tbuckley/cabot-search huggingface dataset:
Gene expression differences in cell-free RNA between prostate cancer patients and healthy individuals.
Authors: Erwin Grussie, Genevieve Danenberg, Kanthi Athreya Kollengode, Kathleen Danenberg, Shahrooz Rabizadeh, Eric Huang, Joshua L. Usher, Peter V. Danenberg, Jacek K. Pinski
Journal: Journal of Clinical Oncology (2018)

e17077 Background: Cell-free circulating RNA (cfRNA) released into the bloodstream by tumors allows non-invasive identification of molecular changes via the quantity of particular genes (i.e., gene expression). In this study, we used cfRNA in order to measure PD-L1, TIM-3, PCA3, AR, and AR-V7 expression in prostate cancer patients (pts) and compared levels of expression and total cfRNA in blood to that taken from healthy individuals. Methods: Blood samples were collected from prostate cancer pts (at various times during therapy) and from healthy volunteers (controls). After plasma was fractionated from blood samples, cfRNA was extracted, reverse transcribed into cDNA using random hexamers, and then analyzed by RT-qPCR using appropriate gene-specific primers. The cDNA of each biomarker of interest was quantitated per volume of blood in cancer pts and the controls. β-actin expression was used as a surrogate for total cfRNA (ng/rxn). Results: PCA3 was detected only in cancer pts (31/55) and not in healthy controls (p = 0.0001, Fisher’s Exact). AR was detected in 41% of pts and 86% of controls, while AR-V7, signifying resistance to ADT, was detected in 7% (4/55) of prostate cancer samples and in none of the controls (0/14). PD-L1 and TIM-3 detection frequencies were similar in cancer pts and controls (35-43% and 82-86%, respectively). All gene expressions show a significantly higher overall level in the blood of cancer patients than in healthy individuals. The median cfRNA level in cancer pts was significantly higher than in healthy controls, 23.8 ng/rxn (0.4-82.5) and 8.6 ng/rxn (2.7-17.1), respectively (p < 0.0001, Pearson chi-square). Conclusions: These data indicate that using cfRNA to quantitate gene expressions of interest from blood may have potential for detection of cancer, monitoring recurrence, and in selecting therapies. The significant difference in median total cfRNA between cancer patients and healthy individuals suggests that the total cfRNA level itself may be useful as a sensitive preliminary indicator of the presence of cancer and/or for recurrence monitoring. Clinical trial information: NCT02853097.
Allogeneic hematopoietic cell transplantation for myelofibrosis (MF) in high risk patients.
Authors: Swapna Narayana, Saurabh Chhabra, Ravi Kishore Narra, Aniko Szabo, Mehdi Hamadani, Marcelo C. Pasquini, Nirav Shah, Parameswaran Hari
Journal: Journal of Clinical Oncology (2017)

7062 Background: Although allogeneic transplantation(alloHCT) is the only curative treatment modality for MF, given the median age of MF, most patients are not candidates for alloHCT due to concerns for treatment-related mortality(TRM), age and comorbidities. Methods: We reviewed the outcomes of 24 recipients of matched related/unrelated donor alloHCT for MF at the Medical College of Wisconsin. All patients with JAK2 mutation(62%) and/or constitutional symptoms recieved Roxulitinib atleast 4 months prior to alloHCT with discontinuation of Ruxolitinib 48 hrs prior to the start of conditioning. Majority(91%) received conditioning with Fludarabine and Busulfan(Flu/Bu4, Flu/Bu3,Flu/Bu4). Only 2 patients received TBI based regimen; Flu/TBI(2-4Gy). Those with splenomegaly &gt; 22cm received pre-transplant splenic radiation(n = 11;49%). Survival outcomes were analyzed using Kaplan-Meier curves and compared between groups using log-rank test. Results: Median age was 57 years(range,40-67) with 29% &gt; 60 years. A 46% had primary ET or PV that evolved to MF and 17% had MDS cytogenetics. Majority(74%) patients MF-3 grade. More than 80% recieved Ruxolitinib and 25% were treated with hypomethylating/cytotoxic chemotherapy. HCT-CI score was≥3 in 62%. Four patients had cirrhosis and portal hypertension(PHTN), and another 3 had PHTN without Cirrhosis.At median follow up of 36months, 3-year overall survival(OS) and relapse-free survival were(RFS) 70%. Marrow fibrosis improved post HCT with only 15% grade 3. One patient relapsed and died from AML 15 months post-HCT. TRM was 25% at 3 years; causes of death were sepsis(n = 3), alveolar hemorrhage(n = 1) and myocardial infarction(n = 1). Variables such as type of donor, DIPSS scoring, MF grade and age of the patient were not significantly associated with OS/RFS on univariate analysis. Conclusions: Despite advanced age and 62% with HCT CI≥3, we report excellent survival outcomes compared to other prior data. Careful patient selection, use of Ruxolitinib pre-HCT, splenic irradiation pre-HCT and Flu/Bu based conditioning regimen all contributed to the remarkable results in this series.
Association of expression of toll-like receptors 2 and 9 in circulating leukocytes with infection and death risk in elderly with cancer.
Authors: Guacyra Magalhaes Pires, Jurema Telles O Lima, Leuridan Torres, Letícia telles Sales, Marina Santaliz De Godoy Moreno, Kleber das neves Jatahy, Gabriela Delgado Soriano, Maria Julia Gonçalves Mello, Vera da silveira Magalhães
Journal: Journal of Clinical Oncology (2018)

e24142 Background: Elderly cancer group is a heterogeneous and growing one. In the elderly, Toll-Like Receptors(TLRs) have been described as related to the immunosenescence process, carcinogenesis and infection. Methods: Between 2015 and 2017, prospective cohort study in 264 eligible cancer patients (≥ 60 years) were included. 71 patients no cancer or infection control is recruited. The collection of the peripheral blood sample was performed during patient admission, prior to treatment and the onset of the first episode of infection. Determination of TLR2 and TLR9 was performed by flow cytometry with monoclonal antibodies antiTLR2 and TLR9. The patients were distributed by tumor type, (prostate, breast, tumors of the gastrointestinal tract and tumors of the female genital tract). Categorical data are expressed as numbers, percentages and mean (±SD). Therefore, a non parametric test was used to compare the two groups (Mann-Whitney U-test) and ≥ three groups (Kruskal – Wallis test). Results: 76 cancer patients infected and 25 died.Values were higher in the cancer patients compared to the control group (TLR2: p < 0.0001). There were high relative levels of leukocytes / TLR2 + in patients with prostate cancer compared to other types of tumors (p < 0.05) and controls ( < 0.0001). High levels of leukocytes / TLR2 + were observed in patients with and without infection when compared to the control group (p = 0.0003 and p = 0.0002, respectively). The relative levels of leukocytes / TRL9 + were elevated in the groups with and without infection when compared to controls ( p < 0.0001). Patients with and without infection had high absolute levels of leukocytes / TLR9 + when compared with the control group (p < 0.0001). It was found that patients with infection had high absolute levels of leukocytes / TLR9 + when compared to those who did not present infection during the study (p = 0.008). Conclusions: the elderly with cancer present high levels of leukocytes with expression of TLR2 and TLR9 when compared to the elderly without cancer and patients with or without infection during clinical follow-up had high levels of TLR2 and TLR9 when compared to controls.
Racial disparities in breast cancer treatment based on ASCO/NCCN quality guidelines.
Authors: Surbhi Agarwal, Ruta D. Rao, David Ansell
Journal: Journal of Clinical Oncology (2018)

e18654 Background: ASCO/NCCN quality measures for breast cancer include 1) radiation therapy administered within 1 year of diagnosis for women under age 70 receiving breast-conserving surgery; 2) chemotherapy considered in 4 months of diagnosis for women under 70 with T1c or Stage II/III ER/PR- tumors; 3) endocrine therapy administered within 1 year of diagnosis for women with AJCC T1 or Stage II/III ER/PR+ breast cancer. These evidence-based measures promote accountability for providers and allow transparency in quality of care. Black women are less likely than white women to receive these therapies that are associated with a survival benefit. Improving adherence to guidelines can decrease the gap in mortality rates for minority women with breast cancer. Methods: We performed a retrospective chart review on breast cancer patients between April 2010 and October 2015 at Rush University. Information collected included time of diagnosis, clinical stage, ER/PR status, surgical procedures, radiation, chemotherapy, endocrine therapy, and demographics. Chi-squared analysis was done to compare percent of black versus white women who met each quality guideline. Results: In total 2,436 women were analyzed, of whom 30.3% were black, 66% were white, and 3.7% were other. Of this cohort, 779 women met inclusion criteria for quality guideline 1, and there was no significant difference between black and white women who did not receive radiation therapy (p = 0.21, 24.7% vs 20.4%). For quality guideline 2 (n = 382), there was also no significant difference between black and white women who did not get chemotherapy within four months of diagnosis (p = 0.32, 36.6% vs 31.4%). However, for quality guideline 3 (n = 1,222), there was a statistically significant difference between black and white women who did not get hormone therapy within a year of diagnosis (p = 0.0008, 36.9% vs 26.1%). Conclusions: Endocrine therapy reduces risk of recurrence and mortality in women with ER/PR positive breast cancer; however, there is a disparity between black versus white women who meet this NCCN quality guideline. Further studies are needed to understand the reason for this gap in quality of care so that specific interventions can be implemented to eliminate this disparity.
Politics and Health Care
Authors: Donald M. Berwick
Journal: JAMA (2018)

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No Sugar Added: A New Strategy to Inhibit Glioblastoma Receptor Tyrosine Kinases
Authors: Daniel R. Wahl, Theodore S. Lawrence
Journal: Clinical Cancer Research (2018)

A novel inhibitor of N-linked glycosylation (NGI-1) inhibits the glycosylation and phosphorylation of multiple receptor tyrosine kinases in glioblastoma (GBM). NGI-1 sensitizes multiple models of GBM to chemotherapy and radiation in vitro and in vivo and may be especially effective in GBMs that retain active PTEN.See related article by Baro et al., p. 784.
A phase II evaluation of temsirolimus in combination with carboplatin and paclitaxel followed by temsirolimus consolidation as first-line therapy in the treatment of stage III-IV clear cell carcinoma of the ovary.
Authors: John H. Farley, William E Brady, Keiichi Fujiwara, Hiroyuki Nomura, Mayu Yunokawa, Hideki Tokunaga, Motoaki Saitou, David Marc Gershenson
Journal: Journal of Clinical Oncology (2016)

5531 Background: The primary objective of the study is to estimate the 12-month progression-free survival (PFS) for carboplatin/paclitaxel + temsirolimus in women with newly diagnosed clear cell ovarian cancer (CCOC) and to compare to historical controls in this patient population from previous GOG protocols. Methods: Patients with Stage III or IV CCOC were enrolled. Patients were treated with Paclitaxel 175 mg/m2 on Day 1, Carboplatin AUC 6 Day 1, and Temsirolimus (CCI-779) 25mg IV Days 1 and 8 every 3 weeks for Cycles 1-6 or disease progression, followed by consolidation therapy with temsirolimus 25 mg Days 1, 8, and 15 every 3 weeks cycles 7-17 or until disease progression. All eligible patients who received therapy were evaluated for efficacy and toxicity. Results: Ninety patients were accrued to the study: 45 in the US and Korea (US/Korea) and 45 in Japan. Efficacy is presented separately for US/Korea and Japan. Most (83%) patients were stage III, and 66% of patients had no measurable disease starting therapy. Twenty-two percent received < 6 cycles of therapy while 28% completed all 17 cycles of chemotherapy. In patients with measurable disease, in the US/Korea, 31% (n = 4) and 23% (n = 3) had complete or partial responses, respectively, while in Japan, 6% (n = 1) and 65% (n = 11) did. Median PFS (OS) was 11 (23) months for US/Korea and 12 (26) months for Japan. Most (85%) patients (88% US/Korea, 82% Japan) were optimally debulked. In the US, 0% of suboptimally debulked patients had PFS > 12 months, and 49% of optimal patients did; in Japan, these were 25% and 59%. In neither the US/Korea nor Japan was the 12-month PFS significantly (p > 0.05) better than historical controls. There was no statistically significant difference in PFS or OS between US/Korea and Japan. Most common G3-4 adverse events were neutropenia, leukopenia, anemia, and thrombocytopenia. Conclusions: Carboplatin/paclitaxel + temsirolimus was well tolerated. Optimally debulked patients benefited most, with 54% having a PFS > 12 months. When compared to historical controls this regimen did not statistically significantly increase PFS at 12 months. Clinical trial information: NCT01196429.
TCT-652 Coronary Artery Calcium Score in Predicting Periprocedural Myocardial Infarction in Patients Undergoing Elective Percutaneous Coronary Intervention
Authors: Min Gyu Kang, Hyun-Woong Park, Yoomee Kang, Hyun Gyung Jang, Kyehwan Kim, Jin-Sin Koh, Seok-Jae Hwang, Jin-Yong Hwang, Jae Seok Bae, Jong-Hwa Ahn, Yongwhi Park, Young-Hoon Jeong
Journal: Journal of the American College of Cardiology (2018)
Survival trend among patients with advanced pancreatic neuroendocrine tumors in United States.
Authors: Ranju Kunwor, Krishna Bilas Ghimire, Mahesh Nepal, RamKaji Baniya, Dominic Ho
Journal: Journal of Clinical Oncology (2018)

e16256 Background: Pancreatic neuroendocrine tumors (PNETs) are rare neoplasms, comprising 1-2% of all pancreatic tumors. Molecularly targeted therapy (MTT) like everolimus, sunitinib were approved by FDA in May 2011 for the treatment of advanced and metastatic PNETs. We conducted this study to compare survival outcome in patients with advanced and metastatic PNET in pre- (2000-2010) and post- (2011-2014) MTT era in the United States using U.S. Surveillance, Epidemiology, and End Result (SEER) registry database. Methods: We selected patients with metastatic PNETs (Insulinoma, Glucagonoma, Gastrinoma, Somatostatinoma, and Mixed Pancreatic Endocrine carcinomas), age ≥18 years at the time of diagnosis from the SEER database. We used SEER 18 registry database to evaluate relative survival (RS) rate during 2000-2010 and 2011-2014. The RS rate at 1, 2 and 3 years were analyzed for cohorts by age (18-50 years, ≥51 years), and gender (male, female). The RS rates accompany standard error (SE). We used Z-test in SEER Stat for statistical analysis. Results: There were a total of 640 (524 in pre- and 116 post-MTT era) metastatic PNET patients; 361 males and 279 females reported in the registry. RS at 1, 2 and 3 years in pre- vs post-MTT era for age group 18-50 was: 89.2 ± 2.5% vs 92.0 ±5.5%, P = 0.777; 82.3± 3.1% vs 83.1 ±10.1%, P = 0.812; and 76.0 ± 3.5 % vs 59.7 ± 16.1% P = 0.570. Similarly, for age group ≥51 years, RS at 1, 2 and 3 years in pre-vs post-MTT era was: 78.5 ± 2.2% vs 73.0 ±5.2 %, P = 0.397; 64.2 ± 2.6 % vs 57.4 ± 6.4%, P = 0.328; and 56.0 ± 2.8% vs 51.8 ± 7.2%, P = 0.443 respectively. RS for adult male was 82.2 ± 2.4 % vs 83.3 ± 4.7%, P = 0.713; 69.5 ±2.9% vs 67.2 ± 6.8%, P = 0.915; and 59.9 ±3.1% vs 59.2 ± 8.5%, P = 0.975 at 1, 2 and 3 years respectively. RS for adult female was 81.1 ± 2.6% vs 64.6 ± 8.4 %, P = 0.038; 69.7 ± 3.1 % vs 53.6 ± 9.6% P 0.078; and 64.7 ± 3.3% vs 41.9 ± 11.3%, P = 0.040 at 1 year, 2 years and 3 years respectively. Conclusions: Our study showed that patients with metastatic PNETs have no improvement in 1, 2 and 3-year RS rates in post MTT era. Subgroup analysis by gender showed no improvement in RS in male and female of all age group. Even with the approval of the newer agents for treatment of advanced and metastatic PNET, the relative survival in the US population has not improved.
Rituximab plus Lenalidomide in Advanced Untreated Follicular Lymphoma
Authors: Franck Morschhauser, Nathan H. Fowler, Pierre Feugier, Reda Bouabdallah, Hervé Tilly, M. Lia Palomba, Christophe Fruchart, Edward N. Libby, Rene-Olivier Casasnovas, Ian W. Flinn, Corinne Haioun, Hervé Maisonneuve, Loic Ysebaert, Nancy L. Bartlett, Kamal Bouabdallah, Pauline Brice, Vincent Ribrag, Nicolas Daguindau, Steven Le Gouill, Gian M. Pica, Alejandro Martin Garcia-Sancho, Armando López-Guillermo, Jean-François Larouche, Kiyoshi Ando, Maria Gomes da Silva, Marc André, Pierre Zachée, Laurie H. Sehn, Kensei Tobinai, Guillaume Cartron, David Liu, Jianming Wang, Luc Xerri, Gilles A. Salles
Journal: New England Journal of Medicine (2018)

Rituximab plus chemotherapy has been shown to be effective in patients with advanced-stage, previously untreated follicular lymphoma; nevertheless, most patients will have a relapse. Combination immunotherapy with lenalidomide and rituximab is an immunomodulatory regimen that has shown promising activity in patients with indolent B-cell non-Hodgkin's lymphoma.
Implementation of a chemotherapy-induced nausea and vomiting dashboard.
Authors: Jennifer Hess, Vinay Vaidya, Melissa Rees, Alexandra Walsh
Journal: Journal of Clinical Oncology (2018)

e22519 Background: Chemotherapy induced nausea and vomiting (CINV) negatively impacts the quality of life of pediatric patients receiving antineoplastic agents. Our objective was to prevent CINV using a hospital wide electronic health record (EHR) based real-time surveillance system for automated CINV detection. Methods: A software program designed to provide hospital-wide data reporting was developed. The program utilizes a dashboard feature that extracts patient specific information on antineoplastic agents, antiemetic medications and frequency of emesis from the EHR. The extracted data are automated and available on a self-updating dashboard. Oncologists and pharmacists can utilize the dashboard to promote adherence to guidelines for medication administration. Results: The dashboard contains color-coded headings to designate low, medium or highly emetogenic potential for antineoplastic agents according to published supportive care guidelines. This color scheme is applied to antiemetic classes to facilitate ordering of the appropriate antiemetic regimen. With this design, adherence to supportive care guidelines can be quickly assessed as a component of patient care. Individual patients can be customized to allow for in depth review of selected cases, clinical outcomes and trends. A CINV surveillance team including a pharmacist and pediatric oncologist review the dashboard daily to direct prevention and treatment strategies. Conclusions: This novel EHR dashboard of a CINV surveillance system serves as a tool for pediatric oncology providers to facilitate optimal antiemetic care for patients. The system is auditable and HIPAA compliant. This tool allows for identification of at risk patients, both prospectively and in response to documented uncontrolled emesis. By identifying these patients efficiently, we are able to intervene with appropriate preventative and breakthrough antiemetic medications to improve the quality of care for pediatric oncology patients and improve compliance with published supportive care guidelines. Subsequent studies will utilize this dashboard to analyze changes in clinical practice and clinical outcomes in pediatric oncology patients in which optimal control of acute CINV is obtained.
Histone deacetylase inhibition alters tumor phenotype and stimulates a productive anti-tumor immune response in preclinical models of ovarian cancer.
Authors: Tyler McCaw, Taylor Turner, Haller M Smith, Donald J. Buchsbaum, Troy Randall, Rebecca Christian Arend
Journal: Journal of Clinical Oncology (2018)

5585 Background: Ovarian cancer remains the most deadly gynecologic malignancy. Chemotherapy and surgical reduction are initially effective but most patients relapse with chemoresistant disease. Immunotherapy is currently being evaluated in multiple clinical trials as a treatment modality for ovarian cancer, but response rates as a single agent have been disappointing. Because an altered epigenetic framework contributes to malignant transformation and immune escape in ovarian cancer, our objective was to evaluate whether histone deacetylase (HDAC) inhibition could reorient the suppressive tumor microenvironment and stimulate a productive anti-tumor immune response. Methods: Syngeneic ovarian cancer cells (ID8 or ID8 p53-/-) were injected into the peritoneal cavity of C57BL/6 mice and treated daily with 20mg/kg entinostat or vehicle, starting on day 21. First, we assayed transcript-level changes in gene expression of whole tumor lysates using the NanoString PanCancer Immune Profiling Panel. Next, we used flow cytometry to assess the number and function of T cells in the tumor and ascites. Results: HDAC inhibition increased expression of genes associated with T and NK cell infiltration, cytolytic functions, major histocompatibility class I and class II, as well as other genes associated with immune recognition. In addition, entinostat significantly reduced the number and suppressive capacity of regulatory T cells in both the tumor and ascites. Notably, HDAC inhibition led to infiltration of higher quality CD8 cytotoxic T cells with superior effector functions. These CD8 T cells expressed lower levels of the exhaustion-associated transcription factor Eomes, suggesting they will remain highly functional for a longer amount of time and are less susceptible to exhaustion. Conclusions: Our results suggest entinostat could dramatically increase tumor immunogenicity and help turn a “cold” (non-inflamed) tumor into a “hot” (T cell inflamed) tumor, while potentiating anti-tumor T cell functions. Thus, inclusion of HDAC inhibition may increase the frequency of patients responding to checkpoint blockade and/or other immunotherapies.