected only three genes, IARS HR = 147.82 (P < 0.001, 95% CI: 11.60-1883.35); IGF1R HR = 0.11 (P < 0.001, 95% CI: 0.04-0.31) and MAKP3 HR = 0.36 (P = 0.012, 95% CI: 0.16-0.80) as significantly associated with the DFS. With the regression coefficients, we developed the follow signature: (-1.026 x MAPK3) + (-2.250 x IGF1R) + (4.996 x IARS). The median score in the discover set (0.544) was able to identified patients at different risk of recurrence (P < 0.001 in the Logrank test), using the median using as cutoff the signature was able to discriminate two groups of different risk of recurrence in GSE42568 and GSE1456 validation sets (P > 0.02 and P > 0.03, respectively). Conclusions: We were able to develop a genomic predictor based in the network of IGF1R. In ours study IGF1R was associated to good prognosis.
Association of activin type II receptor mutation with microsatellite instability in gastric cancer.
Authors: Yuza Kizuki , Nagahashi Masayuki , Ichikawa Hiroshi , Nakajima Masato , Hanyu Takaaki , Ishikawa Takashi , Shimada Yoshifumi , Sakata Jun , Kameyama Hitoshi , Kobayashi Takashi , Nakagawa Satoru , Sato Nobuaki , Honma Keiichi , Kawasaki Takashi , Okuda Shujiro , Takabe Kazuaki , Wakai Toshifumi 
Published: September 2018

e23191 Background: Microsatellite instability-high status (MSI-H) and alterations in the DNA mismatch repair pathway associate with the efficacy of 5-FU and immune checkpoint inhibitors in patients with gastrointestinal cancers. The activin type II receptor (ACVR2) that binds to the transforming growth factor beta superfamily of ligands is frequently mutated in MSI-H colorectal cancer. However, the incidence of ACVR2 mutations in gastric cancer patients remains unclear. The aim of this study is to reveal the incidence and to examine the association between the MSI-H and ACVR2A mutations in gastric cancer patients. Methods: 124 archived FFPE gastric cancer tissues (stage I-IV), who were operated at Niigata University Medical and Dental Hospital or Niigata Cancer Center Hospital, were analyzed for ACVR2A mutation and MSI status with the NGS-based comprehensive genomic test platform. Clinicopathological characteristics of the patients were also examined. Results: All 124 gastric cancer patients were successfully analyzed. 13 out of 124 patients (10.4%) showed MSI-H status. Interestingly, 10 of 13 MSI-H patients (76.9%) showed ACVR2A mutation, where none (0%) was found among patients with microsatellite stable status (P < 0.001), indicating the strong association between ACVR2A mutation and MSI status in gastric cancer patients. In the ACVR2A mutated group, there was a female predominance (P < 0.05), and cancers of the lower part of the stomach were more common (P < 0.05), compared with the wild type group. Only one of 10 patients with ACVR2A mutation died, and the patients with ACVR2A mutation show a 5-year overall survival rate of 90%. No statistically significant difference in survival was achieved between patients with ACVR2A mutation and wild type; this is probably due to the small number of patients. Conclusions: 10 of 13 MSI-H patients showed ACVR2A mutation. Our results indicate a strong association between ACVR2A mutation and MSI-H in gastric cancer patients.
Ginsenoside Rg3 to regulate the EMT induced by TGF-in gastric cancer.
Authors: Zhao Lianjun , Lv Qing , Xv Qiuping , Shao Jie , Su Shu , Meng Fanyan , Wei Jia , Liu Baorui , Qian Xiaoping , Yu Lixia , Zou Zhengyun 
Published: September 2018

e23200 Background: To discuss the regulate effect of Ginsenoside Rg3 during the TGF-β1 induced EMT in human gastric cancer SNU-601 cell line. Methods: In the first part of our experiment, ninety-nine patients who were diagnosed as gastric cancer were admitted to this study eventually. The Luminex® xMAP technology was used to measure the plasma levels of TGF-β1. In the second part, human gastric cancer SNU-601 cell line were cultured normally. Inverted microscope was used to observe morphological changes. The cell relative growth rate of proliferation was analyzed by MTT assay. Wound-healing assay and transwell invasion assay were carried out to predict the capacity of Ginsenoside Rg3 in inhibiting migration and invasion. Western Blot was performed to analyze the influence of Ginsenoside Rg3 and TGF-β1 on the protein expression of E-cadherin and Vimentin. Results: The plasma cytokine levels of TGF-β1 were associated with vessel invasion, peritoneal involvement, TNM stage, T stage, N stage in gastric cancer patients. In Vitro Study, TGF-β1 stimulated epithelial-mesenchymal transition in SNU-601 cell lines. Ginsenoside Rg3 inhibited the TGF-β1 induced morphological changes, cell proliferation increase, cell migration and cell invasion. Ginsenoside Rg3 markedly increased expression of the epithelial marker E-cadherin, and repressed the upregulation and expression of the mesenchymal marker Vimentin during the TGF-β1 induced EMT in SNU-601 cell line. Conclusions: The plasma cytokine levels of TGF-β1 were associated with vessel invasion, peritoneal involvement, tumor stage in gastric cancer patients. TGF-β1 stimulated biological malignant behavior through EMT in gastric cancer. Ginsenoside Rg3 could inhibit the EMT induced by TGF-β1 in SNU-601 cell lines.
Performance of a high-intensity 508-gene circulating-tumor DNA (ctDNA) assay in patients with metastatic breast, lung, and prostate cancer.
Authors: Razavi Pedram , Li Bob T. , Abida Wassim , Aravanis Alex , Jung Byoungsok , Shen Ronglai , Hou Chenlu , De Bruijn Ino , Gnerre Sante , Lim Raymond S. , Reales Dalicia , Maddala Tara , Berger Michael F. , Riely Gregory J. , Scher Howard I. , Novotny William F. , Solit David B. , Lee Mark , Reis-Filho Jorge S. , Baselga Jose 
Published: September 2018

LBA11516 The full, final text of this abstract will be available at abstracts.asco.org at 7:30 AM (EDT) on Saturday, June 3, 2017, and in the Annual Meeting Proceedings online supplement to the June 20, 2017, issue of the Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.
Durable remissions with BCMA-specific chimeric antigen receptor (CAR)-modified T cells in patients with refractory/relapsed multiple myeloma.
Authors: Fan Frank (Xiaohu) , Zhao Wanhong , Liu Jie , He Aili , Chen Yinxia , Cao Xingmei , Yang Nan , Wang Baiyan , Zhang Pengyu , Zhang Yilin , Wang Fangxia , Lei Bo , Gu Liufang , Wang Xugeng , Zhuang Qiuchuan , Zhang Wanggang 
Published: September 2018

LBA3001 The full, final text of this abstract will be available at abstracts.asco.org at 7:30 AM (EDT) on Monday, June 5, 2017, and in the Annual Meeting Proceedings online supplement to the June 20, 2017, issue of the Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Phase 1/2 study of the selective TRK inhibitor larotrectinib in pediatric patients with cancer.
Authors: Federman Noah , Albert Catherine Michelle , Turpin Brian , Mascarenhas Leo , Nagasubramanian Ramamoorthy , Geoerger Birgit , Casanova Michela , Gallego Melcon Maria Soledad , Chisholm Julia , Van Tilburg Cornelis M. , Shukla Neerav Narendra , Spunt Sheri L. , Cox Michael Craig , Hawkins Douglas S. , Pappo Alberto S. , Bielack Stefan S. , Doz Francois P. , Bisogno Gianni , Laetsch Theodore Willis , DuBois Steven G. ,   Larotrectinib SCOUT Investigators
Published: September 2018

TPS10577 Background: Neurotrophin ligands and their receptors TRKA, TRKB, and TRKC (encoded by NTRK1, NTRK2, and NTRK3) are important for growth regulation, differentiation and survival of neurons. Translocations involving the NTRK1/2/3 kinase domain, mutations involving the TRK ligand-binding site, and amplifications of NTRK, have been described in diverse tumor types and may contribute to tumorigenesis. A broad range of pediatric malignancies have been found to harbor NTRK fusions, including infantile fibrosarcoma (IFS), spindle-cell sarcoma, congenital mesoblastic nephroma, pediatric papillary thyroid cancer, pediatric gliomas and Ph-like acute lymphoblastic leukemia. Larotrectinib is the first small-molecule selective inhibitor of TRKA, -B, and -C in clinical development and preliminary data from the adult phase 1 trial demonstrate prolonged responses in patients with TRK fusions and a favorable safety profile. Methods: We have initiated an open-label, multi-center, international Phase 1/2 study with larotrectinib in pediatric patients with solid tumors and primary CNS tumors (NCT02637687). Patients with advanced cancer between the ages of 1 year and 21 years are eligible, as well as patients as young as 1-month of age with a documented NTRK fusion. Patients with IFS who have not had definitive surgery are also eligible. Larotrectinib is administered orally twice daily on a continuous 28-day schedule. Dosing is based on body surface area. Larotrectinib is available in an oral liquid formulation and capsules. Following identification of the maximum tolerated dose of larotrectinib in the phase 1 portion, the phase 2 portion will commence. The phase 2 portion will enroll patients with NTRK-translocated tumors and measurable disease into three cohorts: 1) infantile fibrosarcoma; 2) extracranial solid tumors; and 3) primary CNS tumors. The primary endpoint for the phase 2 portion is objective response rate, with duration of response and progression free survival as secondary efficacy endpoints. Each phase 2 cohort will enroll in a single stage of up to 10 patients per cohort. Molecular abnormalities will be characterized through the analysis of archival tissue. Enrollment began in December 2015 and is ongoing. Clinical trial information: NCT02637687.
Comparative genomic analysis for pediatric cancer patients evaluated in a California Initiative to Advance Precision Medicine Demonstration Project.
Authors: Morozova Olena , Salama Sofie R. , Bjork Isabel , Goldstein Theodore C. , Mueller Sabine , Sender Leonard S. , Sweet-Cordero Alejandro , Haussler David ,   California Kids Cancer Comparison Team
Published: September 2018

TPS10578 Background: California Kids Cancer Comparison (CKCC), a demonstration project for the California Initiative to Advance Precision Medicine, evaluates the utility of incorporating gene expression information into the genomic analysis of difficult-to-treat pediatric cancers. CKCC is a partnership between UC Santa Cruz and clinical genomic trials conducted by Children’s Hospital of Orange County, UC San Francisco (Pacific Pediatric Neuro Oncology Consortium), and Stanford University. Methods: CKCC compares each prospective tumor’s RNA sequencing profile to over 11,000 uniformly analyzed tumor profiles from pediatric and adult cancer patients. These comparisons are used to identify genes and pathways that are significantly over expressed in each patient’s tumor. The pathways are reviewed by data analysis for the potential for clinical impact and presented to the treating oncologist in a molecular tumor board setting.
A randomized phase II trial of fulvestrant with or without ribociclib after progression on aromatase inhibition plus cyclin-dependent kinase 4/6 inhibition in patients with unresectable or metastatic hormone receptor positive, HER2 negative breast cancer.
Authors: Kalinsky Kevin , Mundi Prabhjot Singh , Chiuzan Codruta , Accordino Melissa Kate , Trivedi Meghna S. , Sparano Joseph A. , Young Oh Sun , Tiersten Amy , O'Regan Ruth , Esteva Francisco J. , Jain Sarika , Mayer Ingrid A. , Forero Andres , Baer Lea N. , Crew Katherine D. , Hershman Dawn L. , Vaklavas Christos 
Published: September 2018

TPS1112 Background: CDK4/6i, including palbociclib and ribociclib (R), have demonstrated remarkable benefit in progression free survival (PFS) in patients (pts) with HR+, HER2- MBC with anti-estrogen therapy. Switching between anti-estrogen therapies at disease progression is standard of care in the treatment of HR+ MBC. We evaluate the strategy of switching anti-estrogen therapy to fulvestrant (F) and maintaining CDK4/6 inhibition with R in pts with HR+, HER2- MBC who have progressed on an AI + CDK4/6i. Methods: Trial Design Phase II, multi-center, randomized, double-blind, placebo-controlled trial to evaluate F +/- R in pts with HR+, HER2- MBC who have previously progressed on any AI + CDK4/6i: Screened at 2 different scenarios: Scenario 1: Before receiving any CDK4/6i Scenario 2: Time of progression of disease (POD) while being treated with an AI + CDK4/6i Intervention At randomization, pts assigned 1:1 to either a) F + R or b) F + placebo, with treatment given in 4-week cycles. Major Eligibility Criteria 1, Metastatic BC, 2. HR+ HER2-, 3. Measurable or unmeasurable disease Specific Aims Primary: PFS. Secondary: Objective response rate, clinical benefit rate, overall survival, and duration of response. Biomarker assessment: amplification of cyclin D1 and cyclin E, phosphoRb and TK1 expression, Rb1 and p16 loss, and ctDNA for ESR1 and PIK3CA mutations. Statistical Methods Assuming a median PFS of 3.8 months with F alone, we predict that F + R will lead to a median PFS of at least 6.5 months. A one-sided log-rank test with a sample size of N = 120 and alpha = 0.025, achieves 80% power to detect a difference in PFS of 2.7. With a 10% dropout, n = 132. Clinical trial registry number NCT02632045.
A phase I/II dose escalation and expansion study to investigate the safety, pharmacokinetics, pharmacodynamics and clinical activity of GSK525762 in combination with fulvestrant in subjects with ER+ breast cancer.
Authors: Sparano Joseph A. , Cescon David W. , Oliveira Mafalda , Stover Daniel G. , Tan-Chiu Elizabeth , Kremer Brandon Edward , Barbash Olena , Wu Yuehui , Mathew Lijoy , Cunningham Elizabeth Ann , Carpenter Christopher L. , Ballas Marc S. , Dhar Arindam 
Published: September 2018

TPS1114 Background: Advanced or metastatic ER+BC (estrogen receptor positive breast cancer) is an incurable illness that will prove fatal for most afflicted women. Current standards of care include endocrine, targeted, and chemotherapy. Preclinical data suggest that reducing expression of the estrogen receptor (ER) as well as other ER-responsive genes may provide therapeutic benefit for women for whom endocrine therapy alone has proven inadequate. The bromodomain (BRD) and extra-terminal (BET) family of proteins (BRD2, BRD3, BRD4 and BRDT) bind to acetyl-histone residues and epigenetically control transcription of genes driving cell survival and proliferation. In preclinical models, BET proteins reduce ER expression and down regulate ER-dependent gene expression and may be a novel therapeutic target in multiple tumors e.g. ER+BC. GSK525762 is a pan-BET inhibitor showing strong synergistic activity with fulvestrant in killing ER+BC cells in vitro and in xenograft models. The combination of BET agents with endocrine therapy may provide therapeutic benefit and restore sensitivity to ER targeting agents like fulvestrant. Methods: The study is a Phase I/II dose-escalation, expansion (Phase I) and randomized control (Phase II) study with oral administration of GSK525762 in combination with fulvestrant in advanced or metastatic ER+BC subjects, whose disease has progressed on prior treatment with ≥ 1 line of endocrine therapy. Phase I of the study is designed as parallel single arms to determine the recommended Phase 2 dose based on safety, tolerability, PK, and efficacy profiles in two distinct populations of ER+ BC: 1. Subjects with disease that progressed on anti-estrogen and/or ≥ 1 AIs, OR. 2. Subjects with disease that progressed on CDK4/6 inhibitor plus letrozole. Phase I will employ a Bayesian predictive adaptive design. Phase II of the study is a randomized, double-blind, placebo-controlled study, the composition of which will be selected at the end of Phase I. Patients must have received < 3 lines of anti-cancer therapy (≤1 line of chemo), measurable disease, and PS 0-1. Funding: GSK. Clinical trial information: NCT02964507.
Effect of bariatric surgery on breast tissue and biomarkers in obese women at increased risk for breast cancer.
Authors: Ballinger Tarah Jean , Miller Kathy , Ludwig Kandice , Badve Sunil S. , Selzer Don , Zhang Ying , Storniolo Anna Maria , Mina Lida A. 
Published: September 2018

TPS1592 Background: Obesity represents a challenging epidemic associated with increased risk of several malignancies, including breast cancer in post-menopausal women. Proposed mechanisms for the association between obesity and breast cancer risk include increased insulin resistance, elevated levels of circulating estrogens, and chronic inflammation. Intentional weight loss from bariatric surgery has been associated with decreased risk of breast cancer. While rapid improvements in serologic markers of metabolism and inflammation are seen following bariatric surgery, short- and long- term changes in breast tissue remain less clear. This study investigates the effect of bariatric surgery on breast density and biomarkers of increased risk in breast tissue. Methods: This pilot, single institution, observational study (NCT02681120) is recruiting pre- and post-menopausal women with BMI ≥30 from a University bariatric surgery clinic using the Hughes risk application as a screening tool. Eligible patients must have a lifetime risk for breast cancer of ≥20%. Participants are evaluated by imaging, breast biopsy, and blood samples at baseline, 14 days post-operatively to determine the effects of rapid metabolic changes, and 1 year post-operatively to determine the effects of significant weight loss. The impact of bariatric surgery on known imaging parameters of breast cancer risk is assessed by background parenchymal enhancement on MRI and breast density on mammogram. Breast tissue is evaluated for changes in immune infiltrates, aromatase expression, and the presence of crown-like structures, a marker of inflammation seen in the breast tissue of obese women. Tissue samples at each time point are also compared to samples from lean women in the Susan G. Komen Tissue Bank at the IU Simon Cancer Center. Blood is collected for correlative studies evaluating markers of inflammation, insulin resistance, metabolism, and hormone synthesis. Enrollment is currently ongoing with a planned accrual of 40 patients, and data collection is estimated to complete by the end of 2018. Clinical trial information: NCT02681120.