tbuckley/cabot-search huggingface dataset:
Metformin as an adjuvant treatment for cancer: a systematic review and meta-analysis
Authors: C. Coyle, F.H. Cafferty, C. Vale, R.E. Langley
Journal: Annals of Oncology (2016)

This systematic review and meta-analysis is the first to evaluate the evidence for an association between metformin use and cancer outcomes in patients undergoing treatment with curative intent for individual cancer types. Our findings suggest that adjuvant metformin could have beneficial effects, particularly on cancer outcomes in colorectal and prostate cancer. Randomised trials are warranted.BackgroundMetformin use has been associated with a reduced risk of developing cancer and an improvement in overall cancer survival rates in meta-analyses, but, to date, evidence to support the use of metformin as an adjuvant therapy in individual cancer types has not been presented.Patients and methodsWe systematically searched research databases, conference abstracts and trial registries for any studies reporting cancer outcomes for individual tumour types in metformin users compared with non-users, and extracted data on patients with early-stage cancer. Studies were assessed for design and quality, and a meta-analysis was conducted to quantify the adjuvant effect of metformin on recurrence-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS), to inform future trial design.ResultsOf 7670 articles screened, 27 eligible studies were identified comprising 24 178 participants, all enrolled in observational studies. In those with early-stage colorectal cancer, metformin use was associated with a significant benefit in all outcomes [RFS hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.47–0.85; OS HR 0.69, CI 0.58–0.83; CSS HR 0.58, CI 0.39–0.86]. For men with early-stage prostate cancer, metformin was associated with significant, or borderline significant, benefits in all outcomes (RFS HR 0.83, CI 0.69–1.00; OS HR 0.82, CI 0.73–0.93; CSS HR 0.58, CI 0.37–0.93); however, there was significant heterogeneity between studies. The data suggest that prostate cancer patients treated with radical radiotherapy may benefit more from metformin (RFS HR 0.45, CI 0.29–0.70). In breast and urothelial cancer, no significant benefits were identified. Sufficient data were not available to conduct analyses on the impact of metformin dose and duration.ConclusionsOur findings suggest that metformin could be a useful adjuvant agent, with the greatest benefits seen in colorectal and prostate cancer, particularly in those receiving radical radiotherapy, and randomised, controlled trials which investigate dose and duration, alongside efficacy, are advocated.
Phase I evaluation of an 18-day outpatient IL-2 infusion following AC+t adjuvant chemotherapy of loco-regionally advanced breast cancer (BrCA).
Authors: W. E. Samlowski, J. McGregor, S. S. Buys, J. H. Ward, G. Gregovich, M. Witter, F. B. Petersen
Journal: Journal of Clinical Oncology (2010)

e11051 Background: A high risk for metastatic disease and death exists for patients with loco-regionally advanced BrCA, despite adjuvant chemotherapy. This results from persistence of chemotherapy-resistant tumor cells. IL-2 activated lymphocytes (LAK cells) can kill multidrug resistant cancer cells in vitro. The feasibility of a single 18-day outpatient infusion of IL-2 as consolidation treatment after adjuvant chemotherapy was therefore evaluated. Methods: Eligible patients had breast adenocarcinoma with extensive lymph node involvement (pN2 or pN3), or inflammatory BrCA with no distant metastases. All participants were adult, ambulatory, and had good performance status (ECOG 0-1). Pre-enrollment surgical resection with negative margins and axillary node dissection were required (except for inflammatory breast CA). All patients received 4 cycles of doxorubicin and cyclophosphamide with either subsequent or concurrent taxane therapy (AC+T). Patients were then treated with a single 18-day continuous i.v. IL-2 infusion (3 million IU/d) via ambulatory infusion pump, starting 14 days after last dose of chemotherapy. Patients were evaluated for circulating LAK cells pre- and post-IL-2. Results: This study enrolled 13 patients (median age 47) with adverse features, including advanced nodal status N2 (7) and N3 (7), and inflammatory BrCA (1). Only one patient discontinued the infusion 2 days early, due to fevers. Increases in circulating LAK cells or precursors were detected following IL-2 treatment in all patients. With a minimum of 3 years follow-up (range 3-6 yrs), 11 of 13 patients remain relapse-free and alive. Conclusions: A single 18-day infusion of IL-2 is feasible and well-tolerated following AC+T chemotherapy in women with loco- regionally advanced BrCA. LAK cell activation occurred in all patients. The possible beneficial effect of outpatient IL-2 infusion on progression-free survival will require further evaluation in a planned phase II study. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis
Phase I study of daily or weekly RAD001 (R, everolimus) in combination with pemetrexed (P) in patients with advanced non-small cell lung cancer (NSCLC) previously treated with chemotherapy
Authors: Johan Vansteenkiste, Ben Solomon, Michael Boyer, Juergen Wolf, Neil Miller, Lilla Di Scala, Katarina Petrovic, Sasa Dimitrijevic, Beatrijs Anrys, Eckart Laack
Journal: Journal of Thoracic Oncology (2009)
Telomere Length of Hematopoietic Cells Following Autologous and Allogeneic Stem Cell Transplant (SCT) Reflects That of Grafted Cells: Can the Transplant of Younger Stem Cells Be Exploited To Rejuvenate Hematopoiesis?.
Authors: Alberto Rocci, Marco Ruella, Irene Ricca, Cristiana Carniti, Manuela Zanni, Chiara Lobetti Bodoni, Marco Ladetto, Daniele Caracciolo, Mario Boccadoro, Paolo Corradini, Corrado Tarella
Journal: Blood (2007)
Alisertib (MLN8237)+Paclitaxel versus Placebo+Paclitaxel for Relapsed SCLC
Authors: Taofeek Owonikoko, Tibor Csoszi, Kristiaan Nackaerts, Edgardo Santos, Christina Baik, Erzesbet Juhasz, Vitezslav Kolek, Gyula Ostoros, Jaromir Roubec, Hossein Borghaei, Alberto Chiappori, Christos Chouaid, Margarita Majem, Jane Leonard, Junah Jung, Claudio Dansky Ullmann, David Spigel
Journal: Journal of Thoracic Oncology (2015)
Does sports participation (including level of performance and previous injury) increase risk of osteoarthritis? A systematic review and meta-analysis
Authors: Gui Tran, Toby O Smith, Adam Grice, Sarah R Kingsbury, Paul McCrory, Philip G Conaghan
Journal: British Journal of Sports Medicine (2016)

Background To assess the relationship between sport and osteoarthritis (OA), and specifically to determine whether previous participation, in terms of level (elite or non-elite), type of sport, intensity or previous injury, was associated with OA. Methods This systematic review was developed using PRISMA guidelines. Databases were searched (to May 2016). Narrative review and meta-analysis (with risk ratio (RR) and 95% CIs) approaches were undertaken where appropriate. Study quality was assessed using GRADE. Results 46 studies were included. Narratively, 31 studies reported an increased risk of OA, with 19 demonstrating an increased risk in elite athletes. There was an increased risk after sports exposure (irrespective of type; RR 1.37; 95% CI 1.14 to 1.64; 21 studies). It remained uncertain whether there was a difference in risk of OA between elite and non-elite athletes (RR 1.37; 95% CI 0.84 to 2.22; 17 studies). The risk was higher in soccer (RR 1.42; 95% CI 1.14 to 1.77; 15 studies) but lower in runners (RR 0.86; 95% CI 0.53 to 1.41; 12 studies). 9 studies showed an association with the intensity of sport undertaken and OA. 5 studies demonstrated a higher prevalence of OA following meniscectomies and anterior cruciate ligament tears. Overall, the evidence was of GRADE ‘very low’ quality. Conclusions There was very low-quality evidence to support an increased relationship between sports participation and OA in elite participants. It is unclear whether there is a difference in risk between elite and non-elite participants with further prospective studies needed to evaluate this. Pooled findings suggested that significant injuries were associated with OA in soccer players.
Gender-specific modulation of baseline vascular function and the response to arterial injury by soluble guanylate cyclase
Authors: Pieter Vermeersch, ES Buys, M Glenn, Peter Pokreisz, Marijke Pellens, Hilde Gillijns, Mieke Dewerchin, P Brouckaert, KD Bloch, Stefan Janssens
Journal: Circulation (2005)
Clinical outcome and survival of patients participating in oncology phase I trials.
Authors: A. Florescu, N. G. Chau, K. K. Chan, L. Wang, E. X. Chen, A. M. Oza, L. L. Siu
Journal: Journal of Clinical Oncology (2010)

e13039 Background: The aim of phase I trials is to evaluate safety and pharmacology of a new agent. For patients, the potential for clinical benefit and survival remain key motivators for participation. We examined the RR, OS and CBR (CBR = CR+PD+SD) in phase I trials at our center. Methods: We analyzed 233 consecutive pts who were treated in one of 30 phase I trials from 01/2006 to 07/2009 at Princess Margaret Hospital. Results: Median age was 57 yrs (range 21-88), M:F (%) = 53:47, ECOG 0:1:2 (%) = 45:52:3, median number of prior lines of systemic therapy was 2 (range 0-14), locoregional recurrence = 9%, 1-2 metastatic sites = 59%, >2 metastatic sites = 32%, primary diagnosis of GI malignancy = 46%. 38% of pts received targeted agents alone, 4% received cytotoxic agents alone, and 58% received a targeted agent plus FDA-approved chemotherapy. Median follow-up duration was 224 days (range 23-1,345). Clinical benefit rate (CBR=CR+PR+SD) was 56% (0% CR, 9% PR, 47% SD). CBR at 3 months was 44%, CBR at 6 months was 20%. Median OS for the entire cohort was 320 days (95%CI: 270- 365). Pts with PR had a median OS of 603 days (95%CI 433 -756), pts with SD had a median OS of 501 days (95%CI 365-838), and pts with PD had a median OS of 158 days (95%CI 131-205) (log-rank p<0.0001). Pts with SD ≥ 3 cycles had improved OS compared to pts with PD or SD of 1-2 cycles (log-rank, p <0.0001); median OS was 538 days (95%CI 400-719) vs. 171 days (95%CI 136-204). For pts with SD, the median OS varied according to the number of cycles of SD (log-rank p=0.03). Conclusions: With appropriate pt selection, a significant number of pts with advanced disease may benefit from participation in phase I trials. In the reporting of antitumor activity in phase I trials, it is relevant to specify the proportion of patients with sustained SD (≥ 3 cycles) and/or those with prolonged SD (≥ 6 cycles). Patients with SD lasting < 3 cycles fared poorly and had similar survival outcome as those with PD. Overall survival in pts with SD (based on number of cycles with SD) or PD SD N Dead Censored Median OS 95%CI 1-2 cycles 13 9 4 171 days 78—Not reached 3-4 cycles 23 10 13 400 days 271–719 days 5-6 cycles 29 9 20 414 days 346—Not reached More than 6 25 11 14 606 days 412-963 days PD 87 71 16 158 days 131-205 days No significant financial relationships to disclose.
Senior consultant warns against indiscriminate closures of emergency departments
Authors: Gareth Iacobucci
Journal: BMJ (2016)

One of England’s most senior urgent and emergency care consultants has warned against indiscriminate closures of emergency departments driven by chronic staff shortages.

Several NHS trusts1 2 3 have taken the decision to close or downgrade emergency departments this year owing to a shortage of staff, as the NHS’s performance against key targets, such as percentage of patients seen within four hours in hospital emergency departments, continues to fall amid steadily rising demand.4

Clifford Mann, the former president of the Royal College of Emergency Medicine who was recently appointed as the clinical lead for NHS England’s Accident and Emergency …
P0400 : Microrna signature of early-stage hepatocellular carcinoma arising in HCV-related cirrhosis
Authors: G. Ghittoni, L. Veronese, F. Torello Viera, V. Curti, M. Ghitti, L.L. Rosa, V. Ravetta, L. Siciliani, S. Rossi
Journal: Journal of Hepatology (2015)
Efficacy of a second biologic treatment in androgen receptor-positive (AR+) recurrent/metastatic salivary duct carcinoma (RMSDC).
Authors: Mario Airoldi, Luca Raimondo, Fulvia Pedani, Elisa Bellini, Viviana Contu, Massimiliano Garzaro, Giancarlo Pecorari
Journal: Journal of Clinical Oncology (2014)

e17055 Background: AR+ RMSDC can be treated with an approach including anti-androgen drugs. In case of progression a 2nd line with palliative chemotherapy can be proposed. We report 3 cases of a 2nd line biologic therapy after a complete anti-androgen blockade (CAB) with monthly triptorelin (LHRH analogue) and bicalutamide. Methods: A 59-year-old man with a parotid cancer previously treated with surgery (S) plus post-operative radiation therapy (RT) had a left parotid-region mass + multiple cervical lymphnode metastases who obtained with CAB a 6 months-duration minimal response. Immunohistochemistry evaluation showed a HER 2+++ (FISH amplified) lesion and the patient, with a cardiac left ejection fraction of 70, started a 3-week treatment with Trastuzumab 6 mg/Kg/3 wks. The biologic treatment obtained a partial remission lasting 8 months without any G2 toxicity; after progression a combination of Carboplatin AUC 5.5 d.1 + Taxol 175 mg/m2 d.1 + Trastuzumab 6 mg/Kg d.1 every 3 weeks achieved a minimal response of 4 months duration. A G3 thrombocytopenia was observed. A 65-year-old man previously treated with S+RT for a parotid cancer was treated with CAB for multiple lung mts; patient obtained a partial response of 9 months duration. Immunohistochemistry evaluation showed a strong and diffuse EGFR positivity. The patient received weekly Cetuximab (250 mg/m2) for 10 months achieving a minimal response with a G2 dermatologic toxicity. A 70-year-old man previously treated with S+RT for a parotideal cancer was treated with CAB for a left cervical mass. The patient had obtained a minimal response of 12 months duration with CAB. Results: After progression we started a treatement with Abiraterone Acetate (1000 mg/d) + prednisone (10 mg/d) achieving a minimal reponse lasting 10 months. Due to HER2 +++ (FISH amplified) speciemen positivity a Trastuzumab (6mg/Kg) treatment every 3 weeks obtained an other 9 months-duration minimal response. No toxicity was observed. Conclusions: AR+ RMSDC can be successfully treated with CAB as first line therapy; in our experience a second biologic target therapy can achieve durable objective responses. This approach was well tolerated.
Surveillance du paludisme en Italie en 1997 (et 1998,données provisoires)
Authors: R Romi, D Boccolini, G Majori
Journal: Eurosurveillance (1999)

Le paludisme est la plus frequente des maladies infectieuses importees en Italie. Jusqu'a son eradication il y a pres de 50 ans, le paludisme sevissait a l'etat endemique dans presque tout le pays. Depuis, un systeme de surveillance du paludisme a ete mis en place pour detecter les cas acquis localement qui pourraient indiquer une transmission autochtone.
Nivolumab in Patients (Pts) with Relapsed or Refractory Classical Hodgkin Lymphoma (R/R cHL): Clinical Outcomes from Extended Follow-up of a Phase 1 Study (CA209-039)
Authors: Stephen Ansell, Philippe Armand, John M. Timmerman, Margaret A. Shipp, M Brigid Bradley Garelik, Lili Zhu, Alexander M. Lesokhin
Journal: Blood (2015)
A randomized, double-blind, placebo-controlled phase III trial of zoledronic acid in the prevention of skeletal complications in Japanese women with bone metastases from breast cancer
Authors: N. Kohno, K. Aogi, H. Minami, S. Nakamura, T. Asaga, Y. Iino, T. Watanabe, C. Goessl, Y. Ohashi, S. Takashima
Journal: Journal of Clinical Oncology (2004)

668 Background: In Western populations, zoledronic acid (ZOL) has been proven effective for the prevention of skeletal related events (SREs) from bone metastases. For breast cancer patients, ZOL was shown to be superior to pamidronate. However, the efficacy of ZOL is unknown in Japanese patients. We report here data from the first randomized, placebo-controlled study of ZOL in Japanese patients. Methods: Japanese women with bone metastases from breast cancer were randomized to either ZOL 4mg i.v. infusion over 15 min every 4 weeks or placebo (P). The primary efficacy endpoint was SRE rate ratio (ratio of number of SREs per year for ZOL-treated patients over that for placebo) at 1 year. SREs included pathologic fractures, radiation to bone, spinal cord compression, and surgery to treat or prevent fractures. Secondary endpoints included proportion of patients with ≥1 SRE, time to first SRE and multiple event analysis (MEA: A-G model). Tumor induced hypercalcemia was included in the SRE composite in secondary endpoints. Safety was assessed according to NCI-CTC. Results: 227 patients (median age 53 years) were accrued to the study with 114 in the ZOL arm and 113 in the P arm. Patients were well matched with regard to baseline clinical characteristics. The primary endpoint, SRE rate ratio was 0.61 (p=0.027), indicating that SRE rate was reduced by 39% with ZOL. Proportions of patients with ≥1 SRE were 30.7% and 52.2% for the ZOL and P group, respectively (p=0.001). Median time to first SRE were 360 days in the P group while it did not reach in the ZOL group (p=0.004). Risk ratio of ZOL to P was 0.56 by MEA (p=0.009). ZOL was well tolerated. The most common adverse effects observed more frequently in the ZOL vs. P group were pyrexia (55% vs. 33%), fatigue (44.5% vs. 31.9%) and arthralgia (21.1% vs. 15.9%). One patient in the ZOL group (0.9%) experienced increased serum creatinine. Conclusions: ZOL 4mg demonstrated significant clinical efficacy in Japanese patients for preventing skeletal complications with bone metastases, with an overall 44% reduction in the risk of experiencing SREs as shown by MEA. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Pharmaceuticals Corp.
Adolescent Alcohol Exposure Persistently Impacts Adult Neurobiology and Behavior
Authors: Fulton T. Crews, Ryan P. Vetreno, Margaret A. Broadwater, Donita L. Robinson
Journal: Pharmacological Reviews (2016)

Adolescence is a developmental period when physical and cognitive abilities are optimized, when social skills are consolidated, and when sexuality, adolescent behaviors, and frontal cortical functions mature to adult levels. Adolescents also have unique responses to alcohol compared with adults, being less sensitive to ethanol sedative–motor responses that most likely contribute to binge drinking and blackouts. Population studies find that an early age of drinking onset correlates with increased lifetime risks for the development of alcohol dependence, violence, and injuries. Brain synapses, myelination, and neural circuits mature in adolescence to adult levels in parallel with increased reflection on the consequence of actions and reduced impulsivity and thrill seeking. Alcohol binge drinking could alter human development, but variations in genetics, peer groups, family structure, early life experiences, and the emergence of psychopathology in humans confound studies. As adolescence is common to mammalian species, preclinical models of binge drinking provide insight into the direct impact of alcohol on adolescent development. This review relates human findings to basic science studies, particularly the preclinical studies of the Neurobiology of Adolescent Drinking in Adulthood (NADIA) Consortium. These studies focus on persistent adult changes in neurobiology and behavior following adolescent intermittent ethanol (AIE), a model of underage drinking. NADIA studies and others find that AIE results in the following: increases in adult alcohol drinking, disinhibition, and social anxiety; altered adult synapses, cognition, and sleep; reduced adult neurogenesis, cholinergic, and serotonergic neurons; and increased neuroimmune gene expression and epigenetic modifiers of gene expression. Many of these effects are specific to adolescents and not found in parallel adult studies. AIE can cause a persistence of adolescent-like synaptic physiology, behavior, and sensitivity to alcohol into adulthood. Together, these findings support the hypothesis that adolescent binge drinking leads to long-lasting changes in the adult brain that increase risks of adult psychopathology, particularly for alcohol dependence.
Unraveling the prognostic heterogeneity in patients with advanced melanoma between Australia (OZ) and the United States (US): Preliminary report of the PHAMOUS study.
Authors: M. B. Atkins, G. V. Long, C. L. Warneke, M. Carlino, E. R. DeRose, M. M. Johnson, P. T. Brown, M. Lee, R. Kefford, J. E. Gershenwald
Journal: Journal of Clinical Oncology (2010)

8516 Background: The AJCC Melanoma Task Force analyzed nearly 10,000 patients (pts) with either index or newly diagnosed (dx) distant metastatic melanoma (MM) in order to update the 7th Edition Cancer Staging Manual. A significant disparity in overall survival (OS) from date of MM dx was observed in pts from OZ vs. the US. We hypothesized that this disparity related to either an imbalance in prognostic or treatment factors, and/or tumor biology. Methods: Pts dx with MM between 1/02 and 1/07 known to the MIA (OZ), BIDMC and MDACC (US) surgical units and seen by the associated medical oncology units were identified. Data were collected on prognostic factors analyzed for the AJCC (including more complete LDH levels) as well as additional diagnostic, clinical, and treatment related variables including: number of metastatic sites (met sites), ECOG performance status (PS), diagnostic methods, intensity of follow-up (f/up), extent of CNS disease, as well as treatment approaches. Pts were compared between OZ and US using the Kruskal-Wallis and chi-square tests as appropriate. Cox proportional hazards regression was used to identify independent predictors of OS. Results: Data were collected from 1,031 pts (313 OZ, 718 US). Age and gender at MM dx were similar between the two populations. A significant difference in OS from date of MM dx by country was again observed. The median OS in the US was 15.90 mos (95% CI 14.36, 17.97) compared to 10.18 mos in OZ (95% CI 8.97, 11.60) (p < 0.0001). In a multivariate analysis including site of stage IV disease (M1a vs. M1b/M1c), number of met sites (1 vs. > 1), serum LDH (normal vs. high) and ECOG PS (0 vs. ≥ 1), country remained a significant independent predictor of OS (HR 1.39, 95% CI 1.15-1.68, p = 0.0006). Conclusions: Median OS in pts with MM was significantly worse in OZ than in the US even when major established prognostic variables were included in the model. These data suggest that yet to be discovered clinical or tumor-related prognostic factors or biases related to differences in f/up intensity and/or treatment may explain this survival disparity. The potential independent contribution of these additional factors is currently being explored. No significant financial relationships to disclose.