tbuckley/cabot-search huggingface dataset:
Adipokines derived from peritumoral visceral fat may promote lymphovascular invasion in colorectal cancer.
Authors: Yuji Miyamoto, Mayuko Ohuchi, Yukiharu Hiyoshi, Nobuya Daitoku, Hiroshi Sawayama, Masaaki Iwatsuki, Yoshifumi Baba, Naoya Yoshida, Hideo Baba
Journal: Journal of Clinical Oncology (2018)

e24023 Background: Excess adipose tissue releases proinflammatory cytokines known as adipokines. Recent evidence suggests that visceral adipose tissue has proinflammatory and protumorigenic effects. The aim of this study was to evaluate whether adipokine secreted from peritumoral visceral fat influenced tumor progression in patients with colorectal cancer (CRC). Methods: Peritumoral visceral fat and blood samples were obtained from 128 CRC patients receiving primary tumor resection. Adipokines expressions (LEP, IL-6, TNFa, and VEGF) were analyzed using ELISA or real-time PCR. CD163(+) macrophage infiltration was analyzed in tumor FFPE samples. The visceral fat area (VFA) was measured on preoperative CT scans. Associations between adipokine expression and clinicopathological factors were evaluated. Results: Main characteristics were the following: male/female = 73/55; median age = 69; Stage I/II/III/IV = 40/37/36/15; median BMI = 22.4kg/m2; median VFA = 100cm2. The VFA was positively correlated with the expression of LEP (r2 = 0.44, p < 0.01), IL-6 (r2 = 0.22, p = 0.01) and VEGF (r2 = -0.18, p = 0.04) in peritumoral visceral fat. Tumor vascular invasion was significantly associated with high LEP expression (p = 0.01), and tumor lymphatic invasion was significantly associated with high IL-6 expression (p = 0.01). Patients with CD163(+) macrophage infiltration showed significantly higher LEP (p = 0.02) and IL-6 expression (p = 0.03) in peritumoral visceral fat compared with those without CD163 (+) macrophage infiltration. Patients with lymphatic or vascular invasion showed significantly shorter relapse-free survival compared with those without lymphovascular invasion (p = 0.048 and 0.042, respectively). Conclusions: Our results suggest that adipokine secreted from peritumoral visceral fat is associated with CD163 (+) macrophage infiltration and tumor lymphovascular invasion and may lead to poor prognosis in CRC patients.
P04.03 BMP4 regulatesglioblastoma invasion through negative regulation of Snail1 signaling pathway
Authors: L Baohui, Q Chen
Journal: Neuro-Oncology (2018)

Glioblastoma multiforme (GBM) is the most common and deadliest type of primary malignant tumor in the adult central nervous system which has high invasion and high proliferation capacities. The GBM cell invasion and migration can occur at any stage of tumor progression which is one of the main challenges in treating GBM. It is considered that inhibition of GBM cell invasion and migration can improve treatment efficacy in patients with GBM.In our previous studies, we found that BMP4 expression was significantly lower in GBM, low expression of BMP4 promoted the proliferation and tumorigenesis abilities of GBM cells, indicating that BMP4 may act as a tumor suppressor gene in GBM. However, up to now, the role of BMP4 on the invasion and migration in GBM and its underlying mechanism remain unclear.in this study, we aimed to investigate the role and related mechanism of BMP4 in GBM cell invasion. Human brain tissues samples (including GBM and normal brain tissues) were collected. The correlation between BMP4 expression and the expression of invasion markers E-cadherin and Claudin in GBM tissues were detected by using immunohistochemistry staining. Human malignant glioma U251 and U87 cells were cultured, changes on the invasive ability of cells with high and low BMP4 expression were detected by Scratch wound healing assay and Transwell migration assay; then stable glioblastoma cell line with high BMP4 expression were established, tumor cells were implanted orthotopically into the brain of rats, changes on GBM invasion ability and the expression of invasion markers in control brain tissues and GBM tissues were detected; After knocking down BMP4, the related gene expression were detected by gene chip technology, the regulation of BMP4 on related protein and gene expression were observed using RT-PCR and western blot assay. The expression of BMP4 in GBM tissues was negatively correlated with the expression of E-cadherin and Claudin; in vitro experiments showed that high BMP4 expression in U87 and U251 cells decreased cell invasion, and low BMP4 expression increased cell invasion; in vivo experimental results show that high BMP4 expression significantly weakened GBM cell invasion. Gene chip results showed that after knocking down BMP4, the expression of several target genes of Snail1 signaling pathway were decreased, RT-PCR and Western blot assay results showed that high BMP4 expression significantly increase E-cadherin expression, low BMP4 expression significantly decrease E-cadherin expression, when BMP4 expression was high, Snail1 protein expression was decreased, but no change was observed in Snail1 mRNA expression. RT-PCR results showed that after silencing the Snail1 signaling pathway, BMP4 knockdown did not promote the cell invasion. BMP4 can regulate GBM cell invasion through negative regulation of Snail1 signaling pathway.
Abstract 18040: Advanced Treatment of Submassive Pulmonary Embolism in 135 Patients Triaged by a Multidisciplinary Pulmonary Embolism Response Team
Authors: Julius I Ejiofor, Gregory Piazza, Anthony V Norman, Maroun Yammine, Siobhan McGurk, James M McCabe, Samuel Z Goldhaber, Sary F Aranki, Prem S Shekar, Piotr Sobieszczyk, Tsuyoshi Kaneko
Journal: Circulation (2016)

Introduction: Acute pulmonary embolism (PE) with hemodynamic stability and right ventricular(RV) dysfunction carries a high risk of mortality and is classified as submassive PE(SMPE). We report the...
Psychosocial needs assessment of underserved prostate cancer patients: Survivorship program planning.
Authors: Alyson Moadel, Evelyn Kolidas, Reza Ghavamian
Journal: Journal of Clinical Oncology (2016)

10107 Background: The ACoS Commission on Cancer has recommended national standards for cancer centers to meet that emphasize patient-centered care including distress screening and survivorship treatment plans (Standard 4.7). However, there are few roadmaps in which to guide Survivorship Program planning among underserved, ethnic minority men with prostate cancer (PC), a population at risk for medical nonadherence. We report findings of a psychosocial needs assessment among a convenience sample of 37 PC patients relative to 240 men with other cancers at a major cancer center in Bronx, NY. Methods: Patients were approached in oncology waiting rooms or by telephone via referral to psychosocial services and administered a brief assessment that included the Distress Thermometer (DT), a QoL symptom checklist, and screening of preferences for various psychosocial interventions. Results: The sample was comprised of 47% African American, 31% Hispanic, 22% Caucasian, 19% Spanish-speaking, M age = 68+-10.43 (48-91) years, and M years since diagnosis = 3+-3.74 (.04-14.80). In comparison to men with other cancers, PC patients reported more sadness (44% vs 29%; p < 0.05), more problems with urination; 39% vs 19% (p < 0.02), and a trend towards more sexual dysfunction (41% vs 27%; p < 0.06). PC patients were marginally more likely to endorse clinical distress; 53% vs 37% (p < 0.06), and were nearly twice as likely to accept a referral to counseling, 48% vs 25% (p < 0.01). Other interventions of interest included: mind-body programs (87%), health education/fitness (70%), support groups (53%), complementary medicine (44%), creative arts (39%), and smoking cessation (12%). Up to 16% wanted a “Treatment Buddy” and 24% reported an interest in volunteering to help other cancer patients. Conclusions: This pilot needs assessment study suggests that underserved PC patients may be more emotionally vulnerable and receptive to psychosocial intervention than those with other cancers. Further this assessment highlights several types of interventions that should be considered in PC Survivorship treatment plans, including counseling, mind-body therapies and health and fitness promotion.
Prevalence and risk factors of HBV, HCV and HIV infections among cervical cancer patients in a tertiary care institution in Brazil.
Authors: Rafael Correa Coelho, Alvaro Henrique Ingles Garces, Mariane Fontes Dias, Eduardo Paulino, Solange Bizzo, Carlos G. M. Ferreira, Luiz Claudio Santos Thuler, Andreia Cristina De Melo
Journal: Journal of Clinical Oncology (2016)

e17009 Background: Cervical cancer (CC) is a major public health problem, especially in developing countries as Brazil. Viral hepatitis B and C, as well HIV infection are sexually transmitted diseases and share similar risk factors with HPV infection and, therefore, CC. Despite advances in CC prevention as HPV vaccines and Papanicolau smear, the access to health care in developing countries is far from the ideal. In this setting, both CC and infectious diseases remain as an important cause of morbidity and death. The objective of this study was to evaluate the prevalence of HIV, hepatitis B and C infection and coinfection in patients with CC. Methods: A retrospective study of HBV, HCV and HIV was carried out. All patients from the Brazilian National Cancer Institute (INCA) diagnosed with CC between 2009 and 2012 were included in the cohort. Information on HBV, HCV and HIV status and patient data were retrospectively obtained by chart review. We also evaluated demographic, independent predictors, clinical and behavioral variables as well the prevalence of HBV current or past infection, HCV and HIV markers. Results: A total of 1,659 patients were enrolled. Eighteen women (1.5%) were positive for HIV, 17 (1.2%) for hepatitis C and 186 (13.9%) had prior exposure to hepatitis B virus. Anti-HBs was positive in 102 cases (6.1%). Coinfection with HIV and HCV was detected in 0.3%, HCV and HBV in 0.2%, HIV and HBV in 0.6% of the cases. The prevalence of anti-HBc IgG, anti-HCV and HIV antibody was compared to the estimated prevalence in the Brazilian population. Previous contact with HBV and HIV infection was higher in the current cohort; the prevalence ratio was 1.7 and 3.3, respectively. The multivariate analysis showed as independent predictors of HBV (age higher than 50 years, first sexual intercourse in an age lower than 18 years and non-white patients), HCV (age higher than 50 years and non-white patients) and HIV (more than 3 sexual partners during their lifetime) infection. Conclusions: CC patients have a higher prevalence than general population of HIV and HBV infection. The presented results support the importance of serological evaluation of patients recently diagnosed with CC.
Bisphosphonates for Patients Diagnosed With Multiple Myeloma
Authors: Rahul Mhaskar, Benjamin Djulbegovic
Journal: JAMA (2018)

<h3>Clinical Question</h3> Among patients with multiple myeloma, is bisphosphonate therapy associated with lower rates of mortality, vertebral fractures, nonvertebral fractures, and skeletal-related events compared with placebo or no treatment? <h3>Bottom Line</h3> Among patients with myeloma, bisphosphonates were associated with lower rates of pathological fractures and skeletal-related events compared with placebo or no treatment. Direct meta-analysis showed no association between bisphosphonates and mortality. In network meta-analysis, zoledronate was associated with lower risk of mortality compared with placebo or no treatment.
Noncardiac Production of Soluble ST2 in ST-Segment Elevation Myocardial Infarction
Authors: María T. Pérez-Martínez, Javier Lacunza-Ruiz, Juan García de Lara, Jose A. Noguera-Velasco, Antonio Lax, Álvaro Hernández-Vicente, Mari C. Asensio-López, James L. Januzzi, Borja Ibañez, Domingo A. Pascual-Figal
Journal: Journal of the American College of Cardiology (2018)
Clinical trial in progress: A study of VB-111 combined with paclitaxel vs. paclitaxel for treatment of recurrent platinum-resistant ovarian cancer (OVAL, VB-111-701/GOG-3018).
Authors: Richard T. Penson, Kathleen N. Moore, Thomas J. Herzog, Robert Allen Burger, Laurence S Freedman, Noa Lowenton-Spier, Dror Harats, Naamit Sher, Yael Chava Cohen, Bradley J. Monk
Journal: Journal of Clinical Oncology (2018)

TPS5609 Background: Ofranergene obadenovec (VB-111) is a targeted anti-cancer gene therapy with a dual mechanism: an antiangiogenic broad effect and induction of a tumor directed viral immune response. Over 400 cancer patients have been treated with VB-111, with evidence of anti-tumor activity across three phase 2 studies and a favorable safety profile. A phase 2 trial in patients with platinum resistant ovarian cancer treated with VB-111 in combination with weekly paclitaxel was conducted. In a population with 50% platinum refractoriness and 52% prior antiangiogenics, CA-125 response was observed in 60% of patients with a dose response pattern and a significant increase in overall survival (OS) at therapeutic vs. low dose level (median 810 vs. 172 days, p = 0.042) as well as evidence of an immunotherapeutic effect. Based on these observations, a phase 3 study of VB-111 in combination with weekly paclitaxel in patients with recurrent platinum-resistant ovarian cancer was initiated (NCT03398655) in collaboration with The GOG Foundation, Inc. Methods: This is a multicenter, randomized, double-blind, placebo-controlled, phase 3 study of patients with platinum-resistant ovarian cancer, a deadly indication with significant unmet need. Patients with recurrent epithelial ovarian cancer, who have platinum-resistant and measurable disease (RECIST 1.1) previously treated with no more than 5 treatment lines are randomized 1:1 to receive VB-111 (1x1013 VPs) combined with paclitaxel (80mg/m2) or placebo combined with paclitaxel (80mg/m2). Randomization is stratified by number of prior treatment lines and prior antiangiogenic therapy. Treatment beyond RECIST progression is allowed in the absence of significant deterioration. The primary endpoint is OS; secondary endpoints include objective response rate, progression free survival (both by RECIST 1.1), combined CA-125 and RECIST 1.1 response, and CA-125 response (GCIG). The sample size calculation of 350 patients (event driven) provides 88% power to detect a difference in survival at the two-sided 5% significance level using the logrank test. To date, 2 patients have been randomized. Clinical trial information: NCT03398655.
Clinical experience with talimogene laherparepvec in a melanoma population at a university based cancer center.
Authors: Alyssa Hinchman, Ivo Abraham, Abdulaali Almutairi, Srinath Sundararajan, Lois Lattimore, Hani M. Babiker, Ali McBride
Journal: Journal of Clinical Oncology (2018)

e21547 Background: Talimogene laherparepvec (Imlygic or T-VEC) is a first-in-class oncolytic virus that received FDA approval for recurrent unresectable melanoma based on the OPTiM trial. Since its approval, data regarding the ongoing effectiveness and safety of T-VEC in real-world populations remains limited. Methods: Records for 20 adult patients treated with at least 1 dose of T-VEC between 1/2013 and 9/2016 at the University of Arizona Cancer Center were reviewed. Response assessment and data analysis were modeled after the OPTiM trial, with a primary outcome of durable response rate (DRR). Descriptive statistics and Kaplan Meier analysis were used. Results: All patients had stage III/ IV disease, and 70% had received previous anticancer therapies. Five patients (25%) received T-VEC in combination with ipilimumab in a clinical trial setting. Three patients with no measurable lesions and 1 patient lost to follow-up were excluded from outcomes analysis. The DRR was 18.8%, objective response rate (ORR) was 43.8%, and disease control rate was 81.3%. The median time to response (TTR) was 5.4 months, while median overall survival (OS) was not reached. Fever (80%), chills (75%), and injection-site reactions, including pain, erythema, and pruritus (15-50%) were the most common toxicities. An immunocompetent patient had biopsy-proven disseminated herpes infection from T-VEC and had complete resolution with a 3-week course of therapeutic valacyclovir. Conclusions: T-VEC maintains effectiveness in uncontrolled populations at rates comparable to the OPTiM trial. Commonly reported side effects such as fever and chills were observed more frequently than in OPTiM. Moreover, a serious reaction (disseminated herpetic rash) requiring T-VEC discontinuation occurred in one patient. Hence, careful patient education about potential adverse effects is recommended. T-VEC N = 16 T-VEC in OPTiM N = 295 DRR – n (%)a 3 (18.8) 48 (16.3) ORR – n (%)b 7 (43.8) 78 (26.4) Disease control rate – n (%)c 12 (81.3) Not reported Median TTR – months 5.4 4.1 Median OS – months Not reached 23.3 aComplete/partial response (CR/PR) lasting > / = 6 months and onset within first 12 months of treatment; bCR/PR; cCR/PR/Stable disease
Nivolumab (Nivo) + Ipilimumab (Ipi) vs Platinum-Doublet Chemotherapy (Chemo) as First-line (1L) Treatment (Tx) for Advanced Non-Small Cell Lung Cancer (NSCLC): Safety Analysis and Patient-Reported Outcomes (PROs) From CheckMate 227.
Authors: Martin Reck, Matthew David Hellmann, Luis G. Paz-Ares, Suresh S. Ramalingam, Julie R. Brahmer, Kenneth John O'Byrne, Prabhu Bhagavatheeswaran, Faith Ellen Nathan, Hossein Borghaei
Journal: Journal of Clinical Oncology (2018)

9020 Background: CheckMate 227 (NCT02477826) is a large phase 3 study of 1L nivo + ipi, nivo, or nivo + chemo vs chemo in advanced NSCLC. The study met its co-primary endpoint demonstrating significantly prolonged progression-free survival with nivo + ipi vs chemo in patients (pts) with tumor mutational burden ≥10 mutations/Mb. The safety profile of 1L nivo + low-dose ipi was consistent with previous reports. Additional detailed analyses may inform the management of immune-related adverse events. Methods: Pts (N = 1739) with chemo-naive, stage IV/recurrent NSCLC without known sensitizing EGFR/ALK mutations were randomized 1:1:1 to nivo (3 mg/kg Q2W) + ipi (1 mg/kg Q6W), nivo monotherapy (240 mg Q2W), or chemo for pts with ≥1% tumor PD-L1 expression and to nivo + ipi, nivo (360 mg Q3W) + chemo, or chemo for pts with < 1% tumor PD-L1 expression. Tx continued until disease progression or unacceptable toxicity for up to 2 yr. Safety and PROs were exploratory endpoints. Safety analyses included time to onset and resolution of select treatment-related adverse events (select TRAEs; those with a potential immunologic cause) and corticosteroid use. PROs were assessed using the Lung Cancer Symptom Scale and EQ-5D instruments. Results: Minimum follow-up was 11.2 mo. Median duration of therapy was 4.2 mo with nivo + ipi and 2.6 mo with chemo. Rates of any grade and grade 3–4 TRAEs were 75% and 31% with nivo + ipi, and 81% and 36% with chemo, respectively. TRAEs led to discontinuation in 17% of pts receiving nivo + ipi and in 9% of pts receiving chemo. Most frequent grade 3–4 select TRAEs in pts receiving nivo + ipi were hepatic (8%), endocrine (4%), skin (4%), pulmonary (3%), and gastrointestinal (2%). Median time to onset of select TRAEs ranged from 2–15 wk, and the majority resolved with corticosteroid use (median time to resolution was ≤10 wk). PRO results will be reported in the final presentation. Conclusions: In CheckMate 227, nivo + low-dose ipi was well tolerated in NSCLC. Toxicities were manageable with previously established tx algorithms, including corticosteroids. Clinical trial information: NCT02477826.
Randomized controlled trial of monopolar cautery versus clips for staple line bleeding control in Roux-en-Y gastric bypass
Authors: Ersin Gundogan, Cuneyt Kayaalp, Aydin Aktas, Kutay Saglam, Mufit Sansal, Ufuk Uylas, Cihan Gokler, Egemen Cicek, Fatih Sumer
Journal: International Journal of Surgery (2018)
Interest in and outcomes with web-based education for return of genetic research results for inherited susceptibility to breast cancer.
Authors: Angela R. Bradbury, Jill B Gaieski, Brian L. Egleston, Linda J. Patrick-Miller, Wendy Chung, Olufunmilayo I. Olopade, Kara Noelle Maxwell, Sarah Walser, Dominique Fetzer, Jamie Brower, Amanda C. Brandt, Dana Clark, Laura DiGiovanni, Jessica M. Long, Jacquelyn Powers, Danielle Mckenna, Jill Stopfer, Caroline M. Weipert, Kate Nathanson, Susan M. Domchek
Journal: Journal of Clinical Oncology (2018)

1531 Background: How frequently research participants are interested in receiving genetic individual research results (IRR) and the best method for returning IRR remains unknown. Methods: Woman at three centers with a personal or family history of cancer, who provided a bio-sample for research, were offered the opportunity to receive IRR for 25 cancer susceptibility genes. Participants could complete pre-disclosure education by a self-directed web-education (WebED) or by telephone with a genetic counselor (GC). All participants received IRR by phone with a GC. Participants completed surveys at baseline, after pre-disclosure education and disclosure. We used t-tests and multiple linear regressions of change scores. Results: 1277 participants were contacted. Mean age was 61.4 years, 68% were white, 68% had a history of cancer and 56% had a college education. 393 (31%) enrolled to receive IRR, 120 (9%) actively declined, and 764 (60%) have not responded to multiple contacts. Age, education and race/ethnicity were not significantly associated with interest in IRR. To date, 211 (81%) completed pre-disclosure education by WebEd and 50 (19%) by GC. Younger age was associated with completing WebEd v GC. 250 (95%) received IRR; 12 (4%) declined. 12 (5%) received a positive result and 56 (22%) a VUS. Knowledge increased significantly after pre-disclosure education and disclosure of IRR, and was not associated with WebEd v. GC pre-disclosure. Depression, anxiety, cancer specific distress and perceived utility declined significantly after pre-disclosure education and disclosure. Change in knowledge, anxiety, cancer-specific distress and uncertainty did not differ from baseline to post-disclosure between WebEd v. GC education. After IRR, having WebEd and receiving a positive result were associated with greater reduction in depression as compared to GC pre-disclosure. Conclusions: Among participants interested in receiving genetic IRR, there was high interest in a web-based pre-disclosure education. Web-education was not associated with negative outcomes after receipt of IRR with a genetic counselor, suggesting a potential alternative resource reducing model for return of IRR.