tbuckley/cabot-search huggingface dataset:
Treatment patterns for resected gastric cancer using the National Cancer Database.
Authors: Foluso Nelson Ogunleye, Karna Tushar Sura, Leann Blankenship, Daniel Ezekwudo, Bolanle Gbadamosi, Ishmael A. Jaiyesimi, Peyman Kabolizadeh
Journal: Journal of Clinical Oncology (2017)

4061 Background: The optimal management of patients with resected gastric cancer remains a therapeutic challenge. Although the benefit of peri-operative chemotherapy or adjuvant concurrent chemoradiotherapy for these patients is clearly established, recurrence and mortality rates remain high despite aggressive treatment. The goal of this study was to characterize the treatment patterns employed for patients with resected gastric cancer using the National Cancer Database (NCDB). Methods: The NCDB was queried between 2004-2013 for patients with invasive resected gastric cancer and negative margins, excluding those with metastatic disease. Results: We identified a total of 21,156 cases. The median age was 67 (range 55-79). A majority of patients were white (74%) followed by black (14%) and other (12%). Most patients had either insurance through the government (58%) or private insurance (37%). 47% of patients had surgery alone with approximately 53% of these patients diagnosed with stage I gastric cancer. The remainder of the patients had radiation alone (1.4%), chemotherapy alone (15.2%), or combined chemotherapy and radiation (36.7%). Table 1 includes the further breakdown of treatment. Conclusions: A majority of patients with resected gastric cancer had treatment with either radiation, chemotherapy, or a combination of both. However, it is interesting to note that in patients receiving adjuvant or neoadjuvant treatment, only a portion of the patients received treatment options with level 1 evidence such as the MAGIC or McDonald regimens. [Table: see text]
BRCA1 subcellular localization regulated by PI3K signaling pathway in triple negative breast cancer MDA-MB-231 cells and hormone-sensitve T47D cells.
Authors: Gang Sun, Bin MA, Wenjia Guo, Meihui Shan, Binlin Ma
Journal: Journal of Clinical Oncology (2018)

e13115 Background: This study is to investigate the effect of PI3K signaling pathway on the subcellular location and phosphorylation of BRCA1 in triple-negative breast cancer (TNBC) and hormone-sensitive breast cancer cell lines. Methods: The TNBC MDA-MB-231 and hormone-sensitive T47D cells were used. LY294002 was used to block PI3K signaling pathway, and ShRNA was used to silence Akt. The subcellular localization of BRCA1 protein was detected by immunofluorescence staining. Cell apoptosis was detected by flow cytometry. The mRNA expressions of Akt and BRCA1 were determined by RT-PCR, and the protein levels were detected by Western blot. Results: HRG-activated T47D cells showed more nuclear localization of BRCA1, but BRCA1 nuclear localization decreased after the PI3K signaling pathway was blocked. In MDA-MB-231 cells, activation or inhibition of PI3K signaling pathway did not change cell apoptosis and BRCA1 nuclear translocation (P > 0.05) significantly. On the contrary, in T47D cells, the activation of PI3K pathway significantly increased cell apoptosis (P < 0.05), but the cell apoptosis rate after the inhibition of PI3K pathway had no significant difference from that of the activation group (P > 0.05). In the HRG-activated MDA-MB-231 and T47D cells, the phosphorylation of Akt 、BRCA1 and NF-κb was significantly increased (P < 0.05), while that was significantly reduced after PI3K pathway was inhibited (P < 0.05). The changing trends of the mRNA levels of Akt and BRCA1 in the PI3K-pathway-activated- and inhibited MDA-MB-231 and T47D cells were consistent with the trends of their phosphorylation. Conclusions: In both MDA-MB-231 and T47D cells, BRCA1 phosphorylation of BRCA1 was regulated by PI3K signaling pathway, but the nuclear localization of BRCA1 was different in these two cell lines. Moreover, the apoptosis rates of these two cell lines were different.
ATG16L1 orchestrates interleukin-22 signaling in the intestinal epithelium via cGAS–STING
Authors: Konrad Aden, Florian Tran, Go Ito, Raheleh Sheibani-Tezerji, Simone Lipinski, Jan W. Kuiper, Markus Tschurtschenthaler, Svetlana Saveljeva, Joya Bhattacharyya, Robert Häsler, Kareen Bartsch, Anne Luzius, Marlene Jentzsch, Maren Falk-Paulsen, Stephanie T. Stengel, Lina Welz, Robin Schwarzer, Björn Rabe, Winfried Barchet, Stefan Krautwald, Gunther Hartmann, Manolis Pasparakis, Richard S. Blumberg, Stefan Schreiber, Arthur Kaser, Philip Rosenstiel
Journal: The Journal of Experimental Medicine (2018)

A coding variant of the inflammatory bowel disease (IBD) risk gene ATG16L1 has been associated with defective autophagy and deregulation of endoplasmic reticulum (ER) function. IL-22 is a barrier protective cytokine by inducing regeneration and antimicrobial responses in the intestinal mucosa. We show that ATG16L1 critically orchestrates IL-22 signaling in the intestinal epithelium. IL-22 stimulation physiologically leads to transient ER stress and subsequent activation of STING-dependent type I interferon (IFN-I) signaling, which is augmented in Atg16l1ΔIEC intestinal organoids. IFN-I signals amplify epithelial TNF production downstream of IL-22 and contribute to necroptotic cell death. In vivo, IL-22 treatment in Atg16l1ΔIEC and Atg16l1ΔIEC/Xbp1ΔIEC mice potentiates endogenous ileal inflammation and causes widespread necroptotic epithelial cell death. Therapeutic blockade of IFN-I signaling ameliorates IL-22–induced ileal inflammation in Atg16l1ΔIEC mice. Our data demonstrate an unexpected role of ATG16L1 in coordinating the outcome of IL-22 signaling in the intestinal epithelium.
A machine learning approach for somatic mutation discovery
Authors: Derrick E. Wood, James R. White, Andrew Georgiadis, Beth Van Emburgh, Sonya Parpart-Li, Jason Mitchell, Valsamo Anagnostou, Noushin Niknafs, Rachel Karchin, Eniko Papp, Christine McCord, Peter LoVerso, David Riley, Luis A. Diaz, Siân Jones, Mark Sausen, Victor E. Velculescu, Samuel V. Angiuoli
Journal: Science Translational Medicine (2018)

A machine learning approach to detect somatic mutations in cancer patients outperforms existing methods and may improve clinical outcome.
TCT-462 Drug-Eluting Stent Therapy for Recurrent In-Stent Restenosis Following Failed Vascular Brachytherapy
Authors: Kyle Buchanan, Deepakraj Gajanana, Micaela Iantorno, Rebecca Torguson, Toby Rogers, Itsik Ben-Dor, Lowell Satler, Ron Waksman
Journal: Journal of the American College of Cardiology (2018)
Treatment of multi-drug-resistant hepatoblastoma cells using unique sequence of high-intensity focused ultrasound and low-dose generic chemotherapeutic.
Authors: Howard Q. Vo
Journal: Journal of Clinical Oncology (2016)

e22008 Background: High-intensity focused ultrasound (HIFU) is a noninvasive, radiation-free, and precisely targeted form of cancer therapy. In this study, I evaluate a new strategy in which the unique sequence of HIFU and low-dose generic chemotherapeutic is utilized to kill multidrug-resistant (MDR) hepatoblastoma cells. Methods: My strategy, motivated by clinical HIFU trials in adult hepatocellular cancers, led to the in vitro study in which human hepatoblastoma cell line HepG2 (ATCC HB8065), known for resistance to 5-fluorouracil (5-FU), was paradoxically treated with low-dose 5-FU in the following sequence. Day 0: Each data sample consisted of ~10K HepG2 cells grown inside a well of 8-well glass slides (Lab-Tek). Each well was then filled with growth media and incubated at 37ºC for 24h. Day 1: Each slide was sealed, submerged in a 37ºC degassed water bath and secured onto a fixture. The targets for HIFU therapy are the center points of the 4 quadrants of each well's base and the common origin. The constant HIFU parameters for each slide were acoustic pressure 4.5 MPa, repetition rate 1 Hz, focal-zone depth and 30 sec/sonication/target while HIFU duty cycle (DC) ranged 0-50% among slides. After HIFU treatment, the slides were incubated for 24h. Day 2: Cell media for each slide was replaced with fresh media containing [5-FU] 0-400 uM prior to repeating HIFU procedure from day 1. Day 4: After 48h of exposure to 5-FU, cell survivability study using imaging-based live cell count was performed to determine the contributions of HIFU-mediated necrosis and 5-FU-mediated apoptosis/necrosis. Results: Cell survivability of MDR HepG2 cells decreased further using HIFU/5-FU sequence than with either HIFU or 5-FU alone as shown below (Table). Conclusions: The unique sequence of HIFU and low-dose 5-fluorouracil was successful in eliminating MDR hepatoblastoma cells on day 4. Treatment of HepG2 hepatoblastoma cells using HIFU/5-FU sequence. [5-FU], (uM) 0 1 10 100 200 400 95% CI of cell survivability (%) on day 4 = estimate ± margin of error;HIFU DC 0%, N=4 100± 12 81± 37 44± 13 30± 4 34± 5 39± 3 95% CI of cell survivability (%) on day 4 = estimate ± margin of error; HIFU DC 50%, N=4 30±5 7±1 10± 4 10± 2 11± 3 8±3
Virtual navigation (VNav) provides access to quality care: Program facilitates self-advocacy in cancer care.
Authors: Joyce Rosemarie Schaffer, Susan Haag, Daniel D. Von Hoff, Erkut Hasan Borazanci
Journal: Journal of Clinical Oncology (2018)

e18655 Background: Oncology navigation improves patient engagement and participation in clinical trials and may reduce barriers to cancer care.Despite growing evidence of value, oncology patient navigation is not universally provided.Geographic location also limits patients’ access to care and patients can be confused about their treatment options.A virtual navigation program (VNav) was created with the Oncology Nursing Society Nurse Navigation Core Competencies.Key elements provide patient access and facilitate self-advocacy through the cancer continuum, which were incorporated.In VNav patients have access to care despite geographical location and navigators provide individualized patient education, care coordination, and referrals to promote self-advocacy. Methods: The study was guided by a mixed-methods approach, using an online assessment with the research question:How effective is VNav in providing critical factors to promote self-advocacy along the cancer continuum?Mixed methods provided a complete account of patient experiences navigating their cancer care.A study was conducted on VNav to examine effects on patient care and self-advocacy. Results: Diversity in age, ethnicity, tumor type, and geographical location emerged in the national patient sample of 100.Diverse tumor types were represented (49% pancreas, 11% breast, 7% ovarian, 5% lung, 1% head &neck, 4% colorectal, 10% prostate and 13% rare cancers).24 states were represented. After VNav, 83% of patients are better able to make informed decisions about cancer care (M = 4.30, SD = .91, in a scale of 1 to 5, 5 = Strongly Agree), 84% better understand their diagnosis/ treatment options (M = 4.28, SD = .94), and 82% agree “coordinated cancer care is comprehensive,” (M = 4.15, SD = 1.11) supportive to care. A statistically significant difference revealed increased knowledge on “health issues that come from cancer” post navigation (p < 0.0001). Conclusions: Findings suggest VNav facilitates oncology patients’ self-advocacy with individualized education and coordinated care.VNav provides access to quality patient education and to resources that impact self-advocacy regardless of age, gender, tumor type or geographical location.
Psychosocial care needs for pediatric cancer patients and their families in Ibadan, Nigeria: perspective from experience with patients on the ward.
Authors: Elizabeth Oluwatoyin Akin-Odanye, Biobele Jotham Brown, Chioma Christie Asuzu
Journal: Journal of Clinical Oncology (2016)

e21543 Background: The incidence of pediatric cancer is very low compared to adult cancers. The impact on the patients and their family members is however no less distressing. Methods: This is a descriptive research using observational method. Data was collected from August to December 2015, using the observational notes made by the clinical psychologist during pediatric hematology and oncology consultant ward rounds. Data collected included information on patients' age and gender, the type and stage of disease, as well as ability of patients’ parents to afford hospital care. The notes also included information on patients and family members’ response to psychological care. The notes were thematically analyzed to develop themes and identify areas of psychosocial care needs for the pediatric cancer patients and their family members. Results: 26 pediatric cancer patients (10 females and 16 males) were seen during the observation period. Patients age range between 7months and 16years. The disease types seen include leukemia, retinoblastoma, rhabdomyosarcoma, nephroblastoma, neuroblastoma. Majority of the patients presented with advanced disease. The parents of a good number of the pediatric patients cannot afford to effectively pay for treatment. Some parents demand that their children should be discharged due to financial constraints. A few parents refused to take their critically ill children home even when they could not afford treatment. The medical social workers are often informed for possible assistance. Severally members of the treatment team raise funds from their pockets or outside sources to treat such patients. Patients and their family members do not ask for psychological help. It is nevertheless appreciated when it is offered. Most parents however, expect material/financial assistance along with the psychological support. Some of the children specifically ask for something to play with but most are not very vocal about their needs. Conclusions: Pediatric cancer patients and their families in Ibadan are in need of a lot of psychological and socioeconomic support as they go through the trying period of the diagnosis and treatment for pediatric cancer.
INSPIRE: A randomized phase III trial of intravenous rigosertib in patients with higher-risk myelodysplastic syndromes (HR-MDS) after failure of hypomethylating agents (HMAs)—Study design informed by subgroup analyses of ONTIME.
Authors: Guillermo Garcia-Manero, Aref Al-Kali, Maria R. Baer, Gail J. Roboz, Uwe Platzbecker, Suman Kambhampati, Lucy A. Godley, Robert Collins, Jamile M. Shammo, Valeria Santini, Dr. Azra Raza, Lewis R. Silverman, Nozar Azarnia, Steven M. Fruchtman, Barbara R Snyder, Pierre Fenaux
Journal: Journal of Clinical Oncology (2016)

TPS7077 Background: Encouraging effects of rigosertib on overall survival (OS) seen in subgroups of pts in ONTIME informed the design of a new pivotal trial (Study 04-30; INSPIRE). This Phase III, randomized study has been initiated in pts with HR-MDS failing HMA treatment, testing the hypothesis that a more homogenous HR-MDS pt population (based on prognostic factors defined in ONTIME) will benefit from rigosertib. Methods: Major inclusion criteria: age 18-79 years; RAEB-1, RAEB-2, or RAEB-t; ≥ 1 cytopenia; failure of prior HMA; duration of prior HMA of ≤ 9 months; last dose of HMA ≤ 6 months before screening; ECOG status 0-2. Randomization is stratified by the revised International Prognostic Scoring System (IPSS-R; Greenberg et al, 2012) very high risk (VHR) vs non-VHR and by geographic region. These criteria were influenced by OS results observed in the subgroups of ONTIME listed in the table below. Rigosertib is administered as an 1800 mg/24 hr infusion for 72 hr every 2 weeks for 16 weeks, then every 4 weeks (N~150) vs physician’s choice of treatment (N~75). Primary endpoints: OS in the ITT population and in the IPSS-R VHR subgroup. Secondary endpoints: OS in pts with monosomy 7 and/or trisomy 8 chromosomal aberrations, overall response and bone marrow blast response per IWG 2006, quality-of-life per EuroQol EQ-5D, hematologic improvement, and rigosertib population pharmacokinetics. Genomic studies will be performed at baseline and monitored in both arms. Enrollment opened in December 2015 and is ongoing. Clinical trial registry number: NCT02562443. Clinical trial information: NCT02562443. Rigosertib Best supportive care Log-rank p-value Hazard ratio (Rigosertib / BSC) (95% CI) N Median (months) N Median (months) Months of last HMA ≤ 9 103 7.7 46 4.5 0.0025 0.55 (0.37, 0.81) > 9 96 9.2 52 8.1 0.42 1.18 (0.79, 1.74) Age (years) < 80 155 8.6 86 5.4 0.068 0.76 (0.57, 1.02) ≥ 80 44 4.5 14 6.8 0.21 1.57 (0.77, 3.20) Months since last dose of HMA ≤ 6 173 7.9 91 5.4 0.24 0.84 (0.63, 1.12) > 6 26 9.8 8 11.9 0.99 1.00 (0.41, 2.44) IPSS-R risk level Intermediate/Low 15 9.7 14 12.6 0.21 1.71 (0.56, 5.24) Very high 93 7.6 41 3.2 0.015 0.61 (0.36, 1.03) Very high 93 7.6 41 3.2 0.015 0.61 (0.36, 1.03)
Patient-reported symptom burden and patient satisfaction in 2104 patients with gynaecologic cancers.
Authors: Joerg Peter Schilling, Alexandra Hansen, Petra Angelika Ortner
Journal: Journal of Clinical Oncology (2016)

e21641 Background: Gynaeco-oncologists associated in the BNGO treat patients with gynaecologic cancers in an outpatient setting. The BNGO performs routine surveys on patient satisfaction among their patients. In the 2015 survey, adverse effects of cancer treatment and disease symptoms were also included. Methods: From January to November 2015, 2104 patients with gynaecologic cancers treated in 48 BNGO practices completed a printed questionnaire inquiring about their satisfaction with the equipment and staff of the practice, tumor- and therapy-related symptoms, and symptom burden. Chemotherapy patients reported side effects and rated the most distressing on a scale of 1 (least) to 10 (most). Results: Satisfaction with the practice: At least 96% of all patients regarded the practice equipment, organisation and staff as very good or good. 99% said their physician´s attentiveness was very good or good and almost 100% rated their physician´s competence as good or very good. 99% would seek treatment in the same practice again. Frequency and burden of symptoms: All patients:The most frequent symptom in all patients was fatigue. Most distressing were hot flushes. Chemotherapy patients:71% of patients received chemotherapy. 66% rated the burden chemotherapy high or extremely high. Nausea and vomiting were rare. 84% of patients had no vomiting on the day of chemotherapy and 82% on days 2-5. Conclusions: Patients are well satisfied with their treatment in BNGO practices. Almost all patients would choose to be treated in the same practice again. Hot flushes are the most distressing symptom in the majority of patients. In patients receiving chemotherapy, alopecia is the most frequent and most distressing side effect. Most frequent side effects of chemotherapy and symptom burden in chemotherapy patients. Most frequent Most distressing Alopecia: 87% of chemotherapy patients) Alopecia: 50% Tiredness: 70% Fatigue: 34% Fatigue: 66% Tiredness: 31% Tingling (pins and needles): 46% Delayed nausea (days 2-5): 26% Bone pain: 41% Tingling (pins and needles): 25%
Per protocol analysis and final OS update of the FIRE-3 (AIO KRK-0306) study comparing FOLFIRI plus cetuximab vs. FOLFIRI plus bevacizumab.
Authors: Sebastian Stintzing, Lisa Miller-Phillips, Ludwig Fischer von Weikersthal, Thomas Decker, Alexander Kiani, Ursula Vehling-Kaiser, Salah-Eddin Al-Batran, Christian A. Lerchenmuller, Christoph Kahl, Gernot Seipelt, Frank Kullmann, Markus H. Moehler, Werner Scheithauer, Swantje Held, Dominik Paul Modest, Andreas Jung, Thomas Kirchner, Volker Heinemann
Journal: Journal of Clinical Oncology (2018)

3508 Background: FIRE-3 compared 1st-line therapy with FOLFIRI plus either cetuximab or bevacizumab in 592 KRAS exon 2 wt mCRC patients (pts). Extended RAS analysis showed RAS wild-type (RASwt) in tumors of 400 pts. Methods: Per protocol analyses were done in all patients that received at least 3 cycles of chemotherapy and who had at least one CT scan following baseline allowing to evaluate of objective response rate (ORR) as the primary endpoint. ORR and early tumor shrinkage (ETS) were compared using Fisher's exact test. Overall survival (OS) was compared using Kaplan-Meier estimation and log-rank tests. Follow up time was calculated using the inverse Kaplan-Meier method. Hazard ratios (HR) were estimated according to the Cox proportional hazard method. Results: With data cutoff of July 24th 2017, a total of 400 pts with RASwt tumours were evaluable. The median follow-up time was 70.8 months and 85.3% of OS events have occurred. Of the 400 pts, a total of 351 (87.8%) were evaluable according to the per protocol pre-specified analyses. The final efficacy data is shown in the table below. Conclusions: In the per-protocol analysis of RASwt pts treated in FIRE-3, a significantly higher ORR was demonstrated for FOLFIRI plus cetuximab compared to FOLFIRI plus bevacizumab. This advantage relates to a significantly longer OS after more than 85% of OS events had occurred. Clinical trial information: NCT00433927. RASwt population (n=400) RASwt population evaluable according to protocol (n=351) FOLFIRI CET N= 199 FOLFIRI BEV N=201 p FOLFIRI CET N=169 FOLFIRI BEV N=182 p ETS, % 68.4 48.9 0.0004* OR: 2.26 70.0 50.3 0.0004* OR: 2.31 ORR, % 65.3 58.7 0.18* OR: 1.33 76.9 64.8 0.01* OR: 1.81 mPFS, mo 10.4 10.5 0.58# HR: 0.95 10.5 10.7 0.80# HR: 0.97 mOS, mo 31.1 25.6 0.01# HR: 0.76 32.5 26.1 0.01# HR: 0.75 CET= cetuximab; BEV= Bevacizumab, RASwt= RAS wild-type; ETS= defined as >20% reduction of tumor diameter at week 6, mPFS= median progression-free survival, mOS= median overall survival; *= two-sided Fisher's exact test p; #= log-rank test p; §= Wilcoxon-Test p, OR = Odds ratio, HR = Hazard Ratio Data on left and right sided primaries will be presented at the conference. The study has been funded by grants from Pfizer and Merck KgaA.
Abstract 14607: Pregnancy and Long-Term Heart Failure Risk in Women With Congenital Heart Disease
Authors: Andreas P Kalogeropoulos, Anita Saraf, Trenton Hoffman, Cheryl Raskind-Hood, Fred H Rodriguez, Carol J Hogue, Wendy M Book
Journal: Circulation (2016)

Introduction: There are limited data on long-term risk for heart failure (HF) after pregnancy in women with congenital heart disease (CHD). Hypothesis: We hypothesized that type of CHD would be associated with long-term risk for HF in pregnant women with CHD. Methods: We extracted 20-year (1996-2016) data for women who received CHD services (based on ICD9-CM codes 745-747) in our institution between 2008 and 2014 (cohort inception ). Pregnancy was identified through ICD9-CM codes 630-679, V22-24, V27-28, and V91. The earliest occurrence of a pregnancy-associated service was considered as baseline. We defined HF as ICD9-CM codes 428, 402.X1, 404.X1, and 404.X3 (Medicare definition). Incident HF was defined as new HF-associated services after baseline. We followed a modified Marelli classification for CHD severity. Results: We identified 667 women with CHD who received pregnancy-associated services. Of these, 118 (17.9%) received HF-associated services before receiving any pregnancy-associated service and w...
TCT-19 Predicting TMVR-Related LVOT Obstruction: Concept of Fluid Mechanics Modeling
Authors: Keshav Kohli, Zhenglun Alan Wei, Vahid Sadri, Thomas Easley, Eric Pierce, John Oshinski, Dee Dee Wang, Adam Greenbaum, Norihiko Kamioka, Jaffar Khan, Robert Lederman, Philipp Blanke, Vasilis Babaliaros, Ajit Yoganathan
Journal: Journal of the American College of Cardiology (2018)