tbuckley/cabot-search huggingface dataset:
Phase I trial of enzalutamide in combination with gemcitabine and nab-paclitaxel for the treatment of advanced pancreatic cancer.
Authors: Amit Mahipal, Gregory M. Springett, Nancy Burke, Barbara Bertels, Georgine Wapinsky, Khaldoun Almhanna, Richard D. Kim
Journal: Journal of Clinical Oncology (2015)

467 Background: Despite recent advances, patients with metastatic pancreatic cancer have a very poor prognosis with a median survival of less than 1 year. Sex steroid hormones may play an important role in the growth and progression of pancreatic cancer. Anti-androgen drugs have demonstrated to have activity in pre-clinical pancreatic cancer models. In this Phase 1a/Ib trial, we evaluated the safety and tolerability of the combination of enzalutamide, a novel androgen receptor (AR) antagonist with gemcitabine and nab-paclitaxel. Methods: Pts with histologically confirmed metastatic pancreatic adenocarcinoma were included in this trial as a first-line treatment. Standard 3+3 dose escalation design was used to evaluate 2 dose levels of enzalutamide: 80 mg and 160 mg daily. Gemcitabine 1,000 mg/m2 was administered IV on days 1, 8 and 15 of 28-day cycle. The dose of nab-paclitaxel was 125 mg/m2 IV on days 1, 8 and 15. The DLT period was 28-days or until the beginning of the second cycle. Imaging studies were performed every 2 cycles. Results: Eight pts with stage IV pancreatic cancer have been enrolled in this trial, 5 pts at the first dose level and 3 pts at the second dose level. The median age was 64 years (50-80 years). All pts were male with an ECOG performance status of 1. Five pts had liver metastases. One patient was non-evaluable for DLT. No DLTs have been observed. Grade 3 treatment related AEs include febrile neutropenia (n=1), Neutropenia (n=1), ALT elevation (n=1). Grade 2 anemia and thrombocytopenia was seen in one patient. Grade 1 AEs included anemia (n=2), neutropenia (n=4), thrombocytopenia (n=3), diarrhea (n=1), fatigue (n=2), pruritis (n=1), nausea (n=1), hyponatremia (n=1) and AST elevation (n=1). Three pts had restaging studies performed and all had stable disease by RECIST criteria. There were decreases in size of target lesions in all the 3 patients along with a decrease in CA 19-9 levels. Conclusions: Enzalutamide at the dose of 160 mg daily is safe to administer in combination with gemcitabine and nab-paclitaxel. No unexpected toxicity has been observed. Cytopenias secondary to chemotherapy is common. Preliminary signals of efficacy were observed with this combination. Clinical trial information: NCT02138383.
Curative resection for hilar cholangiocarcinoma: Does adjuvant therapy impact overall survival? A multi-institution analysis from the U.S. Extrahepatic Biliary Malignancy Consortium.
Authors: Bradley Krasnick, Linda Jin, Jesse Davidson, Cecilia Grace Ethun, Timothy M. Pawlik, George A. Poultsides, Thuy Tran, Kamran Idrees, Chelsea A Isom, Sharon M. Weber, Ahmed I. Salem, William G. Hawkins, Steven M. Strasberg, Robert C. G. Martin, Charles Raben Scoggins, Perry Shen, Harveshp Mogal, Carl Richard Schmidt, Shishir Kumar Maithel, Ryan C. Fields
Journal: Journal of Clinical Oncology (2016)

388 Background: Surgical resection is the cornerstone of curative therapy for localized hilar cholangiocarcinoma. However, the effect of adjuvant therapy (AT) on survival is unclear. We analyzed the impact of AT on overall survival (OS) in those patients undergoing curative resection for hilar cholangiocarcinoma. Methods: We reviewed 294 patients who underwent curative resections for hilar cholangiocarcinoma between 1998 and 2015 from ten institutions participating in the U.S Extrahepatic Biliary Malignancy consortium. We analyzed the impact of AT on the primary outcome of OS. Probability of OS was calculated in the method of Kaplan and Meier and analyzed using multivariate Cox regression analysis. Statistical significance was set at p≤0.05. Results: Mean age was 65 years. OS at 5 years was 16%. A total of 146 patients (50%) received AT. Of these patients, 44 patients underwent solely chemotherapy, 5 underwent only radiation therapy (XRT), and 97 underwent combined therapy. On univariate analysis, patients who received AT and those who did not had similar demographic and preoperative features, with the major difference being in the rate of lymph node (LN) positive disease (50% AT group vs. 19% no AT group, p&lt;0.01). In a multivariate Cox regression analysis, AT conferred a significant protective effect on OS (HR 0.578, p&lt;0.01, 95% CI 0.38-0.86), even when adjusting for age, tumor size, R0 resection status, ASA classification, and LN positivity (Table). Conclusions: AT is associated with improved OS in resected hilar cholangiocarcinoma. This association remains even after adjusting for poor prognostic features. We acknowledge that there is an inherent selection bias when looking at those who underwent AT, and thus future prospective randomized trials are needed. [Table: see text]
Prognostic value of multidimensional geriatric assessment (MGA) on survival of a prospective cohort of 880 elderly cancer patients (ECP).
Authors: U. Basso, C. Falci, A. Brunello, V. Zafferri, P. Fiduccia, G. Sergi, S. Lonardi, E. Lamberti, E. Castegnaro, C. Solda', F. Cossutta, V. Chiarion-Sileni, S. Monfardini, V. Zagonel
Journal: Journal of Clinical Oncology (2011)

9065 Background: Estimated tumor-independent life expectancy is a key element for treatment choices in ECP. MGA allows to subdivide them into three categories of Fit, Vulnerable and Frail pts. Whether MGA is able to predict survival independently from tumor type, stage, and treatment is still an open question. Methods: All consecutive pts ≥70 years admitted to our Geriatric Oncology Program underwent MGA (Basso CROH 2009) and were prospectively followed. All-cause survival was compared according to their condition of fitness, vulnerability or frailty. Type of tumor, disease status at first visit (neoadjuvant/adjuvant vs advanced), administration of any treatment (cytotoxic/endocrine/targeted therapy) were assessed. Kaplan-Meier survival method was used with multivariate (Cox) analysis. Results: From 09-2003 to 10-2010, 880 ECP were enrolled, median 77 yrs (range 70-96), 28% males, with breast (54.5%), colorectal (14.1%), lung (8.2%) or other sites (23.2%) of cancer. Seventy-one percent were seen for neoadjuvant/adjuvant treatment; 79.8% were prescribed some oncological treatment. After a median follow-up of 26 mo (1-77), 334 have died (38%). Status at MGA predicted overall survival (p<0.001). Significance was maintained in the subgroups with adjuvant/neoadjuvant vs advanced disease, treated vs untreated pts, and in pts with breast cancer or other sites, but was lost when only colon or lung cancer were considered (Table). At multivariate analysis, Fitness maintained a strong impact on survival compared to Frailty (HR=0.41, CI:0.31–0.54) as well as Vulnerability vs Frailty (HR= 0.59, CI: 0.45 – 0.77). Conclusions: MGA predicts significantly different survival probability in our large cohort of ECP, independently of stage and treatment. Lack of significance in lung or colorectal cancer may be due to lower patient numbers. Survival (%) at 24 mo (univariate log rank test). Fit 338 pts Vulnerable 288 pts Frail 254 pts P value Overall 83 70 60 <0.001 Disease status Adjuvant/neoadjuvant 93 86 79 <0.001 Advanced 52 33 37 0.009 Disease site Breast 94 90 78 <0.001 Colorectal 75 56 51 0.185 Lung 33 17 17 0.241 Other 68 45 41 0.001 Oncological treatment Yes 83 72 65 <0.001 None 87 74 51 <0.001
Effect of sarcopenia on prognosis of patients with gastric cancer.
Authors: Shiro Iwagami, Hideo Baba
Journal: Journal of Clinical Oncology (2015)

192 Background: Recently, some studies reported the correlation between low skeletal muscle mass (sarcopenia) of patients with cancer and poor prognosis. There were no reports mentioned the relationship of sarcopenia to patients with gastric cancer. Objective: To evaluate the impact of sarcopenia on survival of patients with gastric cancer. Methods: From April 2005 to December 2010, 243 patients with gastric cancer underwent gasrectomy. Patients were divided in two groups, sarcopenia and nonsarcopenia group. Sarcopenia was defined as muscle mass below the median on preoperative CT scan. Muscle mass was assessed by psoas muscle density and total psoas area. The third lumbar vertebra (L3) was chosen as the standard landmark. We examined the relationship between sarcopenia and overall survival (OS), cancer specific survival (CSS), and disease free survival (DFS). Results: The mean age was 67.6 years old. 95 patients underwent total gastrectomy, 150 did distal gastrectomy, and 18 did proximal gastrectomy. The number of laparoscopic surgery was 62 cases. The CSS and DFS of patients in sarcopenia group were significantly shorter than nonsarcopenia group (p=0.012, p=0.023). The OS of sarcopenia tented to shorter (p=0.12). Conclusions: The presence of sarcopenia was found to significantly increase a patient’s risk of gastric cancer.
Characteristics and outcomes of persons with advanced cancer associated with having a family caregiver: A classification tree analysis.
Authors: J Nicholas Dionne-Odom, Dheeraj Raju, Jay Hull, Imatullah Akyar, Kathleen Lyons, Andres Azuero, Jennifer Frost, Marie Bakitas
Journal: Journal of Clinical Oncology (2014)

29 Background: Little is known about the impact that having a family caregiver (FCG) has on individuals with advanced cancer. We examined patient characteristics and outcomes most associated with having versus not having a primary FCG. Methods: Secondary data analysis of a randomized controlled trial of an early palliative care intervention (Project ENABLE [Educate, Nuture, Advise, Before Life Ends]) for patients with advanced cancer and their primary FCGs (10/2010-9/2013). Sociodemographic and patient reported outcomes data were abstracted from the baseline questionnaires of 122 patients who enrolled with FCG and 85 patients who enrolled without a FCG. Sociodemographic variables included age, gender, education, race, social support (MSPSS: Multidimensional Scale of Perceived Social Support, score range: 12-84), and Karnofsky Functional status. Patient reported outcomes included symptom impact (QUAL-E Symptom Impact, score range: 4-20), quality of life (QOL) (Functional Assessment of Chronic Illness Therapy-Palliative Care, score range: 0-184), depression (Center for Epidemiological Studies-Depression Scale, score range: 0-60), perceived quality of care (Patient Assessment of Chronic Illness Care, score range: 20-100), and hospital days and emergency department visits in the past 3 months. Structured tree analysis was used to identify a set of variables strongly associated with the presence or lack of a FCG. Results: In the final model, for patients with MSPSS scores &lt;52.5 (N=12), none had a FCG. For male patients with MSPSS scores &gt;52.5 (N=105), 73% (N=77) had a FCG. For female patients with MSPSS scores &gt;77.5 (N=29), 69% (N=20) had a FCG. For female patients with MSPSS scores &lt;77.5 and QOL scores &gt;126.1 (N=25), 20% (N=5) had a FCG. For female patients with MSPSS scores &lt;77.5, QOL scores &lt;126, and depression scores &gt;26 (N=10), 20% (N=2) had a FCG. For female patients with MSPSS scores &lt;77.5, QOL scores &lt;126, and depression scores &lt;26 (N=26), 77% (N=20) had a FCG. Conclusions: The final model suggests that having a FCG is highly associated with having high levels of perceived social support, being male, and lower levels of depression despite having lower QOL.
Simultaneous Transplantation of Three Cord Blood Units in Adults with High Risk Acute Leukemia.
Authors: Wieslaw Wiktor-Jedrzejczak, Malgorzata Rokicka, Elzbieta Urbanowska, Tigran Torosjan, Anna Gronkowska, Elzbieta Graczyk-Pol, Agnieszka Tomaszewska, Monika Paluszewska, Magdalena Tormanowska, Malgorzata Krol, Maria Krol, Justyna Jolkowska, Michal Witt
Journal: Blood (2005)
Effect of lymphadenectomy on survival in patients with esophageal cancer.
Authors: Khaldoun Almhanna, Jill M. Weber, Ravi Shridhar, Sarah E. Hoffe, Richard C. Karl, Kenneth Meredith
Journal: Journal of Clinical Oncology (2012)

65 Background: The number of resected lymph nodes is associated with overall and disease-free survival in some gastrointestinal malignancies. The impact of nodal harvest during esophagectomy remains to be determined. We examined the influence of lymphadenectomy on overall survival in patients with esophageal cancer. Methods: Utilizing a prospectively maintained comprehensive esophageal cancer database we identified patients who underwent esophagectomy with between 1994 and 2011. The association between disease free survival (DFS), overall survival (OS) and nodal harvest was evaluated using multivariable Cox regression models. The number of harvested nodes was examined as a categorical variable based on strata(S): 1) ≤8, 2) 9-12, 3) 13-20, and 4) &gt;20. Results: We identified 635 patients, 541 males and 94 females with a median age of 65 years (28-86) and median follow-up of 22 months (0-168). Adenocarcinoma 559 (88 %) was the predominant histology where as squamous cell carcinoma represented 76 (12%) of the cases. The 5-year OS and DFS rate for S1-S4 was (43%, 42%, 55%, and 36%, p=0.1836) and (44%, 37%, 46%, and 36%, p=0.5166) respectively. There were 209 patients with metastatic disease in 1 or more lymph nodes. The 5-year OS and DFS for S1-S4 was (17%, 31%, 21%, and 27%, p=0.4372) and (17%, 23%, 16%, and 25%, p=0.2726). There were 418 node negative patients. The 5-year OS and DFS rates by S1-S4 was (54%, 51%, 79%, and 26%, p=0.0538) and (55%, 48%, 64%, and 27%, p=0.3703). Multivariate analysis revealed that patients within S3 exhibited a survival benefit adjusted odds ratio (AOR) 0.57 (CI 0.360-0.916, p=0.020). However patients within S1 were more likely to die, AOR 1.74 (CI 1.09-2.78, p=0.020). No survival benefit was demonstrated for patients within (S4) AOR 1.11 (CI 0.60-2.09, p=0.731). There were 171 (27.5%) recurrences with a median time to recurrence of 12.2 (1-101) months. There were no differences in recurrences between strata p=0.129. Conclusions: We demonstrated that patients with ≤8 lymph nodes resected were more likely to die of their disease compared to those with 13-20 nodes resected. Additionally, extended lymphadenectomy (&gt;20 nodes) does not increase the likelihood of proper staging and does not improve patient outcome.
Site-specific relative risks of second primary malignancies among patients with Waldenstrom macroglobulinemia.
Authors: L. M. Brown Philpot, R. P. Ojha, M. J. Felini, S. P. Treon, C. A. Hanzis, Z. R. Hunter, R. Thertulien
Journal: Journal of Clinical Oncology (2011)

e18566 Background: Waldenstrom Macroglobulinemia (WM) is a rare and indolent B-cell malignancy characterized by overproduction of monoclonal immunoglobulin M protein. The long duration of survival for most patients with WM and the use of potentially carcinogenic agents during therapy raise concerns about the development of second primary malignancies. However, the relative risks of second primary malignancies among patients with WM are not well-documented. Therefore, we investigated site-specific relative risks of second primary malignancies among patients with primary WM. Methods: Data from 9 population-based registries of the Surveillance, Epidemiology, and End Results program were used to identify patients diagnosed with primary WM between 1973 and 2007 for whom follow-up data were available. Standardized incidence ratios (SIRs) with corresponding 95% confidence intervals (CIs) of site-specific second primary malignancies were estimated by dividing the number of observed cases of second primary malignancies for the specific site within the WM cohort by the number of expected cases (standardized by age, sex, race/ethnicity, and calendar-year) of secondary primary malignancies for the specific site in the general United States population. Results: The WM cohort (n=1,521) yielded 226 second primary malignancies during 6,958 person-years of follow-up (incidence density = 3,248 cases/100,000 person-years of follow-up). Potentially durable estimates of higher site-specific relative risks were observed for colon (SIR=2.3, 95% CI: 1.6, 3.3), lung (SIR=1.7, 95% CI: 1.2, 2.4), non-Hodgkin lymphoma (SIR=4.9, 95% CI: 3.2, 7.1), myeloma (SIR=4.9, 95% CI: 2.2, 9.2), and acute myeloid leukemia (SIR=5.9, 95% CI: 2.2, 12.8) compared to the general US population. Conclusions: Our results indicate that patients with WM have a higher relative risk of second primary malignancies for several sites. Although the higher relative risks of second primary hematologic malignancies may be treatment- or immunologically-related, the modestly higher relative risks of second primary solid tumors may be the result of detection bias or risk factors shared between WM and the specific solid tumors.
Selective sensitization of human neutrophils to LukGH mediated cytotoxicity by Staphylococcus aureus and IL-8
Authors: Philipp Janesch, Harald Rouha, Susanne Weber, Stefan Malafa, Karin Gross, Barbara Maierhofer, Adriana Badarau, Zehra C. Visram, Lukas Stulik, Eszter Nagy
Journal: Journal of Infection (2017)

Staphylococcus aureus produces up to five bi-component leukocidins - LukSF-PV, gamma-hemolysins AB and CB, LukGH (LukAB) and LukED - to evade innate immunity by lysing phagocytic cells. Species specificity of these leukocidins limits the relevance of animal models, therefore we assessed their individual contribution using human neutrophils.Human polymorphonuclear leukocytes (PMNs) were activated with stimuli relevant during bacterial infections and sensitivity to recombinant leukocidins was measured in cell-viability assays. Leukocidin receptor expression was quantified by flow cytometry.We observed greatly variable sensitivities of different PMN preparations towards LukGH. Activation of PMNs by lipopolysaccharide (LPS) or S. aureus culture supernatant (CS) lacking all leukocidins resulted in higher surface expression of CD11b, the LukGH receptor, and greatly enhanced the sensitivity towards LukGH, eliminating the variability observed with unstimulated cells. In contrast, CS induced a decrease in sensitivity of PMNs to the other four leukocidins and reduced surface staining for their cognate receptors (CXCR1, CXCR2, C5aR, C5L2). Delta-toxin and peptidoglycan mimicked the effect of CS. Moreover, IL-8, an important cytokine in neutrophil activation, also selectively increased LukGH sensitivity. Deletion of lukGH, but not other leukocidin genes, prevented PMN killing upon infection with USA300 CA-MRSA.Inflammatory signals enhance the susceptibility of human PMNs to lysis by LukGH rendering this toxin dominant among the S. aureus leukocidins in vitro.
Clinical significance of SDF-1 isoforms in bladder cancer.
Authors: Marie C Hupe, Miguel Gosalbez, Soum D Lokeshwar, John Shields, Travis J Yates, Vinata B Lokeshwar
Journal: Journal of Clinical Oncology (2015)

334 Background: Stroma-Derived Factor (SDF)-1 is a ligand for chemokine receptors CXCR4 and CXCR7. The six known SDF-1 isoforms are generated by alternative mRNA splicing. While SDF-1 expression has been detected in various malignancies, only a few studies have reported differential expression of SDF-1 isoforms and its clinical significance. In this study we evaluated the expression three SDF-1 isoforms (α,β,γ) in bladder cancer (BCa). Methods: Using quantitative PCR, mRNA levels of SDF-1α, SDF-1β and SDF-1γ were measured in bladder tissues (normal: 25; BCa: 44) and urine specimens (n=210; normal: 28; benign conditions: 74; BCa: 57, history of BCa (HxBCa): 35, Hx other Ca: 8; other Ca: 8) from consecutive patients. The transcript levels were normalized to β-actin. Correlation between SDF1-isoform transcript levels and clinical outcome (metastasis and disease specific mortality (DSM)) was evaluated in univariate and multivariate analyses. Results: Among SDF-1 isoforms, only SDF-1β mRNA was significantly overexpressed by 2.5-6-fold in BCa tissues when compared to normal bladder tissues. While SDF-1α was expressed in bladder tissues, SDF-1γ expression was undetectable. In univariate analysis, pathologic stage, lymph node positivity for tumor, SDF-1α and SDF-1β transcript levels significantly associated with metastasis and DSM. However, in multivariate analysis, stage (P=0.005) and SDF-1β levels (P=0.017) were independent predictors of metastasis and DSM. In exfoliated urothelial cells, only SDF-1β mRNA levels were differentially expressed and having 91.2% sensitivity and 73.8% specificity for detecting BCa. In patients with HxBCa, elevated SDF-1β levels indicated 4.3-fold increased risk (chi-square: 15.1; P=0.0001; relative risk = 4.3) for developing recurrence within 6-months. Conclusions: SDF-1 isoforms are differentially expressed in bladder tissues and exfoliated urothelial cells. SDF-1β mRNA levels in BCa tissues predict poor prognosis. Further, SDF-1β mRNA levels in exfoliated cells detect BCa with high sensitivity and are potential predictors of future recurrence. Support: Grant NCI/NIH R01 CA-72821-14; Women’s Cancer Association – University of Miami.
Using microRNA (miRNA) profiling to differentiate noninvasive and muscle-invasive from metastases of transitional cell carcinoma of the urinary bladder (TCC-UB).
Authors: Obiageli Uchenna Ogbata, Chuan Yang, Lawrence Pfeffer, Somtochukwu Ojukwu, Grant Gaines, Raghavendran Pillappa, Thomas O'Brien, Alva Bowen Weir, Daruka Mahadevan
Journal: Journal of Clinical Oncology (2014)

338 Background: Altered miRNA expression contributes to the pathogenesis of urologic malignancies, including bladder cancer (BC). Individual miRNAs are known to regulate multiple signaling pathways in BC. We hypothesized that identifying miRNA gene expression profiles (GEP) in TCC-UB in the localized (non-invasive Vs invasive) and metastatic setting will help identify predictive and prognostic biomarkers within oncogenic signaling pathways, and novel therapeutic targets. Methods: We conducted a retrospective review of pathology reports of patients with TCC-UB from 2005 - 2013. The samples were categorized into non-invasive, muscle-invasive and metastatic sites. Normal urothelium was used as controls. Bone metastasis and tumors with squamous differentiation were excluded. RNA was extracted from Formalin Fixed Paraffin Embedded (FFPE) tissue blocks and assessed with Nanostring - nCounter miRNA expression assays. The Student t test was used to analyze the data. P value of &lt; 0.05 was considered statistically significant. Results: 36 FFPE tumor samples were identified and analyzed – 18 muscle-invasive (MI), 9 non-invasive (NI), 7 metastatic (M) and 2 normal urothelium (C). Of the over 600 miRNA assessed by the Nanostring microarray, miR21 and 494 were consistently up-regulated, while miR451a, 144-3p, 363-3p, 15b-5p, 200a-3p, 137, 429 were downregulated. Conclusions: MicroRNA profiling differentiates non-muscle invasive versus muscle-invasive BC from metastatic sites. The data provides insights into molecular alterations that will help distinguish signaling pathways of bladder carcinogenesis such as FGFR, PI-3K, STAT-3 and p53. Identified molecular targets will provide an effective and promising strategy to be evaluated in BC cell lines. [Table: see text]