tbuckley/cabot-search huggingface dataset:
Low day 100 transplant-related mortality (TRM) and relapse rate following clofarabine (CLO) in combination with cytarabine, total body irradiation (TBI), and allogeneic stem cell transplantation (AlloSCT) in children, adolescents, and young adults (CAYA) with poor-risk acute leukemia.
Authors: Kavita Radhakrishnan, Angela M Ricci, Mark B Geyer, Lauren Harrison, Deirdre Duffy, Mehmet Fevzi Ozkaynak, Prakash Satwani, Alexandra C Cheerva, Julie Talano, Theodore Moore, Alfred P Gillio, Randal K. Wada, Lee Ann Baxter-Lowe, Mitchell S. Cairo
Journal: Journal of Clinical Oncology (2012)

6537 Background: CAYA with ALL or AML in third complete remission (CR3), refractory relapse (RR) or induction failure (IF) have an extremely poor prognosis, &lt;20% EFS (Gaynon, BJH, 2005;Wells, JCO, 2003). CLO, an inhibitor of DNA polymerase and ribonucleotide reductase, has significant activity in CAYA with relapsed ALL/AML (Jeha, JCO 2006,2009) and synergy with cytarabine (Faderl, Blood, 2005). We sought to determine safety, day-100 TRM, and overall survival (OS) associated with CLO, cytarabine and TBI followed by AlloSCT in CAYA with poor-risk ALL/AML. Methods: This is a multi-center phase I/II trial of a novel conditioning regimen of CLO (dose escalation: 40mg/m 2 [n=3], 46 mg/m 2 [n=3], 52 mg/m 2 [n=19]) x5d, sequential (4 hrs later) cytarabine 1000 mg/m 2 x6d and TBI (1200cGy) followed by AlloSCT from matched related or unrelated donors in CAYA with ALL/AML in CR3, RR or IF. Patients with unrelated donors received R-ATG. GVHD prophylaxis consisted of tacrolimus and MMF (Bhatia/Cairo, BBMT, 2009). Kaplan-Meier method was used to determine the probabilities of engraftment, GVHD, TRM and OS. Results: 25 pts, median age: 11.3 yrs (1.5-20.7); M:F: 19:6, ALL/AML: 22:3 (10 CR3, 3 RR, 12 IF), 10 related donors, 15 unrelated donors (9 BM/PBSCs, 6 UCB). Median TNC and CD34 dose was 4.47x10 8 /kg and 4.84x10 6 /kg for BM/PBSCs and 4.0x10 7 /kg and 2.8x10 5 /kg for UCB, respectively. Probabilities of neutrophil, platelet engraftment and grade II-IV aGVHD were 100%, 92.9% and 47.5%, respectively. CLO dose was tolerable at 52mg/m 2 /d x5d without dose limiting toxicity. Probability of Day 100 TRM was only 4.3%. Probability of 1-yr PFS and OS were 51% (CI 95 : 28-71%), and 43% (CI 95 : 22-63%) respectively. Conclusions: Preliminary results suggest this novel regimen followed by AlloSCT is safe and well tolerated in CAYA with poor-risk ALL/ AML with CLO dose 52 mg/m 2 . Results are encouraging with respect to low risk of day 100 TRM and leukemic relapse associated with this conditioning regimen in this poor-risk population.
Competing causes of mortality in long-term survivors of head and neck cancer.
Authors: Shrujal S. Baxi, Laura C Pinheiro, Sujata Patil, David G. Pfister, Kevin C. Oeffinger, Elena B. Elkin
Journal: Journal of Clinical Oncology (2012)

6001 Background: Most head and neck cancers (HNC) recur within the first 3 yrs of diagnosis. Patients who live beyond this time point continue to have an excess risk of mortality. We investigated the causes of mortality in 3-yr survivors of HNC. Methods: We completed a retrospective cohort study using the Surveillance Epidemiology and End Results (SEER) database. We identified patients with a diagnosis of non-metastatic HNC between 1992 and 2005 who survived 3 yrs from diagnosis. The primary outcome was death from all-causes, HNC, non-HNC malignancy, cardiovascular disease (CVD), and pulmonary disease (PD). We estimated the age-adjusted standardized mortality ratio (SMR; observed-to-expected (O/E)) and the absolute excess risk (AER; O-E), for all-cause and cause-specific mortality compared to US population data. Results: 31,772 long-term survivors were identified with disease arising in the larynx (40%), oral cavity (29%), oropharynx (26%), nasopharynx (3%) and hypopharynx (1%). In this cohort, 8191 (26%) were female, 3021 (10%) were black and 15,321 (48%) were younger than 60 yrs. In this cohort, 16,697 (53%) had locally-advanced disease and 8353 (26%), 8721(27%) and 13,919 (44%) received radiation alone, surgery alone or both. With a median follow-up of 6.4 years (3-17 years), there were 10,757 deaths due to: HNC (24%), non-HNC malignancy (31%), CVD (21%), PD (6%), and other causes (19%). Compared to the US population, the all-cause SMR was 5.4 (95% CI 5.3-5.6) with an AER of 336 deaths per 10,000 person-years (py). The greatest excess risk was attributable to non-HNC malignancies (956 per 10,000 py), CVD (533 per 10,000 py) and pulmonary disease (136 per 10,000 py). Conclusions: HNC survivors experience excess mortality compared to the general population. Competing causes of mortality challenge long-term survival. Additional analytic studies with detailed data on tobacco history, treatment characteristics and co-morbidities are required to further evaluate associations with specific causes of death and individualize risk in this heterogenous population of survivors.
SAFETY AND EFFICACY OF SMALL VESSEL STENTING WITH 2 MM DRUG ELUTING STENTS IN REAL WORLD CLINICAL PRACTICE
Authors: Joshua Ping Yun Loh, Rajiv Ananthakrishna, Hui Wen Sim, Poay Huan Loh, Edgar Tay, Koo Chan, Mark Chan, Ronald C.H. Lee, Adrian Low, Huay-Cheem Tan
Journal: Journal of the American College of Cardiology (2017)
EFFECTIVENESS AND SAFETY OF DIRECT ORAL ANTICOAGULANTS COMPARED WITH VITAMIN-K ANTAGONISTS: INITIAL RESULTS FROM A COHORT STUDY IN THE NATIONWIDE FRENCH CLAIMS AND HOSPITALIZATION DATABASE (SNIIRAM)
Authors: Nicholas Moore, Patrick Blin, Caroline Dureau, Yves Cottin, Patrick Mismetti, Regis Lassalle, Abdelilah Abouelfath, Jacques Benichou, Cecile Droz
Journal: Journal of the American College of Cardiology (2017)
DO WOMEN BENEFIT FROM EARLY CORONARY ARTERY BYPASS GRAFT AND PERCUTANEOUS CORONARY INTERVENTIONS IN ACUTE CORONARY SYNDROMES: ANSWERS FROM THE SECOND GULF REGISTRY OF ACUTE CORONARY EVENTS
Authors: Amar Salam, Khalid Al Habib, Rajvir Singh, Nidal Asaad, Jassim Suwaidi
Journal: Journal of the American College of Cardiology (2017)
Ovarian cancer: Autologous immunotherapy optimized by remote adjuvancy of a silicate-induced granuloma
Authors: E. Garcia-Giralt, E. Lasalvia-Prisco, S. Cucchi, E. Lasalvia-Galante, J. Vazquez, W. Golomar, J. P. Vincent
Journal: Journal of Clinical Oncology (2006)

12515 Background: Advanced ovarian cancer has been included in several studies about an immunotherapy procedure using an Autologous Thermostable Hemoderivative Vaccine (ATHV) with anti-progressive tumor effect in metastatic malignant disease from different primary tumors (Cancer Biol Ther 2003). Like in most cancer vaccines, the net anti-tumoral effect of ATHV has low intensity despite the addition of several adjuvant steps: immune response enhancement by GM-CSF, immune tolerance break by cyclophosphamide or interference with CD4+CD25+ regulatory cells (E. Lasalvia-Prisco et al. ASCO 2003–2005). The inclusion of another adjuvant immunomodulatory step to ATHV in patients with advanced ovarian cancer was explored in this study. The tested adjuvancy was the local and remote immune-stimulation elicited by a subcutaneous silicate-granuloma (SSG), a phenomenon well proven in preclinical models (RM Fauve et al. Immune Lett 1987; E Fontan et al Proc Nat Acad of Sci 1983). Methods: Twenty four metastasic ovarian cancer patients, chemotherapy resistant, performance status ≤ 2 and CA-125 progressing serum level, were included in this institutional-IRB approved phase I/II trial. The patients were 3-group randomized, submitted to 3 different treatments: I only sympthomatic; II the previously reported ATHV and III ATHV + SSG. Tumor Growth was assessed in each case by the tumor size increase (RECIST measured). Mean difference in the 3 groups was statistically assessed (Student’s test). Results: Tumor Growth was slower in Group II and III than in Group I (p&lt;0.02, p&lt;0.005). Tumor growth was slower in Group III than in Group II (p&lt;0.02). No relevant toxicities were detected. Conclusions: The results support that in advanced ovarian cancer an additional subcutaneous silicate granuloma as adjuvant agent optimizes the tumor growth inhibition through immunotherapy with an autologous thermostable hemoderivative vaccine. The bypass of the immune-ignorance could be discussed as its mechanism of action. No significant financial relationships to disclose.
A phase I study of combination S-1 and weekly docetaxel (TXT) for advanced or recurrent gastric cancer
Authors: T. Ozaki, T. Satoh, T. Shimizu, M. Miyazaki, T. Kurata, M. Fukuoka, K. Tamura
Journal: Journal of Clinical Oncology (2006)

14108 Background: S1, a novel oral fluoropyrimidine derivative, and docetaxel (TXT) have both been identified as active against the treatment of gastric cancer. The two drugs have incompletely overlapping principal toxicities, no cross resistance and have reported synergistic anti-tumor effect in vivo. Response rate of S1 and TXT for advanced gastric cancer were 46.5% and 17.1%, respectively. One report showed that full dose of S1: 80 mg/m 2 daily for 2 weeks and TXT: 40 mg/m 2 intravenously on day1, every 3 weeks was recommend dose (RD), however, dose of TXT has been limited low by neutropenia and allergic reactions. Weekly administration schedule of TXT has been reported as safe and effective treatment for advanced gastric cancer. The primary objective of this study was to determine the maximum tolerated dose (MTD) of combination with S-1 and weekly administration schedule of TXT, the toxicity profile and RD for phase II. Methods: Eligibility criteria includes histologically diagnosed metastatic or recurrent, or unresectable locally advanced gastric cancer, 2 prior regimens were permitted, ECOG PS 0–1, age&gt;20, adequate organ function and written informed consent. Fixed full dose of S1: 80 mg/m 2 daily was administrated orally for 3 weeks. TXT was infused intravenously over 60 minutes (Level 1: 15mg/m 2 ; Level 2: 20mg/m 2 ; Level 3: 25mg/m 2 ) on day1, 8 and 15. This schedule was repeated every 5 weeks. Pharmacokinetic study was performed of S1 on day 7, 8 and of TXT on day1, 8 in order to evaluate the drug interactions. Results: Total 14 patients were registered in this study. Three patients were enrolled at the dose level 1, 6 patients at level 2 and 5 patients at level 3, respectively. No DLTs (dose-limiting toxicities) occurred at both level 1. One out of 6 patients developed DLT of Grade 3 diarrhea at Level 2. DLTs were observed in 3 out of 5 patients at level 3. There are febrile neutropenia, Grade3 stomatitis and continuous Grade 4 neutropenia. Pharmacokinetic study suggested no drug interactions between S1 and TXT. Conclusions: MTD was level 3. RD for multi-center phase II trial was Level 2 (S1 80 mg/m 2 for 3 weeks and TXT: 20 mg/m 2 day1, 8 and 15, every 5 weeks). This combination was active and well tolerated for advanced gastric cancer. No significant financial relationships to disclose.
Breast Cancer Risk and Progressive Histology in Serial Benign Biopsies
Authors: Daniel W Visscher, Ryan D Frank, Jodi M Carter, Robert A Vierkant, Stacey J Winham, Ethan P Heinzen, Brendan T Broderick, Lori A Denison, Teresa M Allers, Joanne L Johnson, Marlene H Frost, Lynn C Hartmann, Amy C Degnim, Derek C Radisky
Journal: JNCI Journal of the National Cancer Institute (2017)

More than 1 million women per year in the United States with benign breast biopsies are known to be at elevated risk for breast cancer (BC), with risk stratified on histologic categories of epithelial proliferation. Here we assessed women who had serial benign biopsies over time and how changes in the histologic classification affected BC risk.In the Mayo Clinic Benign Breast Disease Cohort of 13 466 women, 1414 women had multiple metachronous benign biopsies (10.5%). Both initial and subsequent biopsies were assessed histologically. BC risk for clinical and prognostic factors was assessed using subdistribution models to account for competing risks, and logistic regression/Wilcoxon/chi-square tests to assess covariates. All statistical tests were two-sided.Breast cancer risk for women with serial biopsies, stratified by histologic category in the later biopsies, was similar to women with a single biopsy. We found that changes in histological category between initial and subsequent biopsy statistically significantly impacted BC risk. Women with nonproliferative initial findings and subsequent proliferative findings had an increased risk (hazard ratio [HR] = 1.77, 95% confidence interval [CI] = 1.06 to 2.94, P = .03) compared with no change. Among women with proliferative disease without atypia at initial biopsy, risk decreased if later biopsy regressed to nonproliferative (HR = 0.49, 95% CI = 0.25 to 0.98) and increased if later biopsy showed progression to atypical hyperplasia (HR = 1.49, 95% CI = 0.73 to 3.05) compared with no change ( P = .04).We found that breast cancer risk increases in women with progressive epithelial proliferation over time and decreases in women whose biopsies show less proliferation. This finding has important implications for effective clinical management of the 100 000 women per year who have multiple benign breast biopsies.
Is <i>CTNNB1</i> mutational analysis predictive for progression in patients with sporadic desmoid tumors primarily observed?
Authors: Chiara Colombo, Rosalba Miceli, Julien Domont, Federica Perrone, Marco Fiore, Axel Le Cesne, Cécile Le Pechoux, Alessandro Gronchi, Sylvie Bonvalot
Journal: Journal of Clinical Oncology (2012)

10016 Background: Recently, a wait and see (W&amp;S) approach has been proposed for patients affected by desmoid tumor (DT). Specific CTNNB1 mutation has been correlated with higher risk of recurrence after surgical resection. Aim of this study was to evaluate the correlation between CTNNB1 mutation type and time to progression in patients primarily observed (TTP). Methods: We included all consecutive patients:(1) primarily observed at the Fondazione IRCSS Istituto Nazionale Tumori (Milano, Italy) or Institut Gustave Roussy (Paris, France) for primary sporadic DTs (2) with available FFPE preserved tissue for CTNNB1 mutational analysis, (3) with measurable disease and adequate follow-up. TTP from date of diagnosis to date of radiological (PRO-R) or symptomatic (PRO-S) progression were conducted by Kaplan-Meier method and log-rank test to compare strata. Results: A total of 79 patients (August 2002- July 2011) were included (81% female, 19% male); median age was 34 (IQ, 10-77); sites distribution: abdominal/chest wall (75%), extremity (21%), intra-abdominal (4%). CTNNB1 mutations were observed in 76% of DT samples: 41A (48%), 45F (25%), 45P (2%); 24% were WT. Median follow-up was 19 mo (IQ, 11-28). Thirty-six patients experienced progression (86% PRO-R, 14% PRO-S): 41A (47%), 45F (55%), 45P (100%), WT (26%). An inferior TTP at 36 months was observed in mutated patients vs WT, while no difference was detected for specific subtype mutated patients (WT 68%, 45F 24%, 41/45P 35%, p= 0.045). A variety of different treatments including surgery, hormonal therapy, chemotherapy, antiCOX2 or persistent W&amp;S approach were proposed at progression. Forty-two patients did not receive any treatment. Conclusions: A clear trend towards a lower risk of progression was observed in WT patients, but no difference between specific mutated patients (45F vs 41/45P) was observed. Prospective studies to eventually clarify the potential role of CTNNB1 as prognostic tool in tailoring desmoids treatment are presently underway.
QOL and neurocognitive functions in patients with GBM.
Authors: Christine Marosi, Cornelia Sax, Michael Ackerl, Johannes A. Hainfellner, Georg Widhalm, Karin Dieckmann, Adelheid Woehrer, Matthias Preusser, Birgit Flechl
Journal: Journal of Clinical Oncology (2014)

2062 Background: The importance of QOL and neurocognitive functions in patients with GBM is meanwhile beyond controversy. We followed newly diagnosed patients with GBM during first and second line therapy by evaluating their QOL and cognitive functions Methods: Consecutive newly diagnosed patients with GBM were included in this study. To assess QOL we used the EORTC QLQ C30 and BN20 questionnaire and the computer based NeuroCog FX for neurocognitive assessments. The first assessment was done at the beginning of radiotherapy and was followed by further 5 evaluations every three months Results: 42 patients underwent radiation therapy with concomitant and adjuvant temozolomide. Non enzyme enhancing antiepileptic drugs (NEIAED) was prescribed for the majority of the patients (71%). Median progression free survival was 9.6 months (2.5-30.9 months). Second line therapies applied were bevacizumab in 11 patients (26%), dose-dense temozolomide in 10 patients (24%) and imatinib in 8 patients. (19%). Neither QOL nor cognitive scales differed considering prescription of antiepileptic drugs and type of second line therapy, whereas limited data was available after progression of disease (19/42 patients) Conclusions: QOL and cognition of patients with GBM under NEIAEDs did not differ from patients without NEIAED. Similarly, no difference was found between patients receiving different drugs in second line therapy, however, just a minority of the patients is able to do QOL and cognitive assessments after progression of disease. Clinical trial information: EK 976/2009.
INCIDENCE OF VALVE LEAFLET THROMBOSIS IN TRANSCATHETER AND SURGICAL BIOPROSTHETIC AORTIC VALVES BY 4D CT IMAGING
Authors: Elizabeth Mary Holper, Kathryn Hebeler, Deepika Gopal, William Brinkman, Molly Szerlip, Cecile Mahoney, David Brown, Paul Grayburn, Michael Mack, Ambarish Gopal
Journal: Journal of the American College of Cardiology (2017)
Identification of Early RET+ Deep Dorsal Spinal Cord Interneurons in Gating Pain
Authors: Lian Cui, Xuerong Miao, Lingli Liang, Ishmail Abdus-Saboor, William Olson, Michael S. Fleming, Minghong Ma, Yuan-Xiang Tao, Wenqin Luo
Journal: Neuron (2016)
Abstract A33: Understanding the functional role of enhanced FASN activity in regulating protein translation in DLCBL
Authors: Bandish Kapadia, Ronald Gartenhaus
Journal: Cancer Research (2017)

Abstract Fatty acid synthase (FASN) and protein translational machinery are two emerging cancer therapeutic targets, but their mutual dependency on each other for tumor growth especially in diffuse B-cell large lymphoma (DLBCL) is currently unknown. Therefore, we investigated the functional consequences of enhanced FASN activity on protein translational machinery in both DLCBL cell lines as well as primary samples. Inhibition of FASN activity by a specific inhibitor, C75 or shRNA mediated knockdown, suppressed de novo protein synthesis in SUDHL2, Pfeiffer, and HLY-1 cells, whereas SUDHL4 and SUDHL6 cells displayed minimal impact. Assessing the core translational machinery, the eif4b (eukaryotic initiation factor 4b) levels were depleted in a dose dependent manner of C75 treatment or shRNA mediated knock down of FASN. Mechanistically, eif4b undergoes ubiquitin mediated protein degradation upon FASN depletion. Importantly there seems to be a direct correlation between FASN levels and eif4b expression in DLBCL samples. Depleting the expression of eif4b significantly reduced the cell proliferative capacity of both FASN sensitive as well as resistant DLBCL cells. Screening the interacting protein partners from the available databases, we observed that USP11 interacts and deubiquitinates eif4b which increases its overall stability. Furthermore altering the expression of USP11 or its activity by either chemical inhibition or mutations significantly alters nascent peptide synthesis. Significantly, either down regulating USP11 or inhibiting via small molecules significantly reduced the cell proliferation with increased apoptosis of either FASN activity sensitive or resistant DLBCL cells. USP11 expression was also elevated in DLBCL tissues. Importantly, there is a strong correlation between USP11 and FASN as well as eif4b expression in DLBCL with higher level of this proteins associated with poorer survival. Enhanced FASN activity increased the Akt kinase activity, which phosphorylates USP11 at an evolutionary conserved site. FASN stimulated Akt-meditated phosphorylation events is critical for USP11 recruitment on translational initiation machinery as well as interaction with eif4b to alter protein biosynthesis. These results demonstrate that FASN mediated eif4b/USP11 axis is required for cell proliferation and survival by regulating the translation of proliferative and prosurvival mRNAs. Targeting the eif4b/USP11 axis for therapeutic intervention may add additional treatment options for resistant/relapsed DLBCL patients. Citation Format: Bandish Kapadia, Ronald Gartenhaus. Understanding the functional role of enhanced FASN activity in regulating protein translation in DLCBL. [abstract]. In: Proceedings of the AACR Special Conference on Translational Control of Cancer: A New Frontier in Cancer Biology and Therapy; 2016 Oct 27-30; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2017;77(6 Suppl):Abstract nr A33.
Characteristics of Initial Prescription Episodes and Likelihood of Long-Term Opioid Use — United States, 2006–2015
Authors: Anuj Shah, Corey J. Hayes, Bradley C. Martin
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Because long-term opioid use often begins with treatment of acute pain (1), in March 2016, the CDC Guideline for Prescribing Opioids for Chronic Pain included recommendations for the duration of opioid therapy for acute pain and the type of opioid to select when therapy is initiated (2). However, data quantifying the transition from acute to chronic opioid use are lacking. Patient records from the IMS Lifelink+ database were analyzed to characterize the first episode of opioid use among commercially insured, opioid-naïve, cancer-free adults and quantify the increase in probability of long-term use of opioids with each additional day supplied, day of therapy, or incremental increase in cumulative dose. The largest increments in probability of continued use were observed after the fifth and thirty-first days on therapy; the second prescription; 700 morphine milligram equivalents cumulative dose; and first prescriptions with 10- and 30-day supplies. By providing quantitative evidence on risk for long-term use based on initial prescribing characteristics, these findings might inform opioid prescribing practices.