tbuckley/cabot-search huggingface dataset:
Impact of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status on survival in inflammatory breast cancer: Analysis of Surveillance, Epidemiology and End Results (SEER) database.
Authors: Shiva Kumar Reddy Mukkamalla, Hussain M. Naseri, Rabin Niroula, Bharti Rathore
Journal: Journal of Clinical Oncology (2016)

e12548 Background: Inflammatory breast cancer (IBC) is associated with a poor prognosis compared to other subtypes of breast cancer. Very little is known about how HR and HER2 status influence prognosis in IBC. Methods: Patients diagnosed with IBC between 2010 and 2011 were identified from the SEER database. Overall survival (OS) and breast cancer specific survival (BCSS) were analyzed using Kaplan-Meier method and Cox proportional hazards model. Results: Among 348 patients with IBC, 56 (16.1%) were HR+/HER2+, 63 (18.1%) were HR-/HER2+, 107 (30.8%) were HR+/HER2-, and 76 (21.8%) were triple negative (TN). Receptor status was not available for 46 (13.2%) patients. Majority of the population was > 50 years of age (75%), Caucasian (61%), had stage IIIB disease at diagnosis (46%), and underwent mastectomies (62%). TN status was significantly associated with poor OS and BCSS after adjustment for other clinically relevant factors (Table). 2-year OS and BCSS for TN IBC were 46% and 53%, while for non-TN IBC it was 74% and 80%, respectively. (p < 0.0001). Conclusions: HR and HER2 status influences 2-year OS and BCSS in IBC. TN IBC is associated with poor outcomes compared to other subtypes of IBC. Additional studies are required to prospectively validate these findings and develop novel therapies to improve outcomes in this patient cohort. Multivariate analysis of 2-year OS and BCSS, adjusted for age, race, stage, mastectomy, breast reconstruction, radiation, smoking, unemployment, language isolation, income, and education. Hazards ratio (HR) 95% CI p 2-yr OS TNBC Ref (1) HR+/HER2+ 0.203 0.097-0.426 < 0.0001 HR-/HER2+ 0.401 0.233-0.691 0.001 HR+/HER2- 0.295 0.181-0.482 < 0.0001 2-yr BCSS TNBC Ref(1) HR+/HER2+ 0.177 0.081-0.386 < 0.0001 HR-/HER2+ 0.311 0.168-0.574 0.0002 HR+/HER2- 0.244 0.142-0.418 < 0.0001
Head and neck synovial sarcomas: Clinical characteristics and survival.
Authors: Vancheswaran Gopalakrishnan, Michael Wagner, Behrang Amini, Alexander Lazar, Patrick P. Lin, Robert S. Benjamin, Dejka M. Araujo
Journal: Journal of Clinical Oncology (2016)

e22523 Background: Synovial Sarcomas (SS) are malignant, high-grade, soft tissue sarcomas that have variable epithelial differentiation and are associated with the fusion gene SYT-SSX. They have varied prognosis, account for 7-10% of all sarcomas and are rare in the head and neck. Here, we describe the clinical findings and survival of a unique cohort of SS patients. Methods: A retrospective chart review was conducted on 45 patients diagnosed with a primary SS of the head and neck between August 1995 and December 2011 at The University of Texas MD Anderson Cancer Center. Patients were stratified by tumor size ( > 5 cm), location and type of therapy. Overall and Progression Free Survival (OS & PFS) curves were generated by the Kaplan-Meier method and compared using the log-rank (LR) test. Hazard ratios were estimated using the Cox proportional hazards model. This study was approved by our Institutional Review Board. Results: The median age of our cohort was 32 years and most patients were male (35, 78%) and white (33, 73%). 15 (33%) patients had a tumor in the neck. Of the 38 patients on whom we had pre-treatment tumor measurements, 20 (53%) had a tumor size greater than 5 cm. Pathologic subtype and presence of fusion gene could be identified in 33 (73%) patients (21 monophasic, 12 biphasic) and 17 (38%) patients respectively. 23 (51%) patients were treated with systemic therapy in addition to some form of definitive local therapy. PFS at 5 and 10 years was 51.3% and 47.9%, whereas OS at 5 and 10 years was 71.2% and 57.4%, respectively. Only tumor size was significantly associated with PFS (p = 0.005, HR = 5.07; 95% CI = 1.45-17.72) though not OS in univariate analyses. Regardless of tumor size, there was no difference in survival of patients who received systemic therapy compared to local therapy only. Conclusions: Despite the challenges associated with treatment of SS in the head and neck region, our cohort of patients seemed to have a fairly good prognosis. While the analysis was restricted by sample size and potential selection bias, it showed that only tumor size was predictive of PFS. Also, potentiation with systemic therapy did not seem to provide an added benefit. Future studies that are conducted prospectively in larger cohorts may reveal further insights towards therapy.
The role of preoperative breast magnetic resonance (MR) imaging for surgical decision in patients with triple-negative breast cancer.
Authors: Jeeyeon Lee, Jin Hyang Jung, Wan Wook Kim, Seung Ook Hwang, Hye Jung Kim, Ho Yong Park, Jin Ho Chung, Taek Ju Kwon, Yee Soo Chae, Soo Jung Lee, Jung Dug Yang, Jeong Woo Lee, Ji Young Park, Ji Yun Jeong
Journal: Journal of Clinical Oncology (2016)

e12553 Background: Several reliable randomized studies do not recommend routine preoperative breast MR imaging for patients with breast cancer. However, because the principle of MR imaging is based on the dynamics of contrast enhancement, a specific biologic subgroup of tumors should sensitively respond to the imaging process. Methods: From 2008 to 2013, 918 eligible patients with breast cancer underwent breast surgery and were divided into two groups based on preoperative breast MR findings: patients in whom the surgical plan was changed and those in whom the surgical plan remained unchanged. We investigated the changing patterns of breast surgery based on routine mammography, ultrasound, and preoperative breast magnetic resonance (MR) findings and analyzed the association between additional suspicious lesions on breast MR imaging and clinicopathologic factors. Results: Additional suspicious breast lesions were detected on preoperative MR imaging in 104 cases (11.3%), and the surgical strategy was changed as the final decision in 97 cases (10.6%). There was no difference between oncologic results between two groups. However, the triple-negative breast cancer (TNBC) was significantly associated with changing of the surgical strategy based on breast MR findings (P= 0.048). Conclusions: Additional preoperative breast MR imaging may be helpful in surgical decision for patients with TNBC.
First-in-human phase 1 single-dose study of TRX-518, an anti-human glucocorticoid-induced tumor necrosis factor receptor (GITR) monoclonal antibody in adults with advanced solid tumors.
Authors: Henry B. Koon, Dale Randall Shepard, Taha Merghoub, David A. Schaer, Cynthia A. Sirard, Jedd D. Wolchok
Journal: Journal of Clinical Oncology (2016)

3017 Background: TRX518 is a novel, fully humanized agylcosyl IgG1 anti-GITR mAb. GITR is a member of the tumor necrosis factor receptor family expressed on T, B, & NK cells, and antigen presenting cells. GITR is expressed at high levels by Tregs and up-regulated following T cell activation; minimally expressed by nazve CD4+ and CD8+ T cells. Signaling through GITR abrogates Treg mediated suppression and enhances CD4+ and CD8+ T cell proliferation and TCR stimulation. GITR signaling may enhance host immune responses against tumor and aid in tumor rejection. This study evaluated the safety of a single dose of TRX518 in pts with advanced refractory solid tumors. Methods: Pts received a single dose of TRX518 on Day 1; doses ranged from 0.0001 to 8 mg/kg in 9 cohorts of up to 6 pts/cohort. The study was to determine safety and tolerability, maximum tolerated dose (MTD), pharmacokinetic (PK), and pharmacodynamic (PD) profiles of TRX518. Efficacy was evaluated with the immune related response criteria (irRC). Results: 40 pts enrolled; 10 melanoma; 9 NSCLC; 7 colorectal cancer; and 14 pts with 13 other solid tumors; Median age 57.5 yrs; Male 60%; Karnofsky PS 70-80% in 35% pts. Median prior systemic therapies 3 (range 1, 9); 30% with prior immunotherapy. TRX518 was well tolerated with no dose limiting toxicities, related serious adverse events or related treatment emergent adverse events (TEAE) > Grade 2. TEAE ≥ 15% included: cough, fatigue (28% each); vomiting, abdominal pain, nausea (18% each); dyspnea and anorexia (15% each). TRX518 exposure increased dose proportionally; mean half-life ranged from 179 to 364 hours. Saturation of T lymphocytes in peripheral blood was observed in all doses ≥ 0.5 mg/kg. Low levels of anti-drug antibodies was observed in 21 pts with a median titer of 1:184; little-to-no impact on TRX518 levels. Limited efficacy data was available (n = 28); 4 pts achieved a best response of stable disease (irSD). Conclusions: Single dose of TRX518 up to 8 mg/kg was safe and well tolerated. Further investigation is ongoing; a multi-dose study is planned to further evaluate anti-tumor activity. Clinical trial information: NCT01239134.
Prédiction du moment de l'endoscopie au cours des hémorragies aiguës d'origine non variqueuse, d'après les données du registre canadien RUGBE
Authors: EB Da Silveira, P Burtin, A Barkun, E Lam, L Joseph, M Martel, K Bensoussan
Journal: Endoscopy (2006)

L'endoscopie précoce améliore le pronostic et optimise le coût-efficacité de la prise en charge des hémorragies digestives hautes non variqueuses (HDHNV) à faible ou à haut risque d'évolution défavorable. Cependant, il existe peu d'information sur les facteurs qui expliquent le délai entre la survenue de l'hémorragie et la réalisation de l'endoscopie.
Identification of novel gastric cancer associated genes using digital differential display
Authors: J Leyden, A Moss, D Murray, M Arumuguma, E Doyle, G McEntee, C O'Keane, P Doran, P MacMathuna
Journal: Endoscopy (2005)

Aim: To identify novel gastric adenocarcinoma (GA) associated genes using Digital Differential Display (DDD), a high-throughput bioinformatic resource of the NCBI's Unigene cDNA sequence repository, and to verify the expression of these genes in both GA cell lines and ex-vivo GA tissue.
Development and validation of a real-world clinicogenomic database.
Authors: Gaurav Singal, Peter Grant Miller, Vineeta Agarwala, Jie He, Anala Gossai, Shannon Frank, David Bourque, Bryan Bowser, Thomas Caron, Ezra Baydur, Kathi Seidl-Rathkopf, Ivan Ivanov, Alex Parker, Ameet Guria, Garrett Michael Frampton, Ann Jaskiw, Dana Feuchtbaum, Nathan Coleman Nussbaum, Amy Pickar Abernethy, Vincent A. Miller
Journal: Journal of Clinical Oncology (2017)

2514 Background: Genomic findings have diagnostic, prognostic, and predictive utility in clinical oncology. Population studies have been limited by reliance on trials, registries, or institutional chart review, which are costly and represent narrow populations. Integrating electronic health record (EHR) and genomic data collected as part of routine clinical practice may overcome these hurdles. Methods: Patients in the Flatiron Health Database with non-small cell lung cancer (NSCLC) who underwent comprehensive genomic profiling (CGP) by Foundation Medicine were included. EHR processing included structured data harmonization and abstraction of variables from unstructured documents. EHR and CGP data were de-identified and linked in a HIPAA-compliant process. Data included clinical characteristics, alterations across &gt; 300 genes, tumor mutation burden (TMB), therapies and associated real-world responses, progression, and overall survival (OS). Results: The cohort (n = 1619) had expected clinical (mean age 66; 75% with smoking hx; 80% non-squamous) and genomic (18% EGFR; 4% ALK; 1% ROS1) properties of NSCLC. Presence of a driver mutation (EGFR, ALK, ROS1, MET, BRAF, RET, or ERBB2; n = 576) was associated with younger age, female gender, non-smoking, improved OS (35 vs 19 mo, LR p &lt; 0.0001), and prolonged survival when treated with NCCN-recommended therapy (42 vs 28 mo, LR p = 0.001). CGP identified false negative results in up to 30% of single-biomarker tests for EGFR, ALK, and ROS1. CGP accuracy was supported by clinical outcomes. For example, 5 patients with prior negative ALK-fusion testing began ALK-directed therapy after positive CGP results. All 5 exhibited at least a partial response as recorded in the EHR by treating clinicians. Immunotherapy was used in 22% of patients (n = 353). TMB predicted response to nivolumab, including in PD-L1 negative populations. We recapitulated known associations with smoking, histology, and driver mutations. Conclusions: We present and validate a new paradigm for rapidly generating large, research-grade, longitudinal clinico-genomic databases by linking genomic data with EHR clinical annotation. This method offers a powerful tool for understanding cancer genomics and advancing precision medicine.
Multicompartment Drug Release System for Dynamic Modulation of Tissue Responses
Authors: Aaron H. Morris, Rajwant S. Mahal, Jillian Udell, Michelle Wu, Themis R. Kyriakides
Journal: Advanced Healthcare Materials (2017)

Abstract Pharmacological modulation of responses to injury is complicated by the need to deliver multiple drugs with spatiotemporal resolution. Here, a novel controlled delivery system containing three separate compartments with each releasing its contents over different timescales is fabricated. Core–shell electrospun fibers create two of the compartments in the system, while electrosprayed spheres create the third. Utility is demonstrated by targeting the foreign body response to implants because it is a dynamic process resulting in implant failure. Sequential delivery of a drug targeting nuclear factor‐κB (NF‐κB) and an antifibrotic is characterized in in vitro experiments. Specifically, macrophage fusion and p65 nuclear translocation in the presence of releasate or with macrophages cultured on the surfaces of the constructs are evaluated. In addition, releasate from pirfenidone scaffolds is shown to reduce transforming growth factor‐β (TGF‐ β) ‐induced pSMAD3 nuclear localization in fibroblasts. In vivo, drug eluting constructs successfully mitigate macrophage fusion at one week and fibrotic encapsulation in a dose‐dependent manner at four weeks, demonstrating effective release of both drugs over different timescales. Future studies can employ this system to improve and prolong implant lifetimes, or load it with other drugs to modulate other dynamic processes.
Comparison of tissue DNA to circulating tumor DNA in patients with brain metastases.
Authors: Tyler A. Lanman, Santosh Kesari, Sandip Pravin Patel, Lyudmila Bazhenova, Barbara A. Parker, Gregory A. Daniels, Paul T. Fanta, Steven C. Plaxe, Maria Clemence Schwaederle, Razelle Kurzrock, David Eric Piccioni
Journal: Journal of Clinical Oncology (2017)

e13546 Background: Brain metastases are often a late complication of cancer, not easily amenable to biopsy, and may contain additional molecular alterations not found in the original tumor. We sought to analyze the concordance between tissue DNA and cell-free circulating tumor DNA (ctDNA) in patients who developed brain metastases, and determine how the ctDNA profile changed with time. Methods: We retrospectively analyzed 31 patients with brain metastases who underwent next-generation sequencing (NGS) from both ctDNA and tumor tissue DNA. Breast, lung, ovarian, renal, melanoma, and colon primaries were included (42, 32, 13, 7, 3, and 3%, respectively). Tissue DNA was from primary tumor, systemic metastasis or brain (39, 39, and 7%, respectively). A median number of five alterations was found in each tissue group. Alterations in ctDNA were compared to tumor DNA and analyzed for relative frequencies, concordance, and novel alterations. Overall survival (OS) and time between DNA sample collections was analyzed. Results: All 31 patients had detectable mutations in tumor tissue. 25 patients (80.6%) had detectable ctDNA alterations and 14 patients (45.2%) had at least one identical ctDNA alteration that was concordant with tissue DNA. The most commonly altered genes (in both ctDNA and tissue DNA) were TP53 and EGFR. Breast cancer had both the highest proportion of patients with ≥ 1 ctDNA alterations (92.3%) and the highest proportion of patients who had ≥ 1 alterations in common with tissue DNA (61.5%). 23 of the 25 patients (92%) with detectable ctDNA alterations had additional alterations not found in tissue DNA, which increased with time from tumor DNA sampling. Median time between ctDNA extraction and tissue biopsy was 6.5 months for cases with common alterations, and 12.4 months for those without common alterations. There was trend to decreased OS with increasing ctDNA burden. Conclusions: We found that ctDNA is comparable with tissue DNA sequencing in patients with brain metastases. This concordance decreases with increasing time from tissue diagnosis, reflecting the changing nature of tumor genetics and highlighting the utility of ctDNA as a feasible way to monitor changes and identify additional potentially targetable alterations.
Traitement endoscopique des varices oeso-gastriques par injection de colle chez le petit enfant (=2 ans)
Authors: C Rivet, C Robles-Medranda, J Dumortier, C Le Gall, T Ponchon, A Lachaux
Journal: Endoscopy (2009)

Introduction: Chez l'enfant, la sclérothérapie et la ligature élastique sont les traitements endoscopiques les plus utilisés et les mieux évalués pour le traitement de varices oesophagiennes. Ces techniques ne peuvent pas être utilisées pour le traitement des varices gastriques et la ligature endoscopique chez le petit enfant en raison de la taille du matériel. Le but de cette étude était d'évaluer la faisabilité, l'efficacité et la tolérance d'injection de colle (cyanoacrylate) pour le traitement de varices oeso-gastriques ayant saigné chez le petit enfant.
Practice patterns and outcomes for hormone receptor positive and node negative breast cancer patients with intermediate risk Oncotype DX scores: Analysis of the National Cancer Database.
Authors: Jonathan Chen, Xian Wu, Paul J. Christos, Dattatreyudu Nori, Silvia Formenti, Himanshu Nagar
Journal: Journal of Clinical Oncology (2016)

553 Background: The advent of the Oncotype DX (ODX) test has widely affected chemotherapeutic treatment decisions in patients with early stage hormone receptor positive breast cancer. Patients with low risk (0-17) and high risk (31+) scores are often advised to forego or receive chemotherapy, respectively. There has been less clarity in patients with intermediate risk scores (18-30). The TAILORx trial was designed to determine whether patients with ODX scores of 11-25 benefit from chemotherapy. We utilized the same range and examined practice patterns and outcomes for patients from the National Cancer Database (NCDB). Methods: Women with hormone receptor positive and node negative breast cancer who received endocrine therapy and had ODX scores of 11-25 were identified in the NCDB from 2004-2013. A total of 14,752 patients were identified. We examined the impact of patient and treatment variables on receipt of chemotherapy using Cox regression and multivariate analysis. In a subset of patients (n = 4,757) that had a median of 4 years follow-up, we examined the impact of chemotherapy on overall survival (OS). Results: Factors that significantly correlated with receipt of chemotherapy included treatment at a community cancer program, younger age, race, private insurance, year of diagnosis, pathological grade, lymphovascular invasion, patients undergoing mastectomy, and patients undergoing radiation therapy (RT) (all p < 0.05). There was a decrease in patients receiving chemotherapy from 2009 to 2013 (31.0% to 18.4%, p < 0.001). Age, Charlson-Deyo co-morbidity index, tumor size, and RT were correlated with improved OS (all p < 0.05). In the subset of patients with a median follow up of 46.4 months, chemotherapy was not associated with a difference in OS (p = 0.89). Conclusions: Various socioeconomic and clinicopathologic factors were associated with the administration of adjuvant chemotherapy to patients with early stage hormone receptor positive breast cancer who had ODX scores between 11-25. For the subset of patients with a median follow-up of 4 years, receipt of chemotherapy was not associated with improved OS.
Multi-center, phase II trial to evaluate the efficacy and safety of combination chemotherapy with docetaxel and oxaliplatin in recurrent or metastatic breast cancer (STORM): KBCSG-008.
Authors: Seok Yun Kang, Jin-Hyuk Choi, ku Sang Kim, Yongsik Jung, Sehwan Han, Young-Jin Suh, Geumhee Gwak, Seung Pil Jung, Seung Soo Sheen
Journal: Journal of Clinical Oncology (2016)

e12516 Background: An open-label, multi-center phase II trial was conducted to evaluate the efficacy and safety of combination chemotherapy with docetaxel(Detaxel)and oxaliplatin(Oxalitin) in recurrent or metastatic breast cancer patients. Methods: Patients with recurrent or metastatic, human epidermal growth factor receptor-2 negative breast cancer receive docetaxel 75mg/m2 and oxaliplatin 80mg/m2, every 21 days for up to disease progression. The primary end point was overall response rate, and the secondary end points were progression-free survival and safety. Results: From Jun 2011 to Oct 2012, 41 chemotherapy-naive recurrent or metastatic breast cancer patients were treated: 18(44%) had recurrent disease and 23(56%) had metastatic disease. Median age was 48 years(range 33 to 68). Thirty-eight patients were available for response evaluation. Twenty partial response and 17 stable disease were confirmed, giving an overall response rate of 49% and disease control rate of 91%. At a median follow-up of 44 months, the median progression-free survival was 7.0 months(0.8-33.3mos). Grade 3-4 neutropenia occurred in 35 patients (86%) and febrile neutropenia was observed in 13 patients (31.7%). The common non-hematological toxicity was anorexia (grade 1-2, 33%) and sensory neuropathy (grade 1-2, 32.4%). Conclusions: The combination of docetaxel and oxaliplatin was found to be tolerated and effective in patients with chemotherapy-naïve HER-2 negative breast cancer. Clinical trial information: NCT01351597.
Prostate-specific extracellular vesicles as a novel biomarker in human prostate cancer.
Authors: Yong Hyun Park, Hyun Woo Shin, Jaesung Park, Ji Youl Lee
Journal: Journal of Clinical Oncology (2016)

e16557 Background: Extracellular vesicles (EVs) may play an important role in cancer development and progression. We aimed to investigate the prognostic potential of prostate-specific EVs in prostate cancer (PCa) patients. Methods: Plasma and prostate tissue were collected from patients who underwent surgery for PCa (n = 82) or benign prostatic hyperplasia (BPH, n = 28). To analyze the quantity of EVs in prostate, we performed transmission electron microscopy (TEM), immuno-TEM with CD63 and prostate-specific membrane antigen (PSMA), and immunofluorescence staining. After EV isolation from plasma, CD63 and PSMA concentration was measured using ELISA kits. Relationship between plasma EV concentration and clinicopathologic outcomes were analyzed. Results: PSMA-positive areas in prostate differed in patients with BPH, and low-, intermediate-, and high-risk PCa (2.4, 8.2, 17.5, 26.5%, p < 0.001). Plasma PSMA-positive EV concentration differed in patients with BPH, and low-, intermediate-, and high-risk PCa (21.9, 43.4, 49.2, 59.9 ng/mL, p < 0.001), and ROC curve analysis indicated that plasma PSMA-positive EV concentration differentiated PCa from BPH (AUC 0.943, 95% confidence interval 0.866-0.983). Patients with lower plasma PSMA-positive EV concentration had greater prostate volume (50.2 vs. 33.4 cc, p < 0.001) and lower pathologic Gleason score (p = 0.025). During the median follow-up of 18 months, patients with higher plasma PSMA-positive EV concentration tended to have a higher risk of biochemical failure than those with lower levels of prostate-specific EVs (p = 0.085). Conclusions: Plasma prostate-specific EVs have a potential role in differentiating PCa from BPH. In patients with PCa, lower plasma prostate-specific EV concentration was associated with favorable pathologic features and better biochemical recurrence-free survival.