tbuckley/cabot-search huggingface dataset:
A randomized phase II study of gemcitabine (G) and carboplatin (C) with or without cediranib (AZD2171 [CED]) as first-line therapy in advanced non-small cell lung cancer (NSCLC).
Authors: G. K. Dy, S. J. Mandrekar, G. D. Nelson, H. J. Ross, R. H. Ansari, A. P. Lyss, P. J. Stella, S. E. Schild, J. R. Molina, A. A. Adjei
Journal: Journal of Clinical Oncology (2010)

7603 Background: Addition of the vascular endothelial growth factor (VEGF) inhibitor bevacizumab to first-line carboplatin (C) and paclitaxel (P) improved survival and objective response rate (ORR) of patients (pts) with advanced nonsquamous NSCLC and improved ORR and progression-free survival (PFS) when added to first-line cisplatin plus G. The addition of cediranib (CED), a potent oral VEGF receptor tyrosine kinase inhibitor, to C and P resulted in improved ORR and PFS, but was not tolerable at a 30-mg dose in the NCIC BR24 study. The safety and efficacy of CED, with C and G as first-line therapy for advanced NSCLC is reported here. Methods: A lead-in phase to determine the tolerability of CED 45 mg qd was followed by a 2:1 randomization of treatment naïve pts with stage IIIB/IV NSCLC to GC + CED (Arm A) vs GC alone (Arm B) to test the hypothesis that the confirmed objective ORR in A was at least p0+0.15, where p0 is the confirmed ORR in B. The trial had 86% power to test whether the 6-month progression-free survival rate (PFS6) in A was at most 25% versus at least 40% using a type I error rate of 0.09. Results: CED 45 mg qd was not tolerable in the lead-in phase and thus 30 mg qd was used in the randomized pts. 58 and 29 evaluable pts were accrued to (A) and (B), with comparable clinical characteristics in both arms except that proportionately more pts in arm B had squamous histology (28% vs. 16%, p = 0.25). Pts in (A) experienced more grade 3+ nonhematologic adverse events (AEs),71% vs 45%, p = 0.01. The most common grade 3+ AEs in A vs B were: neutropenia (60% vs 45%; p = 0.17), thrombocytopenia (57% vs 45%, p = 0.28), fatigue (14% vs 10%; p = 0.74), and anemia (10% vs. 28%; p = 0.06). Three deaths occurred (1 A, 2 B), none attributed to treatment. The ORR in A vs B was 20% vs. 18% (p = 1.0). PFS6 in A was 46% (26/56; 95% CI: 33%-60%), thus meeting the secondary endpoint. For A vs B, the median PFS was 6.3 vs 4.5 months (HR = 0.69; p = 0.15), and the median OS was 11.8 vs. 9.9 months (HR = 0.66; p = 0.16). Conclusions: CED 30mg qd with GC as first-line therapy is tolerable. While the trial did not meet its primary endpoint of ORR, the secondary endpoint of PFS6 was met with a trend towards improved OS and PFS when CED was added to GC. No significant financial relationships to disclose.
Identification of Genes Associated with Resistance and Response in Vivo to Therapy with Rituximab, Fludarabine and Cyclophosphamide in Patients with Chronic Lymphocytic Leukemia.
Authors: Medhat Shehata, Dita Demirtas, Stefanie Tauber, Susanne Schnabl, Martin Bilban, Martin Hilgarth, Oswald Wagner, Christa Fonatsch, Ilse Schwarzinger, Georg Hopfinger, Karin Eigenberger, Cathrin Skrabs, Daniel Heintel, Edit Anna Porpaczy, Katrina Vanura, Stephan Stilgenbauer, Michael Hallek, Josef D. Schwarzmeier, Rainer Hubmann, Alexander Gaiger, Ulrich Jaeger
Journal: Blood (2008)
<i>AACR Cancer Progress Report 2016:</i> Improving Lives Through Research
Authors: Marlowe S. Tessmer, Kenneth C. Anderson
Journal: Clinical Cancer Research (2016)

Clinical Cancer Research ( CCR ) is once again proud to announce the publication of the journal's annual online supplement, the American Association for Cancer Research (AACR) Cancer Progress Report 2016 . This year's content focuses on the research that contributed to advances in cancer prevention
Integrative Development of a TLR8 Agonist for Ovarian Cancer Chemoimmunotherapy
Authors: Bradley J. Monk, Andrea Facciabene, William E. Brady, Carol A. Aghajanian, Paula M. Fracasso, Joan L. Walker, Heather A. Lankes, Kristi L. Manjarrez, Gwenn-äel H. Danet-Desnoyers, Katherine M. Bell-McGuinn, Carolyn K. McCourt, Alexander Malykhin, Robert M. Hershberg, George Coukos
Journal: Clinical Cancer Research (2016)

Purpose: Immunotherapy is an emerging paradigm for the treatment of cancer, but the potential efficacy of many drugs cannot be sufficiently tested in the mouse. We sought to develop a rational combination of motolimod-a novel Toll-like receptor 8 (TLR8) agonist that stimulates robust innate immune responses in humans but diminished responses in mice-with pegylated liposomal doxorubicin (PLD), a chemotherapeutic that induces immunogenic cell death.Experimental Design: We followed an integrative pharmacologic approach including healthy human volunteers, non-human primates, NSG-HIS ("humanized immune system") mice reconstituted with human CD34+ cells, and patients with cancer to test the effects of motolimod and to assess the combination of motolimod with PLD for the treatment of ovarian cancer.Results: The pharmacodynamic effects of motolimod monotherapy in NSG-HIS mice closely mimicked those in non-human primates and healthy human subjects, whereas the effects of the motolimod/PLD combination in tumor-bearing NSG-HIS mice closely mimicked those in patients with ovarian cancer treated in a phase Ib trial (NCT01294293). The NSG-HIS mouse helped elucidate the mechanism of action of the combination and revealed a positive interaction between the two drugs in vivo The combination produced no dose-limiting toxicities in patients with ovarian cancer. Two subjects (15%) had complete responses and 7 subjects (53%) had disease stabilization. A phase II study was consequently initiated.Conclusions: These results are the first to demonstrate the value of pharmacologic approaches integrating the NSG-HIS mouse, non-human primates, and patients with cancer for the development of novel immunomodulatory anticancer agents with human specificity. Clin Cancer Res; 23(8); 1955-66. ©2016 AACR.
Using flow cytometry to measure MRD as a tool to stratify paediatric patients with ALL and to predict outcome in limited resource countries.
Authors: Oumaya Fawaz, Marianne Karoichane, Lina Assad
Journal: Journal of Clinical Oncology (2015)

e21003 Background: Minimal Residual Disease (MRD) was revealed to be a good predictor of the outcome in children with acute lymphoblastic leukaemia (ALL). This practice is not standard in Low income countries because of lacking resources and expertise. Although RT-PCR is used more often in the measurement of MRD; however it is an expensive procedure that is not available in most of our labs. Therefore multi parametric flow cytometry (MFC) can be an accurate and acceptable alternative in limited-resource countries. We aimed towards finding out reducing the cost by using MFC to assess MRD without affecting the quality of the results. Methods: In our observational retrospective study we evaluated 15 patients (pts) diagnosed between May 2009 and March 2011 with ALL. They were treated according to EORTC 58881 or BFM ALL 2000 protocols. Pts were stratified to standard risk (SR) and high risk (HR) groups (according to the above protocol stratification criteria). MRD by MFC on Bone Marrow samples was measured at different points of therapy staring at the end of induction. If 1stMRD was positive ( > 0.01%) patient was considered to be raised from SR to HR group. The cut-off point was determined at the time of relapse, death, second tumor or last evaluation. Results: Fifteen pts (7 females and 8 males) aged between (8 months and 10.11 years) were treated for ALL. Three pts were in the SR group and the rest were in the HR. One patient was diagnosed as Pre T-ALL and 14 with Pre B-ALL, two of them were CD10 negative and the rest were CD10 positive. Among the 12 pts who had positive MRD at the first measurement (80%), four were from HR group (33%) and relapsed between 7 months to 30 months post diagnosis. One of the SR patient had the 1stMRD positive and according to that he was moved to HR group and treated as such and remained well and alive after 36 months post diagnosis. Event Free Survival (EFS) for 3 years was 46.6% of patients with no relapse, 2nd tumor or death after the diagnosis. Conclusions: We have described a small group of pediatric ALL patients followed up by MRD. Measuring MRD by using MFC made the evaluation and re-stratification of the patients affordable and could be used in the standard management in limited-resource countries.
Multicenter, randomized phase III study of adjuvant chemotherapy for high-risk, node-negative breast cancer comparing tac with fac: 5-year efficacy analysis of the GEICAM 9805 trial
Authors: M. Martin, A. Iluch, M. Segui, A. Ruiz, M. Ramos, E. Adrover Cebrián, A. Rodriguez-Lescure, R. Grosse, L. Calvo Martínez, A. Anton
Journal: Journal of Clinical Oncology (2008)

542 Background: Adjuvant docetaxel improves disease-free survival (DFS) and overall survival (OS) in node-positive breast cancer (BC) patients (pts). However, most BC pts at diagnosis are node-negative, and the role of taxanes in such pts is not established. Methods: Pts aged 18–70, with T1-T3, N0, M0 operable BC and at least one high-risk St Gallen 1998 criterion (grade II/III, size >2 cm, age <35 years, hormone-receptor [HR] negative) were eligible. Pts were stratified by institution and menopausal status and randomized to either TAC (docetaxel 75 mg/m², doxorubicin 50 mg/m², cyclophosphamide 500 mg/m²) or FAC (fluorouracil 500 mg/m², doxorubicin 50 mg/m², cyclophosphamide 500 mg/m²) every 3 weeks for 6 cycles. Radiotherapy was mandatory after conservative surgery and recommended for pts with tumors > 5 cm. Tamoxifen was given for 5 years to all pts with HR-positive tumors. The primary endpoint was DFS defined as BC recurrence, second primary malignancy including contralateral BC, or death from any cause, whichever occurred first. Primary analysis is planned with 5-yr minimum follow-up (f/u). Results: Between July 1999 and December 2001, 1,059 pts were randomized (TAC 539, FAC 520) with 1,047 (98.9%) evaluable. Median age was 50 (TAC) vs 49 years (FAC), with 55% premenopausal in both arms; other characteristics were balanced between arms. Treatment compliance and toxicity have been reported (Martin et al, Ann Oncol 17: 1205). TAC produced significantly more hematologic toxicity than FAC, although primary prophylaxis with G-CSF reduced the rate of neutropenic fever. No toxic deaths were reported. As of June 7, 2007 (median f/u 6 years), 128 pts experienced a DFS event (TAC: 52 pts, FAC 76 pts) with estimated 5-year DFS of 91% for TAC and 86% for FAC (HR 0.66, 95% CI 0.46–0.94, p=0.0202). With 45 deaths (TAC: 19 pts, FAC: 26 pts), the estimated 5-year OS is 97% for TAC and 95% for FAC (HR 0.72, 95% CI 0.40–1.30, p=0.2677). Conclusions: For pts with high-risk node-negative BC, adjuvant TAC was associated with a significant improvement in DFS compared with FAC, with manageable toxicity. Updated results will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis
EpCAM Inhibition Sensitizes Chemoresistant Leukemia to Immune Surveillance
Authors: Xiaohu Zheng, Xiaolei Fan, Binqing Fu, Meijuan Zheng, Aimei Zhang, Kai Zhong, Jialai Yan, Rui Sun, Zhigang Tian, Haiming Wei
Journal: Cancer Research (2016)

The lack of effective tumor-associated antigens restricts the development of targeted therapies against myeloid leukemia. In this study, we compared gene expression patterns of acute myeloid leukemia (AML) and normal bone marrow samples and found that epithelial cell adhesion molecule (EpCAM) is frequently overexpressed in patients with AML, with EpCAM+ leukemic cells exhibiting enhanced chemoresistance and oncogenesis. The chemotherapeutic resistance of EpCAM-positive leukemic cells is a consequence of increased WNT5B signaling. Furthermore, we generated EpCAM antibodies that enabled phagocytosis or cytotoxicity of AML cells by macrophage or natural killer cells, respectively. Finally, EpCAM antibody treatment depleted AML in subcutaneous, disseminated, and intramedullary engrafted mice. In summary, EpCAM exhibits promise as a novel target for the treatment of leukemia. Cancer Res; 77(2); 482-93. ©2016 AACR.
Management of<i>Helicobacter pylori</i>infection—the Maastricht V/Florence Consensus Report
Authors: P Malfertheiner, F Megraud, C A O'Morain, J P Gisbert, E J Kuipers, A T Axon, F Bazzoli, A Gasbarrini, J Atherton, D Y Graham, R Hunt, P Moayyedi, T Rokkas, M Rugge, M Selgrad, S Suerbaum, K Sugano, E M El-Omar
Journal: Gut (2016)

Important progress has been made in the management of Helicobacter pylori infection and in this fifth edition of the Maastricht Consensus Report, key aspects related to the clinical role of H. pylori were re-evaluated in 2015. In the Maastricht V/Florence Consensus Conference, 43 experts from 24 countries examined new data related to H. pylori in five subdivided workshops: (1) Indications/Associations, (2) Diagnosis, (3) Treatment, (4) Prevention/Public Health, (5) H. pylori and the Gastric Microbiota. The results of the individual workshops were presented to a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in the various clinical scenarios.
A LRRK2-Dependent EndophilinA Phosphoswitch Is Critical for Macroautophagy at Presynaptic Terminals
Authors: Sandra-Fausia Soukup, Sabine Kuenen, Roeland Vanhauwaert, Julia Manetsberger, Sergio Hernández-Díaz, Jef Swerts, Nils Schoovaerts, Sven Vilain, Natalia V. Gounko, Katlijn Vints, Ann Geens, Bart De Strooper, Patrik Verstreken
Journal: Neuron (2016)
The Risk of Treatment-Emergent Mania With Methylphenidate in Bipolar Disorder
Authors: Alexander Viktorin, Eleonore Rydén, Michael E. Thase, Zheng Chang, Cecilia Lundholm, Brian M. D’Onofrio, Catarina Almqvist, Patrik K.E. Magnusson, Paul Lichtenstein, Henrik Larsson, Mikael Landén
Journal: American Journal of Psychiatry (2016)

The authors sought to determine the risk of treatment-emergent mania associated with methylphenidate, used in monotherapy or with a concomitant mood-stabilizing medication, in patients with bipolar disorder.Using linked Swedish national registries, the authors identified 2,307 adults with bipolar disorder who initiated therapy with methylphenidate between 2006 and 2014. The cohort was divided into two groups: those with and those without concomitant mood-stabilizing treatment. To adjust for individual-specific confounders, including disorder severity, genetic makeup, and early environmental factors, Cox regression analyses were used, conditioning on individual to compare the rate of mania (defined as hospitalization for mania or a new dispensation of stabilizing medication) 0-3 months and 3-6 months after medication start following nontreated periods.Patients on methylphenidate monotherapy displayed an increased rate of manic episodes within 3 months of medication initiation (hazard ratio=6.7, 95% CI=2.0-22.4), with similar results for the subsequent 3 months. By contrast, for patients taking mood stabilizers, the risk of mania was lower after starting methylphenidate (hazard ratio=0.6, 95% CI=0.4-0.9). Comparable results were observed when only hospitalizations for mania were counted.No evidence was found for a positive association between methylphenidate and treatment-emergent mania among patients with bipolar disorder who were concomitantly receiving a mood-stabilizing medication. This is clinically important given that up to 20% of people with bipolar disorder suffer from comorbid ADHD. Given the markedly increased hazard ratio of mania following methylphenidate initiation in bipolar patients not taking mood stabilizers, careful assessment to rule out bipolar disorder is indicated before initiating monotherapy with psychostimulants.
Preventing tumor escape by targeting a post-proteasomal trimming independent epitope
Authors: Ana Textor, Karin Schmidt, Peter-M. Kloetzel, Bianca Weißbrich, Cynthia Perez, Jehad Charo, Kathleen Anders, John Sidney, Alessandro Sette, Ton N.M. Schumacher, Christin Keller, Dirk H. Busch, Ulrike Seifert, Thomas Blankenstein
Journal: The Journal of Experimental Medicine (2016)

Adoptive T cell therapy (ATT) can achieve regression of large tumors in mice and humans; however, tumors frequently recur. High target peptide-major histocompatibility complex-I (pMHC) affinity and T cell receptor (TCR)-pMHC affinity are thought to be critical to preventing relapse. Here, we show that targeting two epitopes of the same antigen in the same cancer cells via monospecific T cells, which have similar pMHC and pMHC-TCR affinity, results in eradication of large, established tumors when targeting the apparently subdominant but not the dominant epitope. Only the escape but not the rejection epitope required postproteasomal trimming, which was regulated by IFN-γ, allowing IFN-γ–unresponsive cancer variants to evade. The data describe a novel immune escape mechanism and better define suitable target epitopes for ATT.
Prevalence of Severe Joint Pain Among Adults with Doctor-Diagnosed Arthritis — United States, 2002–2014
Authors: Kamil E. Barbour, Michael Boring, Charles G. Helmick, Louise B. Murphy, Jin Qin
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

In the United States, arthritis is a leading cause of disability (1,2); arthritis affected an estimated 52.5 million (22.7%) adults in 2010-2012 and has been projected to affect 78.4 million adults by 2040 (3). Severe joint pain (SJP) can limit function and seriously compromise quality of life (4,5). To determine the prevalence of SJP among adults with doctor-diagnosed arthritis, and the trend in SJP from 2002 to 2014, CDC analyzed data from the National Health Interview Survey. In 2014, approximately one fourth of adults with arthritis had SJP (27.2%). Within selected groups, the age-standardized prevalence of SJP was higher among women (29.2%), non-Hispanic blacks (42.3%), Hispanics (35.8%), and persons with a disability (45.6%), and those who were unable to work (51.9%); prevalence also was higher among those who had fair or poor health (49.1%), obesity (31.7%), heart disease (34.1%), diabetes (40.9%), or serious psychological distress (56.3%). From 2002 to 2014, the age-standardized prevalence of SJP among adults with arthritis did not change (p = 0.14); however, the number of adults with SJP was significantly higher in 2014 (14.6 million) than in 2002 (10.5 million). A strategy to improve pain management (e.g., the 2016 National Pain Strategy*) has been developed, and more widespread dissemination of evidence-based interventions that reduce joint pain in adults with arthritis might reduce the prevalence of SJP.
Effect of hyponatremia on cancer patients' in-patient rehabilitation length of stay.
Authors: Megan Nelson, J. Lynn Palmer, Jack Brian Fu, Janet L. Williams, Rajesh R. Yadav, Ying Guo
Journal: Journal of Clinical Oncology (2013)

e20626 Background: The incidence of hyponatremia in cancer patients has been reported as high as 47%. Hyponatremia is associated with gait and attention impairments, increased falls, increased risk of fractures, and osteoporosis. Our aim is to determine if hyponatremia impact cancer patients’ rehabilitation length of stay, functional outcome, and survival. Methods: Retrospective study was conducted in a tertiary cancer center on two hundreds and ninty-five patients who underwent inpatient cancer rehabilitation between January 27, 2009 through July, 31, 2010. Hyponatremia incidence, rehabilitation length of stay (LOS), functional independence measure (FIM) for ambulation and transfers, and survival information were collected. Results: The incidence of hyponatremia in cancer patients admitted to our inpatient rehabilitation unit was 41.4%. Median rehabilitation LOS for patients with mild (Na 130-134 mEq/L) and moderate-severe (Na&lt;130 mEq/L) hyponatremia was 11 and 15 days, respectively, which was significantly longer than patients with eunatremia (10 days; P = .03). FIM change for ambulation and transfers during inpatient rehabilitation stay was not significantly different, nor was survival significantly different, between different patient groups. Conclusions: A high percentage of patients have hyponatremia upon admission to our inpatient cancer rehabilitation unit, and this is associated with a prolonged rehabilitation LOS.
Predicted cases of U.K. skin squamous cell carcinoma and basal cell carcinoma in 2020 and 2025: horizon planning for National Health Service dermatology and dermatopathology
Authors: P.K.C. Goon, D.C. Greenberg, L. Igali, N.J. Levell
Journal: British Journal of Dermatology (2016)

Dear Editor, Potential skin cancer referrals constitute a dominant and disproportionate number of dermatology referrals from primary care in the U.K. The majority of dermatology and pathology departments in the U.K. are struggling to cope with rising demand for diagnostic and treatment services, and recent austerity measures, with cutbacks in all public service budgets, have also affected the National Health Service (NHS). In this study, we have analysed data from the East of England, specifically East Norfolk and Waveney, and estimated the number of cases of squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) of the skin for 2020 and 2025. It is hoped that the data will assist in the planning of NHS resource allocation in the short and medium term, both for this region and nationally. Data from the Eastern Office, National Cancer Registration Service, Public Health England, were obtained from 2000 to 2013 for SCCs and BCCs and compared with the incidence of these cancers recorded in East Norfolk and Waveney (ENW) (Breckland, Broadland, Great Yarmouth, North Norfolk, Norwich, South Norfolk and Waveney community districts) in the eastern region of the U.K. (East of England), from 2003 to 2015. These areas represent the catchment area of the histopathology service at the Norfolk and Norwich University Hospital. All in situ tumours were excluded.
General practice observed.
Journal: BMJ (1972)

Summary In this paper we describe the use of punched feature cards in a general practice for 18 months. Its advantages are the low cost, speed of information retrieval, visible statistics, computer compatibility, accuracy, confiden tiality, flexibility, and simplicity of setting up and collec tion of information. The system encourages the doctor to ask questions about his practice, and could readily be adopted in other practices.