tbuckley/cabot-search huggingface dataset:
Developing a supportive oncology program in a cancer institute: Needs assessment.
Authors: Diana Martins-Welch, Tara Liberman, James D'Olimpio, Maria Carney
Journal: Journal of Clinical Oncology (2016)

141 Background: Cancer patients experience significant symptom and psychosocial burden (Temel JS, et. al. N Engl J Med. 2010 Aug 19; 363(8):733-42. Early palliative care for patients with metastatic non-small-cell lung cancer.). Integration of supportive oncology programs within cancer centers has developed since the findings of Temel and Jackson. Addressing a growing need to manage patients comprehensively, the Northwell Health Divisions of Geriatric and Palliative Medicine and Hematology and Oncology partnered to initiate a community-based supportive oncology program. A needs assessment was completed of the providers staff, and important stakeholders. Methods: A sixteen-question survey was created and distributed to the staff at the cancer center. Questions focused on providers’ need for support in fifteen areas. The target audience included physicians, fellows, mid-level providers, registered nurses, social workers, dietitians, and care navigators. A student intern administered surveys over a six-week period. Results: A total of 61 surveys were collected. Of these, 30 were completed by registered nurses, 13 by physicians, 9 by mid-level practitioners, and 3 by social workers. Physicians expressed the highest level of need (&gt; 4.5/5) related to nutritional status, psychosocial factors and pharmaceutical review. Mid-level providers expressed highest level of need related to pain and depression. Nurses expressed highest level of need related to psychosocial factors, pain, depression, fatigue and pharmaceutical review. The average level of need across all areas and all respondents was 4.2 on a 5 point scale. The biggest challenge identified was lack of time to perform comprehensive assessments of patients. Conclusions: A high level of need for a supportive oncology program was identified. Per our assessment, providing comprehensive care with an emphasis on symptom control, nutritional and psychosocial support, and pharmaceutical review would benefit both providers and patients. Time constraints were identified as an issue by all practitioners and staff. The survey results supported the need for an added level of multi-disciplinary support for oncologists to care for cancer patients in the community.
Circulating tumor cells in locally advanced pancreatic adenocarcinoma: The ancillary study Circe 07 of the LAP 07 trial.
Authors: Florence Huguet, Francois-Clement Bidard, Christophe Louvet, Laurent Mineur, Olivier Bouche, Benoist Chibaudel, Pascal Artru, Francoise Desseigne, Jean Baptiste Bachet, Mohamed Gasmi, Suzanne Nguyen, Lionel Wander, Claire Mathiot, Jean-Yves Pierga, Pascal Hammel
Journal: Journal of Clinical Oncology (2013)

4046 Background: Pancreatic carcinoma is one of the leading causes of cancer-related mortality. At time of diagnosis, 30% of patients present with a locally advanced unresectable but non metastatic carcinoma (LAPC). Theoretically, patients with micrometastatic dissemination at diagnosis should benefit from systemic treatments, whereas radiation therapy should be favored in the others. Based on the hypothesis that circulating tumor cells (CTC) count is a surrogate of the cancer metastatic abilities, CTC detection rates and prognostic value were studied in a prospective cohort of LAPC patients. Methods: LAP07 international multicenter randomized study assesses in patients whose LAPC is controlled after 4 months of gemcitabine-based chemotherapy whether to administrate a chemoradiotherapy could increase overall survival versus continuation of chemotherapy alone. A subgroup of patients included in LAP 07 trial were prospectively screened for CTC before the start of the chemotherapy and after two months of treatment, using the CellSearch technique. Clinico-pathological characteristics and survival of patients were obtained prospectively and were correlated with CTC detection. Results: Seventy-nine patients were included in this ancillary study. One or more CTC/7.5ml were detected in 5% of patients before treatment and in 9% of patients after two months of chemotherapy (overall detection rate: 11% of patients). CTC positivity was associated with poor tumor differentiation (p=0.04), and with shorter overall survival in multivariable analysis (RR=2.5, p=0.01), together with anemia (p=0.005). Conclusions: The evaluation of micrometastatic disease using CTC detection appears as a promising tool which could help to personalize treatment modalities in LAPC patients. Clinical trial information: NCT00634725.
NVP-AEW541: A Selective Small Molecule IGF-1R Tyrosine Kinase Inhibitor Is Active Against Multiple Myeloma and Other Hematologic Neoplasias and Solid Tumors.
Authors: Nicholas Mitsiades, Ciaran J. McMullan, Vassiliki Poulaki, Reshma Shringarpure, Towia A. Libermann, Teru Hideshima, Dharminder Chauhan, Robert L. Schlossman, Paul G. Richardson, Nikhil C. Munshi, Carlos Garcia-Echeverria, Francesco Hoffmann, Kenneth C. Anderson, Constantine S. Mitsiades
Journal: Blood (2004)
High Expression of the Hedgehog Transcription Factor GLI1 Is Associated with Improved Outcomes in Patients with Acute Myeloid Leukemia Undergoing Hematopoietic Stem Cell Transplantation after Non-Myeloablative Conditioning
Authors: Marius Bill, Madlen Jentzsch, Luba Schuhmann, Juliane Grimm, Maria Knyrim, Laura Katharina Schmalbrock, Schubert Karoline, Michael Cross, Vladan Vucinic, Georg-Nikolaus Franke, Wolfram Poenisch, Gerhard Behre, Thoralf Lange, Dietger Niederwieser, Sebastian Schwind
Journal: Blood (2015)
APRIL-TACI Interactions Mediate Non-Hodgkin Lymphoma B Cell Proliferation through Akt Regulated Cyclin D1 and P21.
Authors: Mamta Gupta, Stephen M. Ansell, Thomas E. Witzig, Steven C. Ziesmer, James R. Cerhan, Stacey R. Dillon, Anne J. Novak
Journal: Blood (2007)
CMV-Specific Immunity and CMV Complications in Seropositive HCT Recipients Depend On Donor Serostatus.
Authors: Alejandra Ugarte-Torres, Yiping Liu, Tyler Williamson, Mette Hoegh-Petersen, Diana Quinlan, Lina Roa, Faisal Khan, James A. Russell, Jan Storek
Journal: Blood (2009)
Conversations about cancer-related infertility: An exploration of online discussion forums.
Authors: Taylor J Sands, Stephanie Smeltzer, Laura Covarrubias, Terri Lynn Woodard
Journal: Journal of Clinical Oncology (2016)

e279 Background: Many patients use Internet discussion forums to seek support and advice on medical conditions, including cancer and fertility. Online discussions about medical issues have been demonstrated to influence patients’ decisions about their care. The objective of this study was to explore online discussions that patients have about cancer and infertility. Methods: An initial search identified the three most popular forums that contained discussions about cancer-related infertility. Within these forums, a search of “cancer” and “infertility” was performed. All threads posted between June 1, 2010, and June 1, 2015 were identified. Qualitative research methods were used to identify, code, and analyze themes within the data. Results: A total of 14 threads and 133 posts were identified. Participants were both male and female and the age range of those disclosing demographic information was 21 to 44 years old. The major themes that were identified were: 1) use of forums as a supportive network, 2) sharing of experiences with fertility counseling and/or treatment, 3) consideration of alternative methods of family building, and 4) challenges encountered when seeking fertility counseling and services. Conclusions: Individuals affected by cancer-related infertility may use online discussion forums to seek information and advice from others who have gone through similar experiences, or to share their personal stories with fertility preservation with the online community. Understanding the role that these online forums play can help health care providers address the unique concerns of this population.
The effect of Wnt9A induced by lithium chloride on β-catenin and colorectal cancer cell proliferation.
Authors: Donald Peter Braun, Irshad Ali
Journal: Journal of Clinical Oncology (2016)

631 Background: Malignant tissues are characterized by uncontrolled proliferation and dysfunctional differentiation which often results from dysregulated Wnt signaling. β-catenin, a second messenger upregulated in neoplastic tissues is utilized by the canonical Wnt pathway (CWP) to promote cellular proliferation. In healthy tissues CWP is stringently controlled by components of the non-canonical Wnt pathway (NCWP). The NCWP, which does not utilize β-catenin for its activity, acts in concert with the CWP to maintain homeostasis in healthy tissues. Our recent studies in CRC cells indicate that LiCl increases expression of the NCWP ligand, Wnt9A leading to activation of the NCWP. Suppressing Wnt9A significantly attenuates LiCl-mediated inhibition of CRC cell proliferation. The present study investigated the capacity of Wnt9A to directly modulate expression of β-catenin mRNA and/or protein levels in CRC cells, and the effects on proliferation and apoptosis. Methods: Primary CRC lines established from resected tumors of 5 patients with metastatic disease were treated with LiCl and Wnt9A protein. Cellular proliferation and apoptosis were determined by MTS and caspase 3 assays. Total and activated β-catenin protein were determined by ELISA and Wnt pathway genes and β-catenin mRNA were determined with PCR arrays. Results: LiCl inhibited CRC proliferation (p&lt;0.001) and increased apoptosis (p&lt;0.01) which coincided with a 23-fold (p&lt;0.025) increase of the NCWP ligand Wnt9A. LiCl decreased β-catenin mRNA (p&lt;0.03) and suppressed protein levels of the total (p&lt;0.025) and the activated form of β-catenin. Recombinant Wnt9A protein emulated LiCl effects by inhibiting proliferation (p&lt;0.001), increasing apoptosis (p&lt;0.03) and suppressing activated β-catenin protein (p&lt;0.001) in CRC cells. Conclusions: This study demonstrates a novel mechanism for inhibiting CRC cell proliferation through suppression of activated β-catenin levels by the non-canonical Wnt ligand, Wnt9A. These results suggest that in CRC tumors that are driven by β-catenin, activation of the non-canonical pathway and/or direct induction of or treatment with Wnt9A protein may be therapeutically beneficial.
Depletion of HDAC7 and de-repression of Nur77: a mechanism for sensitivity of cutaneous lymphoma (CTCL) cells to pan- histone deacetylase inhibitor Panobinostat (LBH589)
Authors: K. Natarajan, J. Chen, R. Kolhe, K. Eaton, W. Fiskus, R. Rao, Y. Wang, P. Lee, P. Atadja, K. N. Bhalla
Journal: Journal of Clinical Oncology (2008)

14542 Background: HDAC7 belongs to the class IIA histone deacetylases (HDACs) and is overexpressed in thymocytes, where it transcriptionally represses the proapoptotic nuclear orphan receptor Nur77. Following an apoptotic stimulus, Nur77 translocates from the nucleus to mitochondria, where it binds and converts Bcl-2 into a pro-apoptotic protein, allowing caspase activation and apoptosis. Panobinostat (P) (Novartis Pharmaceuticals) has a high level of clinical activity against advanced CTCL cells. However, the molecular basis of this activity remains unclear. Methods: RT-PCR, confocal immunofluorescent microscopy and immunoblot analyses were utilized to determine the effects of P on the levels and localization of HDAC7 and Nur77 in cultured CTCL HH and HUT78 cells. Apoptosis was determined by the morphologic features and by estimating the sub-G1 hypodiploid DNA-containing fraction of cells. The sensitizing effects of the ectopic overexpression of Nur77 and its knockdown by Nur77 siRNA on P-induced apoptosis were also determined. Results: Treatment with P (5 to 20 nM) rapidly (4 hours) depleted the in vitro and intracellular activity, as well as depleted the mRNA and protein levels of HDAC7, but simultaneously induced the mRNA and protein expression of Nur77 in human CTCL HH and HUT-78 cells. P induced Nur77 translocation from the nucleus to mitochondria. This was associated with apoptosis of HH and HUT-78 cells. Ectopic overexpression of Nur77 induced apoptosis and sensitized HH cells to P. Conversely, knockdown of Nur77 levels inhibited P-induced apoptosis of HH cells. Co-treatment with ABT-737, a Bcl-2/BclxL antagonist (0,1 to 1.0 uM) significantly increased P-induced apoptosis of CTCL cells. In 5 samples of primary CTCL cells, ex-vivo treatment with P also dose-dependently increased the % of non-viable cells to up to 35 to 82%. Conclusions: These findings mechanistically implicate the role of HDAC7 down regulation and resulting de-repression and mitochondrial translocation of Nur77 in sensitizing human CTCL cells to P-induced cell death. These results also indicate that co-treatment with an anti-Bcl-2 agent e.g., a BH3 domain-only mimetic, would augment the anti-CTCL activity of P. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Institute for Biomedical Research Inc. Novartis Institute for Biomedical Research Inc. Merck & Co., Novartis, Novartis Institute for Biomedical Research Inc.
Impact of postoperative intra-abdominal infection on tumor recurrence and survival in hepatocellular carcinoma after curative liver resection.
Authors: Dan-yun Ruan, Yang Li, Ze-Xiao Lin, Dong-Hao Wu, Tian-tian Wang, Xing Li, Nan Jiang, Xiang-Yuan Wu
Journal: Journal of Clinical Oncology (2014)

374 Background: Postoperative intra-abdominal infection has been reported contributed to higher tumor recurrence rate and poor survival in cancer patients. The study aims to evaluate the impact of postoperative intra-abdominal infection on recurrence free survival (RFS) and overall survival (OS) in patients undergoing curative liver resection for hepatocellular carcinoma (HCC). Methods: ALL patients underwent liver resection from 2003 to 2010 were identified. The Clavien–Dindo (CD) classification was adopted to classify the complications and patients who died of postoperative complications within 30 days of surgery (grade V) were excluded form the study. Univariate and multivariate analyses were used to assess variables. Results: 215 patients were included, the overall 30-day postoperative complication rate was 36.74% (n=79), 13.95% (n=30) were intra-abdominal infectious complication. Patients with intra-abdominal infection had worse RFS (27.6% vs 50%, p&lt;0.001) and OS (46.7% vs 82.2%, p&lt;0.001) than those without it. In multivariate analyses, postoperative intra-abdominal infection was an independent prognostic factor of tumor recurrence (hazard ratio = 2.183; 95% confidence interval, 1.334-3.573) and overall survival (hazard ratio = 4.990; 95% confidence interval, 2.643-9.420). Hepatitis B surface antigen positive, tumor diameter (&gt;5cm) and Child-Pugh class (B) were other three independent factors associated with poor prognosis. Conclusions: According to the study, postoperative intra-abdominal infection predicts tumor recurrence and poor survival after radical liver resection in HCC patients. These findings may have implications of the potential association between inflammatory response and cancer progression.
Human insulin to increase breast cancer risk in Taiwanese women with type 2 diabetes.
Authors: Chin-Hsiao Tseng
Journal: Journal of Clinical Oncology (2015)

26 Background: To investigate whether human insulin use may be associated with risk of breast cancer in Taiwanese women with type 2 diabetes. Methods: The reimbursement databases of all Taiwanese diabetic patients from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2004 and a total of 482,065 women with type 2 diabetes were followed up for breast cancer incidence until the end of 2009. Incidences for ever-users, never-users and subgroups of human insulin exposure (using tertile cutoffs of time since starting insulin, cumulative dose and cumulative duration of insulin) were calculated and the multivariable-adjusted hazard ratios were estimated by Cox regression. Results: There were 59,830 ever-users and 422,235 never-users, with respective numbers of incident breast cancer of 559 (0.93%) and 4,711 (1.12%), and respective incidence of 207.7 and 215.1 per 100,000 person-years. The overall adjusted hazard ratios (95% confidence intervals) did not show a significant association with insulin [1.098 (0.994-1.212)]. However, significant trends for the different categories of the dose-responsive parameters were observed. Patients in the third tertiles consistently showed a significantly higher risk of breast cancer while compared to never-users: 1.263 (1.093-1.458), 1.339 (1.164-1.540) and 1.331 (1.158-1.531) for ≥ 67 months for time since starting insulin, ≥ 39,000 units for cumulative dose of insulin, and ≥ 21.8 months for cumulative duration of insulin, respectively. Conclusions: This study discloses a significantly higher risk of breast cancer associated with the use of human insulin, demonstrating a significant dose-responsive relationship.
Phase III study of regorafenib versus placebo as maintenance therapy in RAS wild type metastatic colorectal cancer (RAVELLO trial).
Authors: Erika Martinelli, Teresa Troiani, Filippo Venturini, Andres Cervantes, Jean Yves Douillard, Alfredo Falcone, Gunnar Folprecht, Claus-Henning Köhne, Julien Taïeb, Josep Tabernero, Claudia Cardone, Vincenzo Sforza, Giulia Martini, Stefania Napolitano, Annalisa Capuano, Fabiana Auricchio, Fortunato Ciardiello
Journal: Journal of Clinical Oncology (2015)

TPS789 Background: Treatment of metastatic colorectal cancer (mCRC) has improved due to the introduction of more active chemotherapies (CT) and novel targeted agents that have significantly increased response rate (RR), progression free survival (PFS) and overall survival (OS). Recently, CORRECT and CONCUR trials have demonstrated both activity and efficacy of regorafenib, a small multi-kinase inhibitor, as monotherapy in pretreated mCRC. The wide range of action of regorafenib makes it an ideal candidate for monotherapy in earlier disease treatment lines in which different pathways could be involved in the acquisition of resistance. To improve long term efficacy of first line therapy several therapeutic approaches of maintenance treatment have been explored in mCRC. Methods: RAVELLO is an academic randomized, double-blind, placebo-controlled, multi-center, phase III study designed to evaluate efficacy and safety of regorafenib as maintenance treatment after first line therapy. Eligible patients: pathologically confirmed mCRC RAS wild type (KRAS and NRAS genes) treated with a first line fluoropyrimidine-based CT in combination with an anti-EGFR (epidermal growth factor receptor) monoclonal antibody for a minimum of 4 to a maximum of 8 months, with a stratification by response to the first line treatment (complete response/partial response or stable disease). 480 patients will be enrolled and randomly assigned in a 1:1 ratio to receive 160 mg regorafenib or placebo per os, every day for 3 weeks of every 4 weeks cycle, until disease progression or unacceptable toxicity. Primary endpoint is PFS. With a two-tailed alpha error of 0.05, the study will have 90% power to detect a 3-month prolongation of median PFS from randomization (corresponding to a hazard ratio of progression of 0.67 with 6-month median PFS expected in the control arm). Secondary endopoint are OS, safety, and biomarker correlative studies. Currently, one patient has been enrolled and is on treatment. EudraCT number: 2013-005428-41. Clinical trial information: 2013-005428-41.
Patterns of Serum Free Light Chain (FLC) Recovery After Reduced Intensity Conditioning (RIC) Allogeneic Transplant for Multiple Myeloma (MM) Predict Long Term Outcomes
Authors: Veerpal Singh, Frank Frank Cornell, Sirisha Paruchuri, Marc Sala, Ayman Saad, Christopher Bredeson, Jeanne Palmer, Parameswaran Hari
Journal: Blood (2010)
A risk stratification schema for predicting diabetes mellitus in cancer survivors.
Authors: A. Moghaddamjou, A. Y. Tashakkor, P. Birks, W. Y. Cheung
Journal: Journal of Clinical Oncology (2011)

9052 Background: In order to ensure that the survival gains from cancer advances are not lost because of competing health risks, quality preventive care should be an essential aspect during the routine follow-up of cancer survivors (CS). The ability to identify CS who are most at risk for potentially modifiable conditions, such as diabetes mellitus (DM), can help to streamline preventive efforts. Our objectives were to 1) identify clinical factors associated with an increased risk of DM among CS and 2) develop a stratification system to predict DM risk in CS. Methods: Using the U.S. National Health and Nutrition Examination Survey, we identified 26,206 patients: 2,374 CS and 23,832 non-cancer controls (NCC). Multivariate logistic regression models were developed to determine demographic characteristics and clinical parameters that were independently correlated with an elevated relative risk (RR) of DM. By assigning a score of 1 for each diabetic risk factor identified, a stratification system was constructed that estimated the prevalence of DM based on the risk score. Results: In the entire cohort, mean age of 45.0 years (SD 17.4), 51.9 % were female, and 88.6% were White. Baseline characteristics were comparable between CS and NCC. DM was significantly more prevalent in CS when compared to NCC (13.2% of CS vs. 6.9% of NCC, p<0.01). Multivariate analyses revealed the following risk factors for DM: age ≥ 60 (RR 2.19, 95% CI 1.78-2.70); racial minorities (RR 1.65, 95% CI 1.16-2.33); less than high school education (RR 1.87, 95% CI 1.33-2.64); obesity (RR 5.90, 95% CI 4.88-7.14); history of ischemic heart disease (RR 2.20, 95% CI 1.45-3.33); history of congestive heart failure (RR 2.95, 95% CI 1.51-5.77); systolic blood pressure ≥120 mmHg (RR 1.66, 95% CI 1.22-2.26); and triglyceride level ≥150 mg/dL (RR 1.49, 95% CI 1.10-2.03). A stratification schema for DM in CS was devised (Table). Conclusions: Through the identification of risk factors for DM, a simple stratification schema was developed, allowing for the identification of CS who may benefit most from appropriate DM preventive care. Risk of diabetes in cancer survivors stratified by score. Risk score ≤1 2 3 4 5 6+ Prevalence of diabetes (%) 4.3% 10.8% 17.2% 32.4% 45.6% 67.8%